WorldWideScience

Sample records for nicotine-sensitive neuronal population

  1. Correlations and Neuronal Population Information.

    Science.gov (United States)

    Kohn, Adam; Coen-Cagli, Ruben; Kanitscheider, Ingmar; Pouget, Alexandre

    2016-07-01

    Brain function involves the activity of neuronal populations. Much recent effort has been devoted to measuring the activity of neuronal populations in different parts of the brain under various experimental conditions. Population activity patterns contain rich structure, yet many studies have focused on measuring pairwise relationships between members of a larger population-termed noise correlations. Here we review recent progress in understanding how these correlations affect population information, how information should be quantified, and what mechanisms may give rise to correlations. As population coding theory has improved, it has made clear that some forms of correlation are more important for information than others. We argue that this is a critical lesson for those interested in neuronal population responses more generally: Descriptions of population responses should be motivated by and linked to well-specified function. Within this context, we offer suggestions of where current theoretical frameworks fall short.

  2. Kappe neurons, a novel population of olfactory sensory neurons

    Science.gov (United States)

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-02-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  3. Population Encoding With Hodgkin-Huxley Neurons.

    Science.gov (United States)

    Lazar, Aurel A

    2010-02-01

    The recovery of (weak) stimuli encoded with a population of Hodgkin-Huxley neurons is investigated. In the absence of a stimulus, the Hodgkin-Huxley neurons are assumed to be tonically spiking. The methodology employed calls for 1) finding an input-output (I/O) equivalent description of the Hodgkin-Huxley neuron and 2) devising a recovery algorithm for stimuli encoded with the I/O equivalent neuron(s). A Hodgkin-Huxley neuron with multiplicative coupling is I/O equivalent with an Integrate-and-Fire neuron with a variable threshold sequence. For bandlimited stimuli a perfect recovery of the stimulus can be achieved provided that a Nyquist-type rate condition is satisfied. A Hodgkin-Huxley neuron with additive coupling and deterministic conductances is first-order I/O equivalent with a Project-Integrate-and-Fire neuron that integrates a projection of the stimulus on the phase response curve. The stimulus recovery is formulated as a spline interpolation problem in the space of finite length bounded energy signals. A Hodgkin-Huxley neuron with additive coupling and stochastic conductances is shown to be first-order I/O equivalent with a Project-Integrate-and-Fire neuron with random thresholds. For stimuli modeled as elements of Sobolev spaces the reconstruction algorithm minimizes a regularized quadratic optimality criterion. Finally, all previous recovery results of stimuli encoded with Hodgkin-Huxley neurons with multiplicative and additive coupling, and deterministic and stochastic conductances are extended to stimuli encoded with a population of Hodgkin-Huxley neurons.

  4. Targeting neuronal populations of the striatum

    Directory of Open Access Journals (Sweden)

    Pierre F Durieux

    2011-07-01

    Full Text Available The striatum is critically involved in motor and motivational functions. The dorsal striatum, caudate-putamen, is primarily implicated in motor control and the learning of habits and skills, whereas the ventral striatum, the nucleus accumbens (NAc, is essential for motivation and drug reinforcement. The GABA medium-sized spiny neurons (MSNs, about 95% of striatal neurons, which are targets of the cerebral cortex and the midbrain dopaminergic neurons, form two pathways. The dopamine D1 receptor–positive (D1R striatonigral MSNs project to the medial globus pallidus and substantia nigra pars reticulata (direct pathway and co-express D1R and substance P, whereas dopamine D2 receptor–positive (D2R striatopallidal MSNs project to the lateral globus pallidus (indirect pathway and co-express D2R, adenosine A2A receptor (A2AR and enkephalin (Enk. The specific role of the two efferent pathways in motor and motivational control remained poorly understood until recently. Indeed, D1R striatonigral and D2R striatopallidal neurons, are intermingled and morphologically indistinguishable, and, hence, cannot be functionally dissociated with techniques such as chemical lesions or surgery.In view of the still debated respective functions of projection D2R-striatopallidal and D1R-striatonigral neurons and striatal interneurons, both in motor control and learning but also in more cognitive processes such as motivation, the present review sum up the development of new models and techniques (BAC transgenesis, optogenetic, viral transgenesis allowing the selective targeting of these striatal neuronal populations in adult animal brain to understand their specific roles.

  5. A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

    Science.gov (United States)

    Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

    2016-03-16

    Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery.

  6. Population Coding in Sparsely Connected Networks of Noisy Neurons

    Directory of Open Access Journals (Sweden)

    Bryan Patrick Tripp

    2012-05-01

    Full Text Available This study examines the relationship between population coding and spatial connection statistics in networks of noisy neurons. Encoding of sensory information in the neocortex is thought to require coordinated neural populations, because individual cortical neurons respond to a wide range of stimuli, and exhibit highly variable spiking in response to repeated stimuli. Population coding is rooted in network structure, because cortical neurons receive information only from other neurons, and because the information they encode must be decoded by other neurons, if it is to affect behaviour. However, population coding theory has often ignored network structure, or assumed discrete, fully-connected populations (in contrast with the sparsely connected, continuous sheet of the cortex. In this study, we model a sheet of cortical neurons with sparse, primarily local connections, and find that a network with this structure can encode multiple internal state variables with high signal-to-noise ratio. However, in our model, although connection probability varies with the distance between neurons, we find that the connections cannot be instantiated at random according to these probabilities, but must have additional structure if information is to be encoded with high fidelity.

  7. Temporal structure of neuronal population oscillations with empirical model decomposition

    Science.gov (United States)

    Li, Xiaoli

    2006-08-01

    Frequency analysis of neuronal oscillation is very important for understanding the neural information processing and mechanism of disorder in the brain. This Letter addresses a new method to analyze the neuronal population oscillations with empirical mode decomposition (EMD). Following EMD of neuronal oscillation, a series of intrinsic mode functions (IMFs) are obtained, then Hilbert transform of IMFs can be used to extract the instantaneous time frequency structure of neuronal oscillation. The method is applied to analyze the neuronal oscillation in the hippocampus of epileptic rats in vivo, the results show the neuronal oscillations have different descriptions during the pre-ictal, seizure onset and ictal periods of the epileptic EEG at the different frequency band. This new method is very helpful to provide a view for the temporal structure of neural oscillation.

  8. Relating normalization to neuronal populations across cortical areas.

    Science.gov (United States)

    Ruff, Douglas A; Alberts, Joshua J; Cohen, Marlene R

    2016-09-01

    Normalization, which divisively scales neuronal responses to multiple stimuli, is thought to underlie many sensory, motor, and cognitive processes. In every study where it has been investigated, neurons measured in the same brain area under identical conditions exhibit a range of normalization, ranging from suppression by nonpreferred stimuli (strong normalization) to additive responses to combinations of stimuli (no normalization). Normalization has been hypothesized to arise from interactions between neuronal populations, either in the same or different brain areas, but current models of normalization are not mechanistic and focus on trial-averaged responses. To gain insight into the mechanisms underlying normalization, we examined interactions between neurons that exhibit different degrees of normalization. We recorded from multiple neurons in three cortical areas while rhesus monkeys viewed superimposed drifting gratings. We found that neurons showing strong normalization shared less trial-to-trial variability with other neurons in the same cortical area and more variability with neurons in other cortical areas than did units with weak normalization. Furthermore, the cortical organization of normalization was not random: neurons recorded on nearby electrodes tended to exhibit similar amounts of normalization. Together, our results suggest that normalization reflects a neuron's role in its local network and that modulatory factors like normalization share the topographic organization typical of sensory tuning properties.

  9. Computational modeling of memory allocation in neuronal and dendritic populations

    Directory of Open Access Journals (Sweden)

    George I Kastellakis

    2014-03-01

    Full Text Available Recent studies using molecular and cellular approaches have established that memory is supported by distributed and sparse populations of neurons. The allocation of neurons and synapses to store a long term memory engram is not random, but depends on properties such as neuronal excitability and CREB activation. The consolidation of synaptic plasticity, which is believed to serve long-term memory storage, is dependent on protein availability, and shaped by the mechanism of synaptic tagging and capture. In addition, dendritic protein synthesis allows for compartmentalized plasticity and synapse clustering. The implications of the rules governing long-term memory allocation in neurons and their dendrites are not yet known. To this aim, we present a model that incorporates multiple plasticity-related mechanisms which are known to be active during memory allocation and consolidation. Using this model, we show that memory allocation in neurons and their dendrites is affected by dendritic protein synthesis, and that the late-LTP associativity mechanisms allow related memories to be stored in overlapping populations of neurons.

  10. Emergent properties of interacting populations of spiking neurons.

    Science.gov (United States)

    Cardanobile, Stefano; Rotter, Stefan

    2011-01-01

    Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system. Here, we present and discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks is faithfully reflected by a set of non-linear rate equations, describing all interactions on the population level. These equations are similar in structure to Lotka-Volterra equations, well known by their use in modeling predator-prey relations in population biology, but abundant applications to economic theory have also been described. We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of interacting neuronal populations.

  11. Emergent Properties of Interacting Populations of Spiking Neurons

    Science.gov (United States)

    Cardanobile, Stefano; Rotter, Stefan

    2011-01-01

    Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system. Here, we present and discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks is faithfully reflected by a set of non-linear rate equations, describing all interactions on the population level. These equations are similar in structure to Lotka-Volterra equations, well known by their use in modeling predator-prey relations in population biology, but abundant applications to economic theory have also been described. We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of interacting neuronal populations. PMID:22207844

  12. Neuronal population dynamic model:An analytic approach

    Institute of Scientific and Technical Information of China (English)

    Wentao Huang; Licheng Jiao; Yuelei Xu; Shiping Ma; Jianhua Jia

    2009-01-01

    rom this,the stationary solution and the firing rate of the stationary states are given.Last,by the Fourier transform,the time dependent solution is also obtained.This method can be used to analyze the various dynamic behaviors of neuronal populations.

  13. Striatal NOS1 has dimorphic expression and activity under stress and nicotine sensitization.

    Science.gov (United States)

    Díaz, David; Murias, Azucena Rodrigo; Ávila-Zarza, Carmelo Antonio; Muñoz-Castañeda, Rodrigo; Aijón, José; Alonso, José Ramón; Weruaga, Eduardo

    2015-10-01

    Nicotine exerts its addictive influence through the meso-cortico-limbic reward system, where the striatum is essential. Nicotine addiction involves different neurotransmitters, nitric oxide (NO) being especially important, since it triggers the release of the others by positive feedback. In the nervous system, NO is mainly produced by nitric oxide synthase 1 (NOS1). However, other subtypes of synthases can also synthesize NO, and little is known about the specific role of each isoform in the process of addiction. In parallel, NOS activity and nicotine addiction are also affected by stress and sexual dimorphism. To determine the specific role of this enzyme, we analyzed both NOS expression and NO synthesis in the striatum of wild-type and NOS1-knocked out (KO) mice of both sexes in situations of nicotine sensitization and stress. Our results demonstrated differences between the caudate-putamen (CP) and nucleus accumbens (NA). With respect to NOS1 expression, the CP is a dimorphic region (27.5% lower cell density in males), but with a stable production of NO, exclusively due to this isoform. Thus, the nitrergic system of CP may not be involved in stress or nicotine addiction. Conversely, the NA is much more variable and strongly involved in both situations: its NO synthesis displays dimorphic variations at both basal (68.5% reduction in females) and stress levels (65.9% reduction in males), which disappear when nicotine is infused. Thus, the KO animals showed an increase in NO production (21.7%) in the NA, probably by NOS3, in an attempt to compensate the lack of NOS1.

  14. Emergent properties of interacting populations of spiking neurons

    Directory of Open Access Journals (Sweden)

    Stefano eCardanobile

    2011-12-01

    Full Text Available Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system.Here, we discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks on the population level is faithfully reflected by a set of non-linear rate equations, describing all interactions on this level. These equations, in turn, are similar in structure to the Lotka-Volterra equations, well known by their use in modeling predator-prey relationships in population biology, but abundant applications to economic theory have also been described.We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of neural populations.

  15. Temporal coding by populations of auditory receptor neurons.

    Science.gov (United States)

    Sabourin, Patrick; Pollack, Gerald S

    2010-03-01

    Auditory receptor neurons of crickets are most sensitive to either low or high sound frequencies. Earlier work showed that the temporal coding properties of first-order auditory interneurons are matched to the temporal characteristics of natural low- and high-frequency stimuli (cricket songs and bat echolocation calls, respectively). We studied the temporal coding properties of receptor neurons and used modeling to investigate how activity within populations of low- and high-frequency receptors might contribute to the coding properties of interneurons. We confirm earlier findings that individual low-frequency-tuned receptors code stimulus temporal pattern poorly, but show that coding performance of a receptor population increases markedly with population size, due in part to low redundancy among the spike trains of different receptors. By contrast, individual high-frequency-tuned receptors code a stimulus temporal pattern fairly well and, because their spike trains are redundant, there is only a slight increase in coding performance with population size. The coding properties of low- and high-frequency receptor populations resemble those of interneurons in response to low- and high-frequency stimuli, suggesting that coding at the interneuron level is partly determined by the nature and organization of afferent input. Consistent with this, the sound-frequency-specific coding properties of an interneuron, previously demonstrated by analyzing its spike train, are also apparent in the subthreshold fluctuations in membrane potential that are generated by synaptic input from receptor neurons.

  16. Linking macroscopic with microscopic neuroanatomy using synthetic neuronal populations.

    Science.gov (United States)

    Schneider, Calvin J; Cuntz, Hermann; Soltesz, Ivan

    2014-10-01

    Dendritic morphology has been shown to have a dramatic impact on neuronal function. However, population features such as the inherent variability in dendritic morphology between cells belonging to the same neuronal type are often overlooked when studying computation in neural networks. While detailed models for morphology and electrophysiology exist for many types of single neurons, the role of detailed single cell morphology in the population has not been studied quantitatively or computationally. Here we use the structural context of the neural tissue in which dendritic trees exist to drive their generation in silico. We synthesize the entire population of dentate gyrus granule cells, the most numerous cell type in the hippocampus, by growing their dendritic trees within their characteristic dendritic fields bounded by the realistic structural context of (1) the granule cell layer that contains all somata and (2) the molecular layer that contains the dendritic forest. This process enables branching statistics to be linked to larger scale neuroanatomical features. We find large differences in dendritic total length and individual path length measures as a function of location in the dentate gyrus and of somatic depth in the granule cell layer. We also predict the number of unique granule cell dendrites invading a given volume in the molecular layer. This work enables the complete population-level study of morphological properties and provides a framework to develop complex and realistic neural network models.

  17. Stochastic synchronization of neuronal populations with intrinsic and extrinsic noise.

    KAUST Repository

    Bressloff, Paul C

    2011-05-03

    We extend the theory of noise-induced phase synchronization to the case of a neural master equation describing the stochastic dynamics of an ensemble of uncoupled neuronal population oscillators with intrinsic and extrinsic noise. The master equation formulation of stochastic neurodynamics represents the state of each population by the number of currently active neurons, and the state transitions are chosen so that deterministic Wilson-Cowan rate equations are recovered in the mean-field limit. We apply phase reduction and averaging methods to a corresponding Langevin approximation of the master equation in order to determine how intrinsic noise disrupts synchronization of the population oscillators driven by a common extrinsic noise source. We illustrate our analysis by considering one of the simplest networks known to generate limit cycle oscillations at the population level, namely, a pair of mutually coupled excitatory (E) and inhibitory (I) subpopulations. We show how the combination of intrinsic independent noise and extrinsic common noise can lead to clustering of the population oscillators due to the multiplicative nature of both noise sources under the Langevin approximation. Finally, we show how a similar analysis can be carried out for another simple population model that exhibits limit cycle oscillations in the deterministic limit, namely, a recurrent excitatory network with synaptic depression; inclusion of synaptic depression into the neural master equation now generates a stochastic hybrid system.

  18. The influence of synaptic weight distribution on neuronal population dynamics.

    Directory of Open Access Journals (Sweden)

    Ramakrishnan Iyer

    2013-10-01

    Full Text Available The manner in which different distributions of synaptic weights onto cortical neurons shape their spiking activity remains open. To characterize a homogeneous neuronal population, we use the master equation for generalized leaky integrate-and-fire neurons with shot-noise synapses. We develop fast semi-analytic numerical methods to solve this equation for either current or conductance synapses, with and without synaptic depression. We show that its solutions match simulations of equivalent neuronal networks better than those of the Fokker-Planck equation and we compute bounds on the network response to non-instantaneous synapses. We apply these methods to study different synaptic weight distributions in feed-forward networks. We characterize the synaptic amplitude distributions using a set of measures, called tail weight numbers, designed to quantify the preponderance of very strong synapses. Even if synaptic amplitude distributions are equated for both the total current and average synaptic weight, distributions with sparse but strong synapses produce higher responses for small inputs, leading to a larger operating range. Furthermore, despite their small number, such synapses enable the network to respond faster and with more stability in the face of external fluctuations.

  19. Small-world networks in neuronal populations: a computational perspective.

    Science.gov (United States)

    Zippo, Antonio G; Gelsomino, Giuliana; Van Duin, Pieter; Nencini, Sara; Caramenti, Gian Carlo; Valente, Maurizio; Biella, Gabriele E M

    2013-08-01

    The analysis of the brain in terms of integrated neural networks may offer insights on the reciprocal relation between structure and information processing. Even with inherent technical limits, many studies acknowledge neuron spatial arrangements and communication modes as key factors. In this perspective, we investigated the functional organization of neuronal networks by explicitly assuming a specific functional topology, the small-world network. We developed two different computational approaches. Firstly, we asked whether neuronal populations actually express small-world properties during a definite task, such as a learning task. For this purpose we developed the Inductive Conceptual Network (ICN), which is a hierarchical bio-inspired spiking network, capable of learning invariant patterns by using variable-order Markov models implemented in its nodes. As a result, we actually observed small-world topologies during learning in the ICN. Speculating that the expression of small-world networks is not solely related to learning tasks, we then built a de facto network assuming that the information processing in the brain may occur through functional small-world topologies. In this de facto network, synchronous spikes reflected functional small-world network dependencies. In order to verify the consistency of the assumption, we tested the null-hypothesis by replacing the small-world networks with random networks. As a result, only small world networks exhibited functional biomimetic characteristics such as timing and rate codes, conventional coding strategies and neuronal avalanches, which are cascades of bursting activities with a power-law distribution. Our results suggest that small-world functional configurations are liable to underpin brain information processing at neuronal level.

  20. A Discrete Population of Neurons in the Lateral Amygdala Is Specifically Activated by Contextual Fear Conditioning

    Science.gov (United States)

    Wilson, Yvette M.; Murphy, Mark

    2009-01-01

    There is no clear identification of the neurons involved in fear conditioning in the amygdala. To search for these neurons, we have used a genetic approach, the "fos-tau-lacZ" (FTL) mouse, to map functionally activated expression in neurons following contextual fear conditioning. We have identified a discrete population of neurons in the lateral…

  1. A Discrete Population of Neurons in the Lateral Amygdala Is Specifically Activated by Contextual Fear Conditioning

    Science.gov (United States)

    Wilson, Yvette M.; Murphy, Mark

    2009-01-01

    There is no clear identification of the neurons involved in fear conditioning in the amygdala. To search for these neurons, we have used a genetic approach, the "fos-tau-lacZ" (FTL) mouse, to map functionally activated expression in neurons following contextual fear conditioning. We have identified a discrete population of neurons in the lateral…

  2. Spatio-temporal credit assignment in neuronal population learning.

    Science.gov (United States)

    Friedrich, Johannes; Urbanczik, Robert; Senn, Walter

    2011-06-01

    In learning from trial and error, animals need to relate behavioral decisions to environmental reinforcement even though it may be difficult to assign credit to a particular decision when outcomes are uncertain or subject to delays. When considering the biophysical basis of learning, the credit-assignment problem is compounded because the behavioral decisions themselves result from the spatio-temporal aggregation of many synaptic releases. We present a model of plasticity induction for reinforcement learning in a population of leaky integrate and fire neurons which is based on a cascade of synaptic memory traces. Each synaptic cascade correlates presynaptic input first with postsynaptic events, next with the behavioral decisions and finally with external reinforcement. For operant conditioning, learning succeeds even when reinforcement is delivered with a delay so large that temporal contiguity between decision and pertinent reward is lost due to intervening decisions which are themselves subject to delayed reinforcement. This shows that the model provides a viable mechanism for temporal credit assignment. Further, learning speeds up with increasing population size, so the plasticity cascade simultaneously addresses the spatial problem of assigning credit to synapses in different population neurons. Simulations on other tasks, such as sequential decision making, serve to contrast the performance of the proposed scheme to that of temporal difference-based learning. We argue that, due to their comparative robustness, synaptic plasticity cascades are attractive basic models of reinforcement learning in the brain.

  3. Formation of Neuronal Circuits by Interactions between Neuronal Populations Derived from Different Origins in the Drosophila Visual Center

    Directory of Open Access Journals (Sweden)

    Takumi Suzuki

    2016-04-01

    Full Text Available A wide variety of neurons, including populations derived from different origins, are precisely arranged and correctly connected with their partner to establish a functional neural circuit during brain development. The molecular mechanisms that orchestrate the production and arrangement of these neurons have been obscure. Here, we demonstrate that cell-cell interactions play an important role in establishing the arrangement of neurons of different origins in the Drosophila visual center. Specific types of neurons born outside the medulla primordium migrate tangentially into the developing medulla cortex. During their tangential migration, these neurons express the repellent ligand Slit, and the two layers that the neurons intercalate between express the receptors Robo2 and Robo3. Genetic analysis suggests that Slit-Robo signaling may control the positioning of the layer cells or their processes to form a path for migration. Our results suggest that conserved axon guidance signaling is involved in the interactions between neurons of different origins during brain development.

  4. Deciphering neuronal population codes for acute thermal pain

    Science.gov (United States)

    Chen, Zhe; Zhang, Qiaosheng; Phuong Sieu Tong, Ai; Manders, Toby R.; Wang, Jing

    2017-06-01

    Objective. Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Current pain research mostly focuses on molecular and synaptic changes at the spinal and peripheral levels. However, a complete understanding of pain mechanisms requires the physiological study of the neocortex. Our goal is to apply a neural decoding approach to read out the onset of acute thermal pain signals, which can be used for brain-machine interface. Approach. We used micro wire arrays to record ensemble neuronal activities from the primary somatosensory cortex (S1) and anterior cingulate cortex (ACC) in freely behaving rats. We further investigated neural codes for acute thermal pain at both single-cell and population levels. To detect the onset of acute thermal pain signals, we developed a novel latent state-space framework to decipher the sorted or unsorted S1 and ACC ensemble spike activities, which reveal information about the onset of pain signals. Main results. The state space analysis allows us to uncover a latent state process that drives the observed ensemble spike activity, and to further detect the ‘neuronal threshold’ for acute thermal pain on a single-trial basis. Our method achieved good detection performance in sensitivity and specificity. In addition, our results suggested that an optimal strategy for detecting the onset of acute thermal pain signals may be based on combined evidence from S1 and ACC population codes. Significance. Our study is the first to detect the onset of acute pain signals based on neuronal ensemble spike activity. It is important from a mechanistic viewpoint as it relates to the significance of S1 and ACC activities in the regulation of the acute pain onset.

  5. The effect of correlated neuronal firing and neuronal heterogeneity on population coding accuracy in guinea pig inferior colliculus.

    Directory of Open Access Journals (Sweden)

    Oran Zohar

    Full Text Available It has been suggested that the considerable noise in single-cell responses to a stimulus can be overcome by pooling information from a large population. Theoretical studies indicated that correlations in trial-to-trial fluctuations in the responses of different neurons may limit the improvement due to pooling. Subsequent theoretical studies have suggested that inherent neuronal diversity, i.e., the heterogeneity of tuning curves and other response properties of neurons preferentially tuned to the same stimulus, can provide a means to overcome this limit. Here we study the effect of spike-count correlations and the inherent neuronal heterogeneity on the ability to extract information from large neural populations. We use electrophysiological data from the guinea pig Inferior-Colliculus to capture inherent neuronal heterogeneity and single cell statistics, and introduce response correlations artificially. To this end, we generate pseudo-population responses, based on single-cell recording of neurons responding to auditory stimuli with varying binaural correlations. Typically, when pseudo-populations are generated from single cell data, the responses within the population are statistically independent. As a result, the information content of the population will increase indefinitely with its size. In contrast, here we apply a simple algorithm that enables us to generate pseudo-population responses with variable spike-count correlations. This enables us to study the effect of neuronal correlations on the accuracy of conventional rate codes. We show that in a homogenous population, in the presence of even low-level correlations, information content is bounded. In contrast, utilizing a simple linear readout, that takes into account the natural heterogeneity, even of neurons preferentially tuned to the same stimulus, within the neural population, one can overcome the correlated noise and obtain a readout whose accuracy grows linearly with the size of

  6. Representation of dynamical stimuli in populations of threshold neurons.

    Directory of Open Access Journals (Sweden)

    Tatjana Tchumatchenko

    2011-10-01

    Full Text Available Many sensory or cognitive events are associated with dynamic current modulations in cortical neurons. This raises an urgent demand for tractable model approaches addressing the merits and limits of potential encoding strategies. Yet, current theoretical approaches addressing the response to mean- and variance-encoded stimuli rarely provide complete response functions for both modes of encoding in the presence of correlated noise. Here, we investigate the neuronal population response to dynamical modifications of the mean or variance of the synaptic bombardment using an alternative threshold model framework. In the variance and mean channel, we provide explicit expressions for the linear and non-linear frequency response functions in the presence of correlated noise and use them to derive population rate response to step-like stimuli. For mean-encoded signals, we find that the complete response function depends only on the temporal width of the input correlation function, but not on other functional specifics. Furthermore, we show that both mean- and variance-encoded signals can relay high-frequency inputs, and in both schemes step-like changes can be detected instantaneously. Finally, we obtain the pairwise spike correlation function and the spike triggered average from the linear mean-evoked response function. These results provide a maximally tractable limiting case that complements and extends previous results obtained in the integrate and fire framework.

  7. PINP: a new method of tagging neuronal populations for identification during in vivo electrophysiological recording.

    Directory of Open Access Journals (Sweden)

    Susana Q Lima

    Full Text Available Neural circuits are exquisitely organized, consisting of many different neuronal subpopulations. However, it is difficult to assess the functional roles of these subpopulations using conventional extracellular recording techniques because these techniques do not easily distinguish spikes from different neuronal populations. To overcome this limitation, we have developed PINP (Photostimulation-assisted Identification of Neuronal Populations, a method of tagging neuronal populations for identification during in vivo electrophysiological recording. The method is based on expressing the light-activated channel channelrhodopsin-2 (ChR2 to restricted neuronal subpopulations. ChR2-tagged neurons can be detected electrophysiologically in vivo since illumination of these neurons with a brief flash of blue light triggers a short latency reliable action potential. We demonstrate the feasibility of this technique by expressing ChR2 in distinct populations of cortical neurons using two different strategies. First, we labeled a subpopulation of cortical neurons-mainly fast-spiking interneurons-by using adeno-associated virus (AAV to deliver ChR2 in a transgenic mouse line in which the expression of Cre recombinase was driven by the parvalbumin promoter. Second, we labeled subpopulations of excitatory neurons in the rat auditory cortex with ChR2 based on projection target by using herpes simplex virus 1 (HSV1, which is efficiently taken up by axons and transported retrogradely; we find that this latter population responds to acoustic stimulation differently from unlabeled neurons. Tagging neurons is a novel application of ChR2, used in this case to monitor activity instead of manipulating it. PINP can be readily extended to other populations of genetically identifiable neurons, and will provide a useful method for probing the functional role of different neuronal populations in vivo.

  8. Discontinuous Galerkin finite element method for solving population density functions of cortical pyramidal and thalamic neuronal populations.

    Science.gov (United States)

    Huang, Chih-Hsu; Lin, Chou-Ching K; Ju, Ming-Shaung

    2015-02-01

    Compared with the Monte Carlo method, the population density method is efficient for modeling collective dynamics of neuronal populations in human brain. In this method, a population density function describes the probabilistic distribution of states of all neurons in the population and it is governed by a hyperbolic partial differential equation. In the past, the problem was mainly solved by using the finite difference method. In a previous study, a continuous Galerkin finite element method was found better than the finite difference method for solving the hyperbolic partial differential equation; however, the population density function often has discontinuity and both methods suffer from a numerical stability problem. The goal of this study is to improve the numerical stability of the solution using discontinuous Galerkin finite element method. To test the performance of the new approach, interaction of a population of cortical pyramidal neurons and a population of thalamic neurons was simulated. The numerical results showed good agreement between results of discontinuous Galerkin finite element and Monte Carlo methods. The convergence and accuracy of the solutions are excellent. The numerical stability problem could be resolved using the discontinuous Galerkin finite element method which has total-variation-diminishing property. The efficient approach will be employed to simulate the electroencephalogram or dynamics of thalamocortical network which involves three populations, namely, thalamic reticular neurons, thalamocortical neurons and cortical pyramidal neurons.

  9. Towards a theory of cortical columns: From spiking neurons to interacting neural populations of finite size.

    Directory of Open Access Journals (Sweden)

    Tilo Schwalger

    2017-04-01

    Full Text Available Neural population equations such as neural mass or field models are widely used to study brain activity on a large scale. However, the relation of these models to the properties of single neurons is unclear. Here we derive an equation for several interacting populations at the mesoscopic scale starting from a microscopic model of randomly connected generalized integrate-and-fire neuron models. Each population consists of 50-2000 neurons of the same type but different populations account for different neuron types. The stochastic population equations that we find reveal how spike-history effects in single-neuron dynamics such as refractoriness and adaptation interact with finite-size fluctuations on the population level. Efficient integration of the stochastic mesoscopic equations reproduces the statistical behavior of the population activities obtained from microscopic simulations of a full spiking neural network model. The theory describes nonlinear emergent dynamics such as finite-size-induced stochastic transitions in multistable networks and synchronization in balanced networks of excitatory and inhibitory neurons. The mesoscopic equations are employed to rapidly integrate a model of a cortical microcircuit consisting of eight neuron types, which allows us to predict spontaneous population activities as well as evoked responses to thalamic input. Our theory establishes a general framework for modeling finite-size neural population dynamics based on single cell and synapse parameters and offers an efficient approach to analyzing cortical circuits and computations.

  10. Distinct neuronal populations in the basal forebrain encode motivational salience and movement

    Directory of Open Access Journals (Sweden)

    Irene eAvila

    2014-12-01

    Full Text Available Basal forebrain (BF is one of the largest cortically-projecting neuromodulatory systems in the mammalian brain, and plays a key role in attention, arousal, learning and memory. The cortically projecting BF neurons, comprised of mainly magnocellular cholinergic and GABAergic neurons, are widely distributed across several brain regions that spatially overlap with the ventral striatopallidal system at the ventral pallidum (VP. As a first step toward untangling the respective functions of spatially overlapping BF and VP systems, the goal of this study was to comprehensively characterize the behavioral correlates and physiological properties of heterogeneous neuronal populations in the BF region. We found that, while rats performed a reward-biased simple reaction time task, distinct neuronal populations encode either motivational salience or movement information. The motivational salience of attended stimuli is encoded by phasic bursting activity of a large population of slow-firing neurons that have large, broad, and complex action potential waveforms. In contrast, two other separate groups of neurons encode movement-related information, and respectively increase and decrease firing rates while rats maintained fixation. These two groups of neurons mostly have higher firing rates and small, narrow action potential waveforms. These results support the conclusion that multiple neurophysiologically distinct neuronal populations in the BF region operate independently of each other as parallel functional circuits. These observations also caution against interpreting neuronal activity in this region as a homogeneous population reflecting the function of either BF or VP alone. We suggest that salience- and movement-related neuronal populations likely correspond to BF corticopetal neurons and VP neurons, respectively.

  11. Neuronal population coding of perceived and memorized visual features in the lateral prefrontal cortex

    Science.gov (United States)

    Mendoza-Halliday, Diego; Martinez-Trujillo, Julio C.

    2017-01-01

    The primate lateral prefrontal cortex (LPFC) encodes visual stimulus features while they are perceived and while they are maintained in working memory. However, it remains unclear whether perceived and memorized features are encoded by the same or different neurons and population activity patterns. Here we record LPFC neuronal activity while monkeys perceive the motion direction of a stimulus that remains visually available, or memorize the direction if the stimulus disappears. We find neurons with a wide variety of combinations of coding strength for perceived and memorized directions: some neurons encode both to similar degrees while others preferentially or exclusively encode either one. Reading out the combined activity of all neurons, a machine-learning algorithm reliably decode the motion direction and determine whether it is perceived or memorized. Our results indicate that a functionally diverse population of LPFC neurons provides a substrate for discriminating between perceptual and mnemonic representations of visual features. PMID:28569756

  12. Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

    Directory of Open Access Journals (Sweden)

    Siebler Mario

    2009-08-01

    Full Text Available Abstract Background The present work was performed to investigate the ability of two different embryonic stem (ES cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs, progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far. Results While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2, only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2–4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated

  13. Context Fear Learning Specifically Activates Distinct Populations of Neurons in Amygdala and Hypothalamus

    Science.gov (United States)

    Trogrlic, Lidia; Wilson, Yvette M.; Newman, Andrew G.; Murphy, Mark

    2011-01-01

    The identity and distribution of neurons that are involved in any learning or memory event is not known. In previous studies, we identified a discrete population of neurons in the lateral amygdala that show learning-specific activation of a c-"fos"-regulated transgene following context fear conditioning. Here, we have extended these studies to…

  14. Generalized cable formalism to calculate the magnetic field of single neurons and neuronal populations.

    Science.gov (United States)

    Bedard, Claude; Destexhe, Alain

    2014-10-01

    Neurons generate magnetic fields which can be recorded with macroscopic techniques such as magnetoencephalography. The theory that accounts for the genesis of neuronal magnetic fields involves dendritic cable structures in homogeneous resistive extracellular media. Here we generalize this model by considering dendritic cables in extracellular media with arbitrarily complex electric properties. This method is based on a multiscale mean-field theory where the neuron is considered in interaction with a "mean" extracellular medium (characterized by a specific impedance). We first show that, as expected, the generalized cable equation and the standard cable generate magnetic fields that mostly depend on the axial current in the cable, with a moderate contribution of extracellular currents. Less expected, we also show that the nature of the extracellular and intracellular media influence the axial current, and thus also influence neuronal magnetic fields. We illustrate these properties by numerical simulations and suggest experiments to test these findings.

  15. Interconnection and synchronization of neuronal populations in the mouse medial septum/diagonal band of Broca.

    Science.gov (United States)

    Leão, Richardson N; Targino, Zé H; Colom, Luis V; Fisahn, André

    2015-02-01

    The medial septum/diagonal band of Broca (MS/DBB) is crucial for hippocampal theta rhythm generation (4-12 Hz). However, the mechanisms behind theta rhythmogenesis are still under debate. The MS/DBB consists, in its majority, of three neuronal populations that use acetylcholine, GABA, or glutamate as neurotransmitter. While the firing patterns of septal neurons enable the MS/DBB to generate rhythmic output critical for the generation of the hippocampal theta rhythm, the ability to synchronize these action potentials is dependent on the interconnectivity between the three major MS/DBB neuronal populations, yet little is known about intraseptal connections. Here we assessed the connectivity between pairs of MS/DBB neurons with paired patch-clamp recordings. We found that glutamatergic and GABAergic neurons provide intraseptal connections and produce sizable currents in MS/DBB postsynaptic cells. We also analyzed linear and nonlinear relationships between the action potentials fired by pairs of neurons belonging to various MS/DBB neuronal populations. Our results show that while the synchrony index for action potential firing was significantly higher in pairs of GABAergic neurons, coherence of action potential firing in the theta range was similarly low in all pairs analyzed. Recurrence analysis demonstrated that individual action potentials were more recurrent in cholinergic neurons than in other cell types. Implementing sparse connectivity in a computer model of the MS/DBB network reproduced our experimental data. We conclude that the interplay between the intrinsic membrane properties of different MS/DBB neuronal populations and the connectivity among these populations underlie the ability of the MS/DBB network to critically contribute to hippocampal theta rhythmogenesis.

  16. Convergent processing of both positive and negative motivational signals by the VTA dopamine neuronal populations.

    Directory of Open Access Journals (Sweden)

    Dong V Wang

    Full Text Available Dopamine neurons in the ventral tegmental area (VTA have been traditionally studied for their roles in reward-related motivation or drug addiction. Here we study how the VTA dopamine neuron population may process fearful and negative experiences as well as reward information in freely behaving mice. Using multi-tetrode recording, we find that up to 89% of the putative dopamine neurons in the VTA exhibit significant activation in response to the conditioned tone that predict food reward, while the same dopamine neuron population also respond to the fearful experiences such as free fall and shake events. The majority of these VTA putative dopamine neurons exhibit suppression and offset-rebound excitation, whereas ∼25% of the recorded putative dopamine neurons show excitation by the fearful events. Importantly, VTA putative dopamine neurons exhibit parametric encoding properties: their firing change durations are proportional to the fearful event durations. In addition, we demonstrate that the contextual information is crucial for these neurons to respectively elicit positive or negative motivational responses by the same conditioned tone. Taken together, our findings suggest that VTA dopamine neurons may employ the convergent encoding strategy for processing both positive and negative experiences, intimately integrating with cues and environmental context.

  17. Different requirements for GFRα2-signaling in three populations of cutaneous sensory neurons.

    Directory of Open Access Journals (Sweden)

    Jussi Kupari

    Full Text Available Many primary sensory neurons in mouse dorsal root ganglia (DRG express one or several GFRα's, the ligand-binding receptors of the GDNF family, and their common signaling receptor Ret. GFRα2, the principal receptor for neurturin, is expressed in most of the small nonpeptidergic DRG neurons, but also in some large DRG neurons that start to express Ret earlier. Previously, GFRα2 has been shown to be crucial for the soma size of small nonpeptidergic nociceptors and for their target innervation of glabrous epidermis. However, little is known about this receptor in other Ret-expressing DRG neuron populations. Here we have investigated two populations of Ret-positive low-threshold mechanoreceptors that innervate different types of hair follicles on mouse back skin: the small C-LTMRs and the large Aβ-LTMRs. Using GFRα2-KO mice and immunohistochemistry we found that, similar to the nonpeptidergic nociceptors, GFRα2 controls the cell size but not the survival of both C-LTMRs and Aβ-LTMRs. In contrast to the nonpeptidergic neurons, GFRα2 is not required for the target innervation of C-LTMRs and Aβ-LTMRs in the back skin. These results suggest that different factors drive target innervation in these three populations of neurons. In addition, the observation that the large Ret-positive DRG neurons lack GFRα2 immunoreactivity in mature animals suggests that these neurons switch their GFRα signaling pathways during postnatal development.

  18. Energy-efficient population coding constrains network size of a neuronal array system

    Science.gov (United States)

    Yu, Lianchun; Zhang, Chi; Liu, Liwei; Yu, Yuguo

    2016-01-01

    We consider the open issue of how the energy efficiency of the neural information transmission process, in a general neuronal array, constrains the network size, and how well this network size ensures the reliable transmission of neural information in a noisy environment. By direct mathematical analysis, we have obtained general solutions proving that there exists an optimal number of neurons in the network, where the average coding energy cost (defined as energy consumption divided by mutual information) per neuron passes through a global minimum for both subthreshold and superthreshold signals. With increases in background noise intensity, the optimal neuronal number decreases for subthreshold signals and increases for suprathreshold signals. The existence of an optimal number of neurons in an array network reveals a general rule for population coding that states that the neuronal number should be large enough to ensure reliable information transmission that is robust to the noisy environment but small enough to minimize energy cost.

  19. Transient neuronal populations are required to guide callosal axons: a role for semaphorin 3C.

    Directory of Open Access Journals (Sweden)

    Mathieu Niquille

    2009-10-01

    Full Text Available The corpus callosum (CC is the main pathway responsible for interhemispheric communication. CC agenesis is associated with numerous human pathologies, suggesting that a range of developmental defects can result in abnormalities in this structure. Midline glial cells are known to play a role in CC development, but we here show that two transient populations of midline neurons also make major contributions to the formation of this commissure. We report that these two neuronal populations enter the CC midline prior to the arrival of callosal pioneer axons. Using a combination of mutant analysis and in vitro assays, we demonstrate that CC neurons are necessary for normal callosal axon navigation. They exert an attractive influence on callosal axons, in part via Semaphorin 3C and its receptor Neuropilin-1. By revealing a novel and essential role for these neuronal populations in the pathfinding of a major cerebral commissure, our study brings new perspectives to pathophysiological mechanisms altering CC formation.

  20. Faithful representation of stimuli with a population of integrate-and-fire neurons.

    Science.gov (United States)

    Lazar, Aurel A; Pnevmatikakis, Eftychios A

    2008-11-01

    We consider a formal model of stimulus encoding with a circuit consisting of a bank of filters and an ensemble of integrate-and-fire neurons. Such models arise in olfactory systems, vision, and hearing. We demonstrate that bandlimited stimuli can be faithfully represented with spike trains generated by the ensemble of neurons. We provide a stimulus reconstruction scheme based on the spike times of the ensemble of neurons and derive conditions for perfect recovery. The key result calls for the spike density of the neural population to be above the Nyquist rate. We also show that recovery is perfect if the number of neurons in the population is larger than a threshold value. Increasing the number of neurons to achieve a faithful representation of the sensory world is consistent with basic neurobiological thought. Finally we demonstrate that in general, the problem of faithful recovery of stimuli from the spike train of single neurons is ill posed. The stimulus can be recovered, however, from the information contained in the spike train of a population of neurons.

  1. Phase-coherence transitions and communication in the gamma range between delay-coupled neuronal populations.

    Directory of Open Access Journals (Sweden)

    Alessandro Barardi

    2014-07-01

    Full Text Available Synchronization between neuronal populations plays an important role in information transmission between brain areas. In particular, collective oscillations emerging from the synchronized activity of thousands of neurons can increase the functional connectivity between neural assemblies by coherently coordinating their phases. This synchrony of neuronal activity can take place within a cortical patch or between different cortical regions. While short-range interactions between neurons involve just a few milliseconds, communication through long-range projections between different regions could take up to tens of milliseconds. How these heterogeneous transmission delays affect communication between neuronal populations is not well known. To address this question, we have studied the dynamics of two bidirectionally delayed-coupled neuronal populations using conductance-based spiking models, examining how different synaptic delays give rise to in-phase/anti-phase transitions at particular frequencies within the gamma range, and how this behavior is related to the phase coherence between the two populations at different frequencies. We have used spectral analysis and information theory to quantify the information exchanged between the two networks. For different transmission delays between the two coupled populations, we analyze how the local field potential and multi-unit activity calculated from one population convey information in response to a set of external inputs applied to the other population. The results confirm that zero-lag synchronization maximizes information transmission, although out-of-phase synchronization allows for efficient communication provided the coupling delay, the phase lag between the populations, and the frequency of the oscillations are properly matched.

  2. [Selective histochemical identification of neuronal cell populations using fucose-specific lectins].

    Science.gov (United States)

    Akkuratov, E G; Nozdrachev, A D

    2004-01-01

    We studied lectin histochemical properties of structures of caudal ganglia of the vagus nerve and ganglion of the trigeminal nerve in white rats using fucose-specific conjugates to peroxidase. Morphological samples were processed on a computer video analyzer. Metrical and optical indices of the afferent neurons were analyzed. The obtained data demonstrate different topography of glycoconjugates in the afferent ganglia. Application of recent image processing techniques allows revealing neuron populations in afferent ganglia of rats undetectable by standard morphological techniques.

  3. Glut4 expression defines an insulin-sensitive hypothalamic neuronal population.

    Science.gov (United States)

    Ren, Hongxia; Yan, Shijun; Zhang, Baifang; Lu, Taylor Y; Arancio, Ottavio; Accili, Domenico

    2014-07-01

    Insulin signaling in the CNS modulates satiety and glucose metabolism, but insulin target neurons are poorly defined. We have previously shown that ablation of insulin receptors (InsR) in Glut4-expressing tissues results in systemic abnormalities of insulin action. We propose that Glut4 neurons constitute an insulin-sensitive neuronal subset. We determined their gene expression profiles using flow-sorted hypothalamic Glut4 neurons. Gene ontology analyses demonstrated that Glut4 neurons are enriched in olfacto-sensory receptors, M2 acetylcholine receptors, and pathways required for the acquisition of insulin sensitivity. Following genetic ablation of InsR, transcriptome profiling of Glut4 neurons demonstrated impairment of the insulin, peptide hormone, and cAMP signaling pathways, with a striking upregulation of anion homeostasis pathway. Accordingly, hypothalamic InsR-deficient Glut4 neurons showed reduced firing activity. The molecular signature of Glut4 neurons is consistent with a role for this neural population in the integration of olfacto-sensory cues with hormone signaling to regulate peripheral metabolism.

  4. An integrated calcium imaging processing toolbox for the analysis of neuronal population dynamics.

    Directory of Open Access Journals (Sweden)

    Sebastián A Romano

    2017-06-01

    Full Text Available The development of new imaging and optogenetics techniques to study the dynamics of large neuronal circuits is generating datasets of unprecedented volume and complexity, demanding the development of appropriate analysis tools. We present a comprehensive computational workflow for the analysis of neuronal population calcium dynamics. The toolbox includes newly developed algorithms and interactive tools for image pre-processing and segmentation, estimation of significant single-neuron single-trial signals, mapping event-related neuronal responses, detection of activity-correlated neuronal clusters, exploration of population dynamics, and analysis of clusters' features against surrogate control datasets. The modules are integrated in a modular and versatile processing pipeline, adaptable to different needs. The clustering module is capable of detecting flexible, dynamically activated neuronal assemblies, consistent with the distributed population coding of the brain. We demonstrate the suitability of the toolbox for a variety of calcium imaging datasets. The toolbox open-source code, a step-by-step tutorial and a case study dataset are available at https://github.com/zebrain-lab/Toolbox-Romano-et-al.

  5. An integrated calcium imaging processing toolbox for the analysis of neuronal population dynamics.

    Science.gov (United States)

    Romano, Sebastián A; Pérez-Schuster, Verónica; Jouary, Adrien; Boulanger-Weill, Jonathan; Candeo, Alessia; Pietri, Thomas; Sumbre, Germán

    2017-06-01

    The development of new imaging and optogenetics techniques to study the dynamics of large neuronal circuits is generating datasets of unprecedented volume and complexity, demanding the development of appropriate analysis tools. We present a comprehensive computational workflow for the analysis of neuronal population calcium dynamics. The toolbox includes newly developed algorithms and interactive tools for image pre-processing and segmentation, estimation of significant single-neuron single-trial signals, mapping event-related neuronal responses, detection of activity-correlated neuronal clusters, exploration of population dynamics, and analysis of clusters' features against surrogate control datasets. The modules are integrated in a modular and versatile processing pipeline, adaptable to different needs. The clustering module is capable of detecting flexible, dynamically activated neuronal assemblies, consistent with the distributed population coding of the brain. We demonstrate the suitability of the toolbox for a variety of calcium imaging datasets. The toolbox open-source code, a step-by-step tutorial and a case study dataset are available at https://github.com/zebrain-lab/Toolbox-Romano-et-al.

  6. Deciphering elapsed time and predicting action timing from neuronal population signals

    Directory of Open Access Journals (Sweden)

    Shigeru eShinomoto

    2011-06-01

    Full Text Available The proper timing of actions is necessary for the survival of animals, whether in hunting prey or escaping predators. Researchers in the field of neuroscience have begun to explore neuronal signals correlated to behavioral interval timing. Here, we attempt to decode the lapse of time from neuronal population signals recorded from the frontal cortex of monkeys performing a multiple-interval timing task. We designed a Bayesian algorithm that deciphers temporal information hidden in noisy signals dispersed within the activity of individual neurons recorded from monkeys trained to determine the passage of time before initiating an action. With this decoder, we succeeded in estimating the elapsed time with a precision of approximately 1 sec throughout the relevant behavioral period from firing rates of 25 neurons in the pre-supplementary motor area. Further, an extended algorithm makes it possible to determine the total length of the time interval required to wait in each trial. This enables observers to predict the moment at which the subject will take action from the neuronal activity in the brain. A separate population analysis reveals that the neuronal ensemble represents the lapse of time in a manner scaled relative to the scheduled interval, rather than representing it as the real physical time.

  7. Identification of specific sensory neuron populations for study of expressed ion channels.

    Science.gov (United States)

    Ramachandra, Renuka; McGrew, Stephanie; Elmslie, Keith

    2013-12-24

    Sensory neurons transmit signals from various parts of the body to the central nervous system. The soma for these neurons are located in the dorsal root ganglia that line the spinal column. Understanding the receptors and channels expressed by these sensory afferent neurons could lead to novel therapies for disease. The initial step is to identify the specific subset of sensory neurons of interest. Here we describe a method to identify afferent neurons innervating the muscles by retrograde labeling using a fluorescent dye DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate). Understanding the contribution of ion channels to excitation of muscle afferents could help to better control excessive excitability induced by certain disease states such as peripheral vascular disease or heart failure. We used two approaches to identify the voltage dependent ion channels expressed by these neurons, patch clamp electrophysiology and immunocytochemistry. While electrophysiology plus pharmacological blockers can identify functional ion channel types, we used immunocytochemistry to identify channels for which specific blockers were unavailable and to better understand the ion channel distribution pattern in the cell population. These techniques can be applied to other areas of the nervous system to study specific neuronal groups.

  8. Mouse V1 population correlates of visual detection rely on heterogeneity within neuronal response patterns

    NARCIS (Netherlands)

    J.S. Montijn; P.M. Goltstein; C.M.A. Pennartz

    2015-01-01

    Previous studies have demonstrated the importance of the primary sensory cortex for the detection, discrimination and awareness of visual stimuli, but it is unknown how neuronal populations in this area process detected and undetected stimuli differently. Critical differences may reside in the mean

  9. A journey through neural space: Neuronal population correlates of visual processing and perception

    NARCIS (Netherlands)

    J.S. Montijn

    2016-01-01

    Single neurons can often show strong correlations with an animal’s behavioral output, but it is currently unclear what role population-level interactions play in visual processing and perception. To address these questions, I performed several two-photon calcium imaging experiments in layers 2/3 of

  10. Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states

    Directory of Open Access Journals (Sweden)

    Allison eGraebner

    2015-08-01

    Full Text Available A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools have greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

  11. Conditional Viral Tract Tracing Delineates the Projections of the Distinct Kisspeptin Neuron Populations to Gonadotropin-Releasing Hormone (GnRH) Neurons in the Mouse.

    Science.gov (United States)

    Yip, Siew Hoong; Boehm, Ulrich; Herbison, Allan E; Campbell, Rebecca E

    2015-07-01

    Kisspeptin neurons play an essential role in the regulation of fertility through direct regulation of the GnRH neurons. However, the relative contributions of the two functionally distinct kisspeptin neuron subpopulations to this critical regulation are not fully understood. Here we analyzed the specific projection patterns of kisspeptin neurons originating from either the rostral periventricular nucleus of the third ventricle (RP3V) or the arcuate nucleus (ARN) using a cell-specific, viral-mediated tract-tracing approach. We stereotaxically injected a Cre-dependent recombinant adenovirus encoding farnesylated enhanced green fluorescent protein into the ARN or RP3V of adult male and female mice expressing Cre recombinase in kisspeptin neurons. Fibers from ARN kisspeptin neurons projected widely; however, we did not find any evidence for direct contact with GnRH neuron somata or proximal dendrites in either sex. In contrast, we identified RP3V kisspeptin fibers in close contact with GnRH neuron somata and dendrites in both sexes. Fibers originating from both the RP3V and ARN were observed in close contact with distal GnRH neuron processes in the ARN and in the lateral and internal aspects of the median eminence. Furthermore, GnRH nerve terminals were found in close contact with the proximal dendrites of ARN kisspeptin neurons in the ARN, and ARN kisspeptin fibers were found contacting RP3V kisspeptin neurons in both sexes. Together these data delineate selective zones of kisspeptin neuron inputs to GnRH neurons and demonstrate complex interconnections between the distinct kisspeptin populations and GnRH neurons.

  12. Coding and decoding with adapting neurons: a population approach to the peri-stimulus time histogram.

    Science.gov (United States)

    Naud, Richard; Gerstner, Wulfram

    2012-01-01

    The response of a neuron to a time-dependent stimulus, as measured in a Peri-Stimulus-Time-Histogram (PSTH), exhibits an intricate temporal structure that reflects potential temporal coding principles. Here we analyze the encoding and decoding of PSTHs for spiking neurons with arbitrary refractoriness and adaptation. As a modeling framework, we use the spike response model, also known as the generalized linear neuron model. Because of refractoriness, the effect of the most recent spike on the spiking probability a few milliseconds later is very strong. The influence of the last spike needs therefore to be described with high precision, while the rest of the neuronal spiking history merely introduces an average self-inhibition or adaptation that depends on the expected number of past spikes but not on the exact spike timings. Based on these insights, we derive a 'quasi-renewal equation' which is shown to yield an excellent description of the firing rate of adapting neurons. We explore the domain of validity of the quasi-renewal equation and compare it with other rate equations for populations of spiking neurons. The problem of decoding the stimulus from the population response (or PSTH) is addressed analogously. We find that for small levels of activity and weak adaptation, a simple accumulator of the past activity is sufficient to decode the original input, but when refractory effects become large decoding becomes a non-linear function of the past activity. The results presented here can be applied to the mean-field analysis of coupled neuron networks, but also to arbitrary point processes with negative self-interaction.

  13. Separate populations of neurons in ventral striatum encode value and motivation.

    Directory of Open Access Journals (Sweden)

    Gregory B Bissonette

    Full Text Available Neurons in the ventral striatum (VS fire to cues that predict differently valued rewards. It is unclear whether this activity represents the value associated with the expected reward or the level of motivation induced by reward anticipation. To distinguish between the two, we trained rats on a task in which we varied value independently from motivation by manipulating the size of the reward expected on correct trials and the threat of punishment expected upon errors. We found that separate populations of neurons in VS encode expected value and motivation.

  14. Separate populations of neurons in ventral striatum encode value and motivation.

    Science.gov (United States)

    Bissonette, Gregory B; Burton, Amanda C; Gentry, Ronny N; Goldstein, Brandon L; Hearn, Taylor N; Barnett, Brian R; Kashtelyan, Vadim; Roesch, Matthew R

    2013-01-01

    Neurons in the ventral striatum (VS) fire to cues that predict differently valued rewards. It is unclear whether this activity represents the value associated with the expected reward or the level of motivation induced by reward anticipation. To distinguish between the two, we trained rats on a task in which we varied value independently from motivation by manipulating the size of the reward expected on correct trials and the threat of punishment expected upon errors. We found that separate populations of neurons in VS encode expected value and motivation.

  15. HIPPOCAMPAL SCLEROSIS, HIPPOCAMPAL NEURON LOSS PATTERNS AND TDP-43 IN THE AGED POPULATION.

    Science.gov (United States)

    Hokkanen, Suvi R K; Hunter, Sally; Polvikoski, Tuomo M; Keage, Hannah A D; Minett, Thais; Matthews, Fiona E; Brayne, Carol

    2017-08-18

    Hippocampal neuron loss is a common neuropathological feature in old age with various underlying aetiologies. Hippocampal sclerosis of aging (HS-Aging) is neuropathologically characterized by severe CA1 neuronal loss and frequent presence of transactive response DNA-binding protein of 43kDa (TDP-43) aggregations. Its aetiology is unclear and currently no standardized approaches to measure HS-Aging exist. We developed a semi-quantitative protocol, which captures various hippocampal neuron loss patterns, and compared their occurrence in the context of HS-Aging, TDP-43, vascular and tau pathology in 672 brains (TDP-43 staining n=642/672, 96%) donated for the population-based Cambridge City over-75s Cohort and the Cognitive Function and Ageing Study. HS-Aging was first evaluated independently from the protocol using the most common criteria defined in literature, and then described in detail through examination of neuron loss patterns and associated pathologies. 34 (5%) cases were identified, with a maximum of five pyramidal neurons in each of over half CA1 fields-of-view (x200 magnification), no vascular damage, no neuron loss in CA2-CA4, but consistent TDP-43 neuronal solid inclusions and neurites. We also report focal CA1 neuron loss with vascular pathology to affect predominantly CA1 bordering CA2 (Fisher's exact, p=0.009), whereas neuron loss in the subicular end of CA1 was associated with TDP-43 inclusions (Fisher's exact, pTDP-43. We conclude that hippocampal neuron loss patterns are associated with different aetiologies within CA1, and propose that these patterns can be used to form objective criteria for HS-Aging diagnosis. Finally, based on our results we hypothesize that neuron loss leading to HS-Aging starts from the subicular end of CA1 when it is associated with TDP-43 pathology, and that this neurodegenerative process is likely to be significantly more common than "end-stage" HS-Aging only. This article is protected by copyright. All rights reserved.

  16. Effects of photoperiod on kisspeptin neuronal populations of the ewe diencephalon in connection with reproductive function.

    Science.gov (United States)

    Chalivoix, S; Bagnolini, A; Caraty, A; Cognié, J; Malpaux, B; Dufourny, L

    2010-02-01

    Kisspeptin (Kiss) is a key regulator of reproductive function in both prepubertal and adult mammals. Its expression appears to vary throughout the year in seasonal species. We aimed to determine the impact of a change of photoperiod on the size of Kiss neuronal populations found in the preoptic area (POA) and arcuate nucleus (ARC) of the ewe brain. Using immunocytochemistry, we first examined the proportion of neurones expressing Kiss, using HuC/D as a neuronal marker, at different time-points after transition from long days (LD; 16 : 8 h light/dark cycle) to short days (SD; 8 : 16 h light/dark cycle). Luteinising hormone (LH) secretion was measured in ovariectomised oestradiol replaced ewes from the month preceding the transition to SD until the sacrifice of the animals at days 0, 45 and 112 from this photoperiodic transition. High LH levels were only observed in animals killed at day 112. The number of Kiss neurones/mm(2) doubled in the caudal ARC at day 112. The percentage of neurones showing Kiss immunoreactivity increased significantly in both the POA and ARC in the day 112 group. In a second experiment, ewes kept in LD received an i.c.v. injection of colchicine 20 h before sacrifice. Colchicine treatment increased the number and the percentage of neurones with Kiss in both the POA and caudal ARC. The data obtained suggest that the increase in Kiss neurones detected in the POA and caudal ARC after transition to SD stemmed from an increase in Kiss synthesis. This up-regulation of Kiss content under the shorter day condition appears to be a late event within the cascade activated by a longer secretion of melatonin, which is a critical factor in switching gonadotrophin-releasing hormone secretion to a breeding season profile.

  17. Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons.

    Science.gov (United States)

    Leao, Ricardo M; Li, Shuang; Doiron, Brent; Tzounopoulos, Thanos

    2012-06-01

    Homeostatic mechanisms maintain homogeneous neuronal behavior among neurons that exhibit substantial variability in the expression levels of their ionic conductances. In contrast, the mechanisms, which generate heterogeneous neuronal behavior across a neuronal population, remain poorly understood. We addressed this problem in the dorsal cochlear nucleus, where principal neurons exist in two qualitatively distinct states: spontaneously active or not spontaneously active. Our studies reveal that distinct activity states are generated by the differential levels of a Ba(2+)-sensitive, inwardly rectifying potassium conductance (K(ir)). Variability in K(ir) maximal conductance causes variations in the resting membrane potential (RMP). Low K(ir) conductance depolarizes RMP to voltages above the threshold for activating subthreshold-persistent sodium channels (Na(p)). Once Na(p) channels are activated, the RMP becomes unstable, and spontaneous firing is triggered. Our results provide a biophysical mechanism for generating neural heterogeneity, which may play a role in the encoding of sensory information.

  18. Differences in the regenerative response of neuronal cell populations and indications for plasticity in intraspinal neurons after spinal cord transection in adult zebrafish.

    Science.gov (United States)

    Becker, Thomas; Lieberoth, Bettina C; Becker, Catherina G; Schachner, Melitta

    2005-10-01

    In zebrafish, the capacity to regenerate long axons varies among different populations of axotomized neurons after spinal cord transection. In specific brain nuclei, 84-92% of axotomized neurons upregulate expression of the growth-related genes GAP-43 and L1.1 and 32-51% of these neurons regrow their descending axons. In contrast, 16-31% of spinal neurons with axons ascending to the brainstem upregulate these genes and only 2-4% regrow their axons. Dorsal root ganglion (DRG) neurons were not observed to regrow their ascending axons or to increase expression of GAP-43 mRNA. Expression of L1.1 mRNA is high in unlesioned and axotomized DRG neurons. In the lesioned spinal cord, expression of growth-related molecules is increased in a substantial population of non-axotomized neurons, suggesting morphological plasticity in the spinal-intrinsic circuitry. We propose that locomotor recovery in spinal-transected adult zebrafish is influenced less by recovery of ascending pathways, but more by regrowth of descending tracts and rearrangement of intraspinal circuitry.

  19. Characterization of neuronal populations in the human trigeminal ganglion and their association with latent herpes simplex virus-1 infection.

    Directory of Open Access Journals (Sweden)

    Sarah E Flowerdew

    Full Text Available Following primary infection Herpes simplex virus-1 (HSV-1 establishes lifelong latency in the neurons of human sensory ganglia. Upon reactivation HSV-1 can cause neurological diseases such as facial palsy, vestibular neuritis or encephalitis. Certain populations of sensory neurons have been shown to be more susceptible to latent infection in the animal model, but this has not been addressed in human tissue. In the present study, trigeminal ganglion (TG neurons expressing six neuronal marker proteins were characterized, based on staining with antibodies against the GDNF family ligand receptor Ret, the high-affinity nerve growth factor receptor TrkA, neuronal nitric oxide synthase (nNOS, the antibody RT97 against 200 kDa neurofilament, calcitonin gene-related peptide and peripherin. The frequencies of marker-positive neurons and their average neuronal sizes were assessed, with TrkA-positive (61.82% neurons being the most abundant, and Ret-positive (26.93% the least prevalent. Neurons positive with the antibody RT97 (1253 µm(2 were the largest, and those stained against peripherin (884 µm(2 were the smallest. Dual immunofluorescence revealed at least a 4.5% overlap for every tested marker combination, with overlap for the combinations TrkA/Ret, TrkA/RT97 and Ret/nNOS lower, and the overlap between Ret/CGRP being higher than would be expected by chance. With respect to latent HSV-1 infection, latency associated transcripts (LAT were detected using in situ hybridization (ISH in neurons expressing each of the marker proteins. In contrast to the mouse model, co-localization with neuronal markers Ret or CGRP mirrored the magnitude of these neuron populations, whereas for the other four neuronal markers fewer marker-positive cells were also LAT-ISH+. Ret and CGRP are both known to label neurons related to pain signaling.

  20. From individual spiking neurons to population behavior: Systematic elimination of short-wavelength spatial modes

    Science.gov (United States)

    Steyn-Ross, Moira L.; Steyn-Ross, D. A.

    2016-02-01

    Mean-field models of the brain approximate spiking dynamics by assuming that each neuron responds to its neighbors via a naive spatial average that neglects local fluctuations and correlations in firing activity. In this paper we address this issue by introducing a rigorous formalism to enable spatial coarse-graining of spiking dynamics, scaling from the microscopic level of a single type 1 (integrator) neuron to a macroscopic assembly of spiking neurons that are interconnected by chemical synapses and nearest-neighbor gap junctions. Spiking behavior at the single-neuron scale ℓ ≈10 μ m is described by Wilson's two-variable conductance-based equations [H. R. Wilson, J. Theor. Biol. 200, 375 (1999), 10.1006/jtbi.1999.1002], driven by fields of incoming neural activity from neighboring neurons. We map these equations to a coarser spatial resolution of grid length B ℓ , with B ≫1 being the blocking ratio linking micro and macro scales. Our method systematically eliminates high-frequency (short-wavelength) spatial modes q ⃗ in favor of low-frequency spatial modes Q ⃗ using an adiabatic elimination procedure that has been shown to be equivalent to the path-integral coarse graining applied to renormalization group theory of critical phenomena. This bottom-up neural regridding allows us to track the percolation of synaptic and ion-channel noise from the single neuron up to the scale of macroscopic population-average variables. Anticipated applications of neural regridding include extraction of the current-to-firing-rate transfer function, investigation of fluctuation criticality near phase-transition tipping points, determination of spatial scaling laws for avalanche events, and prediction of the spatial extent of self-organized macrocolumnar structures. As a first-order exemplar of the method, we recover nonlinear corrections for a coarse-grained Wilson spiking neuron embedded in a network of identical diffusively coupled neurons whose chemical synapses have

  1. Temporal expectation and spectral expectation operate in distinct fashion on neuronal populations.

    Science.gov (United States)

    Hsu, Yi-Fang; Hämäläinen, Jarmo A; Waszak, Florian

    2013-11-01

    The formation of temporal expectation (i.e., the prediction of "when") is of prime importance to sensory processing. It can modulate sensory processing at early processing stages probably via the entrainment of low-frequency neuronal oscillations in the brain. However, sensory predictions involve not only temporal expectation but also spectral expectation (i.e., the prediction of "what"). Here we investigated how temporal expectation may interrelate with spectral expectation by explicitly setting up temporal expectation and spectral expectation in a target detection task. We found that reaction time (RT) was shorter when targets were temporally expected than when they were temporally unexpected. The temporal expectation effect was larger with than without spectral expectation. However, this interaction in the behavioural data did not result from an interaction in the electroencephalography (EEG), where we observed independent main effects of temporal expectation and spectral expectation. More precisely, we found that the N1 and P2 event-related potential (ERP) components and the entrainment of low-frequency neuronal oscillations were exclusively modulated by temporal expectation, whilst only the P3 ERP component was modulated by spectral expectation. Our results, thus, support the idea that temporal expectation and spectral expectation operate in distinct fashion on neuronal populations.

  2. Neuronal populations mediating the effects of endocannabinoids on stress and emotionality.

    Science.gov (United States)

    Häring, M; Guggenhuber, S; Lutz, B

    2012-03-01

    An adequate emotional response to stress is essential for survival and requires the fine-tuned regulation of several distinct neuronal circuits. Therefore, a precise control of these circuits is necessary to prevent behavioral imbalances. During the last decade, numerous investigations have evidenced that the endocannabinoid (eCB) system is able to crucially control stress coping. Its central component, the cannabinoid type 1 receptor (CB1 receptor), is located at the presynapse, where it is able to attenuate neurotransmitter release after its activation by postsynaptically produced and released eCBs. To date, the eCB system has been found to control the neurotransmitter release from several neuron populations (e.g. GABA, glutamate, catecholamines and monoamines), suggesting a general mechanism for tuning neuronal activity, and thereby regulating emotion and stress responses. In this review, we aim at summarizing the anatomical and functional relation of the eCB system to an adequate response to stressful situations. Of special interest will be neuronal connections to the hypothalamic-pituitary-adrenal axis, but also circuits between cortical structures, such as prefrontal cortex, amygdala and hippocampus, and subcortical regions, such as raphe nuclei and locus coeruleus. We further like to step toward allocating eCB system functions to distinct cellular subpopulations in the brain. It has emerged that the eCB system is spatially well defined, and its detailed knowledge is a prerequisite for understanding the eCB system in the context of controlling behavior. Thus, advanced approaches combining different genetic and pharmacological tools to dissect specific eCB system functions are of particular interest. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Ih equalizes membrane input resistance in a heterogeneous population of fusiform neurons in the dorsal cochlear nucleus.

    Directory of Open Access Journals (Sweden)

    Cesar Celis Ceballos

    2016-10-01

    Full Text Available In a neuronal population, several combinations of its ionic conductances are used to attain a specific firing phenotype. Some neurons present heterogeneity in their firing, generally produced by expression of a specific conductance, but how additional conductances vary along in order to homeostatically regulate membrane excitability is less known. Dorsal cochlear nucleus principal neurons, fusiform neurons, display heterogeneous spontaneous action potential activity and thus represent an appropriate model to study the role of different conductances in establishing firing heterogeneity. Particularly, fusiform neurons are divided into quiet, with no spontaneous firing, or active neurons, presenting spontaneous, regular firing. These modes are determined by the expression levels of an intrinsic membrane conductance, an inwardly rectifying potassium current (IKir. In this work, we tested whether other subthreshold conductances vary homeostatically to maintain membrane excitability constant across the two subtypes. We found that Ih expression covaries specifically with IKir in order to maintain membrane resistance constant. The impact of Ih on membrane resistance is dependent on the level of IKir expression, being much smaller in quiet neurons with bigger IKir, but Ih variations are not relevant for creating the quiet and active phenotypes. Finally, we demonstrate that the individual proportion of each conductance, and not their absolute conductance, is relevant for determining the neuronal firing mode. We conclude that in fusiform neurons the variations of their different subthreshold conductances are limited to specific conductances in order to create firing heterogeneity and maintain membrane homeostasis.

  4. Real-time prediction of neuronal population spiking activity using FPGA.

    Science.gov (United States)

    Li, Will X Y; Cheung, Ray C C; Chan, Rosa H M; Song, Dong; Berger, Theodore W

    2013-08-01

    A field-programmable gate array (FPGA)-based hardware architecture is proposed and utilized for prediction of neuronal population firing activity. The hardware system adopts the multi-input multi-output (MIMO) generalized Laguerre-Volterra model (GLVM) structure to describe the nonlinear dynamic neural process of mammalian brain and can switch between the two important functions: estimation of GLVM coefficients and prediction of neuronal population spiking activity (model outputs). The model coefficients are first estimated using the in-sample training data; then the output is predicted using the out-of-sample testing data and the field estimated coefficients. Test results show that compared with previous software implementation of the generalized Laguerre-Volterra algorithm running on an Intel Core i7-2620M CPU, the FPGA-based hardware system can achieve up to 2.66×10(3) speedup in doing model parameters estimation and 698.84 speedup in doing model output prediction. The proposed hardware platform will facilitate research on the highly nonlinear neural process of the mammal brain, and the cognitive neural prosthesis design.

  5. Metastable states and quasicycles in a stochastic Wilson-Cowan model of neuronal population dynamics

    KAUST Repository

    Bressloff, Paul C.

    2010-11-03

    We analyze a stochastic model of neuronal population dynamics with intrinsic noise. In the thermodynamic limit N→∞, where N determines the size of each population, the dynamics is described by deterministic Wilson-Cowan equations. On the other hand, for finite N the dynamics is described by a master equation that determines the probability of spiking activity within each population. We first consider a single excitatory population that exhibits bistability in the deterministic limit. The steady-state probability distribution of the stochastic network has maxima at points corresponding to the stable fixed points of the deterministic network; the relative weighting of the two maxima depends on the system size. For large but finite N, we calculate the exponentially small rate of noise-induced transitions between the resulting metastable states using a Wentzel-Kramers- Brillouin (WKB) approximation and matched asymptotic expansions. We then consider a two-population excitatory or inhibitory network that supports limit cycle oscillations. Using a diffusion approximation, we reduce the dynamics to a neural Langevin equation, and show how the intrinsic noise amplifies subthreshold oscillations (quasicycles). © 2010 The American Physical Society.

  6. Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium.

    Science.gov (United States)

    Stern, S; Santos, R; Marchetto, M C; Mendes, A P D; Rouleau, G A; Biesmans, S; Wang, Q-W; Yao, J; Charnay, P; Bang, A G; Alda, M; Gage, F H

    2017-02-28

    Bipolar disorder (BD) is a progressive psychiatric disorder with more than 3% prevalence worldwide. Affected individuals experience recurrent episodes of depression and mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and genetic heterogeneity of psychiatric disorders have challenged the development of animal and cellular models. We recently reported that hippocampal dentate gyrus (DG) neurons differentiated from induced pluripotent stem cell (iPSC)-derived fibroblasts of BD patients are electrophysiologically hyperexcitable. Here we used iPSCs derived from Epstein-Barr virus-immortalized B-lymphocytes to verify that the hyperexcitability of DG-like neurons is reproduced in this different cohort of patients and cells. Lymphocytes are readily available for research with a large number of banked lines with associated patient clinical description. We used whole-cell patch-clamp recordings of over 460 neurons to characterize neurons derived from control individuals and BD patients. Extensive functional analysis showed that intrinsic cell parameters are very different between the two groups of BD neurons, those derived from lithium (Li)-responsive (LR) patients and those derived from Li-non-responsive (NR) patients, which led us to partition our BD neurons into two sub-populations of cells and suggested two different subdisorders. Training a Naïve Bayes classifier with the electrophysiological features of patients whose responses to Li are known allows for accurate classification with more than 92% success rate for a new patient whose response to Li is unknown. Despite their very different functional profiles, both populations of neurons share a large, fast after-hyperpolarization (AHP). We therefore suggest that the large, fast AHP is a key feature of BD and a main contributor to the fast, sustained spiking abilities of BD neurons. Confirming our previous report with fibroblast-derived DG neurons, chronic Li treatment reduced

  7. Analyzing dendritic growth in a population of immature neurons in the adult dentate gyrus using laminar quantification of disjointed dendrites

    Directory of Open Access Journals (Sweden)

    Shira eRosenzweig

    2011-03-01

    Full Text Available In the dentate gyrus of the hippocampus, new granule neurons are continuously produced throughout adult life. A prerequisite for the successful synaptic integration of these neurons is the sprouting and extension of dendrites into the molecular layer of the dentate gyrus. Thus, studies aimed at investigating the developmental stages of adult neurogenesis often use dendritic growth as an important indicator of neuronal health and maturity. Based on the known topography of the dentate gyrus, characterized by distinct laminar arrangement of granule neurons and their extensions, we have developed a new method for analysis of dendritic growth in immature adult-born granule neurons. The method is comprised of laminar quantification of cell bodies, primary, secondary and tertiary dendrites separately and independently from each other. In contrast to most existing methods, laminar quantification of dendrites does not require the use of exogenous markers and does not involve arbitrary selection of individual neurons. The new method relies on immonuhistochemical detection of endogenous markers such as doublecortin to perform a comprehensive analysis of a sub-population of immature neurons. Disjointed, orphan dendrites that often appear in the thin histological sections are taken into account. Using several experimental groups of rats and mice, we demonstrate here the suitable techniques for quantifying neurons and dendrites, and explain how the ratios between the quantified values can be used in a comparative analysis to indicate variations in dendritic growth and complexity.

  8. Vertical binocular disparity is encoded implicitly within a model neuronal population tuned to horizontal disparity and orientation.

    Directory of Open Access Journals (Sweden)

    Jenny C A Read

    2010-04-01

    Full Text Available Primary visual cortex is often viewed as a "cyclopean retina", performing the initial encoding of binocular disparities between left and right images. Because the eyes are set apart horizontally in the head, binocular disparities are predominantly horizontal. Yet, especially in the visual periphery, a range of non-zero vertical disparities do occur and can influence perception. It has therefore been assumed that primary visual cortex must contain neurons tuned to a range of vertical disparities. Here, I show that this is not necessarily the case. Many disparity-selective neurons are most sensitive to changes in disparity orthogonal to their preferred orientation. That is, the disparity tuning surfaces, mapping their response to different two-dimensional (2D disparities, are elongated along the cell's preferred orientation. Because of this, even if a neuron's optimal 2D disparity has zero vertical component, the neuron will still respond best to a non-zero vertical disparity when probed with a sub-optimal horizontal disparity. This property can be used to decode 2D disparity, even allowing for realistic levels of neuronal noise. Even if all V1 neurons at a particular retinotopic location are tuned to the expected vertical disparity there (for example, zero at the fovea, the brain could still decode the magnitude and sign of departures from that expected value. This provides an intriguing counter-example to the common wisdom that, in order for a neuronal population to encode a quantity, its members must be tuned to a range of values of that quantity. It demonstrates that populations of disparity-selective neurons encode much richer information than previously appreciated. It suggests a possible strategy for the brain to extract rarely-occurring stimulus values, while concentrating neuronal resources on the most commonly-occurring situations.

  9. Vertical Binocular Disparity is Encoded Implicitly within a Model Neuronal Population Tuned to Horizontal Disparity and Orientation

    Science.gov (United States)

    Read, Jenny C. A.

    2010-01-01

    Primary visual cortex is often viewed as a “cyclopean retina”, performing the initial encoding of binocular disparities between left and right images. Because the eyes are set apart horizontally in the head, binocular disparities are predominantly horizontal. Yet, especially in the visual periphery, a range of non-zero vertical disparities do occur and can influence perception. It has therefore been assumed that primary visual cortex must contain neurons tuned to a range of vertical disparities. Here, I show that this is not necessarily the case. Many disparity-selective neurons are most sensitive to changes in disparity orthogonal to their preferred orientation. That is, the disparity tuning surfaces, mapping their response to different two-dimensional (2D) disparities, are elongated along the cell's preferred orientation. Because of this, even if a neuron's optimal 2D disparity has zero vertical component, the neuron will still respond best to a non-zero vertical disparity when probed with a sub-optimal horizontal disparity. This property can be used to decode 2D disparity, even allowing for realistic levels of neuronal noise. Even if all V1 neurons at a particular retinotopic location are tuned to the expected vertical disparity there (for example, zero at the fovea), the brain could still decode the magnitude and sign of departures from that expected value. This provides an intriguing counter-example to the common wisdom that, in order for a neuronal population to encode a quantity, its members must be tuned to a range of values of that quantity. It demonstrates that populations of disparity-selective neurons encode much richer information than previously appreciated. It suggests a possible strategy for the brain to extract rarely-occurring stimulus values, while concentrating neuronal resources on the most commonly-occurring situations. PMID:20421992

  10. Anatomical and molecular consequences of Unilateral Naris Closure on two populations of olfactory sensory neurons expressing defined odorant receptors.

    Science.gov (United States)

    Molinas, Adrien; Aoudé, Imad; Soubeyre, Vanessa; Tazir, Bassim; Cadiou, Hervé; Grosmaitre, Xavier

    2016-07-28

    Mammalian olfactory sensory neurons (OSNs), the primary elements of the olfactory system, are located in the olfactory epithelium lining the nasal cavity. Exposed to the environment, their lifespan is short. Consequently, OSNs are regularly regenerated and several reports show that activity strongly modulates their development and regeneration: the peripheral olfactory system can adjust to the amount of stimulus through compensatory mechanisms. Unilateral naris occlusion (UNO) was frequently used to investigate this mechanism at the entire epithelium level. However, there is little data regarding the effects of UNO at the cellular level, especially on individual neuronal populations expressing a defined odorant receptor. Here, using UNO during the first three postnatal weeks, we analyzed the anatomical and molecular consequences of sensory deprivation in OSNs populations expressing the MOR23 and M71 receptors. The density of MOR23-expressing neurons is decreased in the closed side while UNO does not affect the density of M71-expressing neurons. Using Real Time qPCR on isolated neurons, we observed that UNO modulates the transcript levels for transduction pathway proteins (odorant receptors, CNGA2, PDE1c). The transcripts modulated by UNO will differ between populations depending on the receptor expressed. These results suggest that sensory deprivation will have different effects on different OSNs' populations. As a consequence, early experience will shape the functional properties of OSNs differently depending on the type of odorant receptor they express.

  11. Mean-field dynamics of a population of stochastic map neurons

    Science.gov (United States)

    Franović, Igor; Maslennikov, Oleg V.; Bačić, Iva; Nekorkin, Vladimir I.

    2017-07-01

    We analyze the emergent regimes and the stimulus-response relationship of a population of noisy map neurons by means of a mean-field model, derived within the framework of cumulant approach complemented by the Gaussian closure hypothesis. It is demonstrated that the mean-field model can qualitatively account for stability and bifurcations of the exact system, capturing all the generic forms of collective behavior, including macroscopic excitability, subthreshold oscillations, periodic or chaotic spiking, and chaotic bursting dynamics. Apart from qualitative analogies, we find a substantial quantitative agreement between the exact and the approximate system, as reflected in matching of the parameter domains admitting the different dynamical regimes, as well as the characteristic properties of the associated time series. The effective model is further shown to reproduce with sufficient accuracy the phase response curves of the exact system and the assembly's response to external stimulation of finite amplitude and duration.

  12. Differences in neuronal activity explain differences in memory forming abilities of different populations of Lymnaea stagnalis.

    Science.gov (United States)

    Braun, Marvin H; Lukowiak, Kai; Karnik, Vikram; Lukowiak, Ken

    2012-01-01

    The ability to learn and form long-term memory (LTM) can enhance an animal's fitness, for example, by allowing them to remember predators, food sources or conspecific interactions. Here we use the pond snail, Lymnaea stagnalis, to assess whether variability between natural populations (i.e., strains) in memory forming capabilities correlates with electrophysiological properties at the level of a single neuron, RPeD1. RPeD1 is a necessary site of LTM formation of aerial respiratory behaviour following operant conditioning. We used strains from two small, separate permanent ponds (TC1 and TC2). A comparison of the two populations showed that the TC1 strain had enhanced memory forming capabilities. Further, the behavioural phenotype of enhanced memory strain was explained, in part, by differences in the electrophysiology of RPeD1. Compared to RPeD1 from the naive TC2 strain, RPeD1 from the TC1 strain has both a decreased resistance and decreased excitability. Moreover, 24h after a single 0.5h training session, those membrane properties, as well as the firing and bursting rate, decrease further in the TC1 strain but not in the TC2 strain. The initial differences in RPeD1 properties in the TC1 strain coupled with their ability to further change these properties with a single training session suggests that RPeD1 neurons from the TC1 strain are "primed" to rapidly form memory. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Distribution of Kv3.3 potassium channel subunits in distinct neuronal populations of mouse brain.

    Science.gov (United States)

    Chang, Su Ying; Zagha, Edward; Kwon, Elaine S; Ozaita, Andres; Bobik, Marketta; Martone, Maryann E; Ellisman, Mark H; Heintz, Nathaniel; Rudy, Bernardo

    2007-06-20

    Kv3.3 proteins are pore-forming subunits of voltage-dependent potassium channels, and mutations in the gene encoding for Kv3.3 have recently been linked to human disease, spinocerebellar ataxia 13, with cerebellar and extracerebellar symptoms. To understand better the functions of Kv3.3 subunits in brain, we developed highly specific antibodies to Kv3.3 and analyzed immunoreactivity throughout mouse brain. We found that Kv3.3 subunits are widely expressed, present in important forebrain structures but particularly prominent in brainstem and cerebellum. In forebrain and midbrain, Kv3.3 expression was often found colocalized with parvalbumin and other Kv3 subunits in inhibitory neurons. In brainstem, Kv3.3 was strongly expressed in auditory and other sensory nuclei. In cerebellar cortex, Kv3.3 expression was found in Purkinje and granule cells. Kv3.3 proteins were observed in axons, terminals, somas, and, unlike other Kv3 proteins, also in distal dendrites, although precise subcellular localization depended on cell type. For example, hippocampal dentate granule cells expressed Kv3.3 subunits specifically in their mossy fiber axons, whereas Purkinje cells of the cerebellar cortex strongly expressed Kv3.3 subunits in axons, somas, and proximal and distal, but not second- and third-order, dendrites. Expression in Purkinje cell dendrites was confirmed by immunoelectron microscopy. Kv3 channels have been demonstrated to rapidly repolarize action potentials and support high-frequency firing in various neuronal populations. In this study, we identified additional populations and subcellular compartments that are likely to sustain high-frequency firing because of the expression of Kv3.3 and other Kv3 subunits.

  14. Eight pairs of descending visual neurons in the dragonfly give wing motor centers accurate population vector of prey direction.

    Science.gov (United States)

    Gonzalez-Bellido, Paloma T; Peng, Hanchuan; Yang, Jinzhu; Georgopoulos, Apostolos P; Olberg, Robert M

    2013-01-08

    Intercepting a moving object requires prediction of its future location. This complex task has been solved by dragonflies, who intercept their prey in midair with a 95% success rate. In this study, we show that a group of 16 neurons, called target-selective descending neurons (TSDNs), code a population vector that reflects the direction of the target with high accuracy and reliability across 360°. The TSDN spatial (receptive field) and temporal (latency) properties matched the area of the retina where the prey is focused and the reaction time, respectively, during predatory flights. The directional tuning curves and morphological traits (3D tracings) for each TSDN type were consistent among animals, but spike rates were not. Our results emphasize that a successful neural circuit for target tracking and interception can be achieved with few neurons and that in dragonflies this information is relayed from the brain to the wing motor centers in population vector form.

  15. Comparison of classifiers for decoding sensory and cognitive information from prefrontal neuronal populations.

    Directory of Open Access Journals (Sweden)

    Elaine Astrand

    Full Text Available Decoding neuronal information is important in neuroscience, both as a basic means to understand how neuronal activity is related to cerebral function and as a processing stage in driving neuroprosthetic effectors. Here, we compare the readout performance of six commonly used classifiers at decoding two different variables encoded by the spiking activity of the non-human primate frontal eye fields (FEF: the spatial position of a visual cue, and the instructed orientation of the animal's attention. While the first variable is exogenously driven by the environment, the second variable corresponds to the interpretation of the instruction conveyed by the cue; it is endogenously driven and corresponds to the output of internal cognitive operations performed on the visual attributes of the cue. These two variables were decoded using either a regularized optimal linear estimator in its explicit formulation, an optimal linear artificial neural network estimator, a non-linear artificial neural network estimator, a non-linear naïve Bayesian estimator, a non-linear Reservoir recurrent network classifier or a non-linear Support Vector Machine classifier. Our results suggest that endogenous information such as the orientation of attention can be decoded from the FEF with the same accuracy as exogenous visual information. All classifiers did not behave equally in the face of population size and heterogeneity, the available training and testing trials, the subject's behavior and the temporal structure of the variable of interest. In most situations, the regularized optimal linear estimator and the non-linear Support Vector Machine classifiers outperformed the other tested decoders.

  16. Comparison of classifiers for decoding sensory and cognitive information from prefrontal neuronal populations.

    Science.gov (United States)

    Astrand, Elaine; Enel, Pierre; Ibos, Guilhem; Dominey, Peter Ford; Baraduc, Pierre; Ben Hamed, Suliann

    2014-01-01

    Decoding neuronal information is important in neuroscience, both as a basic means to understand how neuronal activity is related to cerebral function and as a processing stage in driving neuroprosthetic effectors. Here, we compare the readout performance of six commonly used classifiers at decoding two different variables encoded by the spiking activity of the non-human primate frontal eye fields (FEF): the spatial position of a visual cue, and the instructed orientation of the animal's attention. While the first variable is exogenously driven by the environment, the second variable corresponds to the interpretation of the instruction conveyed by the cue; it is endogenously driven and corresponds to the output of internal cognitive operations performed on the visual attributes of the cue. These two variables were decoded using either a regularized optimal linear estimator in its explicit formulation, an optimal linear artificial neural network estimator, a non-linear artificial neural network estimator, a non-linear naïve Bayesian estimator, a non-linear Reservoir recurrent network classifier or a non-linear Support Vector Machine classifier. Our results suggest that endogenous information such as the orientation of attention can be decoded from the FEF with the same accuracy as exogenous visual information. All classifiers did not behave equally in the face of population size and heterogeneity, the available training and testing trials, the subject's behavior and the temporal structure of the variable of interest. In most situations, the regularized optimal linear estimator and the non-linear Support Vector Machine classifiers outperformed the other tested decoders.

  17. Ascending projections of nociceptive neurons from trigeminal subnucleus caudalis: A population approach.

    Science.gov (United States)

    Saito, Hiroto; Katagiri, Ayano; Okada, Shinji; Mikuzuki, Lou; Kubo, Asako; Suzuki, Tatsuro; Ohara, Kinuyo; Lee, Jun; Gionhaku, Nobuhito; Iinuma, Toshimitsu; Bereiter, David A; Iwata, Koichi

    2017-07-01

    Second-order neurons in trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1) are critical for craniofacial pain processing and project rostrally to terminate in: ventral posteromedial thalamic nucleus (VPM), medial thalamic nuclei (MTN) and parabrachial nuclei (PBN). The contribution of each region to trigeminal nociception was assessed by the number of phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons co-labeled with fluorogold (FG). The phenotype of pERK-IR neurons was further defined by the expression of neurokinin 1 receptor (NK1). The retrograde tracer FG was injected into VPM, MTN or PBN of the right hemisphere and after seven days, capsaicin was injected into the left upper lip in male rats. Nearly all pERK-IR neurons were found in superficial laminae of Vc-C1 ipsilateral to the capsaicin injection. Nearly all VPM and MTN FG-labeled neurons in Vc-C1 were found contralateral to the injection site, whereas FG-labeled neurons were found bilaterally after PBN injection. The percentage of FG-pERK-NK1-IR neurons was significantly greater (>10%) for PBN projection neurons than for VPM and MTN projection neurons (NK1-IR VPM projection neurons were found mainly in the middle-Vc, while pERK-NK1-immunoreactive MTN or PBN projection neurons were found in the middle-Vc and caudal Vc-C1. These results suggest that a significant percentage of capsaicin-responsive neurons in superficial laminae of Vc-C1 project directly to PBN, while neurons that project to VPM and MTN are subject to greater modulation by pERK-IR local interneurons. Furthermore, the rostrocaudal distribution differences of FG-pERK-NK1-IR neurons in Vc-C1 may reflect functional differences between these projection areas regarding craniofacial pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. A SAGE-based screen for genes expressed in sub-populations of neurons in the mouse dorsal root ganglion

    Directory of Open Access Journals (Sweden)

    Garces Alain

    2007-11-01

    Full Text Available Abstract Background The different sensory modalities temperature, pain, touch and muscle proprioception are carried by somatosensory neurons of the dorsal root ganglia. Study of this system is hampered by the lack of molecular markers for many of these neuronal sub-types. In order to detect genes expressed in sub-populations of somatosensory neurons, gene profiling was carried out on wild-type and TrkA mutant neonatal dorsal root ganglia (DRG using SAGE (serial analysis of gene expression methodology. Thermo-nociceptors constitute up to 80 % of the neurons in the DRG. In TrkA mutant DRGs, the nociceptor sub-class of sensory neurons is lost due to absence of nerve growth factor survival signaling through its receptor TrkA. Thus, comparison of wild-type and TrkA mutants allows the identification of transcripts preferentially expressed in the nociceptor or mechano-proprioceptor subclasses, respectively. Results Our comparison revealed 240 genes differentially expressed between the two tissues (P Conclusion We have identified and characterized the detailed expression patterns of three genes in the developing DRG, placing them in the context of the known major neuronal sub-types defined by molecular markers. Further analysis of differentially expressed genes in this tissue promises to extend our knowledge of the molecular diversity of different cell types and forms the basis for understanding their particular functional specificities.

  19. Itch and analgesia resulting from intrathecal application of morphine: contrasting effects on different populations of trigeminothalamic tract neurons.

    Science.gov (United States)

    Moser, Hannah R; Giesler, Glenn J

    2013-04-03

    Intrathecal application of morphine is among the most powerful methods used to treat severe chronic pain. However, this approach commonly produces itch sufficiently severe that patients are forced to choose between relief of pain or itch. The neuronal populations responsible for processing and transmitting information underlying itch caused by intrathecal application of morphine have not been identified and characterized. We describe two populations of antidromically identified trigeminothalamic tract (VTT) neurons in anesthetized rats that are differentially affected by morphine and explain several aspects of opioid-induced itch and analgesia. We found that intrathecal application of morphine increased ongoing activity of itch-responsive VTT neurons. In addition, intrathecal application of morphine increased responses to pruritogens injected into the skin and greatly heightened responses to innocuous mechanical stimuli. In contrast, the ongoing activity and responses to noxious pinches in nociceptive VTT neurons were frequently inhibited by the same dose of morphine. These results reveal that i.t. application of morphine affects specific subpopulations of VTT neurons in ways that may produce itch, hyperknesis, alloknesis, and analgesia.

  20. Conjunctive processing of locomotor signals by the ventral tegmental area neuronal population.

    Directory of Open Access Journals (Sweden)

    Dong V Wang

    Full Text Available The ventral tegmental area (VTA plays an essential role in reward and motivation. How the dopamine (DA and non-DA neurons in the VTA engage in motivation-based locomotor behaviors is not well understood. We recorded activity of putative DA and non-DA neurons simultaneously in the VTA of awake mice engaged in motivated voluntary movements such as wheel running. Our results revealed that VTA non-DA neurons exhibited significant rhythmic activity that was correlated with the animal's running rhythms. Activity of putative DA neurons also correlated with the movement behavior, but to a lesser degree. More importantly, putative DA neurons exhibited significant burst activation at both onset and offset of voluntary movements. These findings suggest that VTA DA and non-DA neurons conjunctively process locomotor-related motivational signals that are associated with movement initiation, maintenance and termination.

  1. Subpallial origin of a population of projecting pioneer neurons during corticogenesis

    OpenAIRE

    Morante-Oria, Javier; Carleton, Alan; Ortino, Barbara; Eric J. Kremer; Fairén, Alfonso; Lledo, Pierre-Marie

    2003-01-01

    Pyramidal neurons of the mammalian cerebral cortex are generated in the ventricular zone of the pallium whereas the subpallium provides the cortex with inhibitory interneurons. The marginal zone contains a subpial stream of migratory interneurons and two different classes of transient neurons, the pioneer neurons provided with corticofugal axons, and the reelin-expressing Cajal–Retzius cells. We found in cultured slices that the medial ganglionic eminence provides the reelin-negative pioneer ...

  2. Subpallial origin of a population of projecting pioneer neurons during corticogenesis.

    Science.gov (United States)

    Morante-Oria, Javier; Carleton, Alan; Ortino, Barbara; Kremer, Eric J; Fairén, Alfonso; Lledo, Pierre-Marie

    2003-10-14

    Pyramidal neurons of the mammalian cerebral cortex are generated in the ventricular zone of the pallium whereas the subpallium provides the cortex with inhibitory interneurons. The marginal zone contains a subpial stream of migratory interneurons and two different classes of transient neurons, the pioneer neurons provided with corticofugal axons, and the reelin-expressing Cajal-Retzius cells. We found in cultured slices that the medial ganglionic eminence provides the reelin-negative pioneer neurons of the marginal zone. Pioneer neurons sent long projection axons that went through the cortical plate and reached the subplate and the lateral border of the lateral ganglionic eminence. In the cultured slices, pioneer neurons were functionally mature: they displayed a voltage-gated sodium current, expressed functional alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and showed gamma-aminobutyric acid type A (GABAA) postsynaptic events that were modulated by presynaptic AMPA receptors. Pioneer neurons expressed the adhesion molecules L1 and TAG-1; the latter has been reported to control tangential migrations to the neocortex [Denaxa, M., Chan, C.-H., Schachner, M., Parnavelas, J. & Karagogeos, D. (2001) Development (Cambridge, U.K.) 128, 4635-4644], and we show here that the pioneer neurons of the marginal zone are the cellular substrate of such a function. Finally, we show that, in early corticogenesis, reelin controls both the tangential migration of cortical interneurons toward the cortical plate and the tangential migration of pioneer neurons toward the marginal zone.

  3. Partial synchronous output of a neuronal population under weak common noise: Analytical approaches to the correlation statistics

    Science.gov (United States)

    Kruscha, Alexandra; Lindner, Benjamin

    2016-08-01

    We consider a homogeneous population of stochastic neurons that are driven by weak common noise (stimulus). To capture and analyze the joint firing events within the population, we introduce the partial synchronous output of the population. This is a time series defined by the events that at least a fixed fraction γ ∈[0 ,1 ] of the population fires simultaneously within a small time interval. For this partial synchronous output we develop two analytical approaches to the correlation statistics. In the Gaussian approach we represent the synchronous output as a nonlinear transformation of the summed population activity and approximate the latter by a Gaussian process. In the combinatorial approach the synchronous output is represented by products of box-filtered spike trains of the single neurons. In both approaches we use linear-response theory to derive approximations for statistical measures that hold true for weak common noise. In particular, we calculate the mean value and power spectrum of the synchronous output and the cross-spectrum between synchronous output and common noise. We apply our results to the leaky integrate-and-fire neuron model and compare them to numerical simulations. The combinatorial approach is shown to provide a more accurate description of the statistics for small populations, whereas the Gaussian approximation yields compact formulas that work well for a sufficiently large population size. In particular, in the Gaussian approximation all statistical measures reveal a symmetry in the synchrony threshold γ around the mean value of the population activity. Our results may contribute to a better understanding of the role of coincidence detection in neural signal processing.

  4. Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure

    DEFF Research Database (Denmark)

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R

    2015-01-01

    of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally...... late pregnancy results in a stable loss of hippocampal neurons and a progressive reduction of hippocampal volume....

  5. Mean Field Analysis of Large-Scale Interacting Populations of Stochastic Conductance-Based Spiking Neurons Using the Klimontovich Method

    Science.gov (United States)

    Gandolfo, Daniel; Rodriguez, Roger; Tuckwell, Henry C.

    2017-01-01

    We investigate the dynamics of large-scale interacting neural populations, composed of conductance based, spiking model neurons with modifiable synaptic connection strengths, which are possibly also subjected to external noisy currents. The network dynamics is controlled by a set of neural population probability distributions (PPD) which are constructed along the same lines as in the Klimontovich approach to the kinetic theory of plasmas. An exact non-closed, nonlinear, system of integro-partial differential equations is derived for the PPDs. As is customary, a closing procedure leads to a mean field limit. The equations we have obtained are of the same type as those which have been recently derived using rigorous techniques of probability theory. The numerical solutions of these so called McKean-Vlasov-Fokker-Planck equations, which are only valid in the limit of infinite size networks, actually shows that the statistical measures as obtained from PPDs are in good agreement with those obtained through direct integration of the stochastic dynamical system for large but finite size networks. Although numerical solutions have been obtained for networks of Fitzhugh-Nagumo model neurons, which are often used to approximate Hodgkin-Huxley model neurons, the theory can be readily applied to networks of general conductance-based model neurons of arbitrary dimension.

  6. Electrophoresis of polar fluorescent tracers through the nerve sheath labels neuronal populations for anatomical and functional imaging

    Science.gov (United States)

    Isaacson, Matthew D.; Hedwig, Berthold

    2017-01-01

    The delivery of tracers into populations of neurons is essential to visualize their anatomy and analyze their function. In some model systems genetically-targeted expression of fluorescent proteins is the method of choice; however, these genetic tools are not available for most organisms and alternative labeling methods are very limited. Here we describe a new method for neuronal labelling by electrophoretic dye delivery from a suction electrode directly through the neuronal sheath of nerves and ganglia in insects. Polar tracer molecules were delivered into the locust auditory nerve without destroying its function, simultaneously staining peripheral sensory structures and central axonal projections. Local neuron populations could be labelled directly through the surface of the brain, and in-vivo optical imaging of sound-evoked activity was achieved through the electrophoretic delivery of calcium indicators. The method provides a new tool for studying how stimuli are processed in peripheral and central sensory pathways and is a significant advance for the study of nervous systems in non-model organisms. PMID:28084413

  7. Mean Field Analysis of Large-Scale Interacting Populations of Stochastic Conductance-Based Spiking Neurons Using the Klimontovich Method

    Science.gov (United States)

    Gandolfo, Daniel; Rodriguez, Roger; Tuckwell, Henry C.

    2017-03-01

    We investigate the dynamics of large-scale interacting neural populations, composed of conductance based, spiking model neurons with modifiable synaptic connection strengths, which are possibly also subjected to external noisy currents. The network dynamics is controlled by a set of neural population probability distributions (PPD) which are constructed along the same lines as in the Klimontovich approach to the kinetic theory of plasmas. An exact non-closed, nonlinear, system of integro-partial differential equations is derived for the PPDs. As is customary, a closing procedure leads to a mean field limit. The equations we have obtained are of the same type as those which have been recently derived using rigorous techniques of probability theory. The numerical solutions of these so called McKean-Vlasov-Fokker-Planck equations, which are only valid in the limit of infinite size networks, actually shows that the statistical measures as obtained from PPDs are in good agreement with those obtained through direct integration of the stochastic dynamical system for large but finite size networks. Although numerical solutions have been obtained for networks of Fitzhugh-Nagumo model neurons, which are often used to approximate Hodgkin-Huxley model neurons, the theory can be readily applied to networks of general conductance-based model neurons of arbitrary dimension.

  8. Unravelling the differential functions and regulation of striatal neuron sub-populations in motor control, reward and motivational processes

    Directory of Open Access Journals (Sweden)

    Sabrina eEna

    2011-07-01

    Full Text Available The striatum, the major input structure of the basal ganglia, is critically involved in motor control and learning of habits and skills, and is also involved in motivational and reward processes. The dorsal striatum, caudate-putamen, is primarily implicated in motor functions whereas the ventral striatum, the nucleus accumbens, is essential for motivation and drug reinforcement. Severe basal ganglia dysfunction occurs in movement disorders as Parkinson’s and Huntington’s disease, and in psychiatric disorders such as schizophrenia and drug addiction. The striatum is essentially composed of GABAergic medium-sized spiny neurons (MSNs that are output neurons giving rise to the so-called direct and indirect pathways and are targets of the cerebral cortex and mesencephalic dopaminergic neurons. Although the involvement of striatal sub-areas in motor control and motivation has been thoroughly characterized, major issues remained concerning the specific and respective functions of the two MSNs sub-populations, D2R-striatopallidal (dopamine D2 receptor-positive and D1R-striatonigral (dopamine D1 receptor-positive neurons, as well as their specific regulation. Here, we review recent advances that gave new insight in the understanding of the differential roles of striatopallidal and striatonigral neurons in the basal ganglia circuit. We discuss innovative techniques developed in the last decade which allowed a much precise evaluation of molecular pathways implicated in motivational processes and functional roles of striatopallidal and striatonigral neurons in motor control and in the establishment of reward-associated behaviour.

  9. Expression of COUP-TFII Nuclear Receptor in Restricted GABAergic Neuronal Populations in the Adult Rat Hippocampus

    Science.gov (United States)

    Fuentealba, Pablo; Klausberger, Thomas; Karayannis, Theofanis; Suen, Wai Yee; Huck, Jojanneke; Tomioka, Ryohei; Rockland, Kathleen; Capogna, Marco; Studer, Michèle; Morales, Marisela; Somogyi, Peter

    2015-01-01

    The COUP-TFII nuclear receptor, also known as NR2F2, is expressed in the developing ventral telencephalon and modulates the tangential migration of a set of subpallial neuronal progenitors during forebrain development. Little information is available about its expression patterns in the adult brain. We have identified the cell populations expressing COUP-TFII and the contribution of some of them to network activity in vivo. Expression of COUP-TFII by hippocampal pyramidal and dentate granule cells, as well as neurons in the neocortex, formed a gradient increasing from undetectable in the dorsal to very strong in the ventral sectors. In the dorsal hippocampal CA1 area, COUP-TFII was restricted to GABAergic interneurons and expressed in several, largely nonoverlapping neuronal populations. Immunoreactivity was present in calretinin-, neuronal nitric oxide synthase-, and reelin-expressing cells, as well as in subsets of cholecystokinin- or calbindin-expressing or radiatum-retrohippocampally projecting GABAergic cells, but not in parvalbumin-and/or somatostatin-expressing interneurons. In vivo recording and juxtacellular labeling of COUP-TFII-expressing cells revealed neurogliaform cells, basket cells in stratum radiatum and tachykinin-expressing radiatum dentate innervating interneurons, identified by their axodendritic distributions. They showed cell type-selective phase-locked firing to the theta rhythm but no activation during sharp wave/ripple oscillations. These basket cells in stratum radiatum and neurogliaform cells fired at the peak of theta oscillations detected extracellularly in stratum pyramidale, unlike previously reported ivy cells, which fired at the trough. The characterization of COUP-TFII-expressing neurons suggests that this developmentally important transcription factor plays cell type-specific role(s)in the adult hippocampus. PMID:20130170

  10. Tracking the Fear Memory Engram: Discrete Populations of Neurons within Amygdala, Hypothalamus, and Lateral Septum Are Specifically Activated by Auditory Fear Conditioning

    Science.gov (United States)

    Butler, Christopher W.; Wilson, Yvette M.; Gunnersen, Jenny M.; Murphy, Mark

    2015-01-01

    Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used "fos-tau-lacZ" ("FTL") transgenic mice to identify…

  11. Tracking the Fear Memory Engram: Discrete Populations of Neurons within Amygdala, Hypothalamus, and Lateral Septum Are Specifically Activated by Auditory Fear Conditioning

    Science.gov (United States)

    Butler, Christopher W.; Wilson, Yvette M.; Gunnersen, Jenny M.; Murphy, Mark

    2015-01-01

    Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used "fos-tau-lacZ" ("FTL") transgenic mice to identify…

  12. A Knockin Reporter Allows Purification and Characterization of mDA Neurons from Heterogeneous Populations

    Directory of Open Access Journals (Sweden)

    Ninuo Xia

    2017-03-01

    Full Text Available Generation of midbrain dopaminergic (mDA neurons from human pluripotent stem cells provides a platform for inquiry into basic and translational studies of Parkinson’s disease (PD. However, heterogeneity in differentiation in vitro makes it difficult to identify mDA neurons in culture or in vivo following transplantation. Here, we report the generation of a human embryonic stem cell (hESC line with a tyrosine hydroxylase (TH-RFP (red fluorescent protein reporter. We validated that RFP faithfully mimicked TH expression during differentiation. Use of this TH-RFP reporter cell line enabled purification of mDA-like neurons from heterogeneous cultures with subsequent characterization of neuron transcriptional and epigenetic programs (global binding profiles of H3K27ac, H3K4me1, and 5-hydroxymethylcytosine [5hmC] at four different stages of development. We anticipate that the tools and data described here will contribute to the development of mDA neurons for applications in disease modeling and/or drug screening and cell replacement therapies for PD.

  13. Characterization of the myenteric neuronal population and subpopulation of the duodenum of adult wistar rat fed with hypoproteic chow

    Directory of Open Access Journals (Sweden)

    Débora M.G. Sant'Ana

    2012-09-01

    Full Text Available The effects of severe protein malnutrition (4% on myenteric neurons of Wistar rat duodenum, in relation to a standard 22%-protein diet for rodents, were assessed in this study. Segments of the duodenum from 10 rats from each nutritional group were submitted to the elaboration of whole mounts - 5 stained with Giemsa to determine the total population of myenteric neurons and the others stained by a histochemical method to detect nervous cells through the NADPH-diaphorase enzyme activity for studying the subpopulation of nitrergic neurons. The area of 100 neurons per animal, totalizing 2,000 neurons, were randomly measured by using the Image Pro-Plus®software. Malnourished rats presented 34.38% lower body weight and 10.60% duodenum length reduction when compared to the control group. Quantitative analysis demonstrated no significant differences between control and malnourished group by using Giemsa; however, as the organ reduction was not followed by an increase inversely proportional to the density of neurons, the condition imposed suggests the loss of neurons from the total population. Nevertheless, through NADPH-d histochemistry, there was a neuronal density increase for the malnourished group. There was no significant difference between the groups for both techniques with respect to the morphometric analysis of the body cell.Objetivou-se avaliar os efeitos da desnutrição protéica severa (4% sobre os neurônios mientéricos do duodeno de ratos Wistar, comparando-se a uma dieta padrão para roedores de 22% de proteína. Para este estudo, segmentos do duodeno de 10 ratos de cada grupo nutricional foram submetidos à elaboração de preparados de membrana, sendo cinco corados pelo método de Giemsa, para estimar a população mientérica total e os demais corados pelo método histoquímico de evidenciação de células nervosas, por meio da atividade da enzima NADPH-diaforase para estudo da subpopulação de neurônios nitr

  14. Imaging neuronal populations in behaving rodents: paradigms for studying neural circuits underlying behavior in the mammalian cortex.

    Science.gov (United States)

    Chen, Jerry L; Andermann, Mark L; Keck, Tara; Xu, Ning-Long; Ziv, Yaniv

    2013-11-06

    Understanding the neural correlates of behavior in the mammalian cortex requires measurements of activity in awake, behaving animals. Rodents have emerged as a powerful model for dissecting the cortical circuits underlying behavior attributable to the convergence of several methods. Genetically encoded calcium indicators combined with viral-mediated or transgenic tools enable chronic monitoring of calcium signals in neuronal populations and subcellular structures of identified cell types. Stable one- and two-photon imaging of neuronal activity in awake, behaving animals is now possible using new behavioral paradigms in head-fixed animals, or using novel miniature head-mounted microscopes in freely moving animals. This mini-symposium will highlight recent applications of these methods for studying sensorimotor integration, decision making, learning, and memory in cortical and subcortical brain areas. We will outline future prospects and challenges for identifying the neural underpinnings of task-dependent behavior using cellular imaging in rodents.

  15. The vertebrate diencephalic MCH system: a versatile neuronal population in an evolving brain.

    Science.gov (United States)

    Croizier, S; Cardot, J; Brischoux, F; Fellmann, D; Griffond, B; Risold, P Y

    2013-04-01

    Neurons synthesizing melanin-concentrating hormone (MCH) are described in the posterior hypothalamus of all vertebrates investigated so far. However, their anatomy is very different according to species: they are small and periventricular in lampreys, cartilaginous fishes or anurans, large and neuroendocrine in bony fishes, or distributed over large regions of the lateral hypothalamus in many mammals. An analysis of their comparative anatomy alongside recent data about the development of the forebrain, suggests that although very different, MCH neurons of the caudal hypothalamus are homologous. We further hypothesize that their divergent anatomy is linked to divergence in the forebrain - in particular telencephalic evolution.

  16. Integration of silicon-based neural probes and micro-drive arrays for chronic recording of large populations of neurons in behaving animals

    Science.gov (United States)

    Michon, Frédéric; Aarts, Arno; Holzhammer, Tobias; Ruther, Patrick; Borghs, Gustaaf; McNaughton, Bruce; Kloosterman, Fabian

    2016-08-01

    Objective. Understanding how neuronal assemblies underlie cognitive function is a fundamental question in system neuroscience. It poses the technical challenge to monitor the activity of populations of neurons, potentially widely separated, in relation to behaviour. In this paper, we present a new system which aims at simultaneously recording from a large population of neurons from multiple separated brain regions in freely behaving animals. Approach. The concept of the new device is to combine the benefits of two existing electrophysiological techniques, i.e. the flexibility and modularity of micro-drive arrays and the high sampling ability of electrode-dense silicon probes. Main results. Newly engineered long bendable silicon probes were integrated into a micro-drive array. The resulting device can carry up to 16 independently movable silicon probes, each carrying 16 recording sites. Populations of neurons were recorded simultaneously in multiple cortical and/or hippocampal sites in two freely behaving implanted rats. Significance. Current approaches to monitor neuronal activity either allow to flexibly record from multiple widely separated brain regions (micro-drive arrays) but with a limited sampling density or to provide denser sampling at the expense of a flexible placement in multiple brain regions (neural probes). By combining these two approaches and their benefits, we present an alternative solution for flexible and simultaneous recordings from widely distributed populations of neurons in freely behaving rats.

  17. Synchronization of neuron population subject to steady DC electric field induced by magnetic stimulation.

    Science.gov (United States)

    Yu, Kai; Wang, Jiang; Deng, Bin; Wei, Xile

    2013-06-01

    Electric fields, which are ubiquitous in the context of neurons, are induced either by external electromagnetic fields or by endogenous electric activities. Clinical evidences point out that magnetic stimulation can induce an electric field that modulates rhythmic activity of special brain tissue, which are associated with most brain functions, including normal and pathological physiological mechanisms. Recently, the studies about the relationship between clinical treatment for psychiatric disorders and magnetic stimulation have been investigated extensively. However, further development of these techniques is limited due to the lack of understanding of the underlying mechanisms supporting the interaction between the electric field induced by magnetic stimulus and brain tissue. In this paper, the effects of steady DC electric field induced by magnetic stimulation on the coherence of an interneuronal network are investigated. Different behaviors have been observed in the network with different topologies (i.e., random and small-world network, modular network). It is found that the coherence displays a peak or a plateau when the induced electric field varies between the parameter range we defined. The coherence of the neuronal systems depends extensively on the network structure and parameters. All these parameters play a key role in determining the range for the induced electric field to synchronize network activities. The presented results could have important implications for the scientific theoretical studies regarding the effects of magnetic stimulation on human brain.

  18. Characterizing contrast adaptation in a population of cat primary visual cortical neurons using Fisher information.

    Science.gov (United States)

    Durant, Szonya; Clifford, Colin W G; Crowder, Nathan A; Price, Nicholas S C; Ibbotson, Michael R

    2007-06-01

    When cat V1/V2 cells are adapted to contrast at their optimal orientation, a reduction in gain and/or a shift in the contrast response function is found. We investigated how these factors combine at the population level to affect the accuracy for detecting variations in contrast. Using the contrast response function parameters from a physiologically measured population, we model the population accuracy (using Fisher information) for contrast discrimination. Adaptation at 16%, 32%, and 100% contrast causes a shift in peak accuracy. Despite an overall drop in firing rate over the whole population, accuracy is enhanced around the adapted contrast and at higher contrasts, leading to greater efficiency of contrast coding at these levels. The estimated contrast discrimination threshold curve becomes elevated and shifted toward higher contrasts after adaptation, as has been found previously in human psychophysical experiments.

  19. Calcium-binding protein-containing neuronal populations in mammalian visual cortex: a comparative study in whales, insectivores, bats, rodents, and primates.

    Science.gov (United States)

    Glezer, I I; Hof, P R; Leranth, C; Morgane, P J

    1993-01-01

    This study is focused on comparative analysis of gamma-aminobutyric acid-positive (GABAergic) neuronal populations in primary visual cortex of totally aquatic toothed whales and select terrestrial mammals with different evolutionary histories and various ecological adaptations. The distribution of neuronal populations containing the calcium-binding proteins calbindin and parvalbumin, which are recognized markers for the GABAergic neurons in cerebral cortex, is compared in five species of toothed whales and in representatives (one species each) of insectivores, bats, rodents, and primates. Computerized image analysis has shown that overall quantitative characteristics of GABAergic cortical neurons in toothed whales are similar to those in other mammalian orders. Thus, GABA-positive neurons represent 26% of the total population of cortical neurons in the visual cortex of whales. Some 97% of GABA-positive cells contain calcium-binding proteins, which is numerically similar to these parameters found in primates and other mammals. On the other hand, the typology and laminar distribution of calcium-binding protein-containing neurons in the primary visual cortex of five whale species (Delphinapterus leucas, Globicephala melaena, Phocoena phocoena, Stenella coeruleoalba, and Tursiops truncatus) differ significantly from those of primates (Macaca mulatta) and rodents (Rattus rattus) and are similar to those found in insectivorous bats (Eptesicus fuscus) and hedgehogs (Erinaceus europaeus). In whales, bats, and hedgehogs a significant concentration of calbindin-positive, vertically oriented bipolar and bitufted neurons was found in layers I, II, and IIIc/V with their axons arranged in a three-dimensional network. In primates and rodents they are distributed evenly across all cortical layers and are predominantly multipolar or bitufted neurons found in all cortical layers with their axons oriented along the vertical axis of the cortical plate. The parvalbumin-positive neurons

  20. ARRHYTHMIA INDUCED BY NICOTINE ACTIVATING CARDIAC INTRINSIC NEURONS IN CANINE ATRIAL AND VENTRICULAR GANGLIAL PLEXUS

    Institute of Scientific and Technical Information of China (English)

    袁秉祥; 刘书勤; 李萍; 李新华

    2002-01-01

    Objective To study the arrhythmia induced by stimulation of nicotine-sensitive neurons in cardiac ganglial plexuses. Methods When nicotine (100μg) was injected into canine right atrial ganglial plexus (RAGP) and ganglial plexus between aorta and pulmonary artery (A-PGP) in 33 anesthetized open-chest dog, electrocardiogram, atrial force and ventricular intramyocardial pressures (IMP) were recorded. The responses were also recorded following administration of atropine or propranolol and after heart acute decentralization. Results Ventricular arrhythmia (VA) was induced by injections of nicotine into A-PGP, but not by injections of nicotine into RAGP in 13 dogs. Atrioventricilar (A-V) block was induced by nicotine activating RAGP in 10 dogs, but not by nicotine activating A-PGP. Propranolol could reduce the frequency of VA elicited by stimulating A-PGP, atropine could reduce the frequency of A-V block elicited by stimulating RAGP. After acute decentralization, VA was still induced by activation of A-PGP in 9 dogs, but A-V block elicited by stimulating RAGP was decreased. Conclusion VA is induced by stimulating N receptor in cardiac nicotine-sensitive efferent sympathetic neurons of ventricular ganglial plexus (A-PGP), and then modifying β receptor of ventricles. A-V block is elicited by stimulating N receptor in atrial ganglial plexus (RAGP), then modifying M receptor of A-V node not only via efferent parasympathetic neurons, but also via afferent pathway.

  1. The Effect of Inhibitory Neuron on the Evolution Model of Higher-Order Coupling Neural Oscillator Population

    Directory of Open Access Journals (Sweden)

    Yi Qi

    2014-01-01

    Full Text Available We proposed a higher-order coupling neural network model including the inhibitory neurons and examined the dynamical evolution of average number density and phase-neural coding under the spontaneous activity and external stimulating condition. The results indicated that increase of inhibitory coupling strength will cause decrease of average number density, whereas increase of excitatory coupling strength will cause increase of stable amplitude of average number density. Whether the neural oscillator population is able to enter the new synchronous oscillation or not is determined by excitatory and inhibitory coupling strength. In the presence of external stimulation, the evolution of the average number density is dependent upon the external stimulation and the coupling term in which the dominator will determine the final evolution.

  2. Synchronization tomography: a method for three-dimensional localization of phase synchronized neuronal populations in the human brain using magnetoencephalography.

    Science.gov (United States)

    Tass, P A; Fieseler, T; Dammers, J; Dolan, K; Morosan, P; Majtanik, M; Boers, F; Muren, A; Zilles, K; Fink, G R

    2003-02-28

    We present a noninvasive technique which allows the anatomical localization of phase synchronized neuronal populations in the human brain with magnetoencephalography. We study phase synchronization between the reconstructed current source density (CSD) of different brain areas as well as between the CSD and muscular activity. We asked four subjects to tap their fingers in synchrony with a rhythmic tone, and to continue tapping at the same rate after the tone was switched off. The phase synchronization behavior of brain areas relevant for movement coordination, inner voice, and time estimation changes drastically when the transition to internal pacing occurs, while their averaged amplitudes remain unchanged. Information of this kind cannot be derived with standard neuroimaging techniques like functional magnetic resonance imaging or positron emission tomography.

  3. Intrinsic excitability state of local neuronal population modulates signal propagation in feed-forward neural networks.

    Science.gov (United States)

    Han, Ruixue; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xilei; Qin, Yingmei; Wang, Haixu

    2015-04-01

    Reliable signal propagation across distributed brain areas is an essential requirement for cognitive function, and it has been investigated extensively in computational studies where feed-forward network (FFN) is taken as a generic model. But it is still unclear how distinct local network states, which are intrinsically generated by synaptic interactions within each layer, would affect the ability of FFN to transmit information. Here we investigate the impact of such network states on propagating transient synchrony (synfire) and firing rate by a combination of numerical simulations and analytical approach. Specifically, local network dynamics is attributed to the competition between excitatory and inhibitory neurons within each layer. Our results show that concomitant with different local network states, the performance of signal propagation differs dramatically. For both synfire propagation and firing rate propagation, there exists an optimal local excitability state, respectively, that optimizes the performance of signal propagation. Furthermore, we find that long-range connections strongly change the dependence of spiking activity propagation on local network state and propose that these two factors work jointly to determine information transmission across distributed networks. Finally, a simple mean field approach that bridges response properties of long-range connectivity and local subnetworks is utilized to reveal the underlying mechanism.

  4. Effects of kisspeptin1 on electrical activity of an extrahypothalamic population of gonadotropin-releasing hormone neurons in medaka (Oryzias latipes).

    Science.gov (United States)

    Zhao, Yali; Wayne, Nancy L

    2012-01-01

    Kisspeptin (product of the kiss1 gene) is the most potent known activator of the hypothalamo-pituitary-gonadal axis. Both kiss1 and the kisspeptin receptor are highly expressed in the hypothalamus of vertebrates, and low doses of kisspeptin have a robust and long-lasting stimulatory effect on the rate of action potential firing of hypophysiotropic gonadotropin releasing hormone-1 (GnRH1) neurons in mice. Fish have multiple populations of GnRH neurons distinguished by their location in the brain and the GnRH gene that they express. GnRH3 neurons located in the terminal nerve (TN) associated with the olfactory bulb are neuromodulatory and do not play a direct role in regulating pituitary-gonadal function. In medaka fish, the electrical activity of TN-GnRH3 neurons is modulated by visual cues from conspecifics, and is thought to act as a transmitter of information from the external environment to the central nervous system. TN-GnRH3 neurons also play a role in sexual motivation and arousal states, making them an important population of neurons to study for understanding coordination of complex behaviors. We investigated the role of kisspeptin in regulating electrical activity of TN-GnRH3 neurons in adult medaka. Using electrophysiology in an intact brain preparation, we show that a relatively brief treatment with 100 nM of kisspeptin had a long-lasting stimulatory effect on the electrical activity of an extrahypothalamic population of GnRH neurons. Dose-response analysis suggests a relatively narrow activational range of this neuropeptide. Further, blocking action potential firing with tetrodotoxin and blocking synaptic transmission with a low Ca(2+)/high Mg(2+) solution inhibited the stimulatory action of kisspeptin on electrical activity, indicating that kisspeptin is acting indirectly through synaptic regulation to excite TN-GnRH3 neurons. Our findings provide a new perspective on kisspeptin's broader functions within the central nervous system, through its

  5. Some details on the method for measuring activity changes of neuronal populations

    Directory of Open Access Journals (Sweden)

    Kalauzi Aleksandar

    2003-01-01

    Full Text Available Simple, complex action potentials (AP and interspike recorded background activity (RBA were detected and extracted from 12 rat cerebellar cortical recordings. For each recording, an averaged simple action potential (SAP was formed. Fourier amplitude spectra of SAP and RBA were similar in all recordings. For one of the recordings, a series of RBA simulations (SBA was generated, superimposing random SAPs, varying the superposition frequency (fsup. Average Fourier amplitude, Amp(SBA, was calculated, in order to use Amp(SBA=f(fsup as a calibration line for reading fsup of RBA, which is a measure of the population activity. A probability distribution for SAP intensities was derived and a family of calibration lines constructed. As all lines were linear and parallel (slope S in log-log plots, a population activity change could be calculated as fsup2/fsup1=[Amp2(RBA/Amp(RBA]1/S.

  6. Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Kathleen M. Keefe

    2017-03-01

    Full Text Available Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI. We focus on nerve growth factor (NGF, brain derived neurotrophic factor (BDNF, and neurotrophin-3 (NT-3, and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.

  7. A heterogeneous population of nuclear-encoded mitochondrial mRNAs is present in the axons of primary sympathetic neurons.

    Science.gov (United States)

    Aschrafi, Armaz; Kar, Amar N; Gale, Jenna R; Elkahloun, Abdel G; Vargas, Jose Noberto S; Sales, Naomi; Wilson, Gabriel; Tompkins, Miranda; Gioio, Anthony E; Kaplan, Barry B

    2016-09-01

    Mitochondria are enriched in subcellular regions of high energy consumption, such as axons and pre-synaptic nerve endings. Accumulating evidence suggests that mitochondrial maintenance in these distal structural/functional domains of the neuron depends on the "in-situ" translation of nuclear-encoded mitochondrial mRNAs. In support of this notion, we recently provided evidence for the axonal targeting of several nuclear-encoded mRNAs, such as cytochrome c oxidase, subunit 4 (COXIV) and ATP synthase, H+ transporting and mitochondrial Fo complex, subunit C1 (ATP5G1). Furthermore, we showed that axonal trafficking and local translation of these mRNAs plays a critical role in the generation of axonal ATP. Using a global gene expression analysis, this study identified a highly diverse population of nuclear-encoded mRNAs that were enriched in the axon and presynaptic nerve terminals. Among this population of mRNAs, fifty seven were found to be at least two-fold more abundant in distal axons, as compared with the parental cell bodies. Gene ontology analysis of the nuclear-encoded mitochondrial mRNAs suggested functions for these gene products in molecular and biological processes, including but not limited to oxidoreductase and electron carrier activity and proton transport. Based on these results, we postulate that local translation of nuclear-encoded mitochondrial mRNAs present in the axons may play an essential role in local energy production and maintenance of mitochondrial function.

  8. Recovering stimulus locations using populations of eye-position modulated neurons in dorsal and ventral visual streams of nonhuman primates

    Directory of Open Access Journals (Sweden)

    Anne B Sereno

    2014-03-01

    Full Text Available We recorded visual responses while monkeys fixated the same target at different gaze angles, both dorsally (lateral intraparietal cortex, LIP and ventrally (anterior inferotemporal cortex, AIT. While eye-position modulations occurred in both areas, they were both more frequent and stronger in LIP neurons. We used an intrinsic population decoding technique, multidimensional scaling, to recover eye positions, equivalent to recovering fixated target locations. We report that eye-position based visual space in LIP was more accurate (i.e., metric. Nevertheless, the AIT spatial representation remained largely topologically correct, perhaps indicative of a categorical spatial representation (i.e., a qualitative description such as left of or above as opposed to a quantitative, metrically precise description. Additionally, we developed a simple neural model of eye position signals and illustrate that differences in single cell characteristics can influence the ability to recover target position in a population of cells. We demonstrate for the first time that the ventral stream contains sufficient information for constructing an eye-position based spatial representation. Furthermore we demonstrate, in dorsal and ventral streams as well as modeling, that target locations can be extracted directly from eye position signals in cortical visual responses without computing coordinate transforms of visual space.

  9. Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio.

    Directory of Open Access Journals (Sweden)

    Yali Zhao

    Full Text Available Kisspeptin1 (product of the Kiss1 gene is the key neuropeptide that gates puberty and maintains fertility by regulating the gonadotropin-releasing hormone (GnRH neuronal system in mammals. Inactivating mutations in Kiss1 and the kisspeptin receptor (GPR54/Kiss1r are associated with pubertal failure and infertility. Kiss2, a paralogous gene for kiss1, has been recently identified in several vertebrates including zebrafish. Using our transgenic zebrafish model system in which the GnRH3 promoter drives expression of emerald green fluorescent protein, we investigated the effects of kisspeptins on development of the GnRH neuronal system during embryogenesis and on electrical activity during adulthood. Quantitative PCR showed detectable levels of kiss1 and kiss2 mRNA by 1 day post fertilization, increasing throughout embryonic and larval development. Early treatment with Kiss1 or Kiss2 showed that both kisspeptins stimulated proliferation of trigeminal GnRH3 neurons located in the peripheral nervous system. However, only Kiss1, but not Kiss2, stimulated proliferation of terminal nerve and hypothalamic populations of GnRH3 neurons in the central nervous system. Immunohistochemical analysis of synaptic vesicle protein 2 suggested that Kiss1, but not Kiss2, increased synaptic contacts on the cell body and along the terminal nerve-GnRH3 neuronal processes during embryogenesis. In intact brain of adult zebrafish, whole-cell patch clamp recordings of GnRH3 neurons from the preoptic area and hypothalamus revealed opposite effects of Kiss1 and Kiss2 on spontaneous action potential firing frequency and membrane potential. Kiss1 increased spike frequency and depolarized membrane potential, whereas Kiss2 suppressed spike frequency and hyperpolarized membrane potential. We conclude that in zebrafish, Kiss1 is the primary stimulator of GnRH3 neuronal development in the embryo and an activator of stimulating hypophysiotropic neuron activities in the adult, while

  10. A Population of Projection Neurons that Inhibits the Lateral Horn but Excites the Antennal Lobe through Chemical Synapses in Drosophila

    Directory of Open Access Journals (Sweden)

    Kazumichi Shimizu

    2017-05-01

    Full Text Available In the insect olfactory system, odor information is transferred from the antennal lobe (AL to higher brain areas by projection neurons (PNs in multiple AL tracts (ALTs. In several species, one of the ALTs, the mediolateral ALT (mlALT, contains some GABAergic PNs; in the Drosophila brain, the great majority of ventral PNs (vPNs are GABAergic and project through this tract to the lateral horn (LH. Most excitatory PNs (ePNs, project through the medial ALT (mALT to the mushroom body (MB and the LH. Recent studies have shown that GABAergic vPNs play inhibitory roles at their axon terminals in the LH. However, little is known about the properties and functions of vPNs at their dendritic branches in the AL. Here, we used optogenetic and patch clamp techniques to investigate the functional roles of vPNs in the AL. Surprisingly, our results show that specific activation of vPNs reliably elicits strong excitatory postsynaptic potentials (EPSPs in ePNs. Moreover, the connections between vPNs and ePNs are mediated by direct chemical synapses. Neither pulses of GABA, nor pharmagological, or genetic blockade of GABAergic transmission gave results consistent with the involvement of GABA in vPN-ePN excitatory transmission. These unexpected results suggest new roles for the vPN population in olfactory information processing.

  11. Recruitment in a heterogeneous population of motor neurons that innervates the depressor muscle of the crayfish walking leg muscle.

    Science.gov (United States)

    Hill, Andrew A V; Cattaert, Daniel

    2008-02-01

    According to the size principle the fine control of muscle tension depends on the orderly recruitment of motor neurons from a heterogeneous pool. We took advantage of the small number of excitatory motor neurons (about 12) that innervate the depressor muscle of the crayfish walking leg to determine if the size principle applies to this muscle. We found that in accordance with the size principle, when stimulated by proprioceptive input, neurons with small extracellular spikes were recruited before neurons with medium or large spikes. Because only a small fraction of the motor neurons responded strongly enough to sensory input to be recruited in this way, we extended our analysis to all neurons by characterizing properties that have classically been associated with recruitment order such as speed of axonal conduction and extracellular spike amplitude. Through a combination of physiological and anatomical criteria we were able to identify seven classes of excitatory depressor motor neurons. The majority of these classes responded to proprioceptive input with a resistance reflex, while a few responded with an assistance reflex, and yet others did not respond. Our results are in general agreement with the size principle. However, we found qualitative differences between neuronal classes in terms of synaptic input and neuronal structure that would in theory be unnecessary, according to a strict interpretation of the size principle. We speculate that the qualitative heterogeneity observed may be due to the fact that the depressor is a complex muscle, consisting of two muscle bundles that share a single insertion but have multiple origins.

  12. Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels

    Science.gov (United States)

    Serotonin 2C receptors (5-HT2CRs) expressed by pro-opiomelanocortin (POMC) neurons of hypothalamic arcuate nucleus regulate food intake, energy homeostasis ,and glucose metabolism. However, the cellular mechanisms underlying the effects of 5-HT to regulate POMC neuronal activity via 5-HT2CRs have no...

  13. Comparison of the activation of somatostatin- and neuropeptide Y-containing neuronal populations of the rat amygdala following two different anxiogenic stressors

    Science.gov (United States)

    Butler, Ryan K.; White, L. Casey; Frederick-Duus, Dani; Kaigler, Kris F.; Fadel, Jim R.; Wilson, Marlene A.

    2012-01-01

    Rats exposed to the odor of a predator or to the elevated plus maze express fear behaviors without a prior exposure to either stimulus. The expression of innate fear provides for an ideal model of anxiety which can aid in the elucidation of brain circuits involved in anxiety-related behaviors. The current experiments compared activation of neuropeptide-containing neuronal populations in the amygdala of rats exposed to either the elevated plus maze (EPM; 5 minutes) versus home cage controls, or predator ferret odor versus butyric acid, or no odor (30 minutes). Sections of the brains were prepared for dual-labeled immunohistochemistry and counts of c-Fos co-localized with somatostatin (SOM) or neuropeptide Y (NPY) were made in the basolateral (BLA), central (CEA), medial (MEA) nucleus of the amygdala. Ferret odor and butyric acid exposure significantly decreased the percentage of SOM–positive neurons also immunoreactive for c-Fos in the anterior BLA compared to controls, whereas EPM exposure yielded a significant increase in the activation of SOM-positive neurons versus home cage controls. In the CEA, ferret odor and butyric exposure significantly decreased the percentage of SOM-positive neurons also immunoreactive for c-Fos compared to no-odor controls whereas EPM exposure yielded no change versus controls. In the MEA, both ferret odor exposure and EPM exposure resulted in increased SOM co-localized with c-Fos compared to control groups whereas NPY co-localized with c-Fos occurred following ferret odor exposure, but not EPM exposure. These results indicate that phenotypically distinct neuronal populations of the amygdala are differentially activated following exposure to different anxiogenic stimuli. These studies further elucidate the fundamental neurocircuitry of anxiety and could possibly explain the differential behavioral effects of predator versus novelty-induced stress. PMID:22917777

  14. Label-free detection of neuronal differentiation in cell populations using high-throughput live-cell imaging of PC12 cells.

    Directory of Open Access Journals (Sweden)

    Sebastian Weber

    Full Text Available Detection of neuronal cell differentiation is essential to study cell fate decisions under various stimuli and/or environmental conditions. Many tools exist that quantify differentiation by neurite length measurements of single cells. However, quantification of differentiation in whole cell populations remains elusive so far. Because such populations can consist of both proliferating and differentiating cells, the task to assess the overall differentiation status is not trivial and requires a high-throughput, fully automated approach to analyze sufficient data for a statistically significant discrimination to determine cell differentiation. We address the problem of detecting differentiation in a mixed population of proliferating and differentiating cells over time by supervised classification. Using nerve growth factor induced differentiation of PC12 cells, we monitor the changes in cell morphology over 6 days by phase-contrast live-cell imaging. For general applicability, the classification procedure starts out with many features to identify those that maximize discrimination of differentiated and undifferentiated cells and to eliminate features sensitive to systematic measurement artifacts. The resulting image analysis determines the optimal post treatment day for training and achieves a near perfect classification of differentiation, which we confirmed in technically and biologically independent as well as differently designed experiments. Our approach allows to monitor neuronal cell populations repeatedly over days without any interference. It requires only an initial calibration and training step and is thereafter capable to discriminate further experiments. In conclusion, this enables long-term, large-scale studies of cell populations with minimized costs and efforts for detecting effects of external manipulation of neuronal cell differentiation.

  15. Stochastic Resonance in an Array of Locally-Coupled McCulloch-Pitts Neurons with Population Heterogeneity

    Science.gov (United States)

    Utagawa, Akira; Sahashi, Tohru; Asai, Tetsuya; Amemiya, Yoshihito

    We found a new class of stochastic resonance (SR) in a simple neural network that consists of i) photoreceptors generating nonuniform outputs for common inputs with random offsets, ii) an ensemble of noisy McCulloch-Pitts (MP) neurons each of which has random threshold values in the temporal domain, iii) local coupling connections between the photoreceptors and the MP neurons with variable receptive fields (RFs), iv) output cells, and v) local coupling connections between the MP neurons and the output cells. We calculated correlation values between the inputs and the outputs as a function of the RF size and intensities of the random components in photoreceptors and the MP neurons. We show the existence of “optimal noise intensities” of the MP neurons under the nonidentical photoreceptors and “nonzero optimal RF sizes, ” which indicated that optimal correlation values of this SR model were determined by two critical parameters; noise intensities (well-known) and RF sizes as a new parameter.

  16. Fgf8-deficient mice compensate for reduced GnRH neuronal population and exhibit normal testicular function

    Directory of Open Access Journals (Sweden)

    Wei eZhang

    2015-09-01

    Full Text Available Gonadotropin-releasing hormone (GnRH is critical for the onset and maintenance of reproduction in vertebrates. The development of GnRH neurons is highly dependent on fibroblast growth factor (Fgf signaling. Mice with a hypomorphic Fgf8 allele (Fgf8 Het exhibited a ~50% reduction in GnRH neuron number at birth. Female Fgf8 Het mice were fertile but showed significantly delayed puberty. However, it was unclear if these mice suffered additional loss of GnRH neurons after birth, and if male Fgf8 Het mice had normal pubertal transition and testicular function. In this study, we examined postnatal GnRH neuron number and hypothalamic GnRH content in Fgf8 Het mice from birth to 120 days of age. Further, we examined seminal vesicle and testicular growth, testicular histology, and circulating luteinizing hormone (LH around and after pubertal transition. Our results showed that GnRH neuron numbers were significantly and consistently reduced in Fgf8 Het mice of both sexes in all ages examined, suggesting these animals were born with an inherently defective GnRH system, and no further postnatal loss of GnRH neurons had occurred. Despite an innately compromised GnRH system, male and female Fgf8 mice exhibited normal levels of immunoassayable hypothalamic GnRH peptide at all ages examined except on 60 days of age, suggesting increased GnRH synthesis or reduced turnover as a compensatory mechanism. Fgf8 Het males also had normal seminal vesicle and testicular mass/body mass ratios, testicular histology, and circulating LH. Overall, our data speak to the extraordinary ability of a GnRH system permanently compromised by developmental defect to overcome pre-existing deficiencies to ensure pubertal progression and reproduction.

  17. Long-Term Two-Photon Calcium Imaging of Neuronal Populations with Subcellular Resolution in Adult Non-human Primates.

    Science.gov (United States)

    Sadakane, Osamu; Masamizu, Yoshito; Watakabe, Akiya; Terada, Shin-Ichiro; Ohtsuka, Masanari; Takaji, Masafumi; Mizukami, Hiroaki; Ozawa, Keiya; Kawasaki, Hiroshi; Matsuzaki, Masanori; Yamamori, Tetsuo

    2015-12-01

    Two-photon imaging with genetically encoded calcium indicators (GECIs) enables long-term observation of neuronal activity in vivo. However, there are very few studies of GECIs in primates. Here, we report a method for long-term imaging of a GECI, GCaMP6f, expressed from adeno-associated virus vectors in cortical neurons of the adult common marmoset (Callithrix jacchus), a small New World primate. We used a tetracycline-inducible expression system to robustly amplify neuronal GCaMP6f expression and up- and downregulate it for more than 100 days. We succeeded in monitoring spontaneous activity not only from hundreds of neurons three-dimensionally distributed in layers 2 and 3 but also from single dendrites and axons in layer 1. Furthermore, we detected selective activities from somata, dendrites, and axons in the somatosensory cortex responding to specific tactile stimuli. Our results provide a way to investigate the organization and plasticity of cortical microcircuits at subcellular resolution in non-human primates.

  18. Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations

    Science.gov (United States)

    Kim, Seungil; Barry, Devin M.; Liu, Xian-Yu; Yin, Shijin; Munanairi, Admire; Meng, Qing-Tao; Cheng, Wei; Mo, Ping; Wan, Li; Liu, Shen-Bin; Ratnayake, Kasun; Zhao, Zhong-Qiu; Gautam, Narasimhan; Zheng, Jie; Ajith Karunarathne, W. K.; Chen, Zhou-Feng

    2017-01-01

    The transient receptor potential channels (TRPs) respond to chemical irritants and temperature. TRPV1 responds to the itch-inducing endogenous signal histamine, and TRPA1 responds to the itch-inducing chemical chloroquine. We showed that, in sensory neurons, TRPV4 is important for both chloroquine-and histamine-induced itch and that TRPV1 has a role in chloroquine-induced itch. Chloroquine-induced scratching was reduced in mice in which TRPV1 was knocked down or pharmacologically inhibited. Both TRPV4 and TRPV1 were present in some sensory neurons. Pharmacological blockade of either TRPV4 or TRPV1 significantly attenuated the Ca2+ response of sensory neurons exposed to histamine or chloroquine. Knockout of Trpv1 impaired Ca2+ responses and reduced scratching behavior evoked by a TRPV4 agonist, whereas knockout of Trpv4 did not alter TRPV1-mediated capsaicin responses. Electrophysiological analysis of human embryonic kidney (HEK) 293 cells coexpressing TRPV4 and TRPV1 revealed that the presence of both channels enhanced the activation kinetics of TRPV4 but not of TRPV1. Biochemical and biophysical studies suggested a close proximity between TRPV4 and TRPV1 in dorsal root ganglion neurons and in cultured cells. Thus, our studies identified TRPV4 as a channel that contributes to both histamine- and chloroquine-induced itch and indicated that the function of TRPV4 in itch signaling involves TRPV1-mediated facilitation. TRP facilitation through the formation of heteromeric complexes could be a prevalent mechanism by which the vast array of somatosensory information is encoded in sensory neurons. PMID:27436359

  19. Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons

    Science.gov (United States)

    Görlich, Andreas; Antolin-Fontes, Beatriz; Ables, Jessica L.; Frahm, Silke; Ślimak, Marta A.; Dougherty, Joseph D.; Ibañez-Tallon, Inés

    2013-01-01

    The discovery of genetic variants in the cholinergic receptor nicotinic CHRNA5-CHRNA3-CHRNB4 gene cluster associated with heavy smoking and higher relapse risk has led to the identification of the midbrain habenula–interpeduncular axis as a critical relay circuit in the control of nicotine dependence. Although clear roles for α3, β4, and α5 receptors in nicotine aversion and withdrawal have been established, the cellular and molecular mechanisms that participate in signaling nicotine use and contribute to relapse have not been identified. Here, using translating ribosome affinity purification (TRAP) profiling, electrophysiology, and behavior, we demonstrate that cholinergic neurons, but not peptidergic neurons, of the medial habenula (MHb) display spontaneous tonic firing of 2–10 Hz generated by hyperpolarization-activated cyclic nucleotide-gated (HCN) pacemaker channels and that infusion of the HCN pacemaker antagonist ZD7288 in the habenula precipitates somatic and affective signs of withdrawal. Further, we show that a strong, α3β4-dependent increase in firing frequency is observed in these pacemaker neurons upon acute exposure to nicotine. No change in the basal or nicotine-induced firing was observed in cholinergic MHb neurons from mice chronically treated with nicotine. We observe, however, that, during withdrawal, reexposure to nicotine doubles the frequency of pacemaking activity in these neurons. These findings demonstrate that the pacemaking mechanism of cholinergic MHb neurons controls withdrawal, suggesting that the heightened nicotine sensitivity of these neurons during withdrawal may contribute to smoking relapse. PMID:24082085

  20. Exploring neuronal activity with photons

    Science.gov (United States)

    Bourdieu, Laurent; Léger, Jean-François

    2015-10-01

    The following sections are included: * Introduction * Information coding * Optical recordings of neuronal activity * Functional organization of the cortex at the level of a cortical column * Microarchitecture of a cortical column * Dynamics of neuronal populations * Outlook * Bibliography

  1. Noise and Neuronal Heterogeneity

    CERN Document Server

    Barber, Michael J

    2010-01-01

    We consider signal transaction in a simple neuronal model featuring intrinsic noise. The presence of noise limits the precision of neural responses and impacts the quality of neural signal transduction. We assess the signal transduction quality in relation to the level of noise, and show it to be maximized by a non-zero level of noise, analogous to the stochastic resonance effect. The quality enhancement occurs for a finite range of stimuli to a single neuron; we show how to construct networks of neurons that extend the range. The range increases more rapidly with network size when we make use of heterogeneous populations of neurons with a variety of thresholds, rather than homogeneous populations of neurons all with the same threshold. The limited precision of neural responses thus can have a direct effect on the optimal network structure, with diverse functional properties of the constituent neurons supporting an economical information processing strategy that reduces the metabolic costs of handling a broad...

  2. Separate populations of neurons within the paraventricular hypothalamic nucleus of the rat project to vagal and thoracic autonomic preganglionic levels and express c-Fos protein induced by lithium chloride.

    Science.gov (United States)

    Portillo, F; Carrasco, M; Vallo, J J

    1998-03-01

    The role of different hypothalamic nuclei, particularly the paraventricular nucleus (PVN), in the control of food intake and feeding behaviour is well known. It is also well established that lithium chloride (LiCl) causes various disorders in feeding behaviour. In this study, we analyzed the precise distribution of hypothalamic neurons activated by i.p. LiCl administration (LCA neurons) and compared it to that of hypothalamic neurons which project to autonomic preganglionic levels (HAP neurons). We also analysed the possibility that some neurons belong to both populations of nerve cells. To this end, a multiple-labelling technique, using two retrograde fluorescent tracers together with c-Fos-like immunohistochemistry, was performed. Fast Blue was injected in the dorsal motor nucleus of the vagus and Fluorogold (FG) in the thoracic intermedial-lateral cell column, to trace parasympathetic and sympathetic pathways, respectively. LiCl was used as stimulus for c-Fos-like immunohistochemistry. HAP neurons were located mainly in the dorsal, ventral and lateral regions of the parvocellular PVN, while LCA neurons were observed predominantly in the magnocellular region of the PVN rostrally to HAP neurons. A significant number of FG/Fos double-labelled neurons were located in the dorsal parvocellular subnucleus of the PVN (dp) in the LiCl-stimulated rats. We concluded that there is a clear segregation of LCA neurons from HAP neurons within the PVN. The presence of FG/Fos double-labelled neurons in the dp suggests that this nucleus could mediate a sympathetic response after LiCl administration.

  3. Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons

    Directory of Open Access Journals (Sweden)

    Matsuzawa Yoshiyasu

    2006-03-01

    Full Text Available Abstract Background Triptans, 5-HT1B/ID agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons (TGNs and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although high-voltage activated (HVA Ca2+ channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca2+ channels are not yet documented. Results In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca2+ channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba2+ currents (IBa passing through Ca2+ channels. Zolmitriptan (0.1–100 μM reduced the size of IBa in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT1B/1D antagonist, and by overnight pretreatment with pertussis toxin (PTX. P/Q-type Ca2+ channel blockers inhibited the inhibitory action of zolmitriptan on IBa, compared to N- and L-type blockers, and R-type blocker did, compared to L-type blocker, respectively (p 1B/1D receptor linked to Gi/o pathway. Conclusion It is concluded that this zolmitriptan inhibition of HVA Ca2+ channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan.

  4. Tracking the Fragile X Mental Retardation Protein in a Highly Ordered Neuronal RiboNucleoParticles Population: A Link between Stalled Polyribosomes and RNA Granules

    Science.gov (United States)

    Tremblay, Sandra; Jaglin, Xavier; Dury, Alain; Robert, Claude; De Koninck, Paul; Khandjian, Edouard W.

    2016-01-01

    Local translation at the synapse plays key roles in neuron development and activity-dependent synaptic plasticity. mRNAs are translocated from the neuronal soma to the distant synapses as compacted ribonucleoparticles referred to as RNA granules. These contain many RNA-binding proteins, including the Fragile X Mental Retardation Protein (FMRP), the absence of which results in Fragile X Syndrome, the most common inherited form of intellectual disability and the leading genetic cause of autism. Using FMRP as a tracer, we purified a specific population of RNA granules from mouse brain homogenates. Protein composition analyses revealed a strong relationship between polyribosomes and RNA granules. However, the latter have distinct architectural and structural properties, since they are detected as close compact structures as observed by electron microscopy, and converging evidence point to the possibility that these structures emerge from stalled polyribosomes. Time-lapse video microscopy indicated that single granules merge to form cargoes that are transported from the soma to distal locations. Transcriptomic analyses showed that a subset of mRNAs involved in cytoskeleton remodelling and neural development is selectively enriched in RNA granules. One third of the putative mRNA targets described for FMRP appear to be transported in granules and FMRP is more abundant in granules than in polyribosomes. This observation supports a primary role for FMRP in granules biology. Our findings open new avenues for the study of RNA granule dysfunctions in animal models of nervous system disorders, such as Fragile X syndrome. PMID:27462983

  5. Pacemaking Kisspeptin Neurons

    Science.gov (United States)

    Kelly, Martin J.; Zhang, Chunguang; Qiu, Jian; Rønnekleiv, Oline K.

    2013-01-01

    Kisspeptin (Kiss1) neurons are vital for reproduction. GnRH neurons express the kisspeptin receptor, GPR 54, and kisspeptins potently stimulate the release of GnRH by depolarising and inducing sustained action potential firing in GnRH neurons. As such Kiss1 neurons may be the pre-synaptic pacemaker neurons in the hypothalamic circuitry that controls reproduction. There are at least two different populations of Kiss1 neurons: one in the rostral periventricular area (RP3V) that is stimulated by oestrogens and the other in the arcuate nucleus that is inhibited by oestrogens. How each of these Kiss1 neuronal populations participate in the regulation of the reproductive cycle is currently under intense investigation. Based on electrophysiological studies in the guinea pig and mouse, Kiss1 neurons in general are capable of generating burst firing behavior. Essentially all Kiss1 neurons, which have been studied thus far in the arcuate nucleus, express the ion channels necessary for burst firing, which include hyperpolarization-activated, cyclic nucleotide gated cation (HCN) channels and the T-type calcium (Cav3.1) channels. Under voltage clamp conditions, these channels produce distinct currents that under current clamp conditions can generate burst firing behavior. The future challenge is to identify other key channels and synaptic inputs involved in the regulation of the firing properties of Kiss1 neurons and the physiological regulation of the expression of these channels and receptors by oestrogens and other hormones. The ultimate goal is to understand how Kiss1 neurons control the different phases of GnRH neurosecretion and hence reproduction. PMID:23884368

  6. Production of high quality brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) RNA from isolated populations of rat spinal cord motor neurons obtained by Laser Capture Microdissection (LCM).

    Science.gov (United States)

    Mehta, Prachi; Premkumar, Brian; Morris, Renée

    2016-08-03

    The mammalian central nervous system (CNS) is composed of multiple cellular elements, making it challenging to segregate one particular cell type to study their gene expression profile. For instance, as motor neurons represent only 5-10% of the total cell population of the spinal cord, meaningful transcriptional analysis on these neurons is almost impossible to achieve from homogenized spinal cord tissue. A major challenge faced by scientists is to obtain good quality RNA from small amounts of starting material. In this paper, we used Laser Capture Microdissection (LCM) techniques to identify and isolate spinal cord motor neurons. The present analysis revealed that perfusion with paraformaldehyde (PFA) does not alter RNA quality. RNA integrity numbers (RINs) of tissue samples from rubrospinal tract (RST)-transected, intact spinal cord or from whole spinal cord homogenate were all above 8, which indicates intact, high-quality RNA. Levels of mRNA for brain-derived neurotrophic factor (BDNF) or for its tropomyosin receptor kinase B (TrkB) were not affected by rubrospinal tract (RST) transection, a surgical procedure that deprive motor neurons from one of their main supraspinal input. The isolation of pure populations of neurons with LCM techniques allows for robust transcriptional characterization that cannot be achieved with spinal cord homogenates. Such preparations of pure population of motor neurons will provide valuable tools to advance our understanding of the molecular mechanisms underlying spinal cord injury and neuromuscular diseases. In the near future, LCM techniques might be instrumental to the success of gene therapy for these debilitating conditions.

  7. Calcium transient evoked by nicotine in isolated rat vagal pulmonary sensory neurons.

    Science.gov (United States)

    Xu, Jennings; Yang, Wenbin; Zhang, Guangfan; Gu, Qihai; Lee, Lu-Yuan

    2007-01-01

    It has been shown that inhaled cigarette smoke activates vagal pulmonary C fibers and rapidly adapting receptors (RARs) in the airways and that nicotine contained in the smoke is primarily responsible. This study was carried out to determine whether nicotine alone can activate pulmonary sensory neurons isolated from rat vagal ganglia; the response of these neurons was determined by fura-2-based ratiometric Ca(2+) imaging. The results showed: 1) Nicotine (10(-4) M, 20 s) evoked a transient increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in 175 of the 522 neurons tested (Delta[Ca(2+)](i) = 142.2 +/- 12.3 nM); the response was reproducible, with a small reduction in peak amplitude in the same neurons when the challenge was repeated 20 min later. 2) A majority (59.7%) of these nicotine-sensitive neurons were also activated by capsaicin (10(-7) M). 3) 1,1-Dimethyl-4-phenylpiperazinium iodide (DMPP; 10(-4) M, 20 s), a selective agonist of the neuronal nicotinic acetylcholine receptors (NnAChRs), evoked a pattern of response similar to that of nicotine. 4) The responses to nicotine and DMPP were either totally abrogated or markedly attenuated by hexamethonium (10(-4) M). 5) In anesthetized rats, right atrial bolus injection of nicotine (75-200 mug/kg) evoked an immediate (latency <1-2 s) and intense burst of discharge in 47.8% of the pulmonary C-fiber endings and 28.6% of the RARs tested. In conclusion, nicotine exerts a direct stimulatory effect on vagal pulmonary sensory nerves, and the effect is probably mediated through an activation of the NnAChRs expressed on the membrane of these neurons.

  8. 5-HT2 and 5-HT7 receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons

    Directory of Open Access Journals (Sweden)

    Urszula eSlawinska

    2014-08-01

    Full Text Available There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT1A/7 receptors leads to activation of the spinal cord circuitry for locomotion. These receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used agonists that are efficient in promoting locomotor recovery in paraplegic rats, 8-OHDPAT (acting on 5-HT1A/7 receptors and quipazine (acting on 5-HT2 receptors, to examine this issue. Analysis of intra- and interlimb coordination confirmed that the locomotor performance was significantly improved by either drug, but the data revealed marked differences in their mode of action. Interlimb coordination was significantly better after 8-OHDPAT application, and the activity of the extensor soleus muscle was significantly longer during the stance phase of locomotor movements enhanced by quipazine. Our results show that activation of both receptors facilitates locomotion, but their effects are likely exerted on different populations of spinal neurons. Activation of 5-HT2 receptors facilitates the output stage of the locomotor system, in part by directly activating motoneurons, and also through activation of interneurons of the locomotor CPG. Activation of 5-HT7/1A receptors facilitates the activity of the locomotor CPG, without direct actions on the output components of the locomotor system, including motoneurons. Although our findings show that the combined use of these two drugs results in production of well-coordinated weight supported locomotion with a reduced need for exteroceptive stimulation, they also indicate that there might be some limitations to the utility of combined treatment. Sensory feedback and some intraspinal circuitry recruited by the drugs can conflict with the locomotor activation.

  9. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    Science.gov (United States)

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

  10. A large population of diverse neurons in the Drosophila central nervous system expresses short neuropeptide F, suggesting multiple distributed peptide functions

    Science.gov (United States)

    Nässel, Dick R; Enell, Lina E; Santos, Jonathan G; Wegener, Christian; Johard, Helena AD

    2008-01-01

    Background Insect neuropeptides are distributed in stereotypic sets of neurons that commonly constitute a small fraction of the total number of neurons. However, some neuropeptide genes are expressed in larger numbers of neurons of diverse types suggesting that they are involved in a greater diversity of functions. One of these widely expressed genes, snpf, encodes the precursor of short neuropeptide F (sNPF). To unravel possible functional diversity we have mapped the distribution of transcript of the snpf gene and its peptide products in the central nervous system (CNS) of Drosophila in relation to other neuronal markers. Results There are several hundreds of neurons in the larval CNS and several thousands in the adult Drosophila brain expressing snpf transcript and sNPF peptide. Most of these neurons are intrinsic interneurons of the mushroom bodies. Additionally, sNPF is expressed in numerous small interneurons of the CNS, olfactory receptor neurons (ORNs) of the antennae, and in a small set of possibly neurosecretory cells innervating the corpora cardiaca and aorta. A sNPF-Gal4 line confirms most of the expression pattern. None of the sNPF immunoreactive neurons co-express a marker for the transcription factor DIMMED, suggesting that the majority are not neurosecretory cells or large interneurons involved in episodic bulk transmission. Instead a portion of the sNPF producing neurons co-express markers for classical neurotransmitters such as acetylcholine, GABA and glutamate, suggesting that sNPF is a co-transmitter or local neuromodulator in ORNs and many interneurons. Interestingly, sNPF is coexpressed both with presumed excitatory and inhibitory neurotransmitters. A few sNPF expressing neurons in the brain colocalize the peptide corazonin and a pair of dorsal neurons in the first abdominal neuromere coexpresses sNPF and insulin-like peptide 7 (ILP7). Conclusion It is likely that sNPF has multiple functions as neurohormone as well as local neuromodulator

  11. A large population of diverse neurons in the Drosophila central nervous system expresses short neuropeptide F, suggesting multiple distributed peptide functions

    Directory of Open Access Journals (Sweden)

    Wegener Christian

    2008-09-01

    Full Text Available Abstract Background Insect neuropeptides are distributed in stereotypic sets of neurons that commonly constitute a small fraction of the total number of neurons. However, some neuropeptide genes are expressed in larger numbers of neurons of diverse types suggesting that they are involved in a greater diversity of functions. One of these widely expressed genes, snpf, encodes the precursor of short neuropeptide F (sNPF. To unravel possible functional diversity we have mapped the distribution of transcript of the snpf gene and its peptide products in the central nervous system (CNS of Drosophila in relation to other neuronal markers. Results There are several hundreds of neurons in the larval CNS and several thousands in the adult Drosophila brain expressing snpf transcript and sNPF peptide. Most of these neurons are intrinsic interneurons of the mushroom bodies. Additionally, sNPF is expressed in numerous small interneurons of the CNS, olfactory receptor neurons (ORNs of the antennae, and in a small set of possibly neurosecretory cells innervating the corpora cardiaca and aorta. A sNPF-Gal4 line confirms most of the expression pattern. None of the sNPF immunoreactive neurons co-express a marker for the transcription factor DIMMED, suggesting that the majority are not neurosecretory cells or large interneurons involved in episodic bulk transmission. Instead a portion of the sNPF producing neurons co-express markers for classical neurotransmitters such as acetylcholine, GABA and glutamate, suggesting that sNPF is a co-transmitter or local neuromodulator in ORNs and many interneurons. Interestingly, sNPF is coexpressed both with presumed excitatory and inhibitory neurotransmitters. A few sNPF expressing neurons in the brain colocalize the peptide corazonin and a pair of dorsal neurons in the first abdominal neuromere coexpresses sNPF and insulin-like peptide 7 (ILP7. Conclusion It is likely that sNPF has multiple functions as neurohormone as well as

  12. Mirror neurons

    National Research Council Canada - National Science Library

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal...

  13. USE OF HIGH CONTENT IMAGE ANALYSES TO DETECT CHEMICAL-MEDIATED EFFECTS ON NEURITE SUB-POPULATIONS IN PRIMARY RAT CORTICAL NEURONS

    Science.gov (United States)

    Traditional developmental neurotoxicity tests performed in vivo are costly, time-consuming and utilize a large number of animals. In order to address these inefficiencies, in vitro models of neuronal development have been used in a first tier screening approach for developmenta...

  14. Specific distribution of the autophagic protein GABARAPL1/GEC1 in the developing and adult mouse brain and identification of neuronal populations expressing GABARAPL1/GEC1.

    Directory of Open Access Journals (Sweden)

    Jaclyn Nicole Le Grand

    Full Text Available Macroautophagy is a highly conserved cellular degradation process, regulated by autophagy-related (atg factors, in which a double membrane autophagosome engulfs cytoplasmic components to target them for degradation. In yeast, the Atg8 protein is indispensable for autophagosome formation. In mammals, this is complicated by the presence of six Atg8 homologues grouped into the GABARAP and MAP1LC3 subfamilies. Although these proteins share a high similarity, their transcript expression, regulation and protein interactions differ, suggesting they may display individual properties and specific functions. GABARAPL1/GEC1 is a member of the GABARAP subfamily and its mRNA is the most highly expressed Atg8 homologue in the central nervous system. Consequently, we performed an in depth study of GABARAPL1 distribution in the developing and adult murine brain. Our results show that GABARAPL1 brain expression is visible as early as embryonic day 11 and progressively increases to a maximum level in the adult. Immunohistochemical staining was detected in both fibers and immature neurons in embryos but was restrained to neurons in adult tissue. By E17, intense punctate-like structures were visible and these accumulated in cortical primary neurons treated with the autophagosome/lysosome fusion inhibitor Bafilomycin A1 (Baf A1, suggesting that they represent autophagosomes. Finally, GABARAPL1 expression was particularly intense in motoneurons in the embryo and in neurons involved in somatomotor and neuroendocrine functions in the adult, particularly in the substantia nigra pars compacta, a region affected in Parkinson's disease. Our study of cerebral GABARAPL1 protein expression provides insight into its role in the development and homeostasis of the mouse brain.

  15. [Mirror neurons].

    Science.gov (United States)

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.

  16. Direct evidence for the co-expression of URP and GnRH in a sub-population of rat hypothalamic neurones: anatomical and functional correlation.

    Directory of Open Access Journals (Sweden)

    Johann-Günther Egginger

    Full Text Available Urotensin-II-related peptide (URP is an eight amino-acid neuropeptide recently isolated from rat brain and considered as the endogenous ligand for the GPR14 receptor. Using single and double immunohistochemical labelling, in situ hybridization and ultrastructural immunocytochemistry, we explored the cellular and subcellular localization of URP in the male rat brain. URP peptide was detected in numerous varicose fibres of the median eminence (ME and organum vasculosum laminae terminalis (OVLT as well as in neuronal cell bodies of the medial septal nucleus and diagonal band of Broca where corresponding mRNA were also detected. Combining in situ hybridization with immunohistochemistry, we showed that cell bodies of the rat anterior hypothalamus contained both URP mRNA and GnRH peptide. In addition, double ultrastructural immunodetection of URP and GnRH peptides clearly revealed, in the median eminence, the co-localization of both peptides in the same neuronal processes in the vicinity of fenestrated portal vessels. This remarkable cellular and subcellular distribution led us to test the effect of URP on the GnRH-induced gonadotrophins release in the anterior pituitary, and to discuss its putative role at the level of the median eminence.

  17. Shape similarity, better than semantic membership, accounts for the structure of visual object representations in a population of monkey inferotemporal neurons.

    Science.gov (United States)

    Baldassi, Carlo; Alemi-Neissi, Alireza; Pagan, Marino; Dicarlo, James J; Zecchina, Riccardo; Zoccolan, Davide

    2013-01-01

    The anterior inferotemporal cortex (IT) is the highest stage along the hierarchy of visual areas that, in primates, processes visual objects. Although several lines of evidence suggest that IT primarily represents visual shape information, some recent studies have argued that neuronal ensembles in IT code the semantic membership of visual objects (i.e., represent conceptual classes such as animate and inanimate objects). In this study, we investigated to what extent semantic, rather than purely visual information, is represented in IT by performing a multivariate analysis of IT responses to a set of visual objects. By relying on a variety of machine-learning approaches (including a cutting-edge clustering algorithm that has been recently developed in the domain of statistical physics), we found that, in most instances, IT representation of visual objects is accounted for by their similarity at the level of shape or, more surprisingly, low-level visual properties. Only in a few cases we observed IT representations of semantic classes that were not explainable by the visual similarity of their members. Overall, these findings reassert the primary function of IT as a conveyor of explicit visual shape information, and reveal that low-level visual properties are represented in IT to a greater extent than previously appreciated. In addition, our work demonstrates how combining a variety of state-of-the-art multivariate approaches, and carefully estimating the contribution of shape similarity to the representation of object categories, can substantially advance our understanding of neuronal coding of visual objects in cortex.

  18. Leader neurons in leaky integrate and fire neural network simulations

    OpenAIRE

    Zbinden, Cyrille

    2010-01-01

    Several experimental studies show the existence of leader neurons in population bursts of 2D living neural networks. A leader neuron is, basically, a neuron which fires at the beginning of a burst (respectively network spike) more often that we expect by looking at its whole mean neural activity. This means that leader neurons have some burst triggering power beyond a simple statistical effect. In this study, we characterize these leader neuron properties. This naturally leads us to simulate ...

  19. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... properties of this facility in the path from synaptic sites to the motor axon is reviewed with emphasis on voltage sensitive ion channels and regulatory metabotropic transmitter pathways. The catalog of the intrinsic response properties, their underlying mechanisms, and regulation obtained from motoneurons...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  20. Selective loss of alpha motor neurons with sparing of gamma motor neurons and spinal cord cholinergic neurons in a mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Powis, Rachael A; Gillingwater, Thomas H

    2016-03-01

    Spinal muscular atrophy (SMA) is a neuromuscular disease characterised primarily by loss of lower motor neurons from the ventral grey horn of the spinal cord and proximal muscle atrophy. Recent experiments utilising mouse models of SMA have demonstrated that not all motor neurons are equally susceptible to the disease, revealing that other populations of neurons can also be affected. Here, we have extended investigations of selective vulnerability of neuronal populations in the spinal cord of SMA mice to include comparative assessments of alpha motor neuron (α-MN) and gamma motor neuron (γ-MN) pools, as well as other populations of cholinergic neurons. Immunohistochemical analyses of late-symptomatic SMA mouse spinal cord revealed that numbers of α-MNs were significantly reduced at all levels of the spinal cord compared with controls, whereas numbers of γ-MNs remained stable. Likewise, the average size of α-MN cell somata was decreased in SMA mice with no change occurring in γ-MNs. Evaluation of other pools of spinal cord cholinergic neurons revealed that pre-ganglionic sympathetic neurons, central canal cluster interneurons, partition interneurons and preganglionic autonomic dorsal commissural nucleus neuron numbers all remained unaffected in SMA mice. Taken together, these findings indicate that α-MNs are uniquely vulnerable among cholinergic neuron populations in the SMA mouse spinal cord, with γ-MNs and other cholinergic neuronal populations being largely spared.

  1. Waves of c-Fos and Arc Proteins Expression in Neuronal Populations of the Hippocampus in Response to a Single Episode of New Experience.

    Science.gov (United States)

    Ivashkina, O I; Toropova, K A; Ivanov, A A; Chekhov, S A; Anokhin, K V

    2016-04-01

    Accumulation of c-Fos and Arc proteins in neurons in different regions of the hippocampus after single trial of contextual fear conditioning was studied by using immunohistochemical staining. We found that the dynamics of the c-Fos and Arc expression has a biphasic pattern: the first peak was observed in 15-30 min after learning and the second less pronounced peak in 1-3 h. Induction of Arc occurred earlier than c-Fos and the overall dynamics of the two waves slightly varied in the dentate gyrus and hippocampal CA1 and CA3 fields. The findings open the possibility of mapping the cognitive neural networks of the brain with higher temporal resolution and draw attention to fluctuations of hippocampal activity after a single brief episode of new experience.

  2. Shape similarity, better than semantic membership, accounts for the structure of visual object representations in a population of monkey inferotemporal neurons.

    Directory of Open Access Journals (Sweden)

    Carlo Baldassi

    Full Text Available The anterior inferotemporal cortex (IT is the highest stage along the hierarchy of visual areas that, in primates, processes visual objects. Although several lines of evidence suggest that IT primarily represents visual shape information, some recent studies have argued that neuronal ensembles in IT code the semantic membership of visual objects (i.e., represent conceptual classes such as animate and inanimate objects. In this study, we investigated to what extent semantic, rather than purely visual information, is represented in IT by performing a multivariate analysis of IT responses to a set of visual objects. By relying on a variety of machine-learning approaches (including a cutting-edge clustering algorithm that has been recently developed in the domain of statistical physics, we found that, in most instances, IT representation of visual objects is accounted for by their similarity at the level of shape or, more surprisingly, low-level visual properties. Only in a few cases we observed IT representations of semantic classes that were not explainable by the visual similarity of their members. Overall, these findings reassert the primary function of IT as a conveyor of explicit visual shape information, and reveal that low-level visual properties are represented in IT to a greater extent than previously appreciated. In addition, our work demonstrates how combining a variety of state-of-the-art multivariate approaches, and carefully estimating the contribution of shape similarity to the representation of object categories, can substantially advance our understanding of neuronal coding of visual objects in cortex.

  3. Improvements in the methodology for analyzing receptor subtypes and neuronal populations affected by anticholinesterase exposure. Annual summary report, 15 November 1983-14 November 1984

    Energy Technology Data Exchange (ETDEWEB)

    Wamsley, J.K.

    1984-11-14

    Conditions were defined that provide a means of selectively labeling subtypes of muscarinic receptors. The so-called M1 receptor population can be labeled with tritiated pirenzepine, while the receptor population labeled with tritiated quinuclidinyl benzilate (QNB) but not labeled with pirenzepine represents M2 receptor population. High- and low-affinity states of the receptors were also defined on the basis of agonist displacement of antagonist binding. Both the M1 and M2 receptor populations undergo axonal transport and the affinity states of these receptors are altered by neurochemical and neurosurgical lesions. Radioactive standards were developed that provide a means of quantitating the femtomoles of receptor bound with each ligand in microscopic regions of the brain. The technology was also devised to directly localize nicotinic cholinergic receptors using tritiated nicotine. It is now possible to localize several peptide receptors associated with cholinergic function including receptors for thyrotropin-releasing hormone (TRH) and somatostatin. The receptor autoradiographic technique was also carried beyond the receptor level of localization by using compounds to label adenylate cyclase and the GTP binding protein. This methodology should provide an elegant means of determining how anticholinesterase exposure has affected these many parameters of cholinergic nerve function.

  4. Calcium Homeostasis in ageing neurons

    Directory of Open Access Journals (Sweden)

    Vassiliki eNikoletopoulou

    2012-10-01

    Full Text Available The nervous system becomes increasingly vulnerable to insults and prone to dysfunction during ageing. Age-related decline of neuronal function is manifested by the late onset of many neurodegenerative disorders, as well as by reduced signalling and processing capacity of individual neuron populations. Recent findings indicate that impairment of Ca2+ homeostasis underlies the increased susceptibility of neurons to damage, associated with the ageing process. However, the impact of ageing on Ca2+ homeostasis in neurons remains largely unknown. Here, we survey the molecular mechanisms that mediate neuronal Ca2+ homeostasis and discuss the impact of ageing on their efficacy. To address the question of how ageing impinges on Ca2+ homeostasis, we consider potential nodes through which mechanisms regulating Ca2+ levels interface with molecular pathways known to influence the process of ageing and senescent decline. Delineation of this crosstalk would facilitate the development of interventions aiming to fortify neurons against age-associated functional deterioration and death by augmenting Ca2+ homeostasis.

  5. Stochastic phase-change neurons

    Science.gov (United States)

    Tuma, Tomas; Pantazi, Angeliki; Le Gallo, Manuel; Sebastian, Abu; Eleftheriou, Evangelos

    2016-08-01

    Artificial neuromorphic systems based on populations of spiking neurons are an indispensable tool in understanding the human brain and in constructing neuromimetic computational systems. To reach areal and power efficiencies comparable to those seen in biological systems, electroionics-based and phase-change-based memristive devices have been explored as nanoscale counterparts of synapses. However, progress on scalable realizations of neurons has so far been limited. Here, we show that chalcogenide-based phase-change materials can be used to create an artificial neuron in which the membrane potential is represented by the phase configuration of the nanoscale phase-change device. By exploiting the physics of reversible amorphous-to-crystal phase transitions, we show that the temporal integration of postsynaptic potentials can be achieved on a nanosecond timescale. Moreover, we show that this is inherently stochastic because of the melt-quench-induced reconfiguration of the atomic structure occurring when the neuron is reset. We demonstrate the use of these phase-change neurons, and their populations, in the detection of temporal correlations in parallel data streams and in sub-Nyquist representation of high-bandwidth signals.

  6. Essential roles of mitochondrial depolarization in neuron loss through microglial activation and attraction toward neurons.

    Science.gov (United States)

    Nam, Min-Kyung; Shin, Hyun-Ah; Han, Ji-Hye; Park, Dae-Wook; Rhim, Hyangshuk

    2013-04-10

    As life spans increased, neurodegenerative disorders that affect aging populations have also increased. Progressive neuronal loss in specific brain regions is the most common cause of neurodegenerative disease; however, key determinants mediating neuron loss are not fully understood. Using a model of mitochondrial membrane potential (ΔΨm) loss, we found only 25% cell loss in SH-SY5Y (SH) neuronal mono-cultures, but interestingly, 85% neuronal loss occurred when neurons were co-cultured with BV2 microglia. SH neurons overexpressing uncoupling protein 2 exhibited an increase in neuron-microglia interactions, which represent an early step in microglial phagocytosis of neurons. This result indicates that ΔΨm loss in SH neurons is an important contributor to recruitment of BV2 microglia. Notably, we show that ΔΨm loss in BV2 microglia plays a crucial role in microglial activation and phagocytosis of damaged SH neurons. Thus, our study demonstrates that ΔΨm loss in both neurons and microglia is a critical determinant of neuron loss. These findings also offer new insights into neuroimmunological and bioenergetical aspects of neurodegenerative disease.

  7. GABA concentration and GABAergic neuron populations in limbic areas are differentially altered by brain serotonin deficiency in Tph2 knockout mice.

    Science.gov (United States)

    Waider, Jonas; Proft, Florian; Langlhofer, Georg; Asan, Esther; Lesch, Klaus-Peter; Gutknecht, Lise

    2013-02-01

    While tryptophan hydroxylase-2 (Tph2) null mutant (Tph2(-/-)) mice are completely deficient in brain serotonin (5-HT) synthesis, the formation of serotonergic neurons and pathfinding of their projections are not impaired. However, 5-HT deficiency, during development and in the adult, might affect morphological and functional parameters of other neural systems. To assess the influence of 5-HT deficiency on γ-amino butyric acid (GABA) systems, we carried out measurements of GABA concentrations in limbic brain regions of adult male wildtype (wt), heterozygous (Tph2(+/-)) and Tph2(-/-) mice. In addition, unbiased stereological estimation of GABAergic interneuron numbers and density was performed in subregions of amygdala and hippocampus. Amygdala and prefrontal cortex displayed significantly increased and decreased GABA concentrations, respectively, exclusively in Tph2(+/-) mice while no changes were detected between Tph2(-/-) and wt mice. In contrast, in the hippocampus, increased GABA concentrations were found in Tph2(-/-) mice. While total cell density in the anterior basolateral amygdala did not differ between genotypes, the number and density of the GABAergic interneurons were significantly decreased in Tph2(-/-) mice, with the group of parvalbumin (PV)-immunoreactive (ir) interneurons contributing somewhat less to the decrease than that of non-PV-ir GABAergic interneurons. Major morphological changes were also absent in the dorsal hippocampus, and only a trend toward reduced density of PV-ir cells was observed in the CA3 region of Tph2(-/-) mice. Our findings are the first to document that life-long reduction or complete lack of brain 5-HT transmission causes differential changes of GABA systems in limbic regions which are key players in emotional learning and memory processes. The changes likely reflect a combination of developmental alterations and functional adaptations of emotion circuits to balance the lack of 5-HT, and may underlie altered emotional

  8. Attractor dynamics in local neuronal networks

    Directory of Open Access Journals (Sweden)

    Jean-Philippe eThivierge

    2014-03-01

    Full Text Available Patterns of synaptic connectivity in various regions of the brain are characterized by the presence of synaptic motifs, defined as unidirectional and bidirectional synaptic contacts that follow a particular configuration and link together small groups of neurons. Recent computational work proposes that a relay network (two populations communicating via a third, relay population of neurons can generate precise patterns of neural synchronization. Here, we employ two distinct models of neuronal dynamics and show that simulated neural circuits designed in this way are caught in a global attractor of activity that prevents neurons from modulating their response on the basis of incoming stimuli. To circumvent the emergence of a fixed global attractor, we propose a mechanism of selective gain inhibition that promotes flexible responses to external stimuli. We suggest that local neuronal circuits may employ this mechanism to generate precise patterns of neural synchronization whose transient nature delimits the occurrence of a brief stimulus.

  9. Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?

    Science.gov (United States)

    Parker, Lindsay M; Le, Sheng; Wearne, Travis A; Hardwick, Kate; Kumar, Natasha N; Robinson, Katherine J; McMullan, Simon; Goodchild, Ann K

    2017-06-15

    Previous studies have demonstrated that a range of stimuli activate neurons, including catecholaminergic neurons, in the ventrolateral medulla. Not all catecholaminergic neurons are activated and other neurochemical content is largely unknown hence whether stimulus specific populations exist is unclear. Here we determine the neurochemistry (using in situ hybridization) of catecholaminergic and noncatecholaminergic neurons which express c-Fos immunoreactivity throughout the rostrocaudal extent of the ventrolateral medulla, in Sprague Dawley rats treated with hydralazine or saline. Distinct neuronal populations containing PPCART, PPPACAP, and PPNPY mRNAs, which were largely catecholaminergic, were activated by hydralazine but not saline. Both catecholaminergic and noncatecholaminergic neurons containing preprotachykinin and prepro-enkephalin (PPE) mRNAs were also activated, with the noncatecholaminergic population located in the rostral C1 region. Few GlyT2 neurons were activated. A subset of these data was then used to compare the neuronal populations activated by 2-deoxyglucose evoked glucoprivation (Brain Structure and Function (2015) 220:117). Hydralazine activated more neurons than 2-deoxyglucose but similar numbers of catecholaminergic neurons. Commonly activated populations expressing PPNPY and PPE mRNAs were defined. These likely include PPNPY expressing catecholaminergic neurons projecting to vasopressinergic and corticotrophin releasing factor neurons in the paraventricular nucleus, which when activated result in elevated plasma vasopressin and corticosterone. Stimulus specific neurons included noncatecholaminergic neurons and a few PPE positive catecholaminergic neuron but neurochemical codes were largely unidentified. Reasons for the lack of identification of stimulus specific neurons, readily detectable using electrophysiology in anaesthetized preparations and for which neural circuits can be defined, are discussed. © 2017 Wiley Periodicals, Inc.

  10. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  11. [Neuronal network].

    Science.gov (United States)

    Langmeier, M; Maresová, D

    2005-01-01

    Function of the central nervous system is based on mutual relations among the nerve cells. Description of nerve cells and their processes, including their contacts was enabled by improvement of optical features of the microscope and by the development of impregnation techniques. It is associated with the name of Antoni van Leeuwenhoek (1632-1723), J. Ev. Purkyne (1787-1869), Camillo Golgi (1843-1926), and Ramón y Cajal (1852-1934). Principal units of the neuronal network are the synapses. The term synapse was introduced into neurophysiology by Charles Scott Sherrington (1857-1952). Majority of the interactions between nerve cells is mediated by neurotransmitters acting at the receptors of the postsynaptic membrane or at the autoreceptors of the presynaptic part of the synapse. Attachment of the vesicles to the presynaptic membrane and the release of the neurotransmitter into the synaptic cleft depend on the intracellular calcium concentration and on the presence of several proteins in the presynaptic element.

  12. Characteristics of sodium currents in rat geniculate ganglion neurons.

    Science.gov (United States)

    Nakamura, Shiro; Bradley, Robert M

    2011-12-01

    Geniculate ganglion (GG) cell bodies of chorda tympani (CT), greater superficial petrosal (GSP), and posterior auricular (PA) nerves transmit orofacial sensory information to the rostral nucleus of the solitary tract. We have used whole cell recording to investigate the characteristics of the Na(+) channels in isolated Fluorogold-labeled GG neurons that innervate different peripheral receptive fields. GG neurons expressed two classes of Na(+) channels, TTX sensitive (TTX-S) and TTX resistant (TTX-R). The majority of GG neurons expressed TTX-R currents of different amplitudes. TTX-R currents were relatively small in 60% of the neurons but were large in 12% of the sampled population. In a further 28% of the neurons, TTX completely abolished all Na(+) currents. Application of TTX completely inhibited action potential generation in all CT and PA neurons but had little effect on the generation of action potentials in 40% of GSP neurons. Most CT, GSP, and PA neurons stained positively with IB(4), and 27% of the GSP neurons were capsaicin sensitive. The majority of IB(4)-positive GSP neurons with large TTX-R Na(+) currents responded to capsaicin, whereas IB(4)-positive GSP neurons with small TTX-R Na(+) currents were capsaicin insensitive. These data demonstrate the heterogeneity of GG neurons and indicate the existence of a subset of GSP neurons sensitive to capsaicin, usually associated with nociceptors. Since there are no reports of nociceptors in the GSP receptive field, the role of these capsaicin-sensitive neurons is not clear.

  13. Leader neurons in leaky integrate and fire neural network simulations.

    Science.gov (United States)

    Zbinden, Cyrille

    2011-10-01

    In this paper, we highlight the topological properties of leader neurons whose existence is an experimental fact. Several experimental studies show the existence of leader neurons in population bursts of activity in 2D living neural networks (Eytan and Marom, J Neurosci 26(33):8465-8476, 2006; Eckmann et al., New J Phys 10(015011), 2008). A leader neuron is defined as a neuron which fires at the beginning of a burst (respectively network spike) more often than we expect by chance considering its mean firing rate. This means that leader neurons have some burst triggering power beyond a chance-level statistical effect. In this study, we characterize these leader neuron properties. This naturally leads us to simulate neural 2D networks. To build our simulations, we choose the leaky integrate and fire (lIF) neuron model (Gerstner and Kistler 2002; Cessac, J Math Biol 56(3):311-345, 2008), which allows fast simulations (Izhikevich, IEEE Trans Neural Netw 15(5):1063-1070, 2004; Gerstner and Naud, Science 326:379-380, 2009). The dynamics of our lIF model has got stable leader neurons in the burst population that we simulate. These leader neurons are excitatory neurons and have a low membrane potential firing threshold. Except for these two first properties, the conditions required for a neuron to be a leader neuron are difficult to identify and seem to depend on several parameters involved in the simulations themselves. However, a detailed linear analysis shows a trend of the properties required for a neuron to be a leader neuron. Our main finding is: A leader neuron sends signals to many excitatory neurons as well as to few inhibitory neurons and a leader neuron receives only signals from few other excitatory neurons. Our linear analysis exhibits five essential properties of leader neurons each with different relative importance. This means that considering a given neural network with a fixed mean number of connections per neuron, our analysis gives us a way of

  14. Epibranchial placode-derived neurons produce BDNF required for early sensory neuron development.

    Science.gov (United States)

    Harlow, Danielle E; Yang, Hui; Williams, Trevor; Barlow, Linda A

    2011-02-01

    In mice, BDNF provided by the developing taste epithelium is required for gustatory neuron survival following target innervation. However, we find that expression of BDNF, as detected by BDNF-driven β-galactosidase, begins in the cranial ganglia before its expression in the central (hindbrain) or peripheral (taste papillae) targets of these sensory neurons, and before gustatory ganglion cells innervate either target. To test early BDNF function, we examined the ganglia of bdnf null mice before target innervation, and found that while initial neuron survival is unaltered, early neuron development is disrupted. In addition, fate mapping analysis in mice demonstrates that murine cranial ganglia arise from two embryonic populations, i.e., epibranchial placodes and neural crest, as has been described for these ganglia in non-mammalian vertebrates. Only placodal neurons produce BDNF, however, which indicates that prior to innervation, early ganglionic BDNF produced by placode-derived cells promotes gustatory neuron development.

  15. GDE2 regulates subtype-specific motor neuron generation through inhibition of Notch signaling.

    Science.gov (United States)

    Sabharwal, Priyanka; Lee, Changhee; Park, Sungjin; Rao, Meenakshi; Sockanathan, Shanthini

    2011-09-22

    The specification of spinal interneuron and motor neuron identities initiates within progenitor cells, while motor neuron subtype diversification is regulated by hierarchical transcriptional programs implemented postmitotically. Here we find that mice lacking GDE2, a six-transmembrane protein that triggers motor neuron generation, exhibit selective losses of distinct motor neuron subtypes, specifically in defined subsets of limb-innervating motor pools that correlate with the loss of force-generating alpha motor neurons. Mechanistically, GDE2 is expressed by postmitotic motor neurons but utilizes extracellular glycerophosphodiester phosphodiesterase activity to induce motor neuron generation by inhibiting Notch signaling in neighboring motor neuron progenitors. Thus, neuronal GDE2 controls motor neuron subtype diversity through a non-cell-autonomous feedback mechanism that directly regulates progenitor cell differentiation, implying that subtype specification initiates within motor neuron progenitor populations prior to their differentiation into postmitotic motor neurons.

  16. Dopamine neurons share common response function for reward prediction error.

    Science.gov (United States)

    Eshel, Neir; Tian, Ju; Bukwich, Michael; Uchida, Naoshige

    2016-03-01

    Dopamine neurons are thought to signal reward prediction error, or the difference between actual and predicted reward. How dopamine neurons jointly encode this information, however, remains unclear. One possibility is that different neurons specialize in different aspects of prediction error; another is that each neuron calculates prediction error in the same way. We recorded from optogenetically identified dopamine neurons in the lateral ventral tegmental area (VTA) while mice performed classical conditioning tasks. Our tasks allowed us to determine the full prediction error functions of dopamine neurons and compare them to each other. We found marked homogeneity among individual dopamine neurons: their responses to both unexpected and expected rewards followed the same function, just scaled up or down. As a result, we were able to describe both individual and population responses using just two parameters. Such uniformity ensures robust information coding, allowing each dopamine neuron to contribute fully to the prediction error signal.

  17. The Neuronal Network Orchestration behind Motor Behaviors

    DEFF Research Database (Denmark)

    Petersen, Peter Christian

    In biological networks, millions of neurons organize themselves from microscopic noisy individuals to robust macroscopic entities. These entities are capable of producing higher functions like sensory processing, decision-making, and elaborate behavioral responses. Every aspect of these behaviors...... is the outcome of an advanced orchestration of the activity of populations of neurons. Through spiking activity, neurons are able to interact; yet we know little about how this interaction occurs in spinal networks. How is the activity distributed across the population? What is the composition of synaptic input...... that is received by the individual neurons and how is the synaptic input processed? This thesis focuses on aspects of these questions for spinal networks involved in the generation of stereotypical motor behaviors. The thesis consists of two studies. In the first study, I investigated the synaptic input...

  18. General artificial neuron

    Science.gov (United States)

    Degeratu, Vasile; Schiopu, Paul; Degeratu, Stefania

    2007-05-01

    In this paper the authors present a model of artificial neuron named the general artificial neuron. Depending on application this neuron can change self number of inputs, the type of inputs (from excitatory in inhibitory or vice versa), the synaptic weights, the threshold, the type of intensifying functions. It is achieved into optoelectronic technology. Also, into optoelectronic technology a model of general McCulloch-Pitts neuron is showed. The advantages of these neurons are very high because we have to solve different applications with the same neural network, achieved from these neurons, named general neural network.

  19. Synchronized views for exploring populations of neurons

    Science.gov (United States)

    Robbins, Kay A.; Grinshpan, Igor; Allen, Kevin; Senseman, David M.

    2004-06-01

    Davis (Data Viewing System) is a general-purpose data viewer designed for the simultaneous display of a large number of dynamic data sets. Davis was inspired by the need to explore computational models of the cerebral cortex. These systems are distinguished by complex dynamic elements interconnected in irregular patterns. Neuroscientists study the detailed behavior of individual elements and how these elements interact to achieve cortical function. This paper describes Davis and its use in cortical visualization. Davis is written in Java and can be run from a browser or as a standalone application. Users must provide an XML description of their data, which Davis uses for its menus, browsing and visualization. Davis visualizations can be applied to any collection of space-time data sets, and the Davis infrastructure allows visualizations to be added easily. Davis handles the synchronization of different visualizations and encapsulates different threading policies.

  20. Juvenil neuronal ceroid lipofuscinosis

    DEFF Research Database (Denmark)

    Ostergaard, J R; Hertz, Jens Michael

    1998-01-01

    Neuronal ceroid-lipofuscinosis is a group of neurodegenerative diseases which are characterized by an abnormal accumulation of lipopigment in neuronal and extraneuronal cells. The diseases can be differentiated into several subgroups according to age of onset, the clinical picture...

  1. NEURON and Python

    OpenAIRE

    Michael Hines; Davison, Andrew P.; Eilif Muller

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because ...

  2. Stomatin and sensory neuron mechanotransduction.

    Science.gov (United States)

    Martinez-Salgado, Carlos; Benckendorff, Anne G; Chiang, Li-Yang; Wang, Rui; Milenkovic, Nevena; Wetzel, Christiane; Hu, Jing; Stucky, Cheryl L; Parra, Marilyn G; Mohandas, Narla; Lewin, Gary R

    2007-12-01

    Somatic sensory neurons of the dorsal root ganglia are necessary for a large part of our mechanosensory experience. However, we only have a good knowledge of the molecules required for mechanotransduction in simple invertebrates such as the nematode Caenorhabiditis elegans. In C. elegans, a number of so-called mec genes have been isolated that are required for the transduction of body touch. One such gene, mec-2 codes for an integral membrane protein of the stomatin family, a large group of genes with a stomatin homology domain. Using stomatin null mutant mice, we have tested the hypothesis that the founding member of this family, stomatin might play a role in the transduction of mechanical stimuli by primary sensory neurons. We used the in vitro mouse skin nerve preparation to record from a large population of low- and high-threshold mechanoreceptors with myelinated A-fiber (n = 553) and unmyelinated C-fiber (n = 157) axons. One subtype of mechanoreceptor, the d-hair receptor, which is a rapidly adapting mechanoreceptor, had reduced sensitivity to mechanical stimulation in the absence of stomatin. Other cutaneous mechanoreceptors, including nociceptive C-fibers were not affected by the absence of a functional stomatin protein. Patch-clamp analysis of presumptive D-hair receptor mechanoreceptive neurons, which were identified by a characteristic rosette morphology in culture, showed no change in membrane excitability in the absence of the stomatin protein. We conclude that stomatin is required for normal mechanotransduction in a subpopulation of vertebrate sensory neurons.

  3. Amygdala neurons differentially encode motivation and reinforcement.

    Science.gov (United States)

    Tye, Kay M; Janak, Patricia H

    2007-04-11

    Lesion studies demonstrate that the basolateral amygdala complex (BLA) is important for assigning motivational significance to sensory stimuli, but little is known about how this information is encoded. We used in vivo electrophysiology procedures to investigate how the amygdala encodes motivating and reinforcing properties of cues that induce reinstatement of reward-seeking behavior. Two groups of rats were trained to respond to a sucrose reward. The "paired" group was trained with a reward-predictive cue, whereas the "unpaired" group was trained with a randomly presented cue. Both groups underwent identical extinction and reinstatement procedures during which the reward was withheld. The proportion of neurons that were phasically cue responsive during reinstatement was significantly higher in the paired group (46 of 100) than in the unpaired group (8 of 112). Cues that induce reward-seeking behavior can do so by acting as incentives or reinforcers. Distinct populations of neurons responded to the cue in trials in which the cue acted as an incentive, triggering a motivated reward-seeking state, or as a reinforcer, supporting continued instrumental responding. The incentive motivation-encoding population of neurons (34 of 46 cue-responsive neurons; 74%) extinguished in temporal agreement with a decrease in the rate of instrumental responding. The conditioned reinforcement-encoding population of neurons (12 of 46 cue-responsive neurons; 26%) maintained their response for the duration of cue-reinforced instrumental responding. These data demonstrate that separate populations of cue-responsive neurons in the BLA encode the motivating or reinforcing properties of a cue previously associated with a reward.

  4. Morphology of parasympathetic neurons innervating rat lingual salivary glands.

    Science.gov (United States)

    Kim, Miwon; Chiego, Daniel J; Bradley, Robert M

    2004-03-31

    Saliva is essential for taste function and not only does saliva influence taste reception, but also taste perception initiates salivation. As a first step in investigating circuits involved in gustatory-salivary reflexes, we have studied the morphology of the rat inferior salivatory nucleus (ISN), which contains parasympathetic secretomotor neurons that control the parotid and lingual (von Ebner) salivary glands. By applying the fluorescent label Fluorogold to the cut end of the glossopharyngeal nerve, the neurons supplying only the lingual salivary glands were labeled. Confocal microscopy and three-dimensional reconstruction were used to analyze the labeled neurons in the horizontal plane to determine their morphological characteristics. Additional neurons were studied in the coronal plane to determine the influence of the plane of section on neuron morphology. Reconstructions indicated that inferior salivatory neurons extend in a rostral-caudal distribution just adjacent to the medial border of the nucleus of the solitary tract (NST). There is considerable morphological variability among neurons, with neurons having up to 6 primary dendrites and 17 dendritic segments that extend a maximum of 834 microm from the soma. However, although ISN neurons vary in the size and complexity of their dendritic trees, distributions of all measures of neuron morphology are unimodal, indicating that distinct groups of neurons are not revealed based on these measures. There is, however, variability in the orientation pattern of the dendritic trees that is not represented in either the population or mean measures. Individual neurons can be categorized with either mediolateral, rostro-caudal or no apparent preferred orientation. Comparisons of neurons in rostral, intermediate or caudal third of the ISN revealed regional differences in neuron morphology; neurons in the caudal third have significantly longer dendrites than those in the intermediate or rostral third. Thus, while ISN

  5. Automatically tracking neurons in a moving and deforming brain

    CERN Document Server

    Nguyen, Jeffrey P; Plummer, George S; Shaevitz, Joshua W; Leifer, Andrew M

    2016-01-01

    Advances in optical neuroimaging techniques now allow neural activity to be recorded with cellular resolution in awake and behaving animals. Brain motion in these recordings pose a unique challenge. The location of individual neurons must be tracked in 3D over time to accurately extract single neuron activity traces. Recordings from small invertebrates like C. elegans are especially challenging because they undergo very large brain motion and deformation during animal movement. Here we present an automated computer vision pipeline to reliably track populations of neurons with single neuron resolution in the brain of a freely moving C. elegans undergoing large motion and deformation. 3D volumetric fluorescent images of the animal's brain are straightened, aligned and registered, and the locations of neurons in the images are found via segmentation. Each neuron is then assigned an identity using a new time-independent machine-learning approach we call Neuron Registration Vector Encoding. In this approach, non-r...

  6. Developmental specification of forebrain cholinergic neurons.

    Science.gov (United States)

    Allaway, Kathryn C; Machold, Robert

    2017-01-01

    Striatal cholinergic interneurons and basal forebrain cholinergic projection neurons, which together comprise the forebrain cholinergic system, regulate attention, memory, reward pathways, and motor activity through the neuromodulation of multiple brain circuits. The importance of these neurons in the etiology of neurocognitive disorders has been well documented, but our understanding of their specification during embryogenesis is still incomplete. All forebrain cholinergic projection neurons and interneurons appear to share a common developmental origin in the embryonic ventral telencephalon, a region that also gives rise to GABAergic projection neurons and interneurons. Significant progress has been made in identifying the key intrinsic and extrinsic factors that promote a cholinergic fate in this precursor population. However, how cholinergic interneurons and projection neurons differentiate from one another during development, as well as how distinct developmental programs contribute to heterogeneity within those two classes, is not yet well understood. In this review we summarize the transcription factors and signaling molecules known to play a role in the specification and early development of striatal and basal forebrain cholinergic neurons. We also discuss the heterogeneity of these populations and its possible developmental origins. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Pelvic nerve injury causes a rapid decrease in expression of choline acetyltransferase and upregulation of c-Jun and ATF-3 in a distinct population of sacral preganglionic neurons

    Directory of Open Access Journals (Sweden)

    Christopher J Peddie

    2011-01-01

    Full Text Available Autonomic regulation of the urogenital organs is impaired by injuries sustained during pelvic surgery or compression of lumbosacral spinal nerves (e.g. cauda equina syndrome. To understand the impact of injury on both sympathetic and parasympathetic components of this nerve supply, we performed an experimental surgical and immunohistochemical study on adult male rats, where the structure of this complex part of the nervous system has been well defined. We performed unilateral transection of pelvic or hypogastric nerves and analysed relevant regions of lumbar and sacral spinal cord, up to four weeks after injury. Expression of c-Jun, the neuronal injury marker activating transcription factor-3 (ATF-3, and choline acetyltransferase (ChAT were examined. We found little evidence for chemical or structural changes in substantial numbers of functionally related but uninjured spinal neurons (e.g. in sacral preganglionic neurons after hypogastric nerve injury, failing to support the concept of compensatory events. The effects of injury were greatest in sacral cord, ipsilateral to pelvic nerve transection. Here, around half of all preganglionic neurons expressed c-Jun within one week of injury, and substantial ATF-3 expression also occurred, especially in neurons with complete loss of ChAT-immunoreactivity. There did not appear to be any death of retrogradely labelled neurons, in contrast to axotomy studies performed on other regions of spinal cord or sacral ventral root avulsion models. Each of the effects we observed occurred in only a subpopulation of preganglionic neurons at that spinal level, raising the possibility that distinct functional subgroups have different susceptibility to trauma-induced degeneration and potentially different regenerative abilities. Identification of the cellular basis of these differences may provide insights into organ-specific strategies for attenuating degeneration or promoting regeneration of these circuits after

  8. Study of a new neuron

    CERN Document Server

    Adler, Stephen Louis; Weckel, J D

    1994-01-01

    We study a modular neuron alternative to the McCulloch-Pitts neuron that arises naturally in analog devices in which the neuron inputs are represented as coherent oscillatory wave signals. Although the modular neuron can compute XOR at the one neuron level, it is still characterized by the same Vapnik-Chervonenkis dimension as the standard neuron. We give the formulas needed for constructing networks using the new neuron and training them using back-propagation. A numerical study of the modular neuron on two data sets is presented, which demonstrates that the new neuron performs at least as well as the standard neuron.

  9. Estimating nonstationary input signals from a single neuronal spike train

    OpenAIRE

    Kim, Hideaki; Shinomoto, Shigeru

    2012-01-01

    Neurons temporally integrate input signals, translating them into timed output spikes. Because neurons nonperiodically emit spikes, examining spike timing can reveal information about input signals, which are determined by activities in the populations of excitatory and inhibitory presynaptic neurons. Although a number of mathematical methods have been developed to estimate such input parameters as the mean and fluctuation of the input current, these techniques are based on the unrealistic as...

  10. Glutamatergic neurons are present in the rat ventral tegmental area

    OpenAIRE

    Yamaguchi, Tsuyoshi; Sheen, Whitney; Morales, Marisela

    2007-01-01

    The ventral tegmental area (VTA) is thought to play an important role in reward function. Two populations of neurons, containing either dopamine (DA) or γ-amino butyric acid (GABA), have been extensively characterized in this area. However, recent electrophysiological studies are consistent with the notion that neurons that utilize neurotransmitters other than DA or GABA are likely to be present in the VTA. Given the pronounced phenotypic diversity of neurons in this region, we have proposed ...

  11. Differential sensitivity to nicotine among hypothalamic magnocellular neurons

    DEFF Research Database (Denmark)

    Mikkelsen, J D; Jacobsen, Julie; Kiss, Adrian Emil

    2012-01-01

    The magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) either contain vasopressin or oxytocin. Even though both hormones are released after systemic administration of nicotine, the mechanism through which the two populations of neurons are activated...... is not known. This study was carried out in the rat to investigate the effect of increasing doses of nicotine on subsets of magnocellular neurons containing either oxytocin or vasopressin....

  12. Mechanosensitive enteric neurons in the guinea pig gastric corpus

    OpenAIRE

    2015-01-01

    For long it was believed that a particular population of enteric neurons, referred to as intrinsic primary afferent neuron (IPAN)s, encodes mechanical stimulation. We recently proposed a new concept suggesting that there are in addition mechanosensitive enteric neurons (MEN) that are multifunctional. Based on firing pattern MEN behaved as rapidly, slowly, or ultra-slowly adapting RAMEN, SAMEN, or USAMEN, respectively. We aimed to validate this concept in the myenteric plexus of the gastric co...

  13. Mechanosensitive enteric neurons in the guinea pig gastric corpus

    OpenAIRE

    2015-01-01

    For long it was believed that a particular population of enteric neurons, referred to as intrinsic primary afferent neuron (IPAN)s, encodes mechanical stimulation. We recently proposed a new concept suggesting that there are in addition mechanosensitive enteric neurons (MEN) that are multifunctional. Based on firing pattern MEN behaved as rapidly, slowly or ultra-slowly adapting RAMEN, SAMEN or USAMEN, respectively. We aimed to validate this concept in the myenteric plexus of the gastric corp...

  14. Differential sensitivity to nicotine among hypothalamic magnocellular neurons

    DEFF Research Database (Denmark)

    Mikkelsen, J D; Jacobsen, Julie; Kiss, Adrian Emil

    2012-01-01

    The magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) either contain vasopressin or oxytocin. Even though both hormones are released after systemic administration of nicotine, the mechanism through which the two populations of neurons are activated...... is not known. This study was carried out in the rat to investigate the effect of increasing doses of nicotine on subsets of magnocellular neurons containing either oxytocin or vasopressin....

  15. BDNF signaling and survival of striatal neurons

    Directory of Open Access Journals (Sweden)

    Maryna eBaydyuk

    2014-08-01

    Full Text Available The striatum, a major component of the basal ganglia, performs multiple functions including control of movement, reward, and addiction. Dysfunction and death of striatal neurons are the main causes for the motor disorders associated with Huntington’s disease (HD. Brain-derived neurotrophic factor (BDNF, a member of the neurotrophin family, is among factors that promote survival and proper function of this neuronal population. Here, we review recent studies showing that BDNF determines the size of the striatum by supporting survival of the immature striatal neurons at their origin, promotes maturation of striatal neurons, and facilitates establishment of striatal connections during brain development. We also examine the role of BDNF in maintaining proper function of the striatum during adulthood, summarize the mechanisms that lead to a deficiency in BDNF signaling and subsequently striatal degeneration in HD, and highlight a potential role of BDNF as a therapeutic target for HD treatment.

  16. Cajal bodies in neurons.

    Science.gov (United States)

    Lafarga, Miguel; Tapia, Olga; Romero, Ana M; Berciano, Maria T

    2016-09-14

    Cajal is commonly regarded as the father of modern neuroscience in recognition of his fundamental work on the structure of the nervous system. But Cajal also made seminal contributions to the knowledge of nuclear structure in the early 1900s, including the discovery of the "accessory body" later renamed "Cajal body" (CB). This important nuclear structure has emerged as a center for the assembly of ribonucleoproteins (RNPs) required for splicing, ribosome biogenesis and telomere maintenance. The modern era of CB research started in the 1990s with the discovery of coilin, now known as a scaffold protein of CBs, and specific probes for small nuclear RNAs (snRNAs). In this review, we summarize what we have learned in the recent decades concerning CBs in post-mitotic neurons, thereby ruling out dynamic changes in CB functions during the cell cycle. We show that CBs are particularly prominent in neurons, where they frequently associate with the nucleolus. Neuronal CBs are transcription-dependent nuclear organelles. Indeed, their number dynamically accommodates to support the high neuronal demand for splicing and ribosome biogenesis required for sustaining metabolic and bioelectrical activity. Mature neurons have canonical CBs enriched in coilin, survival motor neuron protein and snRNPs. Disruption and loss of neuronal CBs associate with severe neuronal dysfunctions in several neurological disorders such as motor neuron diseases. In particular, CB depletion in motor neurons seems to reflect a perturbation of transcription and splicing in spinal muscular atrophy, the most common genetic cause of infant mortality.

  17. The rise and fall of mesodiencephalic dopaminergic neurons : Molecular programming by transcription factors Engrailed 1, Pitx3, and Nkx2.9 during the development of mesodiencephalic neurons

    NARCIS (Netherlands)

    Kouwenhoven, W.M.

    2016-01-01

    The mid- and hindbrain harbor two essential monoaminergic neuronal populations: the mesodiencephalic dopaminergic (mdDA) neurons in the midbrain and the serotonergic (5HT) neurons in the hindbrain. Both systems innervate multiple regions in the forebrain and are involved in the guidance of our mood,

  18. The rise and fall of mesodiencephalic dopaminergic neurons : Molecular programming by transcription factors Engrailed 1, Pitx3, and Nkx2.9 during the development of mesodiencephalic neurons

    NARCIS (Netherlands)

    Kouwenhoven, W.M.

    2016-01-01

    The mid- and hindbrain harbor two essential monoaminergic neuronal populations: the mesodiencephalic dopaminergic (mdDA) neurons in the midbrain and the serotonergic (5HT) neurons in the hindbrain. Both systems innervate multiple regions in the forebrain and are involved in the guidance of our mood,

  19. Brain-derived neurotrophic factor is required for axonal growth of selective groups of neurons in the arcuate nucleus

    Directory of Open Access Journals (Sweden)

    Guey-Ying Liao

    2015-06-01

    Conclusion: This study shows that the majority of TrkB neurons in the ARH are distinct from known neuronal populations and that BDNF plays a critical role in directing projections from these neurons to the DMH and PVH. We propose that hyperphagic obesity due to BDNF deficiency is in part attributable to impaired axonal growth of TrkB-expressing ARH neurons.

  20. Context-aware modeling of neuronal morphologies

    Directory of Open Access Journals (Sweden)

    Benjamin eTorben-Nielsen

    2014-09-01

    Full Text Available Neuronal morphologies are pivotal for brain functioning: physical overlap between dendrites and axons constrain the circuit topology, and the precise shape and composition of dendrites determine the integration of inputs to produce an output signal. At the same time, morphologies are highly diverse and variant. The variance, presumably, originates from neurons developing in a densely packed brain substrate where they interact (e.g., repulsion or attraction with other actors in this substrate. However, when studying neurons their context is never part of the analysis and they are treated as if they existed in isolation.Here we argue that to fully understand neuronal morphology and its variance it is important to consider neurons in relation to each other and to other actors in the surrounding brain substrate, i.e., their context. We propose a context-aware computational framework, NeuroMaC, in which large numbers of neurons can be grown simultaneously according to growth rules expressed in terms of interactions between the developing neuron and the surrounding brain substrate.As a proof of principle, we demonstrate that by using NeuroMaC we can generate accurate virtual morphologies of distinct classes both in isolation and as part of neuronal forests. Accuracy is validated against population statistics of experimentally reconstructed morphologies. We show that context-aware generation of neurons can explain characteristics of variation. Indeed, plausible variation is an inherent property of the morphologies generated by context-aware rules. We speculate about the applicability of this framework to investigate morphologies and circuits, to classify healthy and pathological morphologies, and to generate large quantities of morphologies for large-scale modeling.

  1. Neurons and tumor suppressors.

    Science.gov (United States)

    Zochodne, Douglas W

    2014-08-20

    Neurons choose growth pathways with half hearted reluctance, behavior that may be appropriate to maintain fixed long lasting connections but not to regenerate them. We now recognize that intrinsic brakes on regrowth are widely expressed in these hesitant neurons and include classical tumor suppressor molecules. Here, we review how two brakes, PTEN (phosphatase and tensin homolog deleted on chromosome 10) and retinoblastoma emerge as new and exciting knockdown targets to enhance neuron plasticity and improve outcome from damage or disease.

  2. Estimating neuronal connectivity from axonal and dendritic density fields

    Science.gov (United States)

    van Pelt, Jaap; van Ooyen, Arjen

    2013-01-01

    Neurons innervate space by extending axonal and dendritic arborizations. When axons and dendrites come in close proximity of each other, synapses between neurons can be formed. Neurons vary greatly in their morphologies and synaptic connections with other neurons. The size and shape of the arborizations determine the way neurons innervate space. A neuron may therefore be characterized by the spatial distribution of its axonal and dendritic “mass.” A population mean “mass” density field of a particular neuron type can be obtained by averaging over the individual variations in neuron geometries. Connectivity in terms of candidate synaptic contacts between neurons can be determined directly on the basis of their arborizations but also indirectly on the basis of their density fields. To decide when a candidate synapse can be formed, we previously developed a criterion defining that axonal and dendritic line pieces should cross in 3D and have an orthogonal distance less than a threshold value. In this paper, we developed new methodology for applying this criterion to density fields. We show that estimates of the number of contacts between neuron pairs calculated from their density fields are fully consistent with the number of contacts calculated from the actual arborizations. However, the estimation of the connection probability and the expected number of contacts per connection cannot be calculated directly from density fields, because density fields do not carry anymore the correlative structure in the spatial distribution of synaptic contacts. Alternatively, these two connectivity measures can be estimated from the expected number of contacts by using empirical mapping functions. The neurons used for the validation studies were generated by our neuron simulator NETMORPH. An example is given of the estimation of average connectivity and Euclidean pre- and postsynaptic distance distributions in a network of neurons represented by their population mean density

  3. Strategies to preserve or regenerate spiral ganglion neurons.

    Science.gov (United States)

    Roehm, Pamela C; Hansen, Marlan R

    2005-10-01

    Degeneration of spiral ganglion neurons following hair cell loss carries critical implications for efforts to rehabilitate severe cases of hearing loss with cochlear implants or hair cell regeneration. This review considers recently identified neurotrophic factors and therapeutic strategies which promote spiral ganglion neuron survival and neurite growth. Replacement of these factors may help preserve or regenerate the auditory nerve in patients with extensive hair cell loss. Spiral ganglion neurons depend on neurotrophic factors supplied by hair cells and other targets for their development and continued survival. Loss of this trophic support leads to spiral ganglion neuron death via apoptosis. Hair cells support spiral ganglion neuron survival by producing several peptide neurotrophic factors such as neurotrophin-3 and glial derived neurotrophic factor. In addition, neurotransmitter release from the hair cells drives membrane electrical activity in spiral ganglion neurons which also supports their survival. In animal models, replacement of peptide neurotrophic factors or electrical stimulation with an implanted electrode attenuates spiral ganglion neuron degeneration following deafferentation. Cell death inhibitors can also preserve spiral ganglion neuron populations. Preliminary studies show that transfer of stem cells or neurons from other ganglia are two potential strategies to replace lost spiral ganglion neurons. Inducing the regrowth of spiral ganglion neuron peripheral processes to approximate or contact cochlear implant electrodes may help optimize signaling from a diminished population of neurons. Recent studies of spiral ganglion neuron development and survival have identified several trophic and neuritogenic factors which protect these specialized cells from degeneration following hair cell loss. While still preliminary, such strategies show promise for future clinical applications.

  4. Corticospinal mirror neurons.

    Science.gov (United States)

    Kraskov, A; Philipp, R; Waldert, S; Vigneswaran, G; Quallo, M M; Lemon, R N

    2014-01-01

    Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons' discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like properties (52% F5 and 58% M1). Some PTNs exhibited 'classical' mirror neuron properties, increasing activity for both execution and observation, while others decreased their discharge during observation ('suppression mirror-neurons'). These experiments not only demonstrate the existence of PTNs as mirror neurons in M1, but also reveal some interesting differences between M1 and F5 mirror PTNs. Although observation-related changes in the discharge of PTNs must reach the spinal cord and will include some direct projections to motoneurons supplying grasping muscles, there was no EMG activity in these muscles during action observation. We suggest that the mirror neuron system is involved in the withholding of unwanted movement during action observation. Mirror neurons are differentially recruited in the behaviour that switches rapidly between making your own movements and observing those of others.

  5. Culturing rat hippocampal neurons.

    Science.gov (United States)

    Audesirk, G; Audesirk, T; Ferguson, C

    2001-01-01

    Cultured neurons are widely used to investigate the mechanisms of neurotoxicity. Embryonic rat hippocampal neurons may be grown as described under a wide variety of conditions to suit differing experimental procedures, including electrophysiology, morphological analysis of neurite development, and various biochemical and molecular analyses.

  6. Properties of persistent postnatal cortical subplate neurons.

    Science.gov (United States)

    Torres-Reveron, Juan; Friedlander, Michael J

    2007-09-12

    Subplate (SP) neurons are important for the proper development of thalamocortical innervation. They are necessary for formation of ocular dominance and orientation columns in visual cortex. During the perinatal period, many SP neurons die. The surviving cohort forms interstitial cells in the white matter (WM) and a band of horizontally oriented cells below layer VI (layer VIb, layer VII, or subplate cells). Although the function of embryonic SP neurons has been well established, the functional roles of WM and postnatal SP cells are not known. We used a combination of anatomical, immunohistochemical, and electrophysiological techniques to explore the dendritic morphology, neurotransmitter phenotype, intrinsic electrophysiological, and synaptic input properties of these surviving cells in the rat visual cortex. The density of SP and WM cells significantly decreases during the first month of life. Both populations express neuronal markers and have extensive dendritic arborizations within the SP, WM, and to the overlying visual cortex. Some intrinsic electrophysiological properties of SP and WM cells are similar: each generates high-frequency slowly adapting trains of action potentials in response to a sustained depolarization. However, SP cells exhibit greater frequency-dependent action potential broadening than WM neurons. Both cell types receive predominantly AMPA/kainate receptor-mediated excitatory synaptic input that undergoes paired-pulse facilitation as well as NMDA receptor and GABAergic input. Synaptic inputs to these cells can also undergo long-term synaptic plasticity. Thus, surviving SP and WM cells are functional electrogenic neurons integrated within the postnatal visual cortical circuit.

  7. Oscillatorylike behavior in feedforward neuronal networks

    Science.gov (United States)

    Payeur, Alexandre; Maler, Leonard; Longtin, André

    2015-07-01

    We demonstrate how rhythmic activity can arise in neural networks from feedforward rather than recurrent circuitry and, in so doing, we provide a mechanism capable of explaining the temporal decorrelation of γ -band oscillations. We compare the spiking activity of a delayed recurrent network of inhibitory neurons with that of a feedforward network with the same neural properties and axonal delays. Paradoxically, these very different connectivities can yield very similar spike-train statistics in response to correlated input. This happens when neurons are noisy and axonal delays are short. A Taylor expansion of the feedback network's susceptibility—or frequency-dependent gain function—can then be stopped at first order to a good approximation, thus matching the feedforward net's susceptibility. The feedback network is known to display oscillations; these oscillations imply that the spiking activity of the population is felt by all neurons within the network, leading to direct spike correlations in a given neuron. On the other hand, in the output layer of the feedforward net, the interaction between the external drive and the delayed feedforward projection of this drive by the input layer causes indirect spike correlations: spikes fired by a given output layer neuron are correlated only through the activity of the input layer neurons. High noise and short delays partially bridge the gap between these two types of correlation, yielding similar spike-train statistics for both networks. This similarity is even stronger when the delay is distributed, as confirmed by linear response theory.

  8. Nasal neuron PET imaging quantifies neuron generation and degeneration

    Science.gov (United States)

    Van de Bittner, Genevieve C.; Riley, Misha M.; Cao, Luxiang; Herrick, Scott P.; Ricq, Emily L.; O’Neill, Michael J.; Ahmed, Zeshan; Murray, Tracey K.; Smith, Jaclyn E.; Wang, Changning; Schroeder, Frederick A.; Albers, Mark W.; Hooker, Jacob M.

    2017-01-01

    Olfactory dysfunction is broadly associated with neurodevelopmental and neurodegenerative diseases and predicts increased mortality rates in healthy individuals. Conventional measurements of olfactory health assess odor processing pathways within the brain and provide a limited understanding of primary odor detection. Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality. Notably, OSNs are continually replenished by adult neurogenesis in mammals, including humans, so OSN measurements are primed to provide specialized insights into neurological disease. Here, we have evaluated a PET radiotracer, [11C]GV1-57, that specifically binds mature OSNs and quantifies the mature OSN population in vivo. [11C]GV1-57 monitored native OSN population dynamics in rodents, detecting OSN generation during postnatal development and aging-associated neurodegeneration. [11C]GV1-57 additionally measured rates of neuron regeneration after acute injury and early-stage OSN deficits in a rodent tauopathy model of neurodegenerative disease. Preliminary assessment in nonhuman primates suggested maintained uptake and saturable binding of [18F]GV1-57 in primate nasal epithelium, supporting its translational potential. Future applications for GV1-57 include monitoring additional diseases or conditions associated with olfactory dysregulation, including cognitive decline, as well as monitoring effects of neuroregenerative or neuroprotective therapeutics. PMID:28112682

  9. Imaging calcium in neurons.

    Science.gov (United States)

    Grienberger, Christine; Konnerth, Arthur

    2012-03-08

    Calcium ions generate versatile intracellular signals that control key functions in all types of neurons. Imaging calcium in neurons is particularly important because calcium signals exert their highly specific functions in well-defined cellular subcompartments. In this Primer, we briefly review the general mechanisms of neuronal calcium signaling. We then introduce the calcium imaging devices, including confocal and two-photon microscopy as well as miniaturized devices that are used in freely moving animals. We provide an overview of the classical chemical fluorescent calcium indicators and of the protein-based genetically encoded calcium indicators. Using application examples, we introduce new developments in the field, such as calcium imaging in awake, behaving animals and the use of calcium imaging for mapping single spine sensory inputs in cortical neurons in vivo. We conclude by providing an outlook on the prospects of calcium imaging for the analysis of neuronal signaling and plasticity in various animal models.

  10. NEURON and Python

    Directory of Open Access Journals (Sweden)

    Michael Hines

    2009-01-01

    Full Text Available The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including GUI tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the XML module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  11. NEURON and Python.

    Science.gov (United States)

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  12. Neuron enriched nuclear proteome isolated from human brain.

    Science.gov (United States)

    Dammer, Eric B; Duong, Duc M; Diner, Ian; Gearing, Marla; Feng, Yue; Lah, James J; Levey, Allan I; Seyfried, Nicholas T

    2013-07-05

    The brain consists of diverse cell types including neurons, astrocytes, oligodendrocytes, and microglia. The isolation of nuclei from these distinct cell populations provides an opportunity to identify cell-type-specific nuclear proteins, histone modifications, and regulation networks that are altered with normal brain aging or neurodegenerative disease. In this study, we used a method by which intact neuronal and non-neuronal nuclei were purified from human post-mortem brain employing a modification of fluorescence activated cell sorting (FACS) termed fluorescence activated nuclei sorting (FANS). An antibody against NeuN, a neuron specific splicing factor, was used to isolate neuronal nuclei. Utilizing mass spectrometry (MS) based label-free quantitative proteomics, we identified 1755 proteins from sorted NeuN-positive and negative nuclear extracts. Approximately 20% of these proteins were significantly enriched or depleted in neuronal versus non-neuronal populations. Immunoblots of primary cultured rat neuron, astrocyte, and oligodendrocyte extracts confirmed that distinct members of the major nucleocytoplasmic structural linkage complex (LINC), nesprin-1 and nesprin-3, were differentially enriched in neurons and astrocytes, respectively. These comparative proteomic data sets also reveal a number of transcription and splicing factors that are selectively enriched in a cell-type-specific manner in human brain.

  13. Revisiting the role of neurons in neurovascular coupling

    Directory of Open Access Journals (Sweden)

    Bruno Cauli

    2010-06-01

    Full Text Available In this article, we will review molecular, anatomical, physiological and pharmacological data in an attempt to better understand how excitatory and inhibitory neurons recruited by distinct afferent inputs to the cerebral cortex contribute to the coupled hemodynamic response, and how astrocytes can act as intermediaries to these neuronal populations. We aim at providing the pros and cons to the following statements that, depending on the nature of the afferent input to the neocortex, (i different neuronal or astroglial messengers, likely acting in sequence, mediate the hemodynamic changes, (ii some recruited neurons release messengers that directly alter blood vessel tone, (iii others act by modulating neuronal and astroglial activity, and (iv astrocytes act as intermediaries for both excitatory and inhibitory neurotransmitters. We will stress that a given afferent signal activates a precise neuronal circuitry that determines the mediators of the hemodynamic response as well as the level of interaction with surrounding astrocytes.

  14. AgRP Neurons Can Increase Food Intake during Conditions of Appetite Suppression and Inhibit Anorexigenic Parabrachial Neurons.

    Science.gov (United States)

    Essner, Rachel A; Smith, Alison G; Jamnik, Adam A; Ryba, Anna R; Trutner, Zoe D; Carter, Matthew E

    2017-09-06

    neurons that induce appetite can cause obesity, whereas an abnormal amount of activity in neurons that suppress appetite can cause malnutrition and a severe reduction in body weight. The purpose of this study was to determine whether a population of neurons known to induce appetite ("AgRP neurons") could induce food intake to overcome appetite-suppression following administration of various appetite-suppressing compounds. We found that stimulating AgRP neurons could overcome various forms of appetite suppression and decrease neural activity in a separate population of appetite-suppressing neurons, providing new insights into how the brain regulates food intake. Copyright © 2017 the authors 0270-6474/17/378678-10$15.00/0.

  15. Neurochemical phenotype of cytoglobin‑expressing neurons in the rat hippocampus

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Fahrenkrug, Jan; Hannibal, Jens

    2014-01-01

    in a subpopulation of brain neurons. Recently, it has been shown that stress upregulates Cygb expression in the brain and the majority of neuronal nitric oxide synthase (nNOS)-positive neurons, an enzyme that produces NO, co-express Cygb. However, there are more neurons expressing Cygb than nNOS, thus a large number...... of Cygb neurons remain uncharacterized by the neurochemical content. The aim of the present study was to provide an additional and more detailed neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to the abundance of Cygb, as well as this limbic...... structure being an important target in a number of neurodegenerative diseases. Using triple immunohistochemistry, it was demonstrated that nearly all the parvalbumin- and heme oxygenase 1-positive neurons co-express Cygb and to a large extent, these neuron populations are distinct from the population...

  16. An introduction to modeling neuronal dynamics

    CERN Document Server

    Börgers, Christoph

    2017-01-01

    This book is intended as a text for a one-semester course on Mathematical and Computational Neuroscience for upper-level undergraduate and beginning graduate students of mathematics, the natural sciences, engineering, or computer science. An undergraduate introduction to differential equations is more than enough mathematical background. Only a slim, high school-level background in physics is assumed, and none in biology. Topics include models of individual nerve cells and their dynamics, models of networks of neurons coupled by synapses and gap junctions, origins and functions of population rhythms in neuronal networks, and models of synaptic plasticity. An extensive online collection of Matlab programs generating the figures accompanies the book. .

  17. Asynchronous Rate Chaos in Spiking Neuronal Circuits

    Science.gov (United States)

    Harish, Omri; Hansel, David

    2015-01-01

    The brain exhibits temporally complex patterns of activity with features similar to those of chaotic systems. Theoretical studies over the last twenty years have described various computational advantages for such regimes in neuronal systems. Nevertheless, it still remains unclear whether chaos requires specific cellular properties or network architectures, or whether it is a generic property of neuronal circuits. We investigate the dynamics of networks of excitatory-inhibitory (EI) spiking neurons with random sparse connectivity operating in the regime of balance of excitation and inhibition. Combining Dynamical Mean-Field Theory with numerical simulations, we show that chaotic, asynchronous firing rate fluctuations emerge generically for sufficiently strong synapses. Two different mechanisms can lead to these chaotic fluctuations. One mechanism relies on slow I-I inhibition which gives rise to slow subthreshold voltage and rate fluctuations. The decorrelation time of these fluctuations is proportional to the time constant of the inhibition. The second mechanism relies on the recurrent E-I-E feedback loop. It requires slow excitation but the inhibition can be fast. In the corresponding dynamical regime all neurons exhibit rate fluctuations on the time scale of the excitation. Another feature of this regime is that the population-averaged firing rate is substantially smaller in the excitatory population than in the inhibitory population. This is not necessarily the case in the I-I mechanism. Finally, we discuss the neurophysiological and computational significance of our results. PMID:26230679

  18. Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat

    OpenAIRE

    Nair-Roberts, R.G.; Chatelain-Badie, S.D.; Benson, E.; White-Cooper, H; BOLAM, J. P.; Ungless, M.A.

    2008-01-01

    Midbrain dopamine neurons in the ventral tegmental area, substantia nigra and retrorubral field play key roles in reward processing, learning and memory, and movement. Within these midbrain regions and admixed with the dopamine neurons, are also substantial populations of GABAergic neurons that regulate dopamine neuron activity and have projection targets similar to those of dopamine neurons. Additionally, there is a small group of putative glutamatergic neurons within the ventral tegmental a...

  19. Molecular taxonomy of major neuronal classes in the adult mouse forebrain.

    Science.gov (United States)

    Sugino, Ken; Hempel, Chris M; Miller, Mark N; Hattox, Alexis M; Shapiro, Peter; Wu, Caizi; Huang, Z Josh; Nelson, Sacha B

    2006-01-01

    Identifying the neuronal cell types that comprise the mammalian forebrain is a central unsolved problem in neuroscience. Global gene expression profiles offer a potentially unbiased way to assess functional relationships between neurons. Here, we carried out microarray analysis of 12 populations of neurons in the adult mouse forebrain. Five of these populations were chosen from cingulate cortex and included several subtypes of GABAergic interneurons and pyramidal neurons. The remaining seven were derived from the somatosensory cortex, hippocampus, amygdala and thalamus. Using these expression profiles, we were able to construct a taxonomic tree that reflected the expected major relationships between these populations, such as the distinction between cortical interneurons and projection neurons. The taxonomic tree indicated highly heterogeneous gene expression even within a single region. This dataset should be useful for the classification of unknown neuronal subtypes, the investigation of specifically expressed genes and the genetic manipulation of specific neuronal circuit elements.

  20. Gamma synchrony predicts neuron-neuron correlations and correlations with motor behavior in extrastriate visual area MT.

    Science.gov (United States)

    Lee, Joonyeol; Lisberger, Stephen G

    2013-12-11

    Correlated variability of neuronal responses is an important factor in estimating sensory parameters from a population response. Large correlations among neurons reduce the effective size of a neural population and increase the variation of the estimates. They also allow the activity of one neuron to be informative about impending perceptual decisions or motor actions on single trials. In extrastriate visual area MT of the rhesus macaque, for example, some but not all neurons show nonzero "choice probabilities" for perceptual decisions or non-zero "MT-pursuit" correlations between the trial-by-trial variations in neural activity and smooth pursuit eye movements. To understand the functional implications of zero versus nonzero correlations between neural responses and impending perceptions or actions, we took advantage of prior observations that specific frequencies of local field potentials reflect the correlated activity of neurons. We found that the strength of the spike-field coherence of a neuron in the gamma-band frequency range is related to the size of its MT-pursuit correlations for eye direction, as well as to the size of the neuron-neuron correlations. Spike-field coherence predicts MT-pursuit correlations better for direction than for speed, perhaps because the topographic organization of direction preference in MT is more amenable to creating meaningful local field potentials. We suggest that the relationship between spiking and local-field potentials is stronger for neurons that have larger correlations with their neighbors; larger neuron-neuron correlations create stronger MT-pursuit correlations. Neurons that lack strong correlations with their neighbors also have weaker correlations with pursuit behavior, but still could drive pursuit strongly.

  1. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  2. Mesmerising mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. Copyright 2010 Elsevier Inc. All rights reserved.

  3. Neurons Containing Orexin or Melanin Concentrating Hormone Reciprocally Regulate Wake and Sleep

    Directory of Open Access Journals (Sweden)

    Roda Rani eKonadhode

    2015-01-01

    Full Text Available There is considerable amount of data on arousal neurons whereas there is a paucity of knowledge regarding neurons that make us fall asleep. Indeed, current network models of sleep-wake regulation list many arousal neuronal populations compared to only one sleep group located in the preoptic area. There are neurons outside the preoptic area that are active during sleep, but they have never been selectively manipulated. Indeed, none of the sleep-active neurons have been selectively stimulated. To close this knowledge gap we used optogenetics to selectively manipulate neurons containing melanin concentrating hormone (MCH. The MCH neurons are located in the posterior hypothalamus intermingled with the orexin arousal neurons. Our data indicated that optogenetic stimulation of MCH neurons in wildtype mice (J Neuroscience, 2013 robustly increased both non-REM and REM sleep. MCH neuron stimulation increased sleep during the animal’s normal active period, which is compelling evidence that stimulation of MCH neurons has a powerful effect in counteracting the strong arousal signal from all of the arousal neurons. The MCH neurons represent the only group of sleep-active neurons that when selectively stimulated induce sleep. From a translational perspective this is potentially useful in sleep disorders, such as insomnia, where sleep needs to be triggered against a strong arousal drive. Our studies indicate that the MCH neurons belong within an overall model of sleep-wake regulation.

  4. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

    Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

  5. Direct regulation of GnRH neuron excitability by arcuate nucleus POMC and NPY neuron neuropeptides in female mice.

    Science.gov (United States)

    Roa, Juan; Herbison, Allan E

    2012-11-01

    Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons act to sense and coordinate the brain's responses to metabolic cues. One neuronal network that is very sensitive to metabolic status is that controlling fertility. In this study, we investigated the impact of neuropeptides released by NPY and POMC neurons on the cellular excitability of GnRH neurons, the final output cells of the brain controlling fertility. The majority (∼70%) of GnRH neurons were activated by α-melanocyte-stimulating hormone, and this resulted from the direct postsynaptic activation of melanocortin receptor 3 and melanocortin receptor 4. A small population of GnRH neurons (∼15%) was excited by cocaine and amphetamine-regulated transcript or inhibited by β-endorphin. Agouti-related peptide, released by NPY neurons, was found to have variable inhibitory (∼10%) and stimulatory (∼25%) effects upon subpopulations of GnRH neurons. A variety of NPY and pancreatic polypeptide analogs was used to examine potential NPY interactions with GnRH neurons. Although porcine NPY (Y1/Y2/Y5 agonist) directly inhibited the firing of approximately 45% of GnRH neurons, [Leu(31),Pro(34)]-NPY (Y1/Y4/Y5 agonist) could excite (56%) or inhibit (19%). Experiments with further agonists indicated that Y1 receptors were responsible for suppressing GnRH neuron activity, whereas postsynaptic Y4 receptors were stimulatory. These results show that the activity of GnRH neurons is regulated in a complex manner by neuropeptides released by POMC and NPY neurons. This provides a direct route through which different metabolic cues can regulate fertility.

  6. Motor neurone disease.

    Science.gov (United States)

    2016-03-23

    Essential facts Motor neurone disease describes a group of related diseases, affecting the neurones in the brain and spinal cord. Progressive, incurable and life-limiting, MND is rare, with about 1,100 people developing it each year in the UK and up to 5,000 people affected at any one time. One third of people will die within a year of diagnosis and more than half within two years. About 5% to 10% are alive at ten years.

  7. Neurons and Tumor Suppressors

    OpenAIRE

    Douglas W Zochodne

    2014-01-01

    Neurons choose growth pathways with half hearted reluctance, behavior that may be appropriate to maintain fixed long lasting connections but not to regenerate them. We now recognize that intrinsic brakes on regrowth are widely expressed in these hesitant neurons and include classical tumor suppressor molecules. Here, we review how two brakes, PTEN (phosphatase and tensin homolog deleted on chromosome 10) and retinoblastoma emerge as new and exciting knockdown targets to e...

  8. Neuron division or enucleation.

    Science.gov (United States)

    Sotnikov, O S; Laktionova, A A; Solovieva, I A; Krasnova, T V

    2010-10-01

    The classical Bielschowsky-Gross neurohistological method was used to reproduce all the morphological phenomena interpreted by many authors as signs of neuron division, budding, and fission. It is suggested that these signs are associated with the effects of enucleation, which occurs in many cells of other tissue types in response to a variety of chemical and physical treatments. Studies were performed using neurons isolated from the mollusk Lymnaea stagnalis and exposed in tissue culture to the actin microfilament inhibitor cytochalasin B. Phase contrast time-lapse video recording over periods of 4-8 h demonstrated nuclear displacement, ectopization, and budding, to the level of almost complete fission of the neuron body. This repeats the pattern seen in static fixed preparations in "normal" conditions and after different experimental treatments. Budding of the cytoplasm was also sometimes seen at the early stages of the experiments. Control experiments in which cultured neurons were exposed to the solvent for cytochalasin B, i.e., dimethylsulfoxide (DMSO), did not reveal any changes in neurons over a period of 8 h. We take the view that the picture previously interpreted as neuron division and fission can be explained in terms of the inhibition of actin microfilaments, sometimes developing spontaneously in cells undergoing individual metabolic changes preventing the maintenance of cytoskeleton stability.

  9. NeuronBank: A Tool for Cataloging Neuronal Circuitry.

    Science.gov (United States)

    Katz, Paul S; Calin-Jageman, Robert; Dhawan, Akshaye; Frederick, Chad; Guo, Shuman; Dissanayaka, Rasanjalee; Hiremath, Naveen; Ma, Wenjun; Shen, Xiuyn; Wang, Hsui C; Yang, Hong; Prasad, Sushil; Sunderraman, Rajshekhar; Zhu, Ying

    2010-01-01

    The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

  10. NeuronBank: a tool for cataloging neuronal circuitry

    Directory of Open Access Journals (Sweden)

    Paul S Katz

    2010-04-01

    Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

  11. NeuronBank: A Tool for Cataloging Neuronal Circuitry

    Science.gov (United States)

    Katz, Paul S.; Calin-Jageman, Robert; Dhawan, Akshaye; Frederick, Chad; Guo, Shuman; Dissanayaka, Rasanjalee; Hiremath, Naveen; Ma, Wenjun; Shen, Xiuyn; Wang, Hsui C.; Yang, Hong; Prasad, Sushil; Sunderraman, Rajshekhar; Zhu, Ying

    2010-01-01

    The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models. PMID:20428500

  12. Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

    Science.gov (United States)

    Nishida, Kazuhiko; Matsumura, Shinji; Taniguchi, Wataru; Uta, Daisuke; Furue, Hidemasa; Ito, Seiji

    2014-01-01

    The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET)-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

  13. Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

    Directory of Open Access Journals (Sweden)

    Kazuhiko Nishida

    Full Text Available The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

  14. Reliable neuronal systems: the importance of heterogeneity.

    Directory of Open Access Journals (Sweden)

    Johannes Lengler

    Full Text Available For every engineer it goes without saying: in order to build a reliable system we need components that consistently behave precisely as they should. It is also well known that neurons, the building blocks of brains, do not satisfy this constraint. Even neurons of the same type come with huge variances in their properties and these properties also vary over time. Synapses, the connections between neurons, are highly unreliable in forwarding signals. In this paper we argue that both these fact add variance to neuronal processes, and that this variance is not a handicap of neural systems, but that instead predictable and reliable functional behavior of neural systems depends crucially on this variability. In particular, we show that higher variance allows a recurrently connected neural population to react more sensitively to incoming signals, and processes them faster and more energy efficient. This, for example, challenges the general assumption that the intrinsic variability of neurons in the brain is a defect that has to be overcome by synaptic plasticity in the process of learning.

  15. Neuronal networks and energy bursts in epilepsy.

    Science.gov (United States)

    Wu, Y; Liu, D; Song, Z

    2015-02-26

    Epilepsy can be defined as the abnormal activities of neurons. The occurrence, propagation and termination of epileptic seizures rely on the networks of neuronal cells that are connected through both synaptic- and non-synaptic interactions. These complicated interactions contain the modified functions of normal neurons and glias as well as the mediation of excitatory and inhibitory mechanisms with feedback homeostasis. Numerous spread patterns are detected in disparate networks of ictal activities. The cortical-thalamic-cortical loop is present during a general spike wave seizure. The thalamic reticular nucleus (nRT) is the major inhibitory input traversing the region, and the dentate gyrus (DG) controls CA3 excitability. The imbalance between γ-aminobutyric acid (GABA)-ergic inhibition and glutamatergic excitation is the main disorder in epilepsy. Adjustable negative feedback that mediates both inhibitory and excitatory components affects neuronal networks through neurotransmission fluctuation, receptor and transmitter signaling, and through concomitant influences on ion concentrations and field effects. Within a limited dynamic range, neurons slowly adapt to input levels and have a high sensitivity to synaptic changes. The stability of the adapting network depends on the ratio of the adaptation rates of both the excitatory and inhibitory populations. Thus, therapeutic strategies with multiple effects on seizures are required for the treatment of epilepsy, and the therapeutic functions on networks are reviewed here. Based on the high-energy burst theory of epileptic activity, we propose a potential antiepileptic therapeutic strategy to transfer the high energy and extra electricity out of the foci.

  16. Morphology and ontogeny of rat perirhinal cortical neurons.

    Science.gov (United States)

    Furtak, Sharon Christine; Moyer, James Russell; Brown, Thomas Huntington

    2007-12-10

    Golgi-impregnated neurons from rat perirhinal cortex (PR) were classified into one of 15 distinct morphological categories (N = 6,891). The frequency of neurons in each cell class was determined as a function of the layer of PR and the age of the animal, which ranged from postnatal day 0 (P0) to young adulthood (P45). The developmental appearance of Golgi-impregnated neurons conformed to the expected "inside-out" pattern of development, meaning that cells populated in deep before superficial layers of PR. The relative frequencies of different cell types changed during the first 2 weeks of postnatal development. The largest cells, which were pyramidal and spiny multipolar neurons, appeared earliest. Aspiny stellate neurons were the last to appear. The total number of Golgi-impregnated neurons peaked at P10-12, corresponding to the time of eye-opening. This early increase in the number of impregnated neurons parallels observations in other cortical areas. The relative frequency of the 15 cell types remained constant between P14 to P45. The proportion of pyramidal neurons in PR ( approximately 50%) was much smaller than is typical of neocortex ( approximately 70%). A correspondingly larger proportion of PR neurons were nonpyramidal cells that are less common in neocortex. The relative frequency distribution of cell types creates an overall impression of considerable morphological diversity, which is arguably related to the particular manner in which this periallocortical brain region processes and stores information.

  17. Birthdating of myenteric neuron subtypes in the small intestine of the mouse

    Science.gov (United States)

    Bergner, Annette J.; Stamp, Lincon A.; Gonsalvez, David G.; Allison, Margaret B.; Olson, David P.; Myers, Martin G; Anderson, Colin R.; Young, Heather M.

    2013-01-01

    There are many different types of enteric neurons. Previous studies have identified the time at which some enteric neuron subtypes are born (exit the cell cycle) in the mouse, but the birthdates of some major enteric neuron subtypes are still incompletely characterized or unknown. We combined 5-ethynynl-2’-deoxyuridine (EdU) labeling with antibody markers that identify myenteric neuron subtypes to determine when neuron subtypes are born in the mouse small intestine. We found that different neurochemical classes of enteric neuron differed in their birthdates; serotonin neurons were born first with peak cell cycle exit at E11.5, followed by neurofilament-M neurons, calcitonin gene-related peptide neurons (peak cell cycle exit for both at E12.5-E13.5), tyrosine hydroxylase neurons (E15.5), nitric oxide synthase 1 (NOS1) neurons (E15.5) and calretinin neurons (P0). The vast majority of myenteric neurons had exited the cell cycle by P10. We did not observe any EdU+/NOS1+ myenteric neurons in the small intestine of adult mice following EdU injection at E10.5 or E11.5, which was unexpected as previous studies have shown that NOS1 neurons are present in E11.5 mice. Studies using the proliferation marker, Ki67, revealed that very few NOS1 neurons in the E11.5 and E12.5 gut were proliferating. However, Cre-lox-based genetic fate-mapping revealed a small sub-population of myenteric neurons that appears to express NOS1 only transiently. Together, our results confirm a relationship between enteric neuron subtype and birthdate, and suggest that some enteric neurons exhibit neurochemical phenotypes during development that are different from their mature phenotype. PMID:23861145

  18. Changes in membrane properties of CA1 pyramidal neurons after transient forebrain ischemia in vivo.

    Science.gov (United States)

    Gao, T M; Pulsinelli, W A; Xu, Z C

    1999-03-01

    We have previously identified three distinct populations of CA1 pyramidal neurons after reperfusion based on differences in synaptic response, and named these late depolarizing postsynaptic potential neurons (enhanced synaptic transmission), non-late depolarizing postsynaptic potential and small excitatory postsynaptic neurons (depressed synaptic transmission). In the present study, spontaneous activity and membrane properties of CA1 neurons were examined up to 48 h following approximately 14 min ischemic depolarization using intracellular recording and staining techniques in vivo. In comparison with preischemic properties, the spontaneous firing rate and the spontaneous synaptic activity of CA1 neurons decreased significantly during reperfusion; spontaneous synaptic activity ceased completely 36-48 h after reperfusion, except for a low level of activity which persisted in non-late depolarizing postsynaptic potential neurons. Neuronal hyperactivity as indicated by increasing firing rate was never observed in the present study. The membrane input resistance and time constant decreased significantly in late depolarizing postsynaptic potential neurons at 24-48 h reperfusion. In contrast, similar changes were not observed in non-late depolarizing postsynaptic potential neurons. The rheobase, spike threshold and spike frequency adaptation in late depolarizing postsynaptic potential neurons increased progressively following reperfusion. Only a transient increase in rheobase and spike threshold was detected in non-late depolarizing postsynaptic potential neurons and spike frequency adaptation remained unchanged in these neurons. The amplitude of fast afterhyperpolarization increased in all neurons after reperfusion, with the smallest increment in non-late depolarizing postsynaptic potential neurons. Small excitatory postsynaptic potential neurons shared similar changes to those of late depolarizing postsynaptic potential neurons. These results suggest that the enhancement

  19. Neurons of human nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Sazdanović Maja

    2011-01-01

    Full Text Available Background/Aim. Nucleus accumbens is a part of the ventral striatum also known as a drug active brain region, especially related with drug addiction. The aim of the study was to investigate the Golgi morphology of the nucleus accumbens neurons. Methods. The study was performed on the frontal and sagittal sections of 15 human brains by the Golgi Kopsch method. We classified neurons in the human nucleus accumbens according to their morphology and size into four types: type I - fusiform neurons; type II - fusiform neurons with lateral dendrite, arising from a part of the cell body; type III - pyramidal-like neuron; type IV - multipolar neuron. The medium spiny neurons, which are mostly noted regarding to the drug addictive conditions of the brain, correspond to the type IV - multipolar neurons. Results. Two regions of human nucleus accumbens could be clearly recognized on Nissl and Golgi preparations each containing different predominant neuronal types. Central part of nucleus accumbens, core region, has a low density of impregnated neurons with predominant type III, pyramidal-like neurons, with spines on secondary branches and rare type IV, multipolar neurons. Contrary to the core, peripheral region, shell of nucleus, has a high density of impregnated neurons predominantly contained of type I and type IV - multipolar neurons, which all are rich in spines on secondary and tertiary dendritic branches. Conclusion. Our results indicate great morphological variability of human nucleus accumbens neurons. This requires further investigations and clarifying clinical significance of this important brain region.

  20. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  1. Neuronal avalanches of a self-organized neural network with active-neuron-dominant structure.

    Science.gov (United States)

    Li, Xiumin; Small, Michael

    2012-06-01

    Neuronal avalanche is a spontaneous neuronal activity which obeys a power-law distribution of population event sizes with an exponent of -3/2. It has been observed in the superficial layers of cortex both in vivo and in vitro. In this paper, we analyze the information transmission of a novel self-organized neural network with active-neuron-dominant structure. Neuronal avalanches can be observed in this network with appropriate input intensity. We find that the process of network learning via spike-timing dependent plasticity dramatically increases the complexity of network structure, which is finally self-organized to be active-neuron-dominant connectivity. Both the entropy of activity patterns and the complexity of their resulting post-synaptic inputs are maximized when the network dynamics are propagated as neuronal avalanches. This emergent topology is beneficial for information transmission with high efficiency and also could be responsible for the large information capacity of this network compared with alternative archetypal networks with different neural connectivity.

  2. A dynamic code for economic object valuation in prefrontal cortex neurons.

    Science.gov (United States)

    Tsutsui, Ken-Ichiro; Grabenhorst, Fabian; Kobayashi, Shunsuke; Schultz, Wolfram

    2016-09-13

    Neuronal reward valuations provide the physiological basis for economic behaviour. Yet, how such valuations are converted to economic decisions remains unclear. Here we show that the dorsolateral prefrontal cortex (DLPFC) implements a flexible value code based on object-specific valuations by single neurons. As monkeys perform a reward-based foraging task, individual DLPFC neurons signal the value of specific choice objects derived from recent experience. These neuronal object values satisfy principles of competitive choice mechanisms, track performance fluctuations and follow predictions of a classical behavioural model (Herrnstein's matching law). Individual neurons dynamically encode both, the updating of object values from recently experienced rewards, and their subsequent conversion to object choices during decision-making. Decoding from unselected populations enables a read-out of motivational and decision variables not emphasized by individual neurons. These findings suggest a dynamic single-neuron and population value code in DLPFC that advances from reward experiences to economic object values and future choices.

  3. Neuronal survival in the brain: neuron type-specific mechanisms.

    Science.gov (United States)

    Pfisterer, Ulrich; Khodosevich, Konstantin

    2017-03-02

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.

  4. Stochastic neuron models

    CERN Document Server

    Greenwood, Priscilla E

    2016-01-01

    This book describes a large number of open problems in the theory of stochastic neural systems, with the aim of enticing probabilists to work on them. This includes problems arising from stochastic models of individual neurons as well as those arising from stochastic models of the activities of small and large networks of interconnected neurons. The necessary neuroscience background to these problems is outlined within the text, so readers can grasp the context in which they arise. This book will be useful for graduate students and instructors providing material and references for applying probability to stochastic neuron modeling. Methods and results are presented, but the emphasis is on questions where additional stochastic analysis may contribute neuroscience insight. An extensive bibliography is included. Dr. Priscilla E. Greenwood is a Professor Emerita in the Department of Mathematics at the University of British Columbia. Dr. Lawrence M. Ward is a Professor in the Department of Psychology and the Brain...

  5. Localization of the brainstem GABAergic neurons controlling paradoxical (REM sleep.

    Directory of Open Access Journals (Sweden)

    Emilie Sapin

    Full Text Available Paradoxical sleep (PS is a state characterized by cortical activation, rapid eye movements and muscle atonia. Fifty years after its discovery, the neuronal network responsible for the genesis of PS has been only partially identified. We recently proposed that GABAergic neurons would have a pivotal role in that network. To localize these GABAergic neurons, we combined immunohistochemical detection of Fos with non-radioactive in situ hybridization of GAD67 mRNA (GABA synthesis enzyme in control rats, rats deprived of PS for 72 h and rats allowed to recover after such deprivation. Here we show that GABAergic neurons gating PS (PS-off neurons are principally located in the ventrolateral periaqueductal gray (vlPAG and the dorsal part of the deep mesencephalic reticular nucleus immediately ventral to it (dDpMe. Furthermore, iontophoretic application of muscimol for 20 min in this area in head-restrained rats induced a strong and significant increase in PS quantities compared to saline. In addition, we found a large number of GABAergic PS-on neurons in the vlPAG/dDPMe region and the medullary reticular nuclei known to generate muscle atonia during PS. Finally, we showed that PS-on neurons triggering PS localized in the SLD are not GABAergic. Altogether, our results indicate that multiple populations of PS-on GABAergic neurons are distributed in the brainstem while only one population of PS-off GABAergic neurons localized in the vlPAG/dDpMe region exist. From these results, we propose a revised model for PS control in which GABAergic PS-on and PS-off neurons localized in the vlPAG/dDPMe region play leading roles.

  6. Population Receptive Field Dynamics in Human Visual Cortex

    NARCIS (Netherlands)

    Haak, Koen V.; Cornelissen, Frans W.; Morland, Antony B.

    2012-01-01

    Seminal work in the early nineties revealed that the visual receptive field of neurons in cat primary visual cortex can change in location and size when artificial scotomas are applied. Recent work now suggests that these single neuron receptive field dynamics also pertain to the neuronal population

  7. Hybrid Scheme for Modeling Local Field Potentials from Point-Neuron Networks

    DEFF Research Database (Denmark)

    Hagen, Espen; Dahmen, David; Stavrinou, Maria L

    2016-01-01

    and electrophysiological features of neurons near the recording electrode, as well as synaptic inputs from the entire network. Here we propose a hybrid modeling scheme combining efficient point-neuron network models with biophysical principles underlying LFP generation by real neurons. The LFP predictions rely...... on populations of network-equivalent multicompartment neuron models with layer-specific synaptic connectivity, can be used with an arbitrary number of point-neuron network populations, and allows for a full separation of simulated network dynamics and LFPs. We apply the scheme to a full-scale cortical network...... model for a ∼1 mm(2) patch of primary visual cortex, predict laminar LFPs for different network states, assess the relative LFP contribution from different laminar populations, and investigate effects of input correlations and neuron density on the LFP. The generic nature of the hybrid scheme and its...

  8. From Neurons to Newtons

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2001-01-01

    proteins generate forces, to the macroscopic levels where overt arm movements are vol- untarily controlled within an unpredictable environment by legions of neurons¯ring in orderly fashion. An extensive computer simulation system has been developed for this thesis, which at present contains a neural...... network scripting language for specifying arbitrary neural architectures, de¯nition ¯les for detailed spinal networks, various biologically realistic models of neurons, and dynamic synapses. Also included are structurally accurate models of intrafusal and extra-fusal muscle ¯bers and a general body...

  9. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation...... for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various...

  10. Medial Amygdalar Aromatase Neurons Regulate Aggression in Both Sexes

    Directory of Open Access Journals (Sweden)

    Elizabeth K. Unger

    2015-02-01

    Full Text Available Aromatase-expressing neuroendocrine neurons in the vertebrate male brain synthesize estradiol from circulating testosterone. This locally produced estradiol controls neural circuits underlying courtship vocalization, mating, aggression, and territory marking in male mice. How aromatase-expressing neuronal populations control these diverse estrogen-dependent male behaviors is poorly understood, and the function, if any, of aromatase-expressing neurons in females is unclear. Using targeted genetic approaches, we show that aromatase-expressing neurons within the male posterodorsal medial amygdala (MeApd regulate components of aggression, but not other estrogen-dependent male-typical behaviors. Remarkably, aromatase-expressing MeApd neurons in females are specifically required for components of maternal aggression, which we show is distinct from intermale aggression in pattern and execution. Thus, aromatase-expressing MeApd neurons control distinct forms of aggression in the two sexes. Moreover, our findings indicate that complex social behaviors are separable in a modular manner at the level of genetically identified neuronal populations.

  11. Medial amygdalar aromatase neurons regulate aggression in both sexes.

    Science.gov (United States)

    Unger, Elizabeth K; Burke, Kenneth J; Yang, Cindy F; Bender, Kevin J; Fuller, Patrick M; Shah, Nirao M

    2015-02-03

    Aromatase-expressing neuroendocrine neurons in the vertebrate male brain synthesize estradiol from circulating testosterone. This locally produced estradiol controls neural circuits underlying courtship vocalization, mating, aggression, and territory marking in male mice. How aromatase-expressing neuronal populations control these diverse estrogen-dependent male behaviors is poorly understood, and the function, if any, of aromatase-expressing neurons in females is unclear. Using targeted genetic approaches, we show that aromatase-expressing neurons within the male posterodorsal medial amygdala (MeApd) regulate components of aggression, but not other estrogen-dependent male-typical behaviors. Remarkably, aromatase-expressing MeApd neurons in females are specifically required for components of maternal aggression, which we show is distinct from intermale aggression in pattern and execution. Thus, aromatase-expressing MeApd neurons control distinct forms of aggression in the two sexes. Moreover, our findings indicate that complex social behaviors are separable in a modular manner at the level of genetically identified neuronal populations.

  12. Optogenetic control of human neurons in organotypic brain cultures

    DEFF Research Database (Denmark)

    Andersson, My; Avaliani, Natalia; Svensson, Andreas

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof......-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies....

  13. Interleukin-1ß, seizures and neuronal cell death

    OpenAIRE

    Medel-Matus, Jesús S.; Postgrado en Neuroetología, Universidad Veracruzana. Xalapa, México. Centro de Investigaciones Cerebrales, Universidad Veracruzana. Xalapa, México. Químico clínico maestro en Neuroetología.; Cortijo-Palacios, Libia X.; Postgrado en Neuroetología, Universidad Veracruzana. Xalapa, México. química clínica.; Álvarez-Croda, Dulce M.; Postgrado en Neuroetología, Universidad Veracruzana. Xalapa, México. Centro de Investigaciones Cerebrales, Universidad Veracruzana. Xalapa, México. química farmacéutica bióloga.; Martínez-Quiroz, Joel; Facultad de Química Farmacéutica Biológica, Universidad Veracruzana. Xalapa, México. químico farmacéutico biólogo maestro en Ciencias Químico-Biológicas.; López-Meraz, María L.; Centro de Investigaciones Cerebrales, Universidad Veracruzana. Xalapa, México. Facultad de Medicina, Universidad Veracruzana. Xalapa, México. química farmacéutica bióloga doctora en Neurofarmacología y Terapéutica Experimental.

    2014-01-01

    Epilepsy is a neurological disorder affecting almost 1% of the world population. Experimental human and animal studies suggest that inflammation mediators, like cytokines, participate in the physiopathology of epilepsy. Interleukin-1beta (IL-1β) could influence susceptibility for seizures, as well as neuronal death caused by seizures, although some findings are contradictory. This document reviews the current knowledge establishing a connection between IL-1β, seizures and neuronal death. L...

  14. Comparative functional expression of nAChR subtypes in rodent DRG neurons

    Directory of Open Access Journals (Sweden)

    Nathan J. Smith

    2013-11-01

    Full Text Available We investigated the functional expression of nicotinic acetylcholine receptors (nAChRs in heterogeneous populations of dissociated rat and mouse lumbar dorsal root ganglion (DRG neurons by calcium imaging. By this experimental approach, it is possible to investigate the functional expression of multiple receptor and ion-channel subtypes across more than 100 neuronal and glial cells simultaneously. Based on nAChR expression, DRG neurons could be divided into four subclasses: 1 neurons that express predominantly alpha3beta4 and alpha6beta4 nAChRs; 2 neurons that express predominantly alpha7 nAChRs; 3 neurons that express a combination of alpha3beta4/alpha6beta4 and alpha7 nAChRs; and 4 neurons that do not express nAChRs. In this comparative study, the same four neuronal subclasses were observed in mouse and rat DRG. However, the expression frequency differed between species: substantially more rat DRG neurons were in the first three subclasses than mouse DRG neurons, at all developmental time points tested in our study. Approximately 70-80% of rat DRG neurons expressed functional nAChRs, in contrast to only ~15-30% of mouse DRG neurons. Our study also demonstrated functional coupling between nAChRs, voltage-gated calcium channels and mitochondrial Ca2+ transport in discrete subsets of DRG neurons. In contrast to the expression of nAChRs in DRG neurons, we demonstrated that a subset of non-neuronal DRG cells expressed muscarinic acetylcholine receptors (mAChRs and not nAChRs. The general approach to comparative cellular neurobiology outlined in this paper has the potential to better integrate molecular and systems neuroscience by uncovering the spectrum of neuronal subclasses present in a given cell population and the functionally integrated signaling components expressed in each subclass.

  15. Glutamatergic neurons are present in the rat ventral tegmental area

    Science.gov (United States)

    Yamaguchi, Tsuyoshi; Sheen, Whitney; Morales, Marisela

    2010-01-01

    The ventral tegmental area (VTA) is thought to play an important role in reward function. Two populations of neurons, containing either dopamine (DA) or γ-amino butyric acid (GABA), have been extensively characterized in this area. However, recent electrophysiological studies are consistent with the notion that neurons that utilize neurotransmitters other than DA or GABA are likely to be present in the VTA. Given the pronounced phenotypic diversity of neurons in this region, we have proposed that additional cell types, such as those that express the neurotransmitter glutamate may also be present in this area. Thus, by using in situ hybridization histochemistry we investigated whether transcripts encoded by genes for the two vesicular glutamate transporters, VGluT1 or VGluT2, were expressed in the VTA. We found that VGluT2 mRNA but not VGluT1 mRNA is expressed in the VTA. Neurons expressing VGluT2 mRNA were differentially distributed throughout the rostro-caudal and medio-lateral aspects of the VTA, with the highest concentration detected in rostro-medial areas. Phenotypic characterization with double in situ hybridization of these neurons indicated that they rarely co–expressed mRNAs for tyrosine hydroxylase (TH, marker for DAergic neurons) or glutamic acid decarboxylase (GAD, marker for GABAergic neurons). Based on the results described here, we concluded that the VTA contains glutamatergic neurons that in their vast majority are clearly non-DAergic and non-GABAergic. PMID:17241272

  16. Nanoresolution radiology of neurons

    Energy Technology Data Exchange (ETDEWEB)

    Wu, H.R.; Chen, S.T.; Chu, Y.S.; Conley, R.; Bouet, N.; Chien, C.C.; Chen, H.H.; Lin, C.H.; Tung, H.T.; Chen, Y.S.; Margaritondo, G.; Je, J.H.; Hwu, Y. (IP-Taiwan); (Ecole); (BNL); (POSTECH)

    2013-04-08

    We report recent advances in hard-x-ray optics - including record spatial resolution - and in staining techniques that enable synchrotron microradiology to produce neurobiology images of quality comparable to electron and visible microscopy. In addition, microradiology offers excellent penetration and effective three-dimensional detection as required for many neuron studies. Our tests include tomographic reconstruction based on projection image sets.

  17. New findings on neuron development

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ A mature neuron receives inputs from multiple dendrites and sends its output to other neurons via a single axon.This polarized morphology requires proper axonal/dendritic differentiation during development.

  18. Linking Memories across Time via Neuronal and Dendritic Overlaps in Model Neurons with Active Dendrites

    Directory of Open Access Journals (Sweden)

    George Kastellakis

    2016-11-01

    Full Text Available Memories are believed to be stored in distributed neuronal assemblies through activity-induced changes in synaptic and intrinsic properties. However, the specific mechanisms by which different memories become associated or linked remain a mystery. Here, we develop a simplified, biophysically inspired network model that incorporates multiple plasticity processes and explains linking of information at three different levels: (1 learning of a single associative memory, (2 rescuing of a weak memory when paired with a strong one, and (3 linking of multiple memories across time. By dissecting synaptic from intrinsic plasticity and neuron-wide from dendritically restricted protein capture, the model reveals a simple, unifying principle: linked memories share synaptic clusters within the dendrites of overlapping populations of neurons. The model generates numerous experimentally testable predictions regarding the cellular and sub-cellular properties of memory engrams as well as their spatiotemporal interactions.

  19. Binary neuron with optical devices

    Science.gov (United States)

    Degeratu, Vasile; Degeratu, Ştefania; Şchiopu, Paul; Şchiopu, Carmen

    2009-01-01

    In this paper the authors present a model of binary neuron, a model of McCulloch-Pitts neuron with optical devices. This model of neuron can be implemented not only in the optic integrated circuits but also in the classic optical circuits it being cheap and immune not only into electromagnetic fields but also into any kind of radiation. The transfer speed of information through the neuron is very higher, it being limited only by the light speed from the received medium.

  20. Cholinergic Neurons Excite Cortically Projecting Basal Forebrain GABAergic Neurons

    Science.gov (United States)

    Yang, Chun; McKenna, James T.; Zant, Janneke C.; Winston, Stuart; Basheer, Radhika

    2014-01-01

    The basal forebrain (BF) plays an important role in the control of cortical activation and attention. Understanding the modulation of BF neuronal activity is a prerequisite to treat disorders of cortical activation involving BF dysfunction, such as Alzheimer's disease. Here we reveal the interaction between cholinergic neurons and cortically projecting BF GABAergic neurons using immunohistochemistry and whole-cell recordings in vitro. In GAD67-GFP knock-in mice, BF cholinergic (choline acetyltransferase-positive) neurons were intermingled with GABAergic (GFP+) neurons. Immunohistochemistry for the vesicular acetylcholine transporter showed that cholinergic fibers apposed putative cortically projecting GABAergic neurons containing parvalbumin (PV). In coronal BF slices from GAD67-GFP knock-in or PV-tdTomato mice, pharmacological activation of cholinergic receptors with bath application of carbachol increased the firing rate of large (>20 μm diameter) BF GFP+ and PV (tdTomato+) neurons, which exhibited the intrinsic membrane properties of cortically projecting neurons. The excitatory effect of carbachol was blocked by antagonists of M1 and M3 muscarinic receptors in two subpopulations of BF GABAergic neurons [large hyperpolarization-activated cation current (Ih) and small Ih, respectively]. Ion substitution experiments and reversal potential measurements suggested that the carbachol-induced inward current was mediated mainly by sodium-permeable cation channels. Carbachol also increased the frequency of spontaneous excitatory and inhibitory synaptic currents. Furthermore, optogenetic stimulation of cholinergic neurons/fibers caused a mecamylamine- and atropine-sensitive inward current in putative GABAergic neurons. Thus, cortically projecting, BF GABAergic/PV neurons are excited by neighboring BF and/or brainstem cholinergic neurons. Loss of cholinergic neurons in Alzheimer's disease may impair cortical activation, in part, through disfacilitation of BF cortically

  1. Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

    Science.gov (United States)

    McCarthy, Deirdre M; Bhide, Pradeep G

    2012-01-01

    Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects.

  2. How neurons migrate: a dynamic in-silico model of neuronal migration in the developing cortex

    LENUS (Irish Health Repository)

    Setty, Yaki

    2011-09-30

    Abstract Background Neuronal migration, the process by which neurons migrate from their place of origin to their final position in the brain, is a central process for normal brain development and function. Advances in experimental techniques have revealed much about many of the molecular components involved in this process. Notwithstanding these advances, how the molecular machinery works together to govern the migration process has yet to be fully understood. Here we present a computational model of neuronal migration, in which four key molecular entities, Lis1, DCX, Reelin and GABA, form a molecular program that mediates the migration process. Results The model simulated the dynamic migration process, consistent with in-vivo observations of morphological, cellular and population-level phenomena. Specifically, the model reproduced migration phases, cellular dynamics and population distributions that concur with experimental observations in normal neuronal development. We tested the model under reduced activity of Lis1 and DCX and found an aberrant development similar to observations in Lis1 and DCX silencing expression experiments. Analysis of the model gave rise to unforeseen insights that could guide future experimental study. Specifically: (1) the model revealed the possibility that under conditions of Lis1 reduced expression, neurons experience an oscillatory neuron-glial association prior to the multipolar stage; and (2) we hypothesized that observed morphology variations in rats and mice may be explained by a single difference in the way that Lis1 and DCX stimulate bipolar motility. From this we make the following predictions: (1) under reduced Lis1 and enhanced DCX expression, we predict a reduced bipolar migration in rats, and (2) under enhanced DCX expression in mice we predict a normal or a higher bipolar migration. Conclusions We present here a system-wide computational model of neuronal migration that integrates theory and data within a precise

  3. Neuronal substrate of eating disorders

    OpenAIRE

    Timofeeva, Elena; Calvez, Juliane

    2014-01-01

    Eating disorders are devastating and life-threatening psychiatric diseases. Although clinical and experimental investigations have significantly progressed in discovering the neuronal causes of eating disorders, the exact neuronal and molecular mechanisms of the development and maintenance of these pathologies are not fully understood. The complexity of the neuronal substrate of eating disorders hampers progress in revealing the precise mechanisms. The present re...

  4. CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors

    Directory of Open Access Journals (Sweden)

    Mihalescu-Maingot Maria

    2010-02-01

    Full Text Available Abstract Background Tumor initiating cells (TICs provide a new paradigm for developing original therapeutic strategies. Methods We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas. Results A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs. Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide. Conclusions Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies.

  5. Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus.

    Science.gov (United States)

    Hundahl, Christian Ansgar; Fahrenkrug, Jan; Hannibal, Jens

    2014-09-01

    Cytoglobin (Cygb), a novel oxygen-binding protein, is expressed in the majority of tissues and has been proposed to function in nitric oxide (NO) metabolism in the vasculature and to have cytoprotective properties. However, the overall functions of Cygb remain elusive. Cygb is also expressed in a subpopulation of brain neurons. Recently, it has been shown that stress upregulates Cygb expression in the brain and the majority of neuronal nitric oxide synthase (nNOS)-positive neurons, an enzyme that produces NO, co-express Cygb. However, there are more neurons expressing Cygb than nNOS, thus a large number of Cygb neurons remain uncharacterized by the neurochemical content. The aim of the present study was to provide an additional and more detailed neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to the abundance of Cygb, as well as this limbic structure being an important target in a number of neurodegenerative diseases. Using triple immunohistochemistry, it was demonstrated that nearly all the parvalbumin- and heme oxygenase 1-positive neurons co-express Cygb and to a large extent, these neuron populations are distinct from the population of Cygb neurons co-expressing nNOS. Furthermore, it was shown that the majority of neurons expressing somastostatin and vasoactive intestinal peptide also co-express Cygb and nNOS. Detailed information regarding the neurochemical phenotype of Cygb neurons in the hippocampus can be a valuable tool in determining the function of Cygb in the brain.

  6. Rhythm dynamics of complex neuronal networks with mixed bursting neurons

    Institute of Scientific and Technical Information of China (English)

    Lü Yong-Bing; Shi Xia; Zheng Yan-Hong

    2013-01-01

    The spatiotemporal order and rhythm dynamics of a complex neuronal network with mixed bursting neurons are studied in this paper.A quantitative characteristic,the width factor,is introduced to describe the rhythm dynamics of an individual neuron,and the average width factor is used to characterize the rhythm dynamics of a neuronal network.An r parameter is introduced to denote the ratio of the short bursting neurons in the network.Then we investigate the effect of the ratio on the rhythm dynamics of the neuronal network.The critical value of r is derived,and the neurons in the network always remain short bursting when the r ratio is larger than the critical value.

  7. Morphine decreases enteric neuron excitability via inhibition of sodium channels.

    Directory of Open Access Journals (Sweden)

    Tricia H Smith

    Full Text Available Gastrointestinal peristalsis is significantly dependent on the enteric nervous system. Constipation due to reduced peristalsis is a major side-effect of morphine, which limits the chronic usefulness of this excellent pain reliever in man. The ionic basis for the inhibition of enteric neuron excitability by morphine is not well characterized as previous studies have mainly utilized microelectrode recordings from whole mount myenteric plexus preparations in guinea pigs. Here we have developed a Swiss-Webster mouse myenteric neuron culture and examined their electrophysiological properties by patch-clamp techniques and determined the mechanism for morphine-induced decrease in neuronal excitability. Isolated neurons in culture were confirmed by immunostaining with pan-neuronal marker, β-III tubulin and two populations were identified by calbindin and calretinin staining. Distinct neuronal populations were further identified based on the presence and absence of an afterhyperpolarization (AHP. Cells with AHP expressed greater density of sodium currents. Morphine (3 µM significantly reduced the amplitude of the action potential, increased the threshold for spike generation but did not alter the resting membrane potential. The decrease in excitability resulted from inhibition of sodium currents. In the presence of morphine, the steady-state voltage dependence of Na channels was shifted to the left with almost 50% of channels unavailable for activation from hyperpolarized potentials. During prolonged exposure to morphine (two hours, action potentials recovered, indicative of the development of tolerance in single enteric neurons. These results demonstrate the feasibility of isolating mouse myenteric neurons and establish sodium channel inhibition as a mechanism for morphine-induced decrease in neuronal excitability.

  8. The changing roles of neurons in the cortical subplate

    Directory of Open Access Journals (Sweden)

    Michael J Friedlander

    2009-08-01

    Full Text Available Neurons may serve different functions over the course of an organism’s life. Recent evidence suggests that cortical subplate neurons including those that reside in the white matter may perform longitudinal multi-tasking at different stages of development. These cells play a key role in early cortical development in coordinating thalamocortical reciprocal innervation. At later stages of development, they become integrated within the cortical microcircuitry. This type of longitudinal multi-tasking can enhance the capacity for information processing by populations of cells serving different functions over the lifespan. Subplate cells are initially derived when cells from the ventricular zone underlying the cortex migrate to the cortical preplate that is subsequently split by the differentiating neurons of the cortical plate with some neurons locating in the marginal zone and others settling below in the subplate (SP. While the cortical plate neurons form most of the cortical layers (layers 2-6, the marginal zone neurons form layer 1 and the SP neurons become interstitial cells of the white matter as well as forming a compact sublayer along the bottom of layer 6. After serving as transient innervation targets for thalamocortical axons, most of these cells die and layer 4 neurons become innervated by thalamic axons. However, 10-20% survives, remaining into adulthood along the bottom of layer 6 and as a scattered population of interstitial neurons in the white matter. Surviving subplate cells’ axons project throughout the overlying laminae, reaching layer 1 and issuing axon collaterals within white matter and in lower layer 6. This suggests that they participate in local synaptic networks, as well. Moreover, they receive excitatory and inhibitory synaptic inputs, potentially monitoring outputs from axon collaterals of cortical efferents, from cortical afferents and/or from each other. We explore our understanding of the functional connectivity of

  9. Intrinsic and Extrinsic Neuronal Mechanisms in Temporal Coding: A Further Look at Neuronal Oscillations

    Directory of Open Access Journals (Sweden)

    Rémy Lestienne

    1999-01-01

    case to case. Also, the functions of oscillations in the brain are multiple and are not confined to synchronization. The paradigmatic instantiation of oscillation in physics is given by the harmonic oscillator, a device particularly suited to tell the time, as in clocks. We will thus examine first the case of oscillations or cycling discharges of neurones, which provide a clock or impose a “tempo” for various kinds of information processing. Neuronal oscillators are rarely just clocks clicking at a fixed frequency. Instead, their frequency is often adjustable and controllable, as in the example of the “chattering cells” discovered in the superficial layers of the visual cortex. Moreover, adjustable frequency oscillators are suitable for use in “phase locked loops” (PLL networks, a device that can convert time coding to frequency coding; such PLL units have been found in the somatosensory cortex of guinea pigs. Finally, are oscillations stricto sensu necessary to induce synchronization in the discharges of downstream neurones? We know that this is not the case, at least not for local populations of neurones. As a contribution to this question, we propose that repeating patterns in neuronal discharges production may be looked at as one such alternative solution in relation to the processing of information. We review here the case of precisely repeating triplets, detected in the discharges of olfactory mitral cells of a freely breathing rat under odor stimulation.

  10. Anatomic and Molecular Development of Corticostriatal Projection Neurons in Mice

    Science.gov (United States)

    Sohur, U. Shivraj; Padmanabhan, Hari K.; Kotchetkov, Ivan S.; Menezes, Joao R.L.; Macklis, Jeffrey D.

    2014-01-01

    Corticostriatal projection neurons (CStrPN) project from the neocortex to ipsilateral and contralateral striata to control and coordinate motor programs and movement. They are clinically important as the predominant cortical population that degenerates in Huntington's disease and corticobasal ganglionic degeneration, and their injury contributes to multiple forms of cerebral palsy. Together with their well-studied functions in motor control, these clinical connections make them a functionally, behaviorally, and clinically important population of neocortical neurons. Little is known about their development. “Intratelencephalic” CStrPN (CStrPNi), projecting to the contralateral striatum, with their axons fully within the telencephalon (intratelencephalic), are a major population of CStrPN. CStrPNi are of particular interest developmentally because they share hodological and axon guidance characteristics of both callosal projection neurons (CPN) and corticofugal projection neurons (CFuPN); CStrPNi send axons contralaterally before descending into the contralateral striatum. The relationship of CStrPNi development to that of broader CPN and CFuPN populations remains unclear; evidence suggests that CStrPNi might be evolutionary “hybrids” between CFuPN and deep layer CPN—in a sense “chimeric” with both callosal and corticofugal features. Here, we investigated the development of CStrPNi in mice—their birth, maturation, projections, and expression of molecular developmental controls over projection neuron subtype identity. PMID:23118198

  11. Leaders of neuronal cultures in a quorum percolation model

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Eckmann

    2010-09-01

    Full Text Available We present a theoretical framework using quorum-percolation for describing the initiation of activity in a neural culture. The cultures are modeled as random graphs, whose nodes are neurons with $kin$ inputs and $kout$ outputs, and whose input degrees $kin=k$ obey given distribution functions $p_k$. We examine the firing activity of the population of neurons according to their input degree ($k$ classes and calculate for each class its firing probability $Phi_k(t$ as a function of $t$. The probability of a node to fire is found to be determined by its in-degree $k$, and the first-to-fire neurons are those that have a high $k$. A small minority of high-$k$ classes may be called ``Leaders,'' as they form an inter-connected subnetwork that consistently fires much before the rest of the culture. Once initiated, the activity spreads from the Leaders to the less connected majority of the culture. We then use the distribution of in-degree of the Leaders to study the growth rate of the number of neurons active in a burst, which was experimentally measured to be initially exponential. We find that this kind of growth rate is best described by a population that has an in-degree distribution that is a Gaussian centered around $k=75$ with width $sigma=31$ for the majority of the neurons, but also has a power law tail with exponent $-2$ for ten percent of the population. Neurons in the tail may have as many as $k=4,700$ inputs. We explore and discuss the correspondence between the degree distribution and a dynamic neuronal threshold, showing that from the functional point of view, structure and elementary dynamics are interchangeable. We discuss possible geometric origins of this distribution, and comment on the importance of size, or of having a large number of neurons, in the culture.

  12. Reelin secreted by GABAergic neurons regulates glutamate receptor homeostasis.

    Directory of Open Access Journals (Sweden)

    Cecilia Gonzalez Campo

    Full Text Available BACKGROUND: Reelin is a large secreted protein of the extracellular matrix that has been proposed to participate to the etiology of schizophrenia. During development, reelin is crucial for the correct cytoarchitecture of laminated brain structures and is produced by a subset of neurons named Cajal-Retzius. After birth, most of these cells degenerate and reelin expression persists in postnatal and adult brain. The phenotype of neurons that bind secreted reelin and whether the continuous secretion of reelin is required for physiological functions at postnatal stages remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Combining immunocytochemical and pharmacological approaches, we first report that two distinct patterns of reelin expression are present in cultured hippocampal neurons. We show that in hippocampal cultures, reelin is secreted by GABAergic neurons displaying an intense reelin immunoreactivity (IR. We demonstrate that secreted reelin binds to receptors of the lipoprotein family on neurons with a punctate reelin IR. Secondly, using calcium imaging techniques, we examined the physiological consequences of reelin secretion blockade. Blocking protein secretion rapidly and reversibly changes the subunit composition of N-methyl-D-aspartate glutamate receptors (NMDARs to a predominance of NR2B-containing NMDARs. Addition of recombinant or endogenously secreted reelin rescues the effects of protein secretion blockade and reverts the fraction of NR2B-containing NMDARs to control levels. Therefore, the continuous secretion of reelin is necessary to control the subunit composition of NMDARs in hippocampal neurons. CONCLUSIONS/SIGNIFICANCE: Our data show that the heterogeneity of reelin immunoreactivity correlates with distinct functional populations: neurons synthesizing and secreting reelin and/or neurons binding reelin. Furthermore, we show that continuous reelin secretion is a strict requirement to maintain the composition of NMDARs. We propose

  13. Galanin-Expressing GABA Neurons in the Lateral Hypothalamus Modulate Food Reward and Noncompulsive Locomotion.

    Science.gov (United States)

    Qualls-Creekmore, Emily; Yu, Sangho; Francois, Marie; Hoang, John; Huesing, Clara; Bruce-Keller, Annadora; Burk, David; Berthoud, Hans-Rudolf; Morrison, Christopher D; Münzberg, Heike

    2017-06-21

    The lateral hypothalamus (LHA) integrates reward and appetitive behavior and is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHA (GABA) ), which densely innervate the ventral tegmental area (VTA), with modulation of food reward and consumption; yet, LHA (GABA) projections to the VTA exclusively modulated food consumption, not reward. We identified a subpopulation of LHA (GABA) neurons that coexpress the neuropeptide galanin (LHA (Gal) ). These LHA (Gal) neurons also modulate food reward, but lack direct VTA innervation. We hypothesized that LHA (Gal) neurons may represent a subpopulation of LHA (GABA) neurons that mediates food reward independent of direct VTA innervation. We used chemogenetic activation of LHA (Gal) or LHA (GABA) neurons in mice to compare their role in feeding behavior. We further analyzed locomotor behavior to understand how differential VTA connectivity and transmitter release in these LHA neurons influences this behavior. LHA (Gal) or LHA (GABA) neuronal activation both increased operant food-seeking behavior, but only activation of LHA (GABA) neurons increased overall chow consumption. Additionally, LHA (Gal) or LHA (GABA) neuronal activation similarly induced locomotor activity, but with striking differences in modality. Activation of LHA (GABA) neurons induced compulsive-like locomotor behavior; while LHA (Gal) neurons induced locomotor activity without compulsivity. Thus, LHA (Gal) neurons define a subpopulation of LHA (GABA) neurons without direct VTA innervation that mediate noncompulsive food-seeking behavior. We speculate that the striking difference in compulsive-like locomotor behavior is also based on differential VTA innervation. The downstream neural network responsible for this behavior and a potential role for galanin as neuromodulator remains to be identified.SIGNIFICANCE STATEMENT The lateral hypothalamus (LHA) regulates motivated feeding behavior via GABAergic LHA neurons

  14. Fezf2 expression in layer 5 projection neurons of mature mouse motor cortex.

    Science.gov (United States)

    Tantirigama, Malinda L S; Oswald, Manfred J; Clare, Alison J; Wicky, Hollie E; Day, Robert C; Hughes, Stephanie M; Empson, Ruth M

    2016-03-01

    The mature cerebral cortex contains a wide diversity of neuron phenotypes. This diversity is specified during development by neuron-specific expression of key transcription factors, some of which are retained for the life of the animal. One of these key developmental transcription factors that is also retained in the adult is Fezf2, but the neuron types expressing it in the mature cortex are unknown. With a validated Fezf2-Gfp reporter mouse, whole-cell electrophysiology with morphology reconstruction, cluster analysis, in vivo retrograde labeling, and immunohistochemistry, we identify a heterogeneous population of Fezf2(+) neurons in both layer 5A and layer 5B of the mature motor cortex. Functional electrophysiology identified two distinct subtypes of Fezf2(+) neurons that resembled pyramidal tract projection neurons (PT-PNs) and intratelencephalic projection neurons (IT-PNs). Retrograde labeling confirmed the former type to include corticospinal projection neurons (CSpPNs) and corticothalamic projection neurons (CThPNs), whereas the latter type included crossed corticostriatal projection neurons (cCStrPNs) and crossed-corticocortical projection neurons (cCCPNs). The two Fezf2(+) subtypes expressed either CTIP2 or SATB2 to distinguish their physiological identity and confirmed that specific expression combinations of key transcription factors persist in the mature motor cortex. Our findings indicate a wider role for Fezf2 within gene expression networks that underpin the diversity of layer 5 cortical projection neurons.

  15. Neuronal synchrony 

    OpenAIRE

    Buzsáki, Gyorgy

    2010-01-01

    1. Neuronal synchrony: metabolic and wiring costs of excitatory and inhibitory systems The major part of the brain’s energy budget (~ 60-80%) is devoted to its communication activities. While inhibition is critical to brain function, relatively little attention has been paid to its metabolic costs. Understanding how inhibitory interneurons contribute to brain energy consumption (brain work) is not only of interest in understanding a fundamental aspect of brain function but also in understandi...

  16. Micropatterning neuronal networks.

    Science.gov (United States)

    Hardelauf, Heike; Waide, Sarah; Sisnaiske, Julia; Jacob, Peter; Hausherr, Vanessa; Schöbel, Nicole; Janasek, Dirk; van Thriel, Christoph; West, Jonathan

    2014-07-01

    Spatially organised neuronal networks have wide reaching applications, including fundamental research, toxicology testing, pharmaceutical screening and the realisation of neuronal implant interfaces. Despite the large number of methods catalogued in the literature there remains the need to identify a method that delivers high pattern compliance, long-term stability and is widely accessible to neuroscientists. In this comparative study, aminated (polylysine/polyornithine and aminosilanes) and cytophobic (poly(ethylene glycol) (PEG) and methylated) material contrasts were evaluated. Backfilling plasma stencilled PEGylated substrates with polylysine does not produce good material contrasts, whereas polylysine patterned on methylated substrates becomes mobilised by agents in the cell culture media which results in rapid pattern decay. Aminosilanes, polylysine substitutes, are prone to hydrolysis and the chemistries prove challenging to master. Instead, the stable coupling between polylysine and PLL-g-PEG can be exploited: Microcontact printing polylysine onto a PLL-g-PEG coated glass substrate provides a simple means to produce microstructured networks of primary neurons that have superior pattern compliance during long term (>1 month) culture.

  17. Specification of excitatory neurons in the developing cerebral cortex: progenitor diversity and and environmental influences

    Directory of Open Access Journals (Sweden)

    Marcos R Costa

    2015-01-01

    Full Text Available The mature cerebral cortex harbors a heterogeneous population of glutamatergic neurons, organized into a highly intricate histological architecture. Classically, this mixed population of neurons was thought to be generated sequentially from a seemingly homogenous group of progenitors under the influence of external cues. This view, however, has been challenged in the last decade by evidences pointing to the existence of fate-restricted neuronal progenitors in the developing neocortex. Here, we review classical studies using cell transplantation, retroviral labeling and cell culture, as well as new data from genetic fate-mapping analysis, to discuss the lineage relationships between neocortical progenitors and subclasses of excitatory neurons. We also propose a temporal model to conciliate the existence of fate-restricted progenitors alongside multipotent progenitors in the neocortex. Finally, we discuss evidences for a critical period of plasticity among post mitotic excitatory cortical neurons when environmental influences could change neuronal cell fate.

  18. Radiation induces acute alterations in neuronal function.

    Directory of Open Access Journals (Sweden)

    Peter H Wu

    Full Text Available Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(ARs. These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.

  19. Representation of retrieval confidence by single neurons in the human medial temporal lobe

    Science.gov (United States)

    Rutishauser, Ueli; Ye, Shengxuan; Koroma, Matthieu; Tudusciuc, Oana; Ross, Ian B.; Chung, Jeffrey M.; Mamelak, Adam N.

    2015-01-01

    Memory-based decisions are often accompanied by an assessment of choice certainty, but the mechanisms of such confidence judgments remain unknown. We studied the response of 1065 individual neurons in the human hippocampus and amygdala while neurosurgical patients made memory retrieval decisions together with a confidence judgment. Combining behavioral, neuronal and computational analysis, we identified a population of memory-selective (MS) neurons whose activity signaled stimulus familiarity and confidence as assessed by subjective report. In contrast, the activity of visually selective (VS) neurons was not sensitive to memory strength. The groups further differed in response latency, tuning, and extracellular waveforms. The information provided by MS neurons was sufficient for a race model to decide stimulus familiarity and retrieval confidence. Together, this demonstrates a trial-by-trial relationship between a specific group of neurons and declared memory strength in humans. We suggest that VS and MS neurons are a substrate for declarative memories. PMID:26053402

  20. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.

    Science.gov (United States)

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J

    2016-06-23

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1-D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated.

  1. Artificial spatiotemporal touch inputs reveal complementary decoding in neocortical neurons.

    Science.gov (United States)

    Oddo, Calogero M; Mazzoni, Alberto; Spanne, Anton; Enander, Jonas M D; Mogensen, Hannes; Bengtsson, Fredrik; Camboni, Domenico; Micera, Silvestro; Jörntell, Henrik

    2017-04-04

    Investigations of the mechanisms of touch perception and decoding has been hampered by difficulties in achieving invariant patterns of skin sensor activation. To obtain reproducible spatiotemporal patterns of activation of sensory afferents, we used an artificial fingertip equipped with an array of neuromorphic sensors. The artificial fingertip was used to transduce real-world haptic stimuli into spatiotemporal patterns of spikes. These spike patterns were delivered to the skin afferents of the second digit of rats via an array of stimulation electrodes. Combined with low-noise intra- and extracellular recordings from neocortical neurons in vivo, this approach provided a previously inaccessible high resolution analysis of the representation of tactile information in the neocortical neuronal circuitry. The results indicate high information content in individual neurons and reveal multiple novel neuronal tactile coding features such as heterogeneous and complementary spatiotemporal input selectivity also between neighboring neurons. Such neuronal heterogeneity and complementariness can potentially support a very high decoding capacity in a limited population of neurons. Our results also indicate a potential neuroprosthetic approach to communicate with the brain at a very high resolution and provide a potential novel solution for evaluating the degree or state of neurological disease in animal models.

  2. Neuronal Reward and Decision Signals: From Theories to Data.

    Science.gov (United States)

    Schultz, Wolfram

    2015-07-01

    Rewards are crucial objects that induce learning, approach behavior, choices, and emotions. Whereas emotions are difficult to investigate in animals, the learning function is mediated by neuronal reward prediction error signals which implement basic constructs of reinforcement learning theory. These signals are found in dopamine neurons, which emit a global reward signal to striatum and frontal cortex, and in specific neurons in striatum, amygdala, and frontal cortex projecting to select neuronal populations. The approach and choice functions involve subjective value, which is objectively assessed by behavioral choices eliciting internal, subjective reward preferences. Utility is the formal mathematical characterization of subjective value and a prime decision variable in economic choice theory. It is coded as utility prediction error by phasic dopamine responses. Utility can incorporate various influences, including risk, delay, effort, and social interaction. Appropriate for formal decision mechanisms, rewards are coded as object value, action value, difference value, and chosen value by specific neurons. Although all reward, reinforcement, and decision variables are theoretical constructs, their neuronal signals constitute measurable physical implementations and as such confirm the validity of these concepts. The neuronal reward signals provide guidance for behavior while constraining the free will to act.

  3. Functional diversity and developmental changes in rat neuronal kainate receptors.

    Science.gov (United States)

    Wilding, T J; Huettner, J E

    2001-04-15

    1. Whole-cell currents evoked by kainate and the GluR5-selective agonist (RS)-2-amino-3-(3-hydroxy-5-tertbutylisoxazol-4-yl)propanoic acid (ATPA) were used to compare the physiological properties of kainate receptors expressed by neurons from rat hippocampus, spinal cord and dorsal root ganglia. 2. In contrast to kainate, which evoked desensitizing currents with similar decay rates and steady-state components in all three cell types, responses to ATPA were distinctly different in the three cell populations. Currents evoked by ATPA displayed a significant steady-state component in hippocampal neurons, but decayed rapidly to baseline in dorsal root ganglion (DRG) cells. ATPA failed to evoke current in many of the spinal neurons. 3. ATPA caused steady-state desensitization in DRG cells with an IC50 of 41 nM. Recovery from desensitization of DRG cell receptors by ATPA was significantly slower than for any previously described agonist. In contrast, hippocampal kainate receptors recovered from desensitization by ATPA within a few seconds. 4. Half-maximal activation of kainate receptors in hippocampal neurons required 938 nM ATPA. In DRG cells treated with concanavalin A the EC50 for ATPA was 341 nM. ATPA evoked current in embryonic hippocampal neurons but with lower amplitude relative to kainate than in cultured postnatal neurons. 5. Collectively, these results highlight functional differences between neuronal kainate receptors that may reflect their distinct subunit composition and their diverse roles in synaptic transmission.

  4. Neuronal Reward and Decision Signals: From Theories to Data

    Science.gov (United States)

    Schultz, Wolfram

    2015-01-01

    Rewards are crucial objects that induce learning, approach behavior, choices, and emotions. Whereas emotions are difficult to investigate in animals, the learning function is mediated by neuronal reward prediction error signals which implement basic constructs of reinforcement learning theory. These signals are found in dopamine neurons, which emit a global reward signal to striatum and frontal cortex, and in specific neurons in striatum, amygdala, and frontal cortex projecting to select neuronal populations. The approach and choice functions involve subjective value, which is objectively assessed by behavioral choices eliciting internal, subjective reward preferences. Utility is the formal mathematical characterization of subjective value and a prime decision variable in economic choice theory. It is coded as utility prediction error by phasic dopamine responses. Utility can incorporate various influences, including risk, delay, effort, and social interaction. Appropriate for formal decision mechanisms, rewards are coded as object value, action value, difference value, and chosen value by specific neurons. Although all reward, reinforcement, and decision variables are theoretical constructs, their neuronal signals constitute measurable physical implementations and as such confirm the validity of these concepts. The neuronal reward signals provide guidance for behavior while constraining the free will to act. PMID:26109341

  5. Variance and invariance of neuronal long-term representations

    Science.gov (United States)

    Clopath, Claudia; Bonhoeffer, Tobias; Hübener, Mark

    2017-01-01

    The brain extracts behaviourally relevant sensory input to produce appropriate motor output. On the one hand, our constantly changing environment requires this transformation to be plastic. On the other hand, plasticity is thought to be balanced by mechanisms ensuring constancy of neuronal representations in order to achieve stable behavioural performance. Yet, prominent changes in synaptic strength and connectivity also occur during normal sensory experience, indicating a certain degree of constitutive plasticity. This raises the question of how stable neuronal representations are on the population level and also on the single neuron level. Here, we review recent data from longitudinal electrophysiological and optical recordings of single-cell activity that assess the long-term stability of neuronal stimulus selectivities under conditions of constant sensory experience, during learning, and after reversible modification of sensory input. The emerging picture is that neuronal representations are stabilized by behavioural relevance and that the degree of long-term tuning stability and perturbation resistance directly relates to the functional role of the respective neurons, cell types and circuits. Using a ‘toy’ model, we show that stable baseline representations and precise recovery from perturbations in visual cortex could arise from a ‘backbone’ of strong recurrent connectivity between similarly tuned cells together with a small number of ‘anchor’ neurons exempt from plastic changes. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’. PMID:28093555

  6. Ion Channel Photoswitch Reveals Crosstalk between Intact and Injured Nociceptive Neurons after Nerve Injury

    OpenAIRE

    Herold, Christian

    2015-01-01

    The development of novel techniques utilizing the advantages of light has created an optical revolution for neuroscience research. Controlling and probing neuronal function with light has provided unprecedented insights by being able to manipulate many neurons simultaneously in intact circuits and living organisms.In my dissertation research, I used novel optical methods to probe the cellular permeability of sensory neuron populations. Primary nociceptive afferents detect, modulate and integr...

  7. Neurons controlling voluntary vocalization in the macaque ventral premotor cortex.

    Directory of Open Access Journals (Sweden)

    Gino Coudé

    Full Text Available The voluntary control of phonation is a crucial achievement in the evolution of speech. In humans, ventral premotor cortex (PMv and Broca's area are known to be involved in voluntary phonation. In contrast, no neurophysiological data are available about the role of the oro-facial sector of nonhuman primates PMv in this function. In order to address this issue, we recorded PMv neurons from two monkeys trained to emit coo-calls. Results showed that a population of motor neurons specifically fire during vocalization. About two thirds of them discharged before sound onset, while the remaining were time-locked with it. The response of vocalization-selective neurons was present only during conditioned (voluntary but not spontaneous (emotional sound emission. These data suggest that the control of vocal production exerted by PMv neurons constitutes a newly emerging property in the monkey lineage, shedding light on the evolution of phonation-based communication from a nonhuman primate species.

  8. Visualizing neuronal network connectivity with connectivity pattern tables

    Directory of Open Access Journals (Sweden)

    Eilen Nordlie

    2010-01-01

    Full Text Available Complex ideas are best conveyed through well-designed illustrations. Up to now, computational neuroscientists have mostly relied on box-and-arrow diagrams of even complex neuronal networks, often using ad hoc notations with conflicting use of symbols from paper to paper. This significantly impedes the communication of ideas in neuronal network modeling. We present here Connectivity Pattern Tables (CPTs as a clutter-free visualization of connectivity in large neuronal networks containing two-dimensional populations of neurons. CPTs can be generated automatically from the same script code used to create the actual network in the NEST simulator. Through aggregation, CPTs can be viewed at different levels, providing either full detail or summary information. We also provide the open source ConnPlotter tool as a means to create connectivity pattern tables.

  9. Magnetosensitive neurons mediate geomagnetic orientation in Caenorhabditis elegans.

    Science.gov (United States)

    Vidal-Gadea, Andrés; Ward, Kristi; Beron, Celia; Ghorashian, Navid; Gokce, Sertan; Russell, Joshua; Truong, Nicholas; Parikh, Adhishri; Gadea, Otilia; Ben-Yakar, Adela; Pierce-Shimomura, Jonathan

    2015-06-17

    Many organisms spanning from bacteria to mammals orient to the earth's magnetic field. For a few animals, central neurons responsive to earth-strength magnetic fields have been identified; however, magnetosensory neurons have yet to be identified in any animal. We show that the nematode Caenorhabditis elegans orients to the earth's magnetic field during vertical burrowing migrations. Well-fed worms migrated up, while starved worms migrated down. Populations isolated from around the world, migrated at angles to the magnetic vector that would optimize vertical translation in their native soil, with northern- and southern-hemisphere worms displaying opposite migratory preferences. Magnetic orientation and vertical migrations required the TAX-4 cyclic nucleotide-gated ion channel in the AFD sensory neuron pair. Calcium imaging showed that these neurons respond to magnetic fields even without synaptic input. C. elegans may have adapted magnetic orientation to simplify their vertical burrowing migration by reducing the orientation task from three dimensions to one.

  10. Firing behavior and network activity of single neurons in human epileptic hypothalamic hamartoma

    Directory of Open Access Journals (Sweden)

    Peter N. Steinmetz

    2013-12-01

    Full Text Available Objective: Human hypothalamic hamartomas (HH are intrinsically epileptogenic and are associated with treatment-resistant gelastic seizures. The basic cellular mechanisms responsible for seizure onset within HH are unknown. We used intra-operative microwire recordings of single neuron activity to measure the spontaneous firing rate of neurons and the degree of functional connection between neurons within the tumor.Technique: Fourteen patients underwent transventricular endoscopic resection of HH for treatment-resistant epilepsy. Prior to surgical resection, single neuron recordings from bundled microwires (total of 9 contacts were obtained from HH tissue. Spontaneous activity was recorded for two or three 5-minute epochs under steady-state general anesthesia. Off-line analysis included cluster analysis of single unit activity and probability analysis of firing relationships between pairs of neurons.Results: Altogether, 222 neurons were identified (mean 6 neurons per recording epoch. Cluster analysis of single neuron firing utilizing a mixture of Gaussians model identified two distinct populations on the basis of firing rate (median firing frequency 0.6 versus 15.0 spikes per second; p<10-5. Cluster analysis identified three populations determined by levels of burst-firing (median burst indices of 0.015, 0.18, and 0.39; p<10-15. Unbiased analysis of spontaneous single unit behavior showed that 51% of all possible neuron pairs within each recording epoch had a significant level of firing synchrony (p<10-15. The subgroup of neurons with higher median firing frequencies was more likely to demonstrate synchronous firing (p<10-7. Conclusions: HH tissue in-vivo contains neurons which fire spontaneously. The activity of single neurons is diverse but distributes into at least two electrophysiological phenoytpes. Functional linkage between single neurons suggests that HH neurons exist within local networks that may contribute to ictogenesis.

  11. Differential expression of voltage-gated K+ currents in medial septum/diagonal band complex neurons exhibiting distinct firing phenotypes

    OpenAIRE

    Garrido-Sanabria, Emilio R.; Perez-Cordova, Miriam G.; Colom, Luis V.

    2011-01-01

    The medial septum/diagonal band complex (MSDB) controls hippocampal excitability, rhythms and plastic processes. Medial septal neuronal populations display heterogeneous firing patterns. In addition, some of these populations degenerate during age-related disorders (e.g. cholinergic neurons). Thus, it is particularly important to examine the intrinsic properties of theses neurons in order to create new agents that effectively modulate hippocampal excitability and enhance memory processes. Her...

  12. Evidence for genetic influences on neurotransmitter content of identified neurones of Lymnaea stagnalis.

    Science.gov (United States)

    Audesirk, G; Audesirk, T; McCaman, R E; Ono, J K

    1985-01-01

    Neurotransmitter content was measured in two identified giant neurones in isogenic and wild-type populations of the freshwater pond snail Lymnaea stagnalis. The paired serotonergic cerebral giant neurones (LC1 and RC1) have higher transmitter levels and less variability in inbred animals than in wild-type animals. The transmitter content of the unpaired dopaminergic right pedal giant neurone (RPeD1) does not differ between inbred and wild-type animals in either level or variability. It is proposed that serotonin content of the cerebral giant neurones is under partial genetic control, and that animals of the wild-type population may possess a number of different alleles for the genes influencing serotonin levels. Inbreeding resulted in fixation of an allele promoting high serotonin levels. This particular wild-type population is probably already isogenic for genes influencing dopamine content in the right pedal giant neurone.

  13. Efficient induction of dopaminergic neuron differentiation from induced pluripotent stem cells reveals impaired mitophagy in PARK2 neurons.

    Science.gov (United States)

    Suzuki, Sadafumi; Akamatsu, Wado; Kisa, Fumihiko; Sone, Takefumi; Ishikawa, Kei-Ichi; Kuzumaki, Naoko; Katayama, Hiroyuki; Miyawaki, Atsushi; Hattori, Nobutaka; Okano, Hideyuki

    2017-01-29

    Patient-specific induced pluripotent stem cells (iPSCs) show promise for use as tools for in vitro modeling of Parkinson's disease. We sought to improve the efficiency of dopaminergic (DA) neuron induction from iPSCs by the using surface markers expressed in DA progenitors to increase the significance of the phenotypic analysis. By sorting for a CD184(high)/CD44(-) fraction during neural differentiation, we obtained a population of cells that were enriched in DA neuron precursor cells and achieved higher differentiation efficiencies than those obtained through the same protocol without sorting. This high efficiency method of DA neuronal induction enabled reliable detection of reactive oxygen species (ROS) accumulation and vulnerable phenotypes in PARK2 iPSCs-derived DA neurons. We additionally established a quantitative system using the mt-mKeima reporter system to monitor mitophagy in which mitochondria fuse with lysosomes and, by combining this system with the method of DA neuronal induction described above, determined that mitophagy is impaired in PARK2 neurons. These findings suggest that the efficiency of DA neuron induction is important for the precise detection of cellular phenotypes in modeling Parkinson's disease. Copyright © 2016. Published by Elsevier Inc.

  14. Huntingtin-Mediated Multipolar-Bipolar Transition of Newborn Cortical Neurons Is Critical for Their Postnatal Neuronal Morphology.

    Science.gov (United States)

    Barnat, Monia; Le Friec, Julien; Benstaali, Caroline; Humbert, Sandrine

    2017-01-04

    In the developing cortex, projection neurons undergo multipolar-bipolar transition, radial-directed migration, and maturation. The contribution of these developmental steps to the structure of the adult cortex is not completely understood. Here, we report that huntingtin (HTT), the protein mutated in Huntington's disease, is enriched in polarizing projection neurons. The depletion of HTT in postmitotic projection neurons leads to the mislocalization of layer-specific neuronal populations in the mouse neocortex. HTT is required for the multipolar-bipolar transition of projection neurons and for the maintenance of their bipolar shape during their radial migration. HTT mediates these effects in vivo through the regulation of RAB11-dependent N-Cadherin trafficking. Importantly, HD pathological HTT alters RAB11-dependent neuronal migration. Finally, we show that the cortical defects resulting from the postmitotic loss of HTT specifically during embryonic development affect neuronal morphology at adulthood. Our data reveal a new HTT-RAB11-N-Cadherin pathway regulating multipolar-bipolar transition with direct implications for mature brain. VIDEO ABSTRACT.

  15. Computational modeling of optogenetic neuronal excitation under complex illumination conditions using a Matlab-Neuron interface (Conference Presentation)

    Science.gov (United States)

    Yona, Guy; Weissler, Yonatan; Meitav, Nizan; Guzi, Eliran; Rifold, Dafna D.; Kahn, Itamar; Shoham, Shy

    2016-03-01

    Optogenetics has in recent years become a central tool in neuroscience research. Creating a realistic model of optogenetic neuronal excitation is of crucial importance for controlling the activation levels of various neuronal populations in different depths, predicting experimental results and designing the optical systems. However, current approaches to modeling light propagation through rodents' brain tissue suffer from major shortcomings and comprehensive modeling of local illumination levels together with other important factors governing excitation (i.e., cellular morphology, channel dynamics and expression), are still lacking. To address this challenge we introduce a new simulation tool for optogenetic neuronal excitation under complex and realistic illumination conditions that implements a detailed physical model for light scattering (in MATLAB) together with neuron morphology and channelrhodopsin-2 model (in NEURON). These two disparate simulation environments were interconnected using a newly developed generic interface termed 'NeuroLab'. Applying this method, we show that in a layer-V cortical neuron, the relative contribution of the apical dendrites to neuronal excitation is considerably greater than that of the soma or basal dendrites, when illuminated from the surface.

  16. Midbrain dopamine neurons associated with reward processing innervate the neurogenic subventricular zone.

    Science.gov (United States)

    Lennington, Jessica B; Pope, Sara; Goodheart, Anna E; Drozdowicz, Linda; Daniels, Stephen B; Salamone, John D; Conover, Joanne C

    2011-09-14

    Coordinated regulation of the adult neurogenic subventricular zone (SVZ) is accomplished by a myriad of intrinsic and extrinsic factors. The neurotransmitter dopamine is one regulatory molecule implicated in SVZ function. Nigrostriatal and ventral tegmental area (VTA) midbrain dopamine neurons innervate regions adjacent to the SVZ, and dopamine synapses are found on SVZ cells. Cell division within the SVZ is decreased in humans with Parkinson's disease and in animal models of Parkinson's disease following exposure to toxins that selectively remove nigrostriatal neurons, suggesting that dopamine is critical for SVZ function and nigrostriatal neurons are the main suppliers of SVZ dopamine. However, when we examined the aphakia mouse, which is deficient in nigrostriatal neurons, we found no detrimental effect to SVZ proliferation or organization. Instead, dopamine innervation of the SVZ tracked to neurons at the ventrolateral boundary of the VTA. This same dopaminergic neuron population also innervated the SVZ of control mice. Characterization of these neurons revealed expression of proteins indicative of VTA neurons. Furthermore, exposure to the neurotoxin MPTP depleted neurons in the ventrolateral VTA and resulted in decreased SVZ proliferation. Together, these results reveal that dopamine signaling in the SVZ originates from a population of midbrain neurons more typically associated with motivational and reward processing.

  17. Avalanches in a stochastic model of spiking neurons.

    Directory of Open Access Journals (Sweden)

    Marc Benayoun

    Full Text Available Neuronal avalanches are a form of spontaneous activity widely observed in cortical slices and other types of nervous tissue, both in vivo and in vitro. They are characterized by irregular, isolated population bursts when many neurons fire together, where the number of spikes per burst obeys a power law distribution. We simulate, using the Gillespie algorithm, a model of neuronal avalanches based on stochastic single neurons. The network consists of excitatory and inhibitory neurons, first with all-to-all connectivity and later with random sparse connectivity. Analyzing our model using the system size expansion, we show that the model obeys the standard Wilson-Cowan equations for large network sizes ( neurons. When excitation and inhibition are closely balanced, networks of thousands of neurons exhibit irregular synchronous activity, including the characteristic power law distribution of avalanche size. We show that these avalanches are due to the balanced network having weakly stable functionally feedforward dynamics, which amplifies some small fluctuations into the large population bursts. Balanced networks are thought to underlie a variety of observed network behaviours and have useful computational properties, such as responding quickly to changes in input. Thus, the appearance of avalanches in such functionally feedforward networks indicates that avalanches may be a simple consequence of a widely present network structure, when neuron dynamics are noisy. An important implication is that a network need not be "critical" for the production of avalanches, so experimentally observed power laws in burst size may be a signature of noisy functionally feedforward structure rather than of, for example, self-organized criticality.

  18. Avalanches in a stochastic model of spiking neurons.

    Science.gov (United States)

    Benayoun, Marc; Cowan, Jack D; van Drongelen, Wim; Wallace, Edward

    2010-07-08

    Neuronal avalanches are a form of spontaneous activity widely observed in cortical slices and other types of nervous tissue, both in vivo and in vitro. They are characterized by irregular, isolated population bursts when many neurons fire together, where the number of spikes per burst obeys a power law distribution. We simulate, using the Gillespie algorithm, a model of neuronal avalanches based on stochastic single neurons. The network consists of excitatory and inhibitory neurons, first with all-to-all connectivity and later with random sparse connectivity. Analyzing our model using the system size expansion, we show that the model obeys the standard Wilson-Cowan equations for large network sizes ( neurons). When excitation and inhibition are closely balanced, networks of thousands of neurons exhibit irregular synchronous activity, including the characteristic power law distribution of avalanche size. We show that these avalanches are due to the balanced network having weakly stable functionally feedforward dynamics, which amplifies some small fluctuations into the large population bursts. Balanced networks are thought to underlie a variety of observed network behaviours and have useful computational properties, such as responding quickly to changes in input. Thus, the appearance of avalanches in such functionally feedforward networks indicates that avalanches may be a simple consequence of a widely present network structure, when neuron dynamics are noisy. An important implication is that a network need not be "critical" for the production of avalanches, so experimentally observed power laws in burst size may be a signature of noisy functionally feedforward structure rather than of, for example, self-organized criticality.

  19. Vestibular convergence patterns in vestibular nuclei neurons of alert primates

    Science.gov (United States)

    Dickman, J. David; Angelaki, Dora E.

    2002-01-01

    Sensory signal convergence is a fundamental and important aspect of brain function. Such convergence may often involve complex multidimensional interactions as those proposed for the processing of otolith and semicircular canal (SCC) information for the detection of translational head movements and the effective discrimination from physically congruent gravity signals. In the present study, we have examined the responses of primate rostral vestibular nuclei (VN) neurons that do not exhibit any eye movement-related activity using 0.5-Hz translational and three-dimensional (3D) rotational motion. Three distinct neural populations were identified. Approximately one-fourth of the cells exclusively encoded rotational movements (canal-only neurons) and were unresponsive to translation. The canal-only central neurons encoded head rotation in SCC coordinates, exhibited little orthogonal canal convergence, and were characterized with significantly higher sensitivities to rotation as compared to primary SCC afferents. Another fourth of the neurons modulated their firing rates during translation (otolith-only cells). During rotations, these neurons only responded when the axis of rotation was earth-horizontal and the head was changing orientation relative to gravity. The remaining one-half of VN neurons were sensitive to both rotations and translations (otolith + canal neurons). Unlike primary otolith afferents, however, central neurons often exhibited significant spatiotemporal (noncosine) tuning properties and a wide variety of response dynamics to translation. To characterize the pattern of SCC inputs to otolith + canal neurons, their rotational maximum sensitivity vectors were computed using exclusively responses during earth-vertical axis rotations (EVA). Maximum sensitivity vectors were distributed throughout the 3D space, suggesting strong convergence from multiple SCCs. These neurons were also tested with earth-horizontal axis rotations (EHA), which would activate

  20. Interactions of neurons with topographic nano cues affect branching morphology mimicking neuron-neuron interactions.

    Science.gov (United States)

    Baranes, Koby; Kollmar, Davida; Chejanovsky, Nathan; Sharoni, Amos; Shefi, Orit

    2012-08-01

    We study the effect of topographic nano-cues on neuronal growth-morphology using invertebrate neurons in culture. We use photolithography to fabricate substrates with repeatable line-pattern ridges of nano-scale heights of 10-150 nm. We plate leech neurons atop the patterned-substrates and compare their growth pattern to neurons plated atop non-patterned substrates. The model system allows us the analysis of single neurite-single ridge interactions. The use of high resolution electron microscopy reveals small filopodia processes that attach to the line-pattern ridges. These fine processes, that cannot be detected in light microscopy, add anchoring sites onto the side of the ridges, thus additional physical support. These interactions of the neuronal process dominantly affect the neuronal growth direction. We analyze the response of the entire neuronal branching tree to the patterned substrates and find significant effect on the growth patterns compared to non-patterned substrates. Moreover, interactions with the nano-cues trigger a growth strategy similarly to interactions with other neuronal cells, as reflected in their morphometric parameters. The number of branches and the number of neurites originating from the soma decrease following the interaction demonstrating a tendency to a more simplified neuronal branching tree. The effect of the nano-cues on the neuronal function deserves further investigation and will strengthen our understanding of the interplay between function and form.

  1. Neurons of the dentate molecular layer in the rabbit hippocampus.

    Directory of Open Access Journals (Sweden)

    Francisco J Sancho-Bielsa

    Full Text Available The molecular layer of the dentate gyrus appears as the main entrance gate for information into the hippocampus, i.e., where the perforant path axons from the entorhinal cortex synapse onto the spines and dendrites of granule cells. A few dispersed neuronal somata appear intermingled in between and probably control the flow of information in this area. In rabbits, the number of neurons in the molecular layer increases in the first week of postnatal life and then stabilizes to appear permanent and heterogeneous over the individuals' life span, including old animals. By means of Golgi impregnations, NADPH histochemistry, immunocytochemical stainings and intracellular labelings (lucifer yellow and biocytin injections, eight neuronal morphological types have been detected in the molecular layer of developing adult and old rabbits. Six of them appear as interneurons displaying smooth dendrites and GABA immunoreactivity: those here called as globoid, vertical, small horizontal, large horizontal, inverted pyramidal and polymorphic. Additionally there are two GABA negative types: the sarmentous and ectopic granular neurons. The distribution of the somata and dendritic trees of these neurons shows preferences for a definite sublayer of the molecular layer: small horizontal, sarmentous and inverted pyramidal neurons are preferably found in the outer third of the molecular layer; vertical, globoid and polymorph neurons locate the intermediate third, while large horizontal and ectopic granular neurons occupy the inner third or the juxtagranular molecular layer. Our results reveal substantial differences in the morphology and electrophysiological behaviour between each neuronal archetype in the dentate molecular layer, allowing us to propose a new classification for this neural population.

  2. Neurons in Primary Motor Cortex Engaged During Action Observation

    Science.gov (United States)

    Dushanova, Juliana; Donoghue, John

    2010-01-01

    Neurons in higher cortical areas appear to become active during action observation, either by mirroring observed actions (termed mirror neurons) or by eliciting mental rehearsal of observed motor acts. We report the existence of neurons in primary motor cortex (MI) responding to viewed actions, an area generally considered to initiate and guide movement performance. Multielectrode recordings in monkeys performing or observing a well-learned step tracking task showed that approximately half of MI neurons, active when monkeys performed the task, were also active when they observed the action being performed by a human. These ‘view’ neurons were spatially intermingled with ‘do’ neurons, active only during movement performance. Simultaneously recorded, ‘view’ neurons comprised two groups: ∼38% retained the same preferred direction (PD) and timing during performance and viewing, while the remainder (62%) changed their PDs and time lag during viewing compared with performance. Nevertheless, population activity during viewing was sufficient to predict the direction and trajectory of viewed movements as action unfolded, although less accurately than during performance. ‘View’ neurons became less active and contained poorer representations of action when viewing only sub-components of the task. MI ‘view’ neurons thus appear to reflect the aspects of a learned movement when observed in others and form part of a broadly engaged set of cortical areas routinely responding to learned behaviors. These findings suggest that viewing a learned action elicits replay of aspects of MI activity needed to perform the observed action and could additionally reflect processing related to understanding, learning or mentally rehearsing action. PMID:20074212

  3. High-fidelity coding with correlated neurons.

    Directory of Open Access Journals (Sweden)

    Rava Azeredo da Silveira

    2014-11-01

    Full Text Available Positive correlations in the activity of neurons are widely observed in the brain. Previous studies have shown these correlations to be detrimental to the fidelity of population codes, or at best marginally favorable compared to independent codes. Here, we show that positive correlations can enhance coding performance by astronomical factors. Specifically, the probability of discrimination error can be suppressed by many orders of magnitude. Likewise, the number of stimuli encoded--the capacity--can be enhanced more than tenfold. These effects do not necessitate unrealistic correlation values, and can occur for populations with a few tens of neurons. We further show that both effects benefit from heterogeneity commonly seen in population activity. Error suppression and capacity enhancement rest upon a pattern of correlation. Tuning of one or several effective parameters can yield a limit of perfect coding: the corresponding pattern of positive correlation leads to a 'lock-in' of response probabilities that eliminates variability in the subspace relevant for stimulus discrimination. We discuss the nature of this pattern and we suggest experimental tests to identify it.

  4. Differentiation of Carbon Dioxide-Sensing Neurons in Caenorhabditis elegans Requires the ETS-5 Transcription Factor

    Science.gov (United States)

    Guillermin, Manon L.; Castelletto, Michelle L.; Hallem, Elissa A.

    2011-01-01

    Many animals sense environmental gases such as carbon dioxide and oxygen using specialized populations of gas-sensing neurons. The proper development and function of these neurons is critical for survival, as the inability to respond to changes in ambient carbon dioxide and oxygen levels can result in reduced neural activity and ultimately death. Despite the importance of gas-sensing neurons for survival, little is known about the developmental programs that underlie their formation. Here we identify the ETS-family transcription factor ETS-5 as critical for the normal differentiation of the carbon dioxide-sensing BAG neurons in Caenorhabditis elegans. Whereas wild-type animals show acute behavioral avoidance of carbon dioxide, ets-5 mutant animals do not respond to carbon dioxide. The ets-5 gene is expressed in BAG neurons and is required for the normal expression of the BAG neuron gene battery. ets-5 may also autoregulate its expression in BAG neurons. ets-5 is not required for BAG neuron formation, indicating that it is specifically involved in BAG neuron differentiation and the maintenance of BAG neuron cell fate. Our results demonstrate a novel role for ETS genes in the development and function of gas-detecting sensory neurons. PMID:21954162

  5. Social and asocial prefrontal cortex neurons: a new look at social facilitation and the social brain.

    Science.gov (United States)

    Demolliens, Marie; Isbaine, Faiçal; Takerkart, Sylvain; Huguet, Pascal; Boussaoud, Driss

    2017-08-01

    A fundamental aspect of behavior in many animal species is 'social facilitation', the positive effect of the mere presence of conspecifics on performance. To date, the neuronal counterpart of this ubiquitous phenomenon is unknown. We recorded the activity of single neurons from two prefrontal cortex regions, the dorsolateral part and the anterior cingulate cortex in monkeys as they performed a visuomotor task, either in the presence of a conspecific (Presence condition) or alone. Monkeys performed better in the presence condition than alone (social facilitation), and analyses of outcome-related activity of 342 prefrontal neurons revealed that most of them (86%) were sensitive to the performance context. Two populations of neurons were discovered: 'social neurons', preferentially active under social presence and 'asocial neurons', preferentially active under social isolation. The activity of these neurons correlated positively with performance only in their preferred context (social neurons under social presence; asocial neurons under social isolation), thereby providing a potential neuronal mechanism of social facilitation. More generally, the fact that identical tasks recruited either social or asocial neurons depending on the presence or absence of a conspecific also brings a new look at the social brain hypothesis. © The Author (2017). Published by Oxford University Press.

  6. The Specification and Maturation of Nociceptive Neurons from Human Embryonic Stem Cells.

    Science.gov (United States)

    Boisvert, Erin M; Engle, Sandra J; Hallowell, Shawn E; Liu, Ping; Wang, Zhao-Wen; Li, Xue-Jun

    2015-11-19

    Nociceptive neurons play an essential role in pain sensation by transmitting painful stimuli to the central nervous system. However, investigations of nociceptive neuron biology have been hampered by the lack of accessibility of human nociceptive neurons. Here, we describe a system for efficiently guiding human embryonic stem cells into nociceptive neurons by first inducing these cells to the neural lineage. Subsequent addition of retinoic acid and BMP4 at specific time points and concentrations yielded a high population of neural crest progenitor cells (AP2α(+), P75(+)), which further differentiated into nociceptive neurons (TRKA(+), Nav1.7(+), P2X3(+)). The overexpression of Neurogenin 1 (Neurog1) promoted the neurons to express genes related to sensory neurons (Peripherin, TrkA) and to further mature into TRPV1(+) nociceptive neurons. Importantly, the overexpression of Neurog1 increased the response of these neurons to capsaicin stimulation, a hallmark of mature functional nociceptive neurons. Taken together, this study reveals the important role that Neurog1 plays in generating functional human nociceptive neurons.

  7. STDP in recurrent neuronal networks

    Directory of Open Access Journals (Sweden)

    Matthieu Gilson

    2010-09-01

    Full Text Available Recent results about spike-timing-dependent plasticity (STDP in recurrently connected neurons are reviewed, with a focus on the relationship between the weight dynamics and the emergence of network structure. In particular, the evolution of synaptic weights in the two cases of incoming connections for a single neuron and recurrent connections are compared and contrasted. A theoretical framework is used that is based upon Poisson neurons with a temporally inhomogeneous firing rate and the asymptotic distribution of weights generated by the learning dynamics. Different network configurations examined in recent studies are discussed and an overview of the current understanding of STDP in recurrently connected neuronal networks is presented.

  8. The straintronic spin-neuron.

    Science.gov (United States)

    Biswas, Ayan K; Atulasimha, Jayasimha; Bandyopadhyay, Supriyo

    2015-07-17

    In artificial neural networks, neurons are usually implemented with highly dissipative CMOS-based operational amplifiers. A more energy-efficient implementation is a 'spin-neuron' realized with a magneto-tunneling junction (MTJ) that is switched with a spin-polarized current (representing weighted sum of input currents) that either delivers a spin transfer torque or induces domain wall motion in the soft layer of the MTJ to mimic neuron firing. Here, we propose and analyze a different type of spin-neuron in which the soft layer of the MTJ is switched with mechanical strain generated by a voltage (representing weighted sum of input voltages) and term it straintronic spin-neuron. It dissipates orders of magnitude less energy in threshold operations than the traditional current-driven spin neuron at 0 K temperature and may even be faster. We have also studied the room-temperature firing behaviors of both types of spin neurons and find that thermal noise degrades the performance of both types, but the current-driven type is degraded much more than the straintronic type if both are optimized for maximum energy-efficiency. On the other hand, if both are designed to have the same level of thermal degradation, then the current-driven version will dissipate orders of magnitude more energy than the straintronic version. Thus, the straintronic spin-neuron is superior to current-driven spin neurons.

  9. Overproduction of Upper-Layer Neurons in the Neocortex Leads to Autism-like Features in Mice

    Directory of Open Access Journals (Sweden)

    Wei-Qun Fang

    2014-12-01

    Full Text Available The functional integrity of the neocortex depends upon proper numbers of excitatory and inhibitory neurons; however, the consequences of dysregulated neuronal production during the development of the neocortex are unclear. As excess cortical neurons are linked to the neurodevelopmental disorder autism, we investigated whether the overproduction of neurons leads to neocortical malformation and malfunction in mice. We experimentally increased the number of pyramidal neurons in the upper neocortical layers by using the small molecule XAV939 to expand the intermediate progenitor population. The resultant overpopulation of neurons perturbs development of dendrites and spines of excitatory neurons and alters the laminar distribution of interneurons. Furthermore, these phenotypic changes are accompanied by dysregulated excitatory and inhibitory synaptic connection and balance. Importantly, these mice exhibit behavioral abnormalities resembling those of human autism. Thus, our findings collectively suggest a causal relationship between neuronal overproduction and autism-like features, providing developmental insights into the etiology of autism.

  10. Overproduction of upper-layer neurons in the neocortex leads to autism-like features in mice.

    Science.gov (United States)

    Fang, Wei-Qun; Chen, Wei-Wei; Jiang, Liwen; Liu, Kai; Yung, Wing-Ho; Fu, Amy K Y; Ip, Nancy Y

    2014-12-11

    The functional integrity of the neocortex depends upon proper numbers of excitatory and inhibitory neurons; however, the consequences of dysregulated neuronal production during the development of the neocortex are unclear. As excess cortical neurons are linked to the neurodevelopmental disorder autism, we investigated whether the overproduction of neurons leads to neocortical malformation and malfunction in mice. We experimentally increased the number of pyramidal neurons in the upper neocortical layers by using the small molecule XAV939 to expand the intermediate progenitor population. The resultant overpopulation of neurons perturbs development of dendrites and spines of excitatory neurons and alters the laminar distribution of interneurons. Furthermore, these phenotypic changes are accompanied by dysregulated excitatory and inhibitory synaptic connection and balance. Importantly, these mice exhibit behavioral abnormalities resembling those of human autism. Thus, our findings collectively suggest a causal relationship between neuronal overproduction and autism-like features, providing developmental insights into the etiology of autism.

  11. Primary Neuronal Precursors in Adult Crayfish Brain: Replenishment from a Non-neuronal Source

    Directory of Open Access Journals (Sweden)

    Sandeman David C

    2011-06-01

    Full Text Available Abstract Background Adult neurogenesis, the production and integration of new neurons into circuits in the brains of adult animals, is a common feature of a variety of organisms, ranging from insects and crustaceans to birds and mammals. In the mammalian brain the 1st-generation neuronal precursors, the astrocytic stem cells, reside in neurogenic niches and are reported to undergo self-renewing divisions, thereby providing a source of new neurons throughout an animal's life. In contrast, our work shows that the 1st-generation neuronal precursors in the crayfish (Procambarus clarkii brain, which also have glial properties and lie in a neurogenic niche resembling that of vertebrates, undergo geometrically symmetrical divisions and both daughters appear to migrate away from the niche. However, in spite of this continuous efflux of cells, the number of neuronal precursors in the crayfish niche continues to expand as the animals grow and age. Based on these observations we have hypothesized that (1 the neuronal stem cells in the crayfish brain are not self-renewing, and (2 a source external to the neurogenic niche must provide cells that replenish the stem cell pool. Results In the present study, we tested the first hypothesis using sequential double nucleoside labeling to track the fate of 1st- and 2nd-generation neuronal precursors, as well as testing the size of the labeled stem cell pool following increasing incubation times in 5-bromo-2'-deoxyuridine (BrdU. Our results indicate that the 1st-generation precursor cells in the crayfish brain, which are functionally analogous to neural stem cells in vertebrates, are not a self-renewing population. In addition, these studies establish the cycle time of these cells. In vitro studies examining the second hypothesis show that Cell Tracker™ Green-labeled cells extracted from the hemolymph, but not other tissues, are attracted to and incorporated into the neurogenic niche, a phenomenon that appears to

  12. Searching for Collective Behavior in a Large Network of Sensory Neurons: e1003408

    National Research Council Canada - National Science Library

    Gasper Tkacik; Olivier Marre; Dario Amodei; Elad Schneidman; William Bialek; Michael J Berry II

    2014-01-01

    .... Here we use this principle to construct probabilistic models which describe the correlated spiking activity of populations of up to 120 neurons in the salamander retina as it responds to natural movies...

  13. Searching for collective behavior in a large network of sensory neurons

    National Research Council Canada - National Science Library

    Tkačik, Gašper; Marre, Olivier; Amodei, Dario; Schneidman, Elad; Bialek, William; Berry, 2nd, Michael J

    2014-01-01

    .... Here we use this principle to construct probabilistic models which describe the correlated spiking activity of populations of up to 120 neurons in the salamander retina as it responds to natural movies...

  14. Evaluating the Role of Viral Proteins in HIV-Mediated Neurotoxicity Using Primary Human Neuronal Cultures.

    Science.gov (United States)

    Rao, Vasudev R; Eugenin, Eliseo A; Prasad, Vinayaka R

    2016-01-01

    Despite the inability of HIV-1 to infect neurons, over half of the HIV-1-infected population in the USA suffers from neurocognitive dysfunction. HIV-infected immune cells in the periphery enter the central nervous system by causing a breach in the blood-brain barrier. The damage to the neurons is mediated by viral and host toxic products released by activated and infected immune and glial cells. To evaluate the toxicity of any viral isolate, viral protein, or host inflammatory protein, we describe a protocol to assess the neuronal apoptosis and synaptic compromise in primary cultures of human neurons and astrocytes.

  15. Firing statistics and correlations in spiking neurons: a level-crossing approach.

    Science.gov (United States)

    Badel, Laurent

    2011-10-01

    We present a time-dependent level-crossing theory for linear dynamical systems perturbed by colored Gaussian noise. We apply these results to approximate the firing statistics of conductance-based integrate-and-fire neurons receiving excitatory and inhibitory Poissonian inputs. Analytical expressions are obtained for three key quantities characterizing the neuronal response to time-varying inputs: the mean firing rate, the linear response to sinusoidally modulated inputs, and the pairwise spike correlation for neurons receiving correlated inputs. The theory yields tractable results that are shown to accurately match numerical simulations and provides useful tools for the analysis of interconnected neuronal populations.

  16. Signal-to-noise-optimal scaling of heterogenous population codes.

    Science.gov (United States)

    Leibold, Christian

    2013-01-01

    Similarity measures for neuronal population responses that are based on scalar products can be little informative if the neurons have different firing statistics. Based on signal-to-noise optimality, this paper derives positive weighting factors for the individual neurons' response rates in a heterogeneous neuronal population. The weights only depend on empirical statistics. If firing follows Poisson statistics, the weights can be interpreted as mutual information per spike. The scaling is shown to improve linear separability and clustering as compared to unscaled inputs.

  17. Bilaminar co-culture of primary rat cortical neurons and glia.

    Science.gov (United States)

    Shimizu, Saori; Abt, Anna; Meucci, Olimpia

    2011-11-12

    cell lines do extend processes. A detailed protocol of culturing rat hippocampal neurons using this co-culture system has been described previously(4,12,13). Here we detail a modified protocol suited for cortical neurons. As approximately 20x10(6) cells are recovered from each rat embryo, this method is particularly useful for experiments requiring large numbers of neurons (but not concerned about a highly homogenous neuronal population). The preparation of neurons and glia needs to be planned in a time-specific manner. We will provide the step-by-step protocol for culturing rat cortical neurons as well as culturing glial cells to support the neurons.

  18. Neurones and neuropeptides in coelenterates

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Ebbesen, Ditte Graff; McFarlane, I D

    1989-01-01

    The first nervous system probably evolved in coelenterates. Many neurons in coelenterates have morphological characteristics of both sensory and motor neurones, and appear to be multifunctional. Using immunocytochemistry with antisera to the sequence Arg-Phe-NH2 (RFamide), RFamide-like peptides w...... that these neuropeptides play a role in neurotransmission....

  19. The Neuronal Ceroid-Lipofuscinoses

    Science.gov (United States)

    Bennett, Michael J.; Rakheja, Dinesh

    2013-01-01

    The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in…

  20. Cryopreservation of adherent neuronal networks.

    Science.gov (United States)

    Ma, Wu; O'Shaughnessy, Thomas; Chang, Eddie

    2006-07-31

    Neuronal networks have been widely used for neurophysiology, drug discovery and toxicity testing. An essential prerequisite for future widespread application of neuronal networks is the development of efficient cryopreservation protocols to facilitate their storage and transportation. Here is the first report on cryopreservation of mammalian adherent neuronal networks. Dissociated spinal cord cells were attached to a poly-d-lysine/laminin surface and allowed to form neuronal networks. Adherent neuronal networks were embedded in a thin film of collagen gel and loaded with trehalose prior to transfer to a freezing medium containing DMSO, FBS and culture medium. This was followed by a slow rate of cooling to -80 degrees C for 24 h and then storage for up to 2 months in liquid nitrogen at -196 degrees C. The three components: DMSO, collagen gel entrapment and trehalose loading combined provided the highest post-thaw viability, relative to individual or two component protocols. The post-thaw cells with this protocol demonstrated similar neuronal and astrocytic markers and morphological structure as those detected in unfrozen cells. Fluorescent dye FM1-43 staining revealed active recycling of synaptic vesicles upon depolarizing stimulation in the post-thaw neuronal networks. These results suggest that a combination of DMSO, collagen gel entrapment and trehalose loading can significantly improve conventional slow-cooling methods in cryopreservation of adherent neuronal networks.

  1. Central CRF neurons are not created equal: Phenotypic differences in CRF-containing neurons of the rat paraventricular hypothalamus and the bed nucleus of the stria terminalis.

    Directory of Open Access Journals (Sweden)

    Joanna eDabrowska

    2013-08-01

    Full Text Available Corticotrophin-releasing factor (CRF plays a key role in initiating many of the endocrine, autonomic, and behavioral responses to stress. CRF-containing neurons of the paraventricular nucleus of the hypothalamus (PVN are classically involved in regulating endocrine function through activation of the stress axis. However, CRF is also thought to play a critical role in mediating anxiety-like responses to environmental stressors, and dysfunction of the CRF system in extra-hypothalamic brain regions, like the bed nucleus of stria terminalis (BNST, has been linked to the etiology of many psychiatric disorders including anxiety and depression. Thus, although CRF neurons of the PVN and BNST share a common neuropeptide phenotype, they may represent two functionally diverse neuronal populations. Here, we employed dual-immunofluorescence, single-cell RT-PCR, and electrophysiological techniques to further examine this question and report that CRF neurons of the PVN and BNST are fundamentally different such that PVN CRF neurons are glutamatergic, whereas BNST CRF neurons are GABAergic. Moreover, these two neuronal populations can be further distinguished based on their electrophysiological properties, their co-expression of peptide neurotransmitters such as oxytocin and arginine-vasopressin, and their cognate receptors. Our results suggest that CRF neurons in the PVN and the BNST would not only differ in their response to local neurotransmitter release, but also in their action on downstream target structures.

  2. Control of REM sleep by ventral medulla GABAergic neurons.

    Science.gov (United States)

    Weber, Franz; Chung, Shinjae; Beier, Kevin T; Xu, Min; Luo, Liqun; Dan, Yang

    2015-10-15

    Rapid eye movement (REM) sleep is a distinct brain state characterized by activated electroencephalogram and complete skeletal muscle paralysis, and is associated with vivid dreams. Transection studies by Jouvet first demonstrated that the brainstem is both necessary and sufficient for REM sleep generation, and the neural circuits in the pons have since been studied extensively. The medulla also contains neurons that are active during REM sleep, but whether they play a causal role in REM sleep generation remains unclear. Here we show that a GABAergic (γ-aminobutyric-acid-releasing) pathway originating from the ventral medulla powerfully promotes REM sleep in mice. Optogenetic activation of ventral medulla GABAergic neurons rapidly and reliably initiated REM sleep episodes and prolonged their durations, whereas inactivating these neurons had the opposite effects. Optrode recordings from channelrhodopsin-2-tagged ventral medulla GABAergic neurons showed that they were most active during REM sleep (REMmax), and during wakefulness they were preferentially active during eating and grooming. Furthermore, dual retrograde tracing showed that the rostral projections to the pons and midbrain and caudal projections to the spinal cord originate from separate ventral medulla neuron populations. Activating the rostral GABAergic projections was sufficient for both the induction and maintenance of REM sleep, which are probably mediated in part by inhibition of REM-suppressing GABAergic neurons in the ventrolateral periaqueductal grey. These results identify a key component of the pontomedullary network controlling REM sleep. The capability to induce REM sleep on command may offer a powerful tool for investigating its functions.

  3. Bayesian Inference and Online Learning in Poisson Neuronal Networks.

    Science.gov (United States)

    Huang, Yanping; Rao, Rajesh P N

    2016-08-01

    Motivated by the growing evidence for Bayesian computation in the brain, we show how a two-layer recurrent network of Poisson neurons can perform both approximate Bayesian inference and learning for any hidden Markov model. The lower-layer sensory neurons receive noisy measurements of hidden world states. The higher-layer neurons infer a posterior distribution over world states via Bayesian inference from inputs generated by sensory neurons. We demonstrate how such a neuronal network with synaptic plasticity can implement a form of Bayesian inference similar to Monte Carlo methods such as particle filtering. Each spike in a higher-layer neuron represents a sample of a particular hidden world state. The spiking activity across the neural population approximates the posterior distribution over hidden states. In this model, variability in spiking is regarded not as a nuisance but as an integral feature that provides the variability necessary for sampling during inference. We demonstrate how the network can learn the likelihood model, as well as the transition probabilities underlying the dynamics, using a Hebbian learning rule. We present results illustrating the ability of the network to perform inference and learning for arbitrary hidden Markov models.

  4. Small is beautiful: models of small neuronal networks.

    Science.gov (United States)

    Lamb, Damon G; Calabrese, Ronald L

    2012-08-01

    Modeling has contributed a great deal to our understanding of how individual neurons and neuronal networks function. In this review, we focus on models of the small neuronal networks of invertebrates, especially rhythmically active CPG networks. Models have elucidated many aspects of these networks, from identifying key interacting membrane properties to pointing out gaps in our understanding, for example missing neurons. Even the complex CPGs of vertebrates, such as those that underlie respiration, have been reduced to small network models to great effect. Modeling of these networks spans from simplified models, which are amenable to mathematical analyses, to very complicated biophysical models. Some researchers have now adopted a population approach, where they generate and analyze many related models that differ in a few to several judiciously chosen free parameters; often these parameters show variability across animals and thus justify the approach. Models of small neuronal networks will continue to expand and refine our understanding of how neuronal networks in all animals program motor output, process sensory information and learn.

  5. Phenotypic checkpoints regulate neuronal development.

    Science.gov (United States)

    Ben-Ari, Yehezkel; Spitzer, Nicholas C

    2010-11-01

    Nervous system development proceeds by sequential gene expression mediated by cascades of transcription factors in parallel with sequences of patterned network activity driven by receptors and ion channels. These sequences are cell type- and developmental stage-dependent and modulated by paracrine actions of substances released by neurons and glia. How and to what extent these sequences interact to enable neuronal network development is not understood. Recent evidence demonstrates that CNS development requires intermediate stages of differentiation providing functional feedback that influences gene expression. We suggest that embryonic neuronal functions constitute a series of phenotypic checkpoint signatures; neurons failing to express these functions are delayed or developmentally arrested. Such checkpoints are likely to be a general feature of neuronal development and constitute presymptomatic signatures of neurological disorders when they go awry.

  6. Cell biology of neuronal endocytosis.

    Science.gov (United States)

    Parton, R G; Dotti, C G

    1993-09-01

    Endocytosis is the process by which cells take in fluid and components of the plasma membrane. In this way cells obtain nutrients and trophic factors, retrieve membrane proteins for degradation, and sample their environment. In neuronal cells endocytosis is essential for the recycling of membrane after neurotransmitter release and plays a critical role during early developmental stages. Moreover, alterations of the endocytic pathway have been attributed a crucial role in the pathophysiology of certain neurological diseases. Although well characterized at the ultrastructural level, little is known of the dynamics and molecular organization of the neuronal endocytic pathways. In this respect most of our knowledge comes from studies of non-neuronal cells. In this review we will examine the endocytic pathways in neurons from a cell biological viewpoint by making comparisons with non-neuronal cells and in particular with another polarized cell, the epithelial cell.

  7. The neuronal distribution of cannabinoid receptor type 1 in the trigeminal ganglion of the rat.

    Science.gov (United States)

    Price, T J; Helesic, G; Parghi, D; Hargreaves, K M; Flores, C M

    2003-01-01

    Cannabinoid compounds have been shown to produce antinociception and antihyperalgesia by acting upon cannabinoid receptors located in both the CNS and the periphery. A potential mechanism by which cannabinoids could inhibit nociception in the periphery is the activation of cannabinoid receptors located on one or more classes of primary nociceptive neurons. To address this hypothesis, we evaluated the neuronal distribution of cannabinoid receptor type 1 (CB1) in the trigeminal ganglion (TG) of the adult rat through combined in situ hybridization (ISH) and immunohistochemistry (IHC). CB1 receptor mRNA was localized mainly to medium and large diameter neurons of the maxillary and mandibular branches of the TG. Consistent with this distribution, in a de facto nociceptive sensory neuron population that exhibited vanilloid receptor type 1 immunoreactivity, colocalization with CB1 mRNA was also sparse (CB1 mRNA. In contrast, and consistent with the neuron-size distribution for CB1, nearly 75% of CB1-positive neurons exhibited N52-immunoreactivity, a marker of myelinated axons. These results indicate that in the rat TG, CB1 receptors are expressed predominantly in neurons that are not thought to subserve nociceptive neurotransmission in the noninjured animal. Taken together with the absence of an above background in situ signal for CB2 mRNA in TG neurons, these findings suggest that the peripherally mediated antinociceptive effects of cannabinoids may involve either as yet unidentified receptors or interaction with afferent neuron populations that normally subserve non-nociceptive functions.

  8. Dopaminergic Neurons Controlling Anterior Pituitary Functions: Anatomy and Ontogenesis in Zebrafish.

    Science.gov (United States)

    Fontaine, Romain; Affaticati, Pierre; Bureau, Charlotte; Colin, Ingrid; Demarque, Michaël; Dufour, Sylvie; Vernier, Philippe; Yamamoto, Kei; Pasqualini, Catherine

    2015-08-01

    Dopaminergic (DA) neurons located in the preoptico-hypothalamic region of the brain exert a major neuroendocrine control on reproduction, growth, and homeostasis by regulating the secretion of anterior pituitary (or adenohypophysis) hormones. Here, using a retrograde tract tracing experiment, we identified the neurons playing this role in the zebrafish. The DA cells projecting directly to the anterior pituitary are localized in the most anteroventral part of the preoptic area, and we named them preoptico-hypophyseal DA (POHDA) neurons. During development, these neurons do not appear before 72 hours postfertilization (hpf) and are the last dopaminergic cell group to differentiate. We found that the number of neurons in this cell population continues to increase throughout life proportionally to the growth of the fish. 5-Bromo-2'-deoxyuridine incorporation analysis suggested that this increase is due to continuous neurogenesis and not due to a phenotypic change in already-existing neurons. Finally, expression profiles of several genes (foxg1a, dlx2a, and nr4a2a/b) were different in the POHDA compared with the adjacent suprachiasmatic DA neurons, suggesting that POHDA neurons develop as a distinct DA cell population in the preoptic area. This study offers some insights into the regional identity of the preoptic area and provides the first bases for future functional genetic studies on the development of DA neurons controlling anterior pituitary functions.

  9. Disinhibition Bursting of Dopaminergic Neurons

    Directory of Open Access Journals (Sweden)

    Collin J Lobb

    2011-05-01

    Full Text Available Substantia nigra pars compacta (SNpc dopaminergic neurons receive strong tonic inputs from GABAergic neurons in the substantia nigra pars reticulata (SNpr and globus pallidus (GP, and glutamatergic neurons in the subthalamic nucleus. The presence of these tonic inputs raises the possibility that phasic disinhibition may trigger phasic bursts in dopaminergic neurons. We first applied constant NMDA and GABAA conductances onto a two-compartment single cell model of the dopaminergic neuron (Kuznetsov et al., 2006. The model exhibited disinhibition bursting upon stepwise removal of inhibition. A further bifurcation analysis suggests that disinhibition may be more robust than excitation alone in that for most levels of NMDA conductance, the cell remains capable of bursting even after a complete removal of inhibition, whereas too much excitatory input will drive the cell into depolarization block. To investigate the network dynamics of disinhibition, we used a modified version of an integrate-and-fire based model of the basal ganglia (Humphries et al., 2006. Synaptic activity generated in the network was delivered to the two-compartment single cell dopaminergic neuron. Phasic activation of the D1-expressing medium spiny neurons in the striatum (D1STR produced disinhibition bursts in dopaminergic neurons through the direct pathway (D1STR to SNpr to SNpc. Anatomical studies have shown that D1STR neurons have collaterals that terminate in GP. Adding these collaterals to the model, we found that striatal activation increased the intra-burst firing frequency of the disinhibition burst as the weight of this connection was increased. Our studies suggest that striatal activation is a robust means by which disinhibition bursts can be generated by SNpc dopaminergic neurons, and that recruitment of the indirect pathway via collaterals may enhance disinhibition bursting.

  10. Orexin neurons receive glycinergic innervations.

    Directory of Open Access Journals (Sweden)

    Mari Hondo

    Full Text Available Glycine, a nonessential amino-acid that acts as an inhibitory neurotransmitter in the central nervous system, is currently used as a dietary supplement to improve the quality of sleep, but its mechanism of action is poorly understood. We confirmed the effects of glycine on sleep/wakefulness behavior in mice when administered peripherally. Glycine administration increased non-rapid eye movement (NREM sleep time and decreased the amount and mean episode duration of wakefulness when administered in the dark period. Since peripheral administration of glycine induced fragmentation of sleep/wakefulness states, which is a characteristic of orexin deficiency, we examined the effects of glycine on orexin neurons. The number of Fos-positive orexin neurons markedly decreased after intraperitoneal administration of glycine to mice. To examine whether glycine acts directly on orexin neurons, we examined the effects of glycine on orexin neurons by patch-clamp electrophysiology. Glycine directly induced hyperpolarization and cessation of firing of orexin neurons. These responses were inhibited by a specific glycine receptor antagonist, strychnine. Triple-labeling immunofluorescent analysis showed close apposition of glycine transporter 2 (GlyT2-immunoreactive glycinergic fibers onto orexin-immunoreactive neurons. Immunoelectron microscopic analysis revealed that GlyT2-immunoreactive terminals made symmetrical synaptic contacts with somata and dendrites of orexin neurons. Double-labeling immunoelectron microscopy demonstrated that glycine receptor alpha subunits were localized in the postsynaptic membrane of symmetrical inhibitory synapses on orexin neurons. Considering the importance of glycinergic regulation during REM sleep, our observations suggest that glycine injection might affect the activity of orexin neurons, and that glycinergic inhibition of orexin neurons might play a role in physiological sleep regulation.

  11. Striatal medium-sized spiny neurons: identification by nuclear staining and study of neuronal subpopulations in BAC transgenic mice.

    Directory of Open Access Journals (Sweden)

    Miriam Matamales

    Full Text Available Precise identification of neuronal populations is a major challenge in neuroscience. In the striatum, more than 95% of neurons are GABAergic medium-sized spiny neurons (MSNs, which form two intermingled populations distinguished by their projections and protein content. Those expressing dopamine D(1-receptors (D1Rs project preferentially to the substantia nigra pars reticulata (SNr, whereas those expressing dopamine D(2- receptors (D2Rs project preferentially to the lateral part of the globus pallidus (LGP. The degree of segregation of these populations has been a continuous subject of debate, and the recent introduction of bacterial artificial chromosome (BAC transgenic mice expressing fluorescent proteins driven by specific promoters was a major progress to facilitate striatal neuron identification. However, the fraction of MSNs labeled in these mice has been recently called into question, casting doubt on the generality of results obtained with such approaches. Here, we performed an in-depth quantitative analysis of striatal neurons in drd1a-EGFP and drd2-EGFP mice. We first quantified neuronal and non-neuronal populations in the striatum, based on nuclear staining with TO-PRO-3, and immunolabeling for NeuN, DARPP-32 (dopamine- and cAMP-regulated phosphoprotein Mr approximately 32,000, and various markers for interneurons. TO-PRO-3 staining was sufficient to identify MSNs by their typical nuclear morphology and, with a good probability, interneuron populations. In drd1a-EGFP/drd2-EGFP double transgenic mice all MSNs expressed EGFP, which was driven in about half of them by drd1a promoter. Retrograde labeling showed that all MSNs projecting to the SNr expressed D1R and very few D2R (<1%. In contrast, our results were compatible with the existence of some D1R-EGFP-expressing fibers giving off terminals in the LGP. Thus, our study shows that nuclear staining is a simple method for identifying MSNs and other striatal neurons. It also

  12. Integration of human model neurons (NT2) into embryonic chick nervous system.

    Science.gov (United States)

    Podrygajlo, Grzegorz; Wiegreffe, Christoph; Scaal, Martin; Bicker, Gerd

    2010-02-01

    Postmitotic neurons were generated from the human NT2 teratocarcinoma cell line in a novel cell aggregate differentiation procedure. Approximately a third of the differentiated neurons expressed cell markers related to cholinergic neurotransmission. To examine whether this human cell model system can be directed toward a motoneuronal fate, postmitotic neurons were co-cultured with mouse myotubes. Outgrowing neuronal processes established close contact with the myotubes and formed neuromuscular junction-like structures that bound alpha-bungarotoxin. To determine how grafted precursor cells and neurons respond to embryonic nerve tissue, NT2 cells at different stages of neural development were injected into chick embryo neural tube and brain. Grafted NT2 neurons populated both parts of the nervous system, sometimes migrating away from the site of injection. The neural tube appeared to be more permissive for neurite extensions than the brain. Moreover, extending neurites of spinal grafts were approaching the ventral roots, thus resembling motoneuronal projections.

  13. Adult axolotls can regenerate original neuronal diversity in response to brain injury.

    Science.gov (United States)

    Amamoto, Ryoji; Huerta, Violeta Gisselle Lopez; Takahashi, Emi; Dai, Guangping; Grant, Aaron K; Fu, Zhanyan; Arlotta, Paola

    2016-05-09

    The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species.

  14. Transcriptional co-regulation of neuronal migration and laminar identity in the neocortex.

    Science.gov (United States)

    Kwan, Kenneth Y; Sestan, Nenad; Anton, E S

    2012-05-01

    The cerebral neocortex is segregated into six horizontal layers, each containing unique populations of molecularly and functionally distinct excitatory projection (pyramidal) neurons and inhibitory interneurons. Development of the neocortex requires the orchestrated execution of a series of crucial processes, including the migration of young neurons into appropriate positions within the nascent neocortex, and the acquisition of layer-specific neuronal identities and axonal projections. Here, we discuss emerging evidence supporting the notion that the migration and final laminar positioning of cortical neurons are also co-regulated by cell type- and layer-specific transcription factors that play concomitant roles in determining the molecular identity and axonal connectivity of these neurons. These transcriptional programs thus provide direct links between the mechanisms controlling the laminar position and identity of cortical neurons.

  15. Selective neuronal vulnerability to oxidative stress in the brain

    Directory of Open Access Journals (Sweden)

    Xinkun Wang

    2010-03-01

    Full Text Available Oxidative stress (OS, caused by the imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS, plays an important role in brain aging, neurodegenerative diseases, and other related adverse conditions, such as ischemia. While ROS/RNS serve as signaling molecules at physiological levels, an excessive amount of these molecules leads to oxidative modification and, therefore, dysfunction of proteins, nucleic acids, and lipids. The response of neurons to this pervasive stress, however, is not uniform in the brain. While many brain neurons can cope with a rise in OS, there are select populations of neurons in the brain that are vulnerable. Because of their selective vulnerability, these neurons are usually the first to exhibit functional decline and cell death during normal aging, or in age-associated neurodegenerative diseases, such as Alzheimer’s disease. Understanding the molecular and cellular mechanisms of selective neuronal vulnerability (SNV to OS is important in the development of future intervention approaches to protect such vulnerable neurons from the stresses of the aging process and the pathological states that lead to neurodegeneration. In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized. Included among the major underlying factors are high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons. The contribution to the selective vulnerability of neurons to OS by other intrinsic or extrinsic factors, such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity, are also discussed.

  16. Age-related loss of orexin/hypocretin neurons

    Science.gov (United States)

    Kessler, Brice A.; Stanley, Emily M.; Frederick-Duus, Danielle; Fadel, Jim

    2011-01-01

    Aging is associated with many physiological alterations—such as changes in sleep patterns, metabolism and food intake—suggestive of hypothalamic dysfunction, but the effects of senescence on specific hypothalamic nuclei and neuronal groups that mediate these alterations is unclear. The lateral hypothalamus and contiguous perifornical area (LH/PFA) contains several populations of neurons, including those that express the neuropeptides orexin (hypocretin) or melanin-concentrating hormone (MCH). Collectively, orexin and MCH neurons influence many integrative homeostatic processes related to wakefulness and energy balance. Here, we determined the effect of aging on numbers of orexin and MCH neurons in young adult (3–4 months) and old (26–28 months) Fisher 344/Brown Norway F1 hybrid rats. Aged rats exhibited a loss of greater than 40% of orexin-immunoreactive neurons in both the medial and lateral (relative to the fornix) sectors of the LH/PFA. MCH-immunoreactive neurons were also lost in aged rats, primarily in the medial LH/PFA. Neuronal loss in this area was not global as no change in cells immunoreactive for the pan-neuronal marker, NeuN, was observed in aged rats. Combined with other reports of altered receptor expression or behavioral responses to exogenously-administered neuropeptide, these data suggest that compromised orexin (and, perhaps, MCH) function is an important mediator of age-related homeostatic disturbances of hypothalamic origin. The orexin system may represent a crucial substrate linking homeostatic and cognitive dysfunction in aging, as well as a novel therapeutic target for pharmacological or genetic restoration approaches to preventing or ameliorating these disturbances. PMID:21262323

  17. Mechanosensory Neurons With Bend- and Osmo-sensitivity in Mouthpart Setae From the Spiny Lobster Panulirus argus

    DEFF Research Database (Denmark)

    Garm, Anders; Derby, Charles D; Høeg, Jens T

    2004-01-01

    The mouthparts of the spiny lobster Panulirus argus hold primarily two types of setae--simple setae and cuspidate setae. Mechanosensory neurons from these setae were examined by electrophysiological recordings. The population of simple setae contained two types of mechanosensory neurons: displace......The mouthparts of the spiny lobster Panulirus argus hold primarily two types of setae--simple setae and cuspidate setae. Mechanosensory neurons from these setae were examined by electrophysiological recordings. The population of simple setae contained two types of mechanosensory neurons...

  18. Neuronal coupling by endogenous electric fields: cable theory and applications to coincidence detector neurons in the auditory brain stem.

    Science.gov (United States)

    Goldwyn, Joshua H; Rinzel, John

    2016-04-01

    The ongoing activity of neurons generates a spatially and time-varying field of extracellular voltage (Ve). This Ve field reflects population-level neural activity, but does it modulate neural dynamics and the function of neural circuits? We provide a cable theory framework to study how a bundle of model neurons generates Ve and how this Ve feeds back and influences membrane potential (Vm). We find that these "ephaptic interactions" are small but not negligible. The model neural population can generate Ve with millivolt-scale amplitude, and this Ve perturbs the Vm of "nearby" cables and effectively increases their electrotonic length. After using passive cable theory to systematically study ephaptic coupling, we explore a test case: the medial superior olive (MSO) in the auditory brain stem. The MSO is a possible locus of ephaptic interactions: sounds evoke large (millivolt scale)Vein vivo in this nucleus. The Ve response is thought to be generated by MSO neurons that perform a known neuronal computation with submillisecond temporal precision (coincidence detection to encode sound source location). Using a biophysically based model of MSO neurons, we find millivolt-scale ephaptic interactions consistent with the passive cable theory results. These subtle membrane potential perturbations induce changes in spike initiation threshold, spike time synchrony, and time difference sensitivity. These results suggest that ephaptic coupling may influence MSO function.

  19. Amygdalar auditory neurons contribute to self-other distinction during ultrasonic social vocalization in rats

    Directory of Open Access Journals (Sweden)

    Jumpei Matsumoto

    2016-09-01

    Full Text Available Although clinical studies reported hyperactivation of the auditory system and amygdala in patients with auditory hallucinations (hearing others’ but not one’s own voice, independent of any external stimulus, neural mechanisms of self/other attribution is not well understood. We recorded neuronal responses in the dorsal amygdala including the lateral amygdaloid nucleus to ultrasonic vocalization (USVs emitted by subjects and conspecifics during free social interaction in 16 adult male rats. The animals emitting the USVs were identified by EMG recordings. One-quarter of the amygdalar neurons (15/60 responded to 50 kHz calls by the subject and/or conspecifics. Among the responsive neurons, most neurons (Type-Other neurons (73%, 11/15 responded only to calls by conspecifics but not subjects. Two Type-Self neurons (13%, 2/15 responded to calls by the subject but not those by conspecifics, although their response selectivity to subjects vs. conspecifics was lower than that of Type-Other neurons. The remaining two neurons (13% responded to calls by both the subject and conspecifics. Furthermore, population coding of the amygdalar neurons represented distinction of subject vs. conspecific calls. The present results provide the first neurophysiological evidence that the amygdala discriminately represents affective social calls by subject and conspecifics. These findings suggest that the amygdala is an important brain region for self/other attribution. Furthermore, pathological activation of the amygdala, where Type-Other neurons predominate, could induce external misattribution of percepts of vocalization.

  20. Identification of preoptic sleep neurons using retrograde labelling and gene profiling.

    Science.gov (United States)

    Chung, Shinjae; Weber, Franz; Zhong, Peng; Tan, Chan Lek; Nguyen, Thuc Nghi; Beier, Kevin T; Hörmann, Nikolai; Chang, Wei-Cheng; Zhang, Zhe; Do, Johnny Phong; Yao, Shenqin; Krashes, Michael J; Tasic, Bosiljka; Cetin, Ali; Zeng, Hongkui; Knight, Zachary A; Luo, Liqun; Dan, Yang

    2017-05-25

    In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep. However, the sleep-active neurons are spatially intermingled with wake-active neurons, making it difficult to target the sleep neurons specifically for circuit analysis. Here we identify a population of preoptic area sleep neurons on the basis of their projection target and discover their molecular markers. Using a lentivirus expressing channelrhodopsin-2 or a light-activated chloride channel for retrograde labelling, bidirectional optogenetic manipulation, and optrode recording, we show that the preoptic area GABAergic neurons projecting to the tuberomammillary nucleus are both sleep active and sleep promoting. Furthermore, translating ribosome affinity purification and single-cell RNA sequencing identify candidate markers for these neurons, and optogenetic and pharmacogenetic manipulations demonstrate that several peptide markers (cholecystokinin, corticotropin-releasing hormone, and tachykinin 1) label sleep-promoting neurons. Together, these findings provide easy genetic access to sleep-promoting preoptic area neurons and a valuable entry point for dissecting the sleep control circuit.

  1. Encoding of High Frequencies Improves with Maturation of Action Potential Generation in Cultured Neocortical Neurons

    Science.gov (United States)

    Nikitin, Evgeny S.; Bal, Natalia V.; Malyshev, Aleksey; Ierusalimsky, Victor N.; Spivak, Yulia; Balaban, Pavel M.; Volgushev, Maxim

    2017-01-01

    The ability of neocortical neurons to detect and encode rapid changes at their inputs is crucial for basic neuronal computations, such as coincidence detection, precise synchronization of activity and spike-timing dependent plasticity. Indeed, populations of cortical neurons can respond to subtle changes of the input very fast, on a millisecond time scale. Theoretical studies and model simulations linked the encoding abilities of neuronal populations to the fast onset dynamics of action potentials (APs). Experimental results support this idea, however mechanisms of fast onset of APs in cortical neurons remain elusive. Studies in neuronal cultures, that are allowing for accurate control over conditions of growth and microenvironment during the development of neurons and provide better access to the spike initiation zone, may help to shed light on mechanisms of AP generation and encoding. Here we characterize properties of AP encoding in neocortical neurons grown for 11–25 days in culture. We show that encoding of high frequencies improves upon culture maturation, which is accompanied by the development of passive electrophysiological properties and AP generation. The onset of APs becomes faster with culture maturation. Statistical analysis using correlations and linear model approaches identified the onset dynamics of APs as a major predictor of age-dependent changes of encoding. Encoding of high frequencies strongly correlated also with the input resistance of neurons. Finally, we show that maturation of encoding properties of neurons in cultures is similar to the maturation of encoding in neurons studied in slices. These results show that maturation of AP generators and encoding is, to a large extent, determined genetically and takes place even without normal micro-environment and activity of the whole brain in vivo. This establishes neuronal cultures as a valid experimental model for studying mechanisms of AP generation and encoding, and their maturation. PMID

  2. Feed-forward and feedback projections of midbrain reticular formation neurons in the cat

    Directory of Open Access Journals (Sweden)

    Eddie ePerkins

    2014-01-01

    Full Text Available Gaze changes involving the eyes and head are orchestrated by brainstem gaze centers found within the superior colliculus (SC, paramedian pontine reticular formation (PPRF, and medullary reticular formation (MdRF. The mesencephalic reticular formation (MRF also plays a role in gaze. It receives a major input from the ipsilateral SC and contains cells that fire in relation to gaze changes. Moreover, it provides a feedback projection to the SC and feed-forward projections to the PPRF and MdRF. We sought to determine whether these MRF feedback and feed-forward projections originate from the same or different neuronal populations by utilizing paired fluorescent retrograde tracers in cats. Specifically, we tested: 1. whether MRF neurons that control eye movements form a single population by injecting the SC and PPRF with different tracers, and 2. whether MRF neurons that control head movements form a single population by injecting the SC and MdRF with different tracers. In neither case were double labeled neurons observed, indicating that feedback and feed-forward projections originate from separate MRF populations. In both cases, the labeled reticulotectal and reticuloreticular neurons were distributed bilaterally in the MRF. However, neurons projecting to the MdRF were generally constrained to the medial half of the MRF, while those projecting to the PPRF, like MRF reticulotectal neurons, were spread throughout the mediolateral axis. Thus, the medial MRF may be specialized for control of head movements, with control of eye movements being more widespread in this structure.

  3. Pathogenesis of motor neuron disease

    Institute of Scientific and Technical Information of China (English)

    Xuefei Wang

    2006-01-01

    OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease.DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of "neurodegenerative diseases". Other literatures were collected by retrieving specific journals and articles.STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded.DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded.DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor,injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages.CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms,comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.

  4. Salsolinol modulation of dopamine neurons

    Directory of Open Access Journals (Sweden)

    Guiqin eXie

    2013-05-01

    Full Text Available Salsolinol, a tetrahydroisoquinoline present in the human and rat brains, is the condensation product of dopamine and acetaldehyde, the first metabolite of ethanol. Previous evidence obtained in vivo links salsolinol with the mesolimbic dopaminergic system: salsolinol is self-administered into the posterior of the ventral tegmental area (pVTA of rats; intra-VTA administration of salsolinol induces a strong conditional place preference and increases dopamine release in the nucleus accumbens. However, the underlying neuronal mechanisms are unclear. Here we present an overview of some of the recent research on this topic. Electrophysiological studies reveal that dopaminergic neurons in the posterior ventral tegmental area (pVTA are a target of salsolinol. In acute brain slices from rats, salsolinol increases the excitability and accelerates the ongoing firing of dopamine neurons in the pVTA. Intriguingly, this action of salsolinol involves multiple pre- and post-synaptic mechanisms, including: (a depolarizing the membrane potential of dopamine neurons; (b activating mu opioid receptors on the GABAergic inputs to dopamine neurons, which decreases GABAergic activity and dopamine neurons are disinhibited; and (c enhancing presynaptic glutamatergic transmission onto dopamine neurons via activation of dopamine type 1 receptors, probably situated on the glutamatergic terminals. These novel mechanisms may contribute to the rewarding/reinforcing properties of salsolinol observed in vivo.

  5. Time and dose dependent effects of oxidative stress induced by cumene hydroperoxide in neuronal excitability of rat motor cortex neurons.

    Science.gov (United States)

    Pardillo-Díaz, R; Carrascal, L; Muñoz, M F; Ayala, A; Nunez-Abades, P

    2016-03-01

    It has been claimed that oxidative stress and the production of reactive oxygen radicals can contribute to neuron degeneration and might be one factor in the development of different neurological diseases. In our study, we have attempted to clarify how oxidative damage induces dose dependent changes in functional membrane properties of neurons by means of whole cell patch clamp techniques in brain slices from young adult rats. Our research demonstrates physiological changes in membrane properties of pyramidal motor cortex neurons exposed to 3 concentrations of cumene hydroperoxide (CH; 1, 10 and 100μM) during 30min. Results show that oxidative stress induced by CH evokes important changes, in a concentration and time dependent manner, in the neuronal excitability of motor cortex neurons of the rat: (i) Low concentration of the drug (1μM) already blocks inward rectifications (sag) and decreases action potential amplitude and gain, a drug concentration which has no effects on other neuronal populations, (ii) 10μM of CH depresses the excitability of pyramidal motor cortex neurons by decreasing input resistance, amplitude of the action potential, and gain and maximum frequency of the repetitive firing discharge, and (iii) 100μM completely blocks the capability to produce repetitive discharge of action potentials in all cells. Both larger drug concentrations and/or longer times of exposure to CH narrow the current working range. This happens because of the increase in the rheobase, and the reduction of the cancelation current. The effects caused by oxidative stress, including those produced by the level of lipid peroxidation, are practically irreversible and, this, therefore, indicates that neuroprotective agents should be administered at the first symptoms of alterations to membrane properties. In fact, the pre-treatment with melatonin, acting as an antioxidant, prevented the lipid peroxidation and the physiological changes induced by CH. Larger cells (as estimated

  6. Spatial determinants of multisensory integration in cat superior colliculus neurons.

    Science.gov (United States)

    Meredith, M A; Stein, B E

    1996-05-01

    1. Although a representation of multisensory space is contained in the superior colliculus, little is known about the spatial requirements of multisensory stimuli that influence the activity of neurons here. Critical to this problem is an assessment of the registry of the different receptive fields within individual multisensory neurons. The present study was initiated to determine how closely the receptive fields of individual multisensory neurons are aligned, the physiological role of that alignment, and the possible functional consequences of inducing receptive-field misalignment. 2. Individual multisensory neurons in the superior colliculus of anesthetized, paralyzed cats were studied with the use of standard extracellular recording techniques. The receptive fields of multisensory neurons were large, as reported previously, but exhibited a surprisingly high degree of spatial coincidence. The average proportion of receptive-field overlap was 86% for the population of visual-auditory neurons sampled. 3. Because of this high degree of intersensory receptive-field correspondence, combined-modality stimuli that were coincident in space tended to fall within the excitatory regions of the receptive fields involved. The result was a significantly enhanced neuronal response in 88% of the multisensory neurons studied. If stimuli were spatially disparate, so that one fell outside its receptive field, either a decreased response occurred (56%), or no intersensory effect was apparent (44%). 4. The normal alignment of the different receptive fields of a multisensory neuron could be disrupted by passively displacing the eyes, pinnae, or limbs/body. In no case was a shift in location or size observed in a neuron's other receptive field(s) to compensate for this displacement. The physiological result of receptive-field misalignment was predictable and based on the location of the stimuli relative to the new positions of their respective receptive fields. Now, for example, one

  7. A Neuron Model for FPGA Spiking Neuronal Network Implementation

    Directory of Open Access Journals (Sweden)

    BONTEANU, G.

    2011-11-01

    Full Text Available We propose a neuron model, able to reproduce the basic elements of the neuronal dynamics, optimized for digital implementation of Spiking Neural Networks. Its architecture is structured in two major blocks, a datapath and a control unit. The datapath consists of a membrane potential circuit, which emulates the neuronal dynamics at the soma level, and a synaptic circuit used to update the synaptic weight according to the spike timing dependent plasticity (STDP mechanism. The proposed model is implemented into a Cyclone II-Altera FPGA device. Our results indicate the neuron model can be used to build up 1K Spiking Neural Networks on reconfigurable logic suport, to explore various network topologies.

  8. Single neuron dynamics and computation.

    Science.gov (United States)

    Brunel, Nicolas; Hakim, Vincent; Richardson, Magnus J E

    2014-04-01

    At the single neuron level, information processing involves the transformation of input spike trains into an appropriate output spike train. Building upon the classical view of a neuron as a threshold device, models have been developed in recent years that take into account the diverse electrophysiological make-up of neurons and accurately describe their input-output relations. Here, we review these recent advances and survey the computational roles that they have uncovered for various electrophysiological properties, for dendritic arbor anatomy as well as for short-term synaptic plasticity.

  9. Nonsulfated cholecystokinins in cerebral neurons

    DEFF Research Database (Denmark)

    Agersnap, Mikkel; Zhang, Ming-Dong; Harkany, Tibor

    2016-01-01

    Cholecystokinin (CCK) is a widely expressed neuropeptide system originally discovered in the gut. Both cerebral and peripheral neurons as well as endocrine I-cells in the small intestine process proCCK to tyrosyl-O-sulfated and α-carboxyamidated peptides. Recently, we reported that gut endocrine I...... for nonsulfated CCK-8 with an antibody recognizing both sulfated and nonsulfated CCK. However, nonsulfated CCK immunoreactivity was stronger than that of sulfated CCK in cell bodies and weaker in nerve terminals. We conclude that only a small fraction of neuronal CCK is nonsulfated. The intracellular distribution...... of nonsulfated CCK in neurons suggests that they contribute only modestly to the CCK transmitter activity....

  10. Neuronal activity in the preoptic hypothalamus during sleep deprivation and recovery sleep.

    Science.gov (United States)

    Alam, Md Aftab; Kumar, Sunil; McGinty, Dennis; Alam, Md Noor; Szymusiak, Ronald

    2014-01-01

    The preoptic hypothalamus is implicated in sleep regulation. Neurons in the median preoptic nucleus (MnPO) and the ventrolateral preoptic area (VLPO) have been identified as potential sleep regulatory elements. However, the extent to which MnPO and VLPO neurons are activated in response to changing homeostatic sleep regulatory demands is unresolved. To address this question, we continuously recorded the extracellular activity of neurons in the rat MnPO, VLPO and dorsal lateral preoptic area (LPO) during baseline sleep and waking, during 2 h of sleep deprivation (SD) and during 2 h of recovery sleep (RS). Sleep-active neurons in the MnPO (n = 11) and VLPO (n = 13) were activated in response to SD, such that waking discharge rates increased by 95.8 ± 29.5% and 59.4 ± 17.3%, respectively, above waking baseline values. During RS, non-rapid eye movement (REM) sleep discharge rates of MnPO neurons initially increased to 65.6 ± 15.2% above baseline values, then declined to baseline levels in association with decreases in EEG delta power. Increase in non-REM sleep discharge rates in VLPO neurons during RS averaged 40.5 ± 7.6% above baseline. REM-active neurons (n = 16) in the LPO also exhibited increased waking discharge during SD and an increase in non-REM discharge during RS. Infusion of A2A adenosine receptor antagonist into the VLPO attenuated SD-induced increases in neuronal discharge. Populations of LPO wake/REM-active and state-indifferent neurons and dorsal LPO sleep-active neurons were unresponsive to SD. These findings support the hypothesis that sleep-active neurons in the MnPO and VLPO, and REM-active neurons in the LPO, are components of neuronal circuits that mediate homeostatic responses to sustained wakefulness.

  11. Corticotropin-releasing factor enhances locomotion and medullary neuronal firing in an amphibian.

    Science.gov (United States)

    Lowry, C A; Rose, J D; Moore, F L

    1996-03-01

    Corticotropin-releasing factor (CRF) administration has been shown to act centrally to enhance locomotion in rats and amphibians. In the present study we used an amphibian, the roughskin newt (Taricha granulosa), to characterize changes in medullary neuronal activity associated with CRF-induced walking and swimming in animals chronically implanted with fine-wire microelectrodes. Neuronal activity was recorded from the raphe and adjacent reticular region of the rostral medulla. Under baseline conditions most of the recorded neurons showed low to moderate amounts of neuronal activity during periods of immobility and pronounced increases in firing that were time-locked with episodes of walking. These neurons sometimes showed further increases in discharge during swimming. Injections of CRF but not saline into the lateral ventricle produced a rapidly appearing increase in walking and pronounced changes (mostly increases) in firing rates of the medullary neurons. CRF produced diverse changes in patterns of firing in different neurons, but for these neurons as a group, the effects of CRF showed a close temporal association with the onset and expression of the peptide's effect on locomotion. In neurons that were active exclusively during movement prior to CRF treatment, the post-CRF increase in firing was evident during episodes of walking; in other neurons that also were spontaneously active during immobility prior to CRF infusion, post-CRF activity changes were evident during immobility as well as during episodes of locomotion. Thus, a principal effect of CRF was to potentiate the level of neuronal firing in a population of medullary neurons with locomotor-related properties. Due to the route of administration CRF may have acted on multiple central nervous system sites to enhance locomotion, but the results are consistent with neurophysiological effects involving medullary locomotion-regulating neurons.

  12. Chronic alterations in monoaminergic cells in the locus coeruleus in orexin neuron-ablated narcoleptic mice.

    Directory of Open Access Journals (Sweden)

    Natsuko Tsujino

    Full Text Available Narcolepsy patients often suffer from insomnia in addition to excessive daytime sleepiness. Narcoleptic animals also show behavioral instability characterized by frequent transitions between all vigilance states, exhibiting very short bouts of NREM sleep as well as wakefulness. The instability of wakefulness states in narcolepsy is thought to be due to deficiency of orexins, neuropeptides produced in the lateral hypothalamic neurons, which play a highly important role in maintaining wakefulness. However, the mechanism responsible for sleep instability in this disorder remains to be elucidated. Because firing of orexin neurons ceases during sleep in healthy animals, deficiency of orexins does not explain the abnormality of sleep. We hypothesized that chronic compensatory changes in the neurophysiologica activity of the locus coeruleus (LC and dorsal raphe (DR nucleus in response to the progressive loss of endogenous orexin tone underlie the pathological regulation of sleep/wake states. To evaluate this hypothesis, we examined firing patterns of serotonergic (5-HT neurons and noradrenergic (NA neurons in the brain stem, two important neuronal populations in the regulation of sleep/wakefulness states. We recorded single-unit activities of 5-HT neurons and NA neurons in the DR nucleus and LC of orexin neuron-ablated narcoleptic mice. We found that while the firing pattern of 5-HT neurons in narcoleptic mice was similar to that in wildtype mice, that of NA neurons was significantly different from that in wildtype mice. In narcoleptic mice, NA neurons showed a higher firing frequency during both wakefulness and NREM sleep as compared with wildtype mice. In vitro patch-clamp study of NA neurons of narcoleptic mice suggested a functional decrease of GABAergic input to these neurons. These alterations might play roles in the sleep abnormality in narcolepsy.

  13. A 'tool box' for deciphering neuronal circuits in the developing chick spinal cord.

    Science.gov (United States)

    Hadas, Yoav; Etlin, Alex; Falk, Haya; Avraham, Oshri; Kobiler, Oren; Panet, Amos; Lev-Tov, Aharon; Klar, Avihu

    2014-10-29

    The genetic dissection of spinal circuits is an essential new means for understanding the neural basis of mammalian behavior. Molecular targeting of specific neuronal populations, a key instrument in the genetic dissection of neuronal circuits in the mouse model, is a complex and time-demanding process. Here we present a circuit-deciphering 'tool box' for fast, reliable and cheap genetic targeting of neuronal circuits in the developing spinal cord of the chick. We demonstrate targeting of motoneurons and spinal interneurons, mapping of axonal trajectories and synaptic targeting in both single and populations of spinal interneurons, and viral vector-mediated labeling of pre-motoneurons. We also demonstrate fluorescent imaging of the activity pattern of defined spinal neurons during rhythmic motor behavior, and assess the role of channel rhodopsin-targeted population of interneurons in rhythmic behavior using specific photoactivation.

  14. Tinbergen on mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2014-01-01

    Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology-the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible 'best explanation' for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of 'survival value', should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding-or another social cognitive function-by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories.

  15. Neuronal intestinal dysplasia.

    Science.gov (United States)

    Rintala, R; Rapola, J; Louhimo, I

    1989-01-01

    A series of 21 patients with NID is presented. A histologic and histochemical picture of NID was seen in an heterogenous group of patients. NID was associated with bowel obstruction and/or perforation in six neonates and infants. One neonate died. During follow-up the bowel histology gradually normalized in four of the five patients. NID was found incidentally in four patients with anorectal malformations and two with Hirschsprung's disease. Three patients with Hirschsprung's disease and associated NID had chronic proctitis; one patient with an anorectal anomaly had chronic obstipation and megacolon and one proctitis. Two children with multiple endocrine neoplasia 2b syndrome and chronic obstipation had typical NID in their rectum biopsies, as did a 50-year-old woman with CIIP. The clinical heterogeneity of patients with NID suggests that NID may not be a distinct clinical entity but rather a reaction of the neuronal network of the bowel wall and could be caused either by congenital or secondary factors.

  16. Glycine immunoreactivity of multipolar neurons in the ventral cochlear nucleus which project to the dorsal cochlear nucleus.

    Science.gov (United States)

    Doucet, J R; Ross, A T; Gillespie, M B; Ryugo, D K

    1999-06-14

    Certain distinct populations of neurons in the dorsal cochlear nucleus are inhibited by a neural source that is responsive to a wide range of acoustic frequencies. In this study, we examined the glycine immunoreactivity of two types of ventral cochlear nucleus neurons (planar and radiate) in the rat which project to the dorsal cochlear nucleus (DCN) and thus, might be responsible for this inhibition. Previously, we proposed that planar neurons provided a tonotopic and narrowly tuned input to the DCN, whereas radiate neurons provided a broadly tuned input and thus, were strong candidates as the source of broadband inhibition (Doucet and Ryugo [1997] J. Comp. Neurol. 385:245-264). We tested this idea by combining retrograde labeling and glycine immunohistochemical protocols. Planar and radiate neurons were first retrogradely labeled by injecting biotinylated dextran amine into a restricted region of the dorsal cochlear nucleus. The labeled cells were visualized using streptavidin conjugated to indocarbocyanine (Cy3), a fluorescent marker. Sections that contained planar or radiate neurons were then processed for glycine immunocytochemistry using diaminobenzidine as the chromogen. Immunostaining of planar neurons was light, comparable to that of excitatory neurons (pyramidal neurons in the DCN), whereas immunostaining of radiate neurons was dark, comparable to that of glycinergic neurons (cartwheel cells in the dorsal cochlear nucleus and principal cells in the medial nucleus of the trapezoid body). These results are consistent with the hypothesis that radiate neurons in the ventral cochlear nucleus subserve the wideband inhibition observed in the dorsal cochlear nucleus.

  17. Gene expression profile of neuronal progenitor cells derived from hESCs: activation of chromosome 11p15.5 and comparison to human dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    William J Freed

    Full Text Available BACKGROUND: We initiated differentiation of human embryonic stem cells (hESCs into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription. METHODOLOGY: Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS. Individual genes as well as regions of the genome which were activated were determined. PRINCIPAL FINDINGS: A number of genes known to be involved in the specification of dopaminergic neurons, including MSX1, CDKN1C, Pitx1 and Pitx2, as well as several novel genes not previously associated with dopaminergic differentiation, were expressed. Notably, we found that a specific region of the genome located on chromosome 11p15.5 was highly activated. This region contains several genes which have previously been associated with the function of dopaminergic neurons, including the gene for tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis, IGF2, and CDKN1C, which cooperates with Nurr1 in directing the differentiation of dopaminergic neurons. Other genes in this region not previously recognized as being involved in the functions of dopaminergic neurons were also activated, including H19, TSSC4, and HBG2. IGF2 and CDKN1C were also found to be highly expressed in mature human TH-positive dopamine neurons isolated from human brain samples by laser capture. CONCLUSIONS: The present data suggest that the H19-IGF2 imprinting region on chromosome 11p15.5 is involved in the process through which undifferentiated cells are specified to become neuronal precursors and/or dopaminergic neurons.

  18. Neuronal boost to evolutionary dynamics.

    Science.gov (United States)

    de Vladar, Harold P; Szathmáry, Eörs

    2015-12-06

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild.

  19. Neuronal boost to evolutionary dynamics

    Science.gov (United States)

    de Vladar, Harold P.; Szathmáry, Eörs

    2015-01-01

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild. PMID:26640653

  20. Modeling neuronal vulnerability in ALS.

    Science.gov (United States)

    Roselli, Francesco; Caroni, Pico

    2014-08-20

    Using computational models of motor neuron ion fluxes, firing properties, and energy requirements, Le Masson et al. (2014) reveal how local imbalances in energy homeostasis may self-amplify and contribute to neurodegeneration in ALS.

  1. Distinct forms of synaptic inhibition and neuromodulation regulate calretinin-positive neuron excitability in the spinal cord dorsal horn.

    Science.gov (United States)

    Smith, K M; Boyle, K A; Mustapa, M; Jobling, P; Callister, R J; Hughes, D I; Graham, B A

    2016-06-21

    The dorsal horn (DH) of the spinal cord contains a heterogenous population of neurons that process incoming sensory signals before information ascends to the brain. We have recently characterized calretinin-expressing (CR+) neurons in the DH and shown that they can be divided into excitatory and inhibitory subpopulations. The excitatory population receives high-frequency excitatory synaptic input and expresses delayed firing action potential discharge, whereas the inhibitory population receives weak excitatory drive and exhibits tonic or initial bursting discharge. Here, we characterize inhibitory synaptic input and neuromodulation in the two CR+ populations, in order to determine how each is regulated. We show that excitatory CR+ neurons receive mixed inhibition from GABAergic and glycinergic sources, whereas inhibitory CR+ neurons receive inhibition, which is dominated by glycine. Noradrenaline and serotonin produced robust outward currents in excitatory CR+ neurons, predicting an inhibitory action on these neurons, but neither neuromodulator produced a response in CR+ inhibitory neurons. In contrast, enkephalin (along with selective mu and delta opioid receptor agonists) produced outward currents in inhibitory CR+ neurons, consistent with an inhibitory action but did not affect the excitatory CR+ population. Our findings show that the pharmacology of inhibitory inputs and neuromodulator actions on CR+ cells, along with their excitatory inputs can define these two subpopulations further, and this could be exploited to modulate discrete aspects of sensory processing selectively in the DH.

  2. Neuronal circuits and computations: pattern decorrelation in the olfactory bulb.

    Science.gov (United States)

    Friedrich, Rainer W; Wiechert, Martin T

    2014-08-01

    Neuronal circuits in the olfactory bulb transform odor-evoked activity patterns across the input channels, the olfactory glomeruli, into distributed activity patterns across the output neurons, the mitral cells. One computation associated with this transformation is a decorrelation of activity patterns representing similar odors. Such a decorrelation has various benefits for the classification and storage of information by associative networks in higher brain areas. Experimental results from adult zebrafish show that pattern decorrelation involves a redistribution of activity across the population of mitral cells. These observations imply that pattern decorrelation cannot be explained by a global scaling mechanism but that it depends on interactions between distinct subsets of neurons in the network. This article reviews insights into the network mechanism underlying pattern decorrelation and discusses recent results that link pattern decorrelation in the olfactory bulb to odor discrimination behavior.

  3. A novel subset of enteric neurons revealed by ptf1a:GFP in the developing zebrafish enteric nervous system.

    Science.gov (United States)

    Uribe, Rosa A; Gu, Tiffany; Bronner, Marianne E

    2016-03-01

    The enteric nervous system, the largest division of the peripheral nervous system, is derived from vagal neural crest cells that invade and populate the entire length of the gut to form diverse neuronal subtypes. Here, we identify a novel population of neurons within the enteric nervous system of zebrafish larvae that express the transgenic marker ptf1a:GFP within the midgut. Genetic lineage analysis reveals that enteric ptf1a:GFP(+) cells are derived from the neural crest and that most ptf1a:GFP(+) neurons express the neurotransmitter 5HT, demonstrating that they are serotonergic. This transgenic line, Tg(ptf1a:GFP), provides a novel neuronal marker for a subpopulation of neurons within the enteric nervous system, and highlights the possibility that Ptf1a may act as an important transcription factor for enteric neuron development.

  4. Neuronal Atrophy Early in Degenerative Ataxia Is a Compensatory Mechanism to Regulate Membrane Excitability.

    Science.gov (United States)

    Dell'Orco, James M; Wasserman, Aaron H; Chopra, Ravi; Ingram, Melissa A C; Hu, Yuan-Shih; Singh, Vikrant; Wulff, Heike; Opal, Puneet; Orr, Harry T; Shakkottai, Vikram G

    2015-08-12

    Neuronal atrophy in neurodegenerative diseases is commonly viewed as an early event in a continuum that ultimately results in neuronal loss. In a mouse model of the polyglutamine disorder spinocerebellar ataxia type 1 (SCA1), we tested the hypothesis that cerebellar Purkinje neuron atrophy serves an adaptive role rather than being simply a nonspecific response to injury. In acute cerebellar slices from SCA1 mice, we find that Purkinje neuron pacemaker firing is initially normal but, with the onset of motor dysfunction, becomes disrupted, accompanied by abnormal depolarization. Remarkably, subsequent Purkinje cell atrophy is associated with a restoration of pacemaker firing. The early inability of Purkinje neurons to support repetitive spiking is due to unopposed calcium currents resulting from a reduction in large-conductance calcium-activated potassium (BK) and subthreshold-activated potassium channels. The subsequent restoration of SCA1 Purkinje neuron firing correlates with the recovery of the density of these potassium channels that accompanies cell atrophy. Supporting a critical role for BK channels, viral-mediated increases in BK channel expression in SCA1 Purkinje neurons improves motor dysfunction and partially restores Purkinje neuron morphology. Cerebellar perfusion of flufenamic acid, an agent that restores the depolarized membrane potential of SCA1 Purkinje neurons by activating potassium channels, prevents Purkinje neuron dendritic atrophy. These results suggest that Purkinje neuron dendritic remodeling in ataxia is an adaptive response to increases in intrinsic membrane excitability. Similar adaptive remodeling could apply to other vulnerable neuronal populations in neurodegenerative disease. In neurodegenerative disease, neuronal atrophy has long been assumed to be an early nonspecific event preceding neuronal loss. However, in a mouse model of spinocerebellar ataxia type 1 (SCA1), we identify a previously unappreciated compensatory role for neuronal

  5. High yield derivation of enriched glutamatergic neurons from suspension-cultured mouse ESCs for neurotoxicology research

    Directory of Open Access Journals (Sweden)

    Hubbard Kyle S

    2012-10-01

    Full Text Available Abstract Background Recently, there has been a strong emphasis on identifying an in vitro model for neurotoxicity research that combines the biological relevance of primary neurons with the scalability, reproducibility and genetic tractability of continuous cell lines. Derived neurons should be homotypic, exhibit neuron-specific gene expression and morphology, form functioning synapses and consistently respond to neurotoxins in a fashion indistinguishable from primary neurons. However, efficient methods to produce neuronal populations that are suitable alternatives to primary neurons have not been available. Methods With the objective of developing a more facile, robust and efficient method to generate enriched glutamatergic neuronal cultures, we evaluated the neurogenic capacity of three mouse embryonic stem cell (ESC lines (R1, C57BL/6 and D3 adapted to feeder-independent suspension culture. Neurogenesis and neuronal maturation were characterized as a function of time in culture using immunological, genomic, morphological and functional metrics. The functional responses of ESNs to neurotropic toxins with distinctly different targets and mechanisms of toxicity, such as glutamate, α-latrotoxin (LTX, and botulinum neurotoxin (BoNT, were also evaluated. Results Suspension-adapted ESCs expressed markers of pluripotency through at least 30 passages, and differentiation produced 97×106 neural progenitor cells (NPCs per 10-cm dish. Greater than 99% of embryonic stem cell-derived neurons (ESNs expressed neuron-specific markers by 96 h after plating and rapidly developed complex axodendritic arbors and appropriate compartmentalization of neurotypic proteins. Expression profiling demonstrated the presence of transcripts necessary for neuronal function and confirmed that ESN populations were predominantly glutamatergic. Furthermore, ESNs were functionally receptive to all toxins with sensitivities and responses consistent with primary neurons

  6. Is realistic neuronal modeling realistic?

    Science.gov (United States)

    Almog, Mara; Korngreen, Alon

    2016-11-01

    Scientific models are abstractions that aim to explain natural phenomena. A successful model shows how a complex phenomenon arises from relatively simple principles while preserving major physical or biological rules and predicting novel experiments. A model should not be a facsimile of reality; it is an aid for understanding it. Contrary to this basic premise, with the 21st century has come a surge in computational efforts to model biological processes in great detail. Here we discuss the oxymoronic, realistic modeling of single neurons. This rapidly advancing field is driven by the discovery that some neurons don't merely sum their inputs and fire if the sum exceeds some threshold. Thus researchers have asked what are the computational abilities of single neurons and attempted to give answers using realistic models. We briefly review the state of the art of compartmental modeling highlighting recent progress and intrinsic flaws. We then attempt to address two fundamental questions. Practically, can we realistically model single neurons? Philosophically, should we realistically model single neurons? We use layer 5 neocortical pyramidal neurons as a test case to examine these issues. We subject three publically available models of layer 5 pyramidal neurons to three simple computational challenges. Based on their performance and a partial survey of published models, we conclude that current compartmental models are ad hoc, unrealistic models functioning poorly once they are stretched beyond the specific problems for which they were designed. We then attempt to plot possible paths for generating realistic single neuron models. Copyright © 2016 the American Physiological Society.

  7. Unique aspects of transcriptional regulation in neurons – nuances in NFκB and Sp1-related factors

    Directory of Open Access Journals (Sweden)

    Chen Yuzhi

    2009-05-01

    Full Text Available Abstract The unique physiology and function of neurons create differences in their cellular physiology, including their regulation of gene expression. We began several years ago exploring the relationships between the NFκB transcription factor, neuronal survival, and glutamate receptor activation in telencephalic neurons. These studies led us to conclude that this population of cells is nearly incapable of activating the NFκB that is nonetheless expressed at reasonable levels. A subset of the κB cis elements are instead bound by members of the Sp1 family in neurons. Also surprising was our discovery that Sp1 itself, typically described as ubiquitous, is severely restricted in expression within forebrain neurons; Sp4 seems to be substituted during neuronal differentiation. These findings and their implications for neuronal differentiation – as well as potential dedifferentiation during degenerative processes – are discussed here.

  8. [Some characteristics of vertigo in vestibular neuronitis].

    Science.gov (United States)

    Skliut, I A; Likhachev, S A; Rybina, O V

    2004-01-01

    The authors present a detailed clinical analysis of objective neurological symptoms and vertigo in patients with vestibular neuronitis. Diagnostic criteria are specified allowing differentiation between vertigo and dizziness, pathognomonic signs of vestibular neuronitis are outlined. Peripheral location of the pathological process in vestibular neuronitis is suggested. How rotating vertigo is forming in patients with vestibular neuronitis is hypothesized.

  9. The relationships between neurons containing dopamine and nitric oxide synthase in the ventral tegmental area.

    Directory of Open Access Journals (Sweden)

    S Wójcik

    2004-07-01

    Full Text Available Ventral tegmental area (VTA is a heterogeneous group of dopaminergic cells which contains interfascicular (IF, parabrachial (PBP and rostral linear (RLi nuclei. Neurons of this area are involved in the regulation of motor and motivational aspects of behavior and reveal high neuronal plasticity. Among many various neurotransmitters and neuromodulators, nitric oxide (NO is localized in this region. In the present study, we investigated morphology and distribution of nitric oxide synthase (NOS-positive neurons in VTA and their colocalization with dopaminergic neurons. The study was performed on six adult Wistar rats. After perfusional fixation, the brains were cut, immunostained for tyrosine hydroxylase (TH and NOS and studied by confocal laser microscopy. In each of the three studied nuclei of VTA we investigated three different neuronal populations. Numerous TH-immunoreactive (TH-ir and NOS-immunoreactive (NOS-ir neurons are present in the studied region. Among them, a considerable number showed coexistence of both neurotransmitters. The populations of TH-ir and NOS-ir neurons interact with each other as manifested by the presence of NOS-ir endings on TH-ir neurons and vice versa. Taking the above into account, it may be suspected that NO is involved in the modulation of dopaminergic transmission.

  10. Specific expression of channelrhodopsin-2 in single neurons of Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Cornelia Schmitt

    Full Text Available Optogenetic approaches using light-activated proteins like Channelrhodopsin-2 (ChR2 enable investigating the function of populations of neurons in live Caenorhabditis elegans (and other animals, as ChR2 expression can be targeted to these cells using specific promoters. Sub-populations of these neurons, or even single cells, can be further addressed by restricting the illumination to the cell of interest. However, this is technically demanding, particularly in free moving animals. Thus, it would be helpful if expression of ChR2 could be restricted to single neurons or neuron pairs, as even wide-field illumination would photostimulate only this particular cell. To this end we adopted the use of Cre or FLP recombinases and conditional ChR2 expression at the intersection of two promoter expression domains, i.e. in the cell of interest only. Success of this method depends on precise knowledge of the individual promoters' expression patterns and on relative expression levels of recombinase and ChR2. A bicistronic expression cassette with GFP helps to identify the correct expression pattern. Here we show specific expression in the AVA reverse command neurons and the aversive polymodal sensory ASH neurons. This approach shall enable to generate strains for optogenetic manipulation of each of the 302 C. elegans neurons. This may eventually allow to model the C. elegans nervous system in its entirety, based on functional data for each neuron.

  11. Postembryonic neuronal addition in Zebrafish dorsal root ganglia is regulated by Notch signaling

    Directory of Open Access Journals (Sweden)

    McGraw Hillary

    2012-06-01

    Full Text Available Abstract Background The sensory neurons and glia of the dorsal root ganglia (DRG arise from neural crest cells in the developing vertebrate embryo. In mouse and chick, DRG formation is completed during embryogenesis. In contrast, zebrafish continue to add neurons and glia to the DRG into adulthood, long after neural crest migration is complete. The molecular and cellular regulation of late DRG growth in the zebrafish remains to be characterized. Results In the present study, we use transgenic zebrafish lines to examine neuronal addition during postembryonic DRG growth. Neuronal addition is continuous over the period of larval development. Fate-mapping experiments support the hypothesis that new neurons are added from a population of resident, neural crest-derived progenitor cells. Conditional inhibition of Notch signaling was used to assess the role of this signaling pathway in neuronal addition. An increase in the number of DRG neurons is seen when Notch signaling is inhibited during both early and late larval development. Conclusions Postembryonic growth of the zebrafish DRG comes about, in part, by addition of new neurons from a resident progenitor population, a process regulated by Notch signaling.

  12. Cerebral neurons underlying prey capture movements in the pteropod mollusc, Clione limacina. II. Afterdischarges.

    Science.gov (United States)

    Norekian, T P

    1993-03-01

    The pteropod mollusc Clione limacina is a highly specialized carnivore which feeds on shelled pteropods and uses, for their capture, three pairs of oral appendages, called buccal cones. Contact with the prey induces rapid eversion of buccal cones, which then become tentacle-like and grasp the shell of the prey. In the previous paper, a large group of electrically coupled, normally silent cells (A motoneurons) has been described in the cerebral ganglia of Clione. Activation of A neurons induces opening of oral skin folds and extrusion of the buccal cones. The present study continues the analysis of the electrical properties of A motoneurons. Brief intracellular stimulation of an A neuron can produce prolonged firing (afterdischarge), lasting up to 40 s, in the entire population of A neurons. After-discharge activity is based on an afterdepolarization evoked by an initial strong burst of A neuron spikes. The data suggest that this afterdepolarization represents excitatory synaptic input from unidentified neurons which in turn receive excitatory inputs from A neurons, thus organizing positive feedback. The main functional role of this positive feedback is the spread and synchronization of spike activity among all A neurons in the population. In addition, it serves to transform a brief excitatory input to A neurons into their prolonged and stable firing, which is required during certain phases of feeding behavior in Clione.

  13. More sensitivity of cortical GABAergic neurons than glutamatergic neurons in response to acidosis.

    Science.gov (United States)

    Liu, Hua; Li, Fang; Wang, Chunyan; Su, Zhiqiang

    2016-05-25

    Acidosis impairs brain functions. Neuron-specific mechanisms underlying acidosis-induced brain dysfunction remain elusive. We studied the sensitivity of cortical GABAergic neurons and glutamatergic neurons to acidosis by whole-cell recording in brain slices. The acidification to the neurons was induced by perfusing artificial cerebral spinal fluid with lower pH. This acidification impairs excitability and synaptic transmission in the glutamatergic and GABAergic neurons. Acidosis impairs spiking capacity in the GABAergic neurons more than in the glutamatergic neurons. Acidosis also strengthens glutamatergic synaptic transmission and attenuates GABAergic synaptic transmission on the GABAergic neurons more than the glutamatergic neurons, which results in the functional impairment of these GABAergic neurons. This acidosis-induced dysfunction predominantly in the cortical GABAergic neurons drives the homeostasis of neuronal networks toward overexcitation and exacerbates neuronal impairment.

  14. Neurones in the adult rat anterior medullary velum.

    Science.gov (United States)

    Ibrahim, M; Menoud, P A; Celio, M R

    2000-03-27

    The presence of neurones in the rat anterior medullary velum (AMV) has been investigated by using antibodies to the calcium-binding proteins, parvalbumin (PV), calretinin (CR), and calbindin-D28k (CB). Disparate populations of mainly GABAergic neurones were located in the rostral and caudal regions of the AMV. The rostral region of the AMV was characterised by GABAergic CR-labelled or PV-labelled neurones. CR-labelled neurones were bipolar or multipolar with round to ovoid somata (diameters between 8 and 12 microm), and rostrocaudally running dendrites forming a network. PV-labelled neurones had round somata (diameters between 6 and 10 microm) and were bi-tufted, with beaded dendrites. Both CR-labelled and PV-labelled dendrites formed punctate pericellular associations with unlabelled somatic profiles. In the caudal region of the AMV, PV-labelled neurones were GABAergic, multipolar cells, having round somata (diameters between 9 and 12 microm), with either beaded or nonbeaded dendrites forming a network of interconnecting dendrites. PV-labelled pericellular associations were made around both PV-labelled and unlabelled somatic profiles. CR labelled unipolar brush cells (UBCs) were not GABAergic. UBCs were characterised by a round to oval somata (10-15 microm in diameter) from which a single primary dendrite emerged to form a distal expansion having small terminal dendrites. From the distal expansion, there also appeared to be CR-labelled processes emanating and extending for up to 250 microm. CB occasionally labelled "Purkinje-like cells" (PLCs). The rat AMV is a more complex structure than first envisaged with the presence of predominantly inhibitory neurones expressing different calcium-binding proteins. Functional and anatomic aspects of this circuitry are further discussed.

  15. KNDy Neurons Modulate the Magnitude of the Steroid-Induced Luteinizing Hormone Surges in Ovariectomized Rats.

    Science.gov (United States)

    Helena, Cleyde V; Toporikova, Natalia; Kalil, Bruna; Stathopoulos, Andrea M; Pogrebna, Veronika V; Carolino, Ruither O; Anselmo-Franci, Janete A; Bertram, Richard

    2015-11-01

    Kisspeptin is the most potent stimulator of LH release. There are two kisspeptin neuronal populations in the rodent brain: in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus. The arcuate neurons coexpress kisspeptin, neurokinin B, and dynorphin and are called KNDy neurons. Because estradiol increases kisspeptin expression in the AVPV whereas it inhibits KNDy neurons, AVPV and KNDy neurons have been postulated to mediate the positive and negative feedback effects of estradiol on LH secretion, respectively. Yet the role of KNDy neurons during the positive feedback is not clear. In this study, ovariectomized rats were microinjected bilaterally into the arcuate nucleus with a saporin-conjugated neurokinin B receptor agonist for targeted ablation of approximately 70% of KNDy neurons. In oil-treated animals, ablation of KNDy neurons impaired the rise in LH after ovariectomy and kisspeptin content in both populations. In estradiol-treated animals, KNDy ablation did not influence the negative feedback of steroids during the morning. Surprisingly, KNDy ablation increased the steroid-induced LH surges, accompanied by an increase of kisspeptin content in the AVPV. This increase seems to be due to lack of dynorphin input from KNDy neurons to the AVPV as the following: 1) microinjections of a dynorphin antagonist into the AVPV significantly increased the LH surge in estradiol-treated rats, similar to KNDy ablation, and 2) intra-AVPV microinjections of dynorphin in KNDy-ablated rats restored LH surge levels. Our results suggest that KNDy neurons provide inhibition to AVPV kisspeptin neurons through dynorphin and thus regulate the amplitude of the steroid-induced LH surges.

  16. Glycinergic pacemaker neurons in preBötzinger Complex of neonatal mouse

    Science.gov (United States)

    Morgado-Valle, Consuelo; Baca, Serapio M.; Feldman, Jack L.

    2010-01-01

    The preBötzinger Complex (preBötC) is essential for normal respiratory rhythm generation in rodents, for which the underlying mechanisms remain unknown. Excitatory preBötC pacemaker neurons are proposed to be necessary for rhythm generation. Here we report the presence of a population of preBötC glycinergic pacemaker neurons. We used rhythmic in vitro transverse slice preparations from transgenic mice where neurons expressing the glycine transporter 2 (GlyT2) gene co-express enhanced green fluorescent protein (EGFP). We combined epifluorescence and whole-cell patch-clamp recording to study preBötC EGFP-labeled, i.e., glycinergic, inspiratory-modulated neurons with pacemaker properties. We defined glycinergic pacemaker neurons as those preBötC EGFP neurons that exhibited: 1) ectopic bursting in rhythmic slices when depolarized during their normally silent period, and; 2) bursting when depolarized in non-rhythmic slices (following AMPA receptor blockade). 42% of EGFP-labeled neurons were inspiratory (n=48 of 115), of which 23% (n=11 of 48 inspiratory; 10% of the total recorded) were pacemakers. We conclude that there is a population of preBötC inspiratory-modulated glycinergic, presumably inhibitory, pacemaker neurons that constitute a substantial fraction of all preBötC pacemaker neurons. These findings challenge contemporary models for respiratory rhythmogenesis that assume the excitatory nature of preBötC pacemaker neurons. Testable and non-trivial predictions of the functional role of excitatory and inhibitory pacemaker neurons need to be proposed and the necessary experiments performed. PMID:20219997

  17. Automated identification of neurons and their locations

    CERN Document Server

    Inglis, Andrew; Roe, Dan L; Stanley, H E; Rosene, Douglas L; Urbanc, Brigita

    2007-01-01

    Individual locations of many neuronal cell bodies (>10^4) are needed to enable statistically significant measurements of spatial organization within the brain such as nearest-neighbor and microcolumnarity measurements. In this paper, we introduce an Automated Neuron Recognition Algorithm (ANRA) which obtains the (x,y) location of individual neurons within digitized images of Nissl-stained, 30 micron thick, frozen sections of the cerebral cortex of the Rhesus monkey. Identification of neurons within such Nissl-stained sections is inherently difficult due to the variability in neuron staining, the overlap of neurons, the presence of partial or damaged neurons at tissue surfaces, and the presence of non-neuron objects, such as glial cells, blood vessels, and random artifacts. To overcome these challenges and identify neurons, ANRA applies a combination of image segmentation and machine learning. The steps involve active contour segmentation to find outlines of potential neuron cell bodies followed by artificial ...

  18. Rich-Club Organization in Effective Connectivity among Cortical Neurons

    Science.gov (United States)

    Shimono, Masanori; Ito, Shinya; Yeh, Fang-Chin; Timme, Nicholas; Myroshnychenko, Maxym; Lapish, Christopher C.; Tosi, Zachary; Hottowy, Pawel; Smith, Wesley C.; Masmanidis, Sotiris C.; Litke, Alan M.; Sporns, Olaf; Beggs, John M.

    2016-01-01

    The performance of complex networks, like the brain, depends on how effectively their elements communicate. Despite the importance of communication, it is virtually unknown how information is transferred in local cortical networks, consisting of hundreds of closely spaced neurons. To address this, it is important to record simultaneously from hundreds of neurons at a spacing that matches typical axonal connection distances, and at a temporal resolution that matches synaptic delays. We used a 512-electrode array (60 μm spacing) to record spontaneous activity at 20 kHz from up to 500 neurons simultaneously in slice cultures of mouse somatosensory cortex for 1 h at a time. We applied a previously validated version of transfer entropy to quantify information transfer. Similar to in vivo reports, we found an approximately lognormal distribution of firing rates. Pairwise information transfer strengths also were nearly lognormally distributed, similar to reports of synaptic strengths. Some neurons transferred and received much more information than others, which is consistent with previous predictions. Neurons with the highest outgoing and incoming information transfer were more strongly connected to each other than chance, thus forming a “rich club.” We found similar results in networks recorded in vivo from rodent cortex, suggesting the generality of these findings. A rich-club structure has been found previously in large-scale human brain networks and is thought to facilitate communication between cortical regions. The discovery of a small, but information-rich, subset of neurons within cortical regions suggests that this population will play a vital role in communication, learning, and memory. SIGNIFICANCE STATEMENT Many studies have focused on communication networks between cortical brain regions. In contrast, very few studies have examined communication networks within a cortical region. This is the first study to combine such a large number of neurons (several

  19. Male pheromone protein components activate female vomeronasal neurons in the salamander Plethodon shermani

    Directory of Open Access Journals (Sweden)

    Feldhoff Pamela W

    2006-03-01

    Full Text Available Abstract Background The mental gland pheromone of male Plethodon salamanders contains two main protein components: a 22 kDa protein named Plethodon Receptivity Factor (PRF and a 7 kDa protein named Plethodon Modulating Factor (PMF, respectively. Each protein component individually has opposing effects on female courtship behavior, with PRF shortening and PMF lengthening courtship. In this study, we test the hypothesis that PRF or PMF individually activate vomeronasal neurons. The agmatine-uptake technique was used to visualize chemosensory neurons that were activated by each protein component individually. Results Vomeronasal neurons exposed to agmatine in saline did not demonstrate significant labeling. However, a population of vomeronasal neurons was labeled following exposure to either PRF or PMF. When expressed as a percent of control level labeled cells, PRF labeled more neurons than did PMF. These percentages for PRF and PMF, added together, parallel the percentage of labeled vomeronasal neurons when females are exposed to the whole pheromone. Conclusion This study suggests that two specific populations of female vomeronasal neurons are responsible for responding to each of the two components of the male pheromone mixture. These two neural populations, therefore, could express different receptors which, in turn, transmit different information to the brain, thus accounting for the different female behavior elicited by each pheromone component.

  20. Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network.

    Science.gov (United States)

    Segers, L S; Nuding, S C; Ott, M M; Dean, J B; Bolser, D C; O'Connor, R; Morris, K F; Lindsey, B G

    2015-01-01

    Models of brain stem ventral respiratory column (VRC) circuits typically emphasize populations of neurons, each active during a particular phase of the respiratory cycle. We have proposed that "tonic" pericolumnar expiratory (t-E) neurons tune breathing during baroreceptor-evoked reductions and central chemoreceptor-evoked enhancements of inspiratory (I) drive. The aims of this study were to further characterize the coordinated activity of t-E neurons and test the hypothesis that peripheral chemoreceptors also modulate drive via inhibition of t-E neurons and disinhibition of their inspiratory neuron targets. Spike trains of 828 VRC neurons were acquired by multielectrode arrays along with phrenic nerve signals from 22 decerebrate, vagotomized, neuromuscularly blocked, artificially ventilated adult cats. Forty-eight of 191 t-E neurons fired synchronously with another t-E neuron as indicated by cross-correlogram central peaks; 32 of the 39 synchronous pairs were elements of groups with mutual pairwise correlations. Gravitational clustering identified fluctuations in t-E neuron synchrony. A network model supported the prediction that inhibitory populations with spike synchrony reduce target neuron firing probabilities, resulting in offset or central correlogram troughs. In five animals, stimulation of carotid chemoreceptors evoked changes in the firing rates of 179 of 240 neurons. Thirty-two neuron pairs had correlogram troughs consistent with convergent and divergent t-E inhibition of I cells and disinhibitory enhancement of drive. Four of 10 t-E neurons that responded to sequential stimulation of peripheral and central chemoreceptors triggered 25 cross-correlograms with offset features. The results support the hypothesis that multiple afferent systems dynamically tune inspiratory drive in part via coordinated t-E neurons.

  1. Action observation activates neurons of the monkey ventrolateral prefrontal cortex

    Science.gov (United States)

    Simone, Luciano; Bimbi, Marco; Rodà, Francesca; Fogassi, Leonardo; Rozzi, Stefano

    2017-01-01

    Prefrontal cortex is crucial for exploiting contextual information for the planning and guidance of behavioral responses. Among contextual cues, those provided by others’ behavior are particularly important, in primates, for selecting appropriate reactions and suppressing the inappropriate ones. These latter functions deeply rely on the ability to understand others’ actions. However, it is largely unknown whether prefrontal neurons are activated by action observation. To address this issue, we recorded the activity of ventrolateral prefrontal (VLPF) neurons of macaque monkeys during the observation of videos depicting biological movements performed by a monkey or a human agent, and object motion. Our results show that a population of VLPF neurons respond to the observation of biological movements, in particular those representing goal directed actions. Many of these neurons also show a preference for the agent performing the action. The neural response is present also when part of the observed movement is obscured, suggesting that these VLPF neurons code a high order representation of the observed action rather than a simple visual description of it. PMID:28290511

  2. Estimating nonstationary input signals from a single neuronal spike train.

    Science.gov (United States)

    Kim, Hideaki; Shinomoto, Shigeru

    2012-11-01

    Neurons temporally integrate input signals, translating them into timed output spikes. Because neurons nonperiodically emit spikes, examining spike timing can reveal information about input signals, which are determined by activities in the populations of excitatory and inhibitory presynaptic neurons. Although a number of mathematical methods have been developed to estimate such input parameters as the mean and fluctuation of the input current, these techniques are based on the unrealistic assumption that presynaptic activity is constant over time. Here, we propose tracking temporal variations in input parameters with a two-step analysis method. First, nonstationary firing characteristics comprising the firing rate and non-Poisson irregularity are estimated from a spike train using a computationally feasible state-space algorithm. Then, information about the firing characteristics is converted into likely input parameters over time using a transformation formula, which was constructed by inverting the neuronal forward transformation of the input current to output spikes. By analyzing spike trains recorded in vivo, we found that neuronal input parameters are similar in the primary visual cortex V1 and middle temporal area, whereas parameters in the lateral geniculate nucleus of the thalamus were markedly different.

  3. Correlative microscopy of densely labeled projection neurons using neural tracers.

    Science.gov (United States)

    Oberti, Daniele; Kirschmann, Moritz A; Hahnloser, Richard H R

    2010-01-01

    Three-dimensional morphological information about neural microcircuits is of high interest in neuroscience, but acquiring this information remains challenging. A promising new correlative technique for brain imaging is array tomography (Micheva and Smith, 2007), in which series of ultrathin brain sections are treated with fluorescent antibodies against neurotransmitters and synaptic proteins. Treated sections are repeatedly imaged in the fluorescence light microscope (FLM) and then in the electron microscope (EM). We explore a similar correlative imaging technique in which we differentially label distinct populations of projection neurons, the key routers of electrical signals in the brain. In songbirds, projection neurons can easily be labeled using neural tracers, because the vocal control areas are segregated into separate nuclei. We inject tracers into areas afferent and efferent to the main premotor area for vocal production, HVC, to retrogradely and anterogradely label different classes of projection neurons. We optimize tissue preparation protocols to achieve high fluorescence contrast in the FLM and good ultrastructure in the EM (using osmium tetroxide). Although tracer fluorescence is lost during EM preparation, we localize the tracer molecules after fixation and embedding by using fluorescent antibodies against them. We detect signals mainly in somata and dendrites, allowing us to classify synapses within a single ultrathin section as belonging to a particular type of projection neuron. The use of our method will be to provide statistical information about connectivity among different neuron classes, and to elucidate how signals in the brain are processed and routed among different areas.

  4. Correlative microscopy of densely labeled projection neurons using neural tracers

    Directory of Open Access Journals (Sweden)

    Daniele Oberti

    2010-06-01

    Full Text Available Three-dimensional morphological information about neural microcircuits is of high interest in neuroscience, but acquiring this information remains challenging. A promising new correlative technique for brain imaging is array tomography (Micheva and Smith, 2007, in which series of ultrathin brain sections are treated with fluorescent antibodies against neurotransmitters and synaptic proteins. Treated sections are repeatedly imaged in the fluorescence light microscope (FLM and then in the electron microscope (EM. We explore a similar correlative imaging technique in which we differentially label distinct populations of projection neurons, the key routers of electrical signals in the brain. In songbirds, projection neurons can easily be labeled using neural tracers, because the vocal control areas are segregated into separate nuclei. We inject tracers into areas afferent and efferent to the main premotor area for vocal production, HVC, to retrogradely and anterogradely label different classes of projection neurons. We optimize tissue preparation protocols to achieve high fluorescence contrast in the FLM and good ultrastructure in the EM (using osmium tetroxide. Although tracer fluorescence is lost during EM preparation, we localize the tracer molecules after fixation and embedding by using fluorescent antibodies against them. We detect signals mainly in somata and dendrites, allowing us to classify synapses within a single ultrathin section as belonging to a particular type of projection neuron. The use of our method will be to provide statistical information about connectivity among different neuron classes, and to elucidate how signals in the brain are processed and routed among different areas.

  5. M1 corticospinal mirror neurons and their role in movement suppression during action observation.

    Science.gov (United States)

    Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N; Kraskov, Alexander

    2013-02-04

    Evidence is accumulating that neurons in primary motor cortex (M1) respond during action observation, a property first shown for mirror neurons in monkey premotor cortex. We now show for the first time that the discharge of a major class of M1 output neuron, the pyramidal tract neuron (PTN), is modulated during observation of precision grip by a human experimenter. We recorded 132 PTNs in the hand area of two adult macaques, of which 65 (49%) showed mirror-like activity. Many (38 of 65) increased their discharge during observation (facilitation-type mirror neuron), but a substantial number (27 of 65) exhibited reduced discharge or stopped firing (suppression-type). Simultaneous recordings from arm, hand, and digit muscles confirmed the complete absence of detectable muscle activity during observation. We compared the discharge of the same population of neurons during active grasp by the monkeys. We found that facilitation neurons were only half as active for action observation as for action execution, and that suppression neurons reversed their activity pattern and were actually facilitated during execution. Thus, although many M1 output neurons are active during action observation, M1 direct input to spinal circuitry is either reduced or abolished and may not be sufficient to produce overt muscle activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Histological and functional benefit following transplantation of motor neuron progenitors to the injured rat spinal cord.

    Directory of Open Access Journals (Sweden)

    Sharyn L Rossi

    Full Text Available BACKGROUND: Motor neuron loss is characteristic of cervical spinal cord injury (SCI and contributes to functional deficit. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate the amenability of the injured adult spinal cord to motor neuron differentiation, we transplanted spinal cord injured animals with a high purity population of human motor neuron progenitors (hMNP derived from human embryonic stem cells (hESCs. In vitro, hMNPs displayed characteristic motor neuron-specific markers, a typical electrophysiological profile, functionally innervated human or rodent muscle, and secreted physiologically active growth factors that caused neurite branching and neuronal survival. hMNP transplantation into cervical SCI sites in adult rats resulted in suppression of intracellular signaling pathways associated with SCI pathogenesis, which correlated with greater endogenous neuronal survival and neurite branching. These neurotrophic effects were accompanied by significantly enhanced performance on all parameters of the balance beam task, as compared to controls. Interestingly, hMNP transplantation resulted in survival, differentiation, and site-specific integration of hMNPs distal to the SCI site within ventral horns, but hMNPs near the SCI site reverted to a neuronal progenitor state, suggesting an environmental deficiency for neuronal maturation associated with SCI. CONCLUSIONS/SIGNIFICANCE: These findings underscore the barriers imposed on neuronal differentiation of transplanted cells by the gliogenic nature of the injured spinal cord, and the physiological relevance of transplant-derived neurotrophic support to functional recovery.

  7. Divergent Modulation of Nociception by Glutamatergic and GABAergic Neuronal Subpopulations in the Periaqueductal Gray

    Science.gov (United States)

    Grajales-Reyes, Jose G.; Copits, Bryan A.; O’Brien, Daniel E.; Trigg, Sarah L.; Gomez, Adrian M.

    2017-01-01

    Abstract The ventrolateral periaqueductal gray (vlPAG) constitutes a major descending pain modulatory system and is a crucial site for opioid-induced analgesia. A number of previous studies have demonstrated that glutamate and GABA play critical opposing roles in nociceptive processing in the vlPAG. It has been suggested that glutamatergic neurotransmission exerts antinociceptive effects, whereas GABAergic neurotransmission exert pronociceptive effects on pain transmission, through descending pathways. The inability to exclusively manipulate subpopulations of neurons in the PAG has prevented direct testing of this hypothesis. Here, we demonstrate the different contributions of genetically defined glutamatergic and GABAergic vlPAG neurons in nociceptive processing by employing cell type-specific chemogenetic approaches in mice. Global chemogenetic manipulation of vlPAG neuronal activity suggests that vlPAG neural circuits exert tonic suppression of nociception, consistent with previous pharmacological and electrophysiological studies. However, selective modulation of GABAergic or glutamatergic neurons demonstrates an inverse regulation of nociceptive behaviors by these cell populations. Selective chemogenetic activation of glutamatergic neurons, or inhibition of GABAergic neurons, in vlPAG suppresses nociception. In contrast, inhibition of glutamatergic neurons, or activation of GABAergic neurons, in vlPAG facilitates nociception. Our findings provide direct experimental support for a model in which excitatory and inhibitory neurons in the PAG bidirectionally modulate nociception. PMID:28374016

  8. Ensemble Fractional Sensitivity: A Quantitative Approach to Neuron Selection for Decoding Motor Tasks

    Directory of Open Access Journals (Sweden)

    Girish Singhal

    2010-01-01

    Full Text Available A robust method to help identify the population of neurons used for decoding motor tasks is developed. We use sensitivity analysis to develop a new metric for quantifying the relative contribution of a neuron towards the decoded output, called “fractional sensitivity.” Previous model-based approaches for neuron ranking have been shown to largely depend on the collection of training data. We suggest the use of an ensemble of models that are trained on random subsets of trials to rank neurons. For this work, we tested a decoding algorithm on neuronal data recorded from two male rhesus monkeys while they performed a reach to grasp a bar at three orientations (45∘, 90∘, or 135∘. An ensemble approach led to a statistically significant increase of 5% in decoding accuracy and 25% increase in identification accuracy of simulated noisy neurons, when compared to a single model. Furthermore, ranking neurons based on the ensemble fractional sensitivities resulted in decoding accuracies 10%–20% greater than when randomly selecting neurons or ranking based on firing rates alone. By systematically reducing the size of the input space, we determine the optimal number of neurons needed for decoding the motor output. This selection approach has practical benefits for other BMI applications where limited number of electrodes and training datasets are available, but high decoding accuracies are desirable.

  9. Topographical distribution and morphology of NADPH-diaphorase-stained neurons in the human claustrum.

    Science.gov (United States)

    Hinova-Palova, Dimka V; Edelstein, Lawrence; Landzhov, Boycho; Minkov, Minko; Malinova, Lina; Hristov, Stanislav; Denaro, Frank J; Alexandrov, Alexandar; Kiriakova, Teodora; Brainova, Ilina; Paloff, Adrian; Ovtscharoff, Wladimir

    2014-01-01

    We studied the topographical distribution and morphological characteristics of NADPH-diaphorase-positive neurons and fibers in the human claustrum. These neurons were seen to be heterogeneously distributed throughout the claustrum. Taking into account the size and shape of stained perikarya as well as dendritic and axonal characteristics, Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd)-positive neurons were categorized by diameter into three types: large, medium and small. Large neurons ranged from 25 to 35 μm in diameter and typically displayed elliptical or multipolar cell bodies. Medium neurons ranged from 20 to 25 μm in diameter and displayed multipolar, bipolar and irregular cell bodies. Small neurons ranged from 14 to 20 μm in diameter and most often displayed oval or elliptical cell bodies. Based on dendritic characteristics, these neurons were divided into spiny and aspiny subtypes. Our findings reveal two populations of NADPHd-positive neurons in the human claustrum-one comprised of large and medium cells consistent with a projection neuron phenotype, the other represented by small cells resembling the interneuron phenotype as defined by previous Golgi impregnation studies.

  10. Kölliker-Fuse GABAergic and glutamatergic neurons project to distinct targets.

    Science.gov (United States)

    Geerling, Joel C; Yokota, Shigefumi; Rukhadze, Irma; Roe, Dan; Chamberlin, Nancy L

    2017-06-01

    The Kölliker-Fuse nucleus (KF) is known primarily for its respiratory function as the "pneumotaxic center" or "pontine respiratory group." Considered part of the parabrachial (PB) complex, KF contains glutamatergic neurons that project to respiratory-related targets in the medulla and spinal cord (Yokota, Oka, Tsumori, Nakamura, & Yasui, 2007). Here we describe an unexpected population of neurons in the caudal KF and adjacent lateral crescent subnucleus (PBlc), which are γ-aminobutyric acid (GABA)ergic and have an entirely different pattern of projections than glutamatergic KF neurons. First, immunofluorescence, in situ hybridization, and Cre-reporter labeling revealed that many of these GABAergic neurons express FoxP2 in both rats and mice. Next, using Cre-dependent axonal tracing in Vgat-IRES-Cre and Vglut2-IRES-Cre mice, we identified different projection patterns from GABAergic and glutamatergic neurons in this region. GABAergic neurons in KF and PBlc project heavily and almost exclusively to trigeminal sensory nuclei, with minimal projections to cardiorespiratory nuclei in the brainstem, and none to the spinal cord. In contrast, glutamatergic KF neurons project heavily to the autonomic, respiratory, and motor regions of the medulla and spinal cord previously identified as efferent targets mediating KF cardiorespiratory effects. These findings identify a novel, GABAergic subpopulation of KF/PB neurons with a distinct efferent projection pattern targeting the brainstem trigeminal sensory system. Rather than regulating breathing, we propose that these neurons influence vibrissal sensorimotor function. © 2017 Wiley Periodicals, Inc.

  11. Neuronize: a tool for building realistic neuronal cell morphologies

    Science.gov (United States)

    Brito, Juan P.; Mata, Susana; Bayona, Sofia; Pastor, Luis; DeFelipe, Javier; Benavides-Piccione, Ruth

    2013-01-01

    This study presents a tool, Neuronize, for building realistic three-dimensional models of neuronal cells from the morphological information extracted through computer-aided tracing applications. Neuronize consists of a set of methods designed to build 3D neural meshes that approximate the cell membrane at different resolution levels, allowing a balance to be reached between the complexity and the quality of the final model. The main contribution of the present study is the proposal of a novel approach to build a realistic and accurate 3D shape of the soma from the incomplete information stored in the digitally traced neuron, which usually consists of a 2D cell body contour. This technique is based on the deformation of an initial shape driven by the position and thickness of the first order dendrites. The addition of a set of spines along the dendrites completes the model, building a final 3D neuronal cell suitable for its visualization in a wide range of 3D environments. PMID:23761740

  12. Isoflurane-induced neuronal apoptosis in developing hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Hongliang Liu; Tijun Dai; Weitao Guo

    2013-01-01

    We hypothesized that the P2X7 receptor may be the target of isoflurane, so we investigated the roles of the P2X7 receptor and inositol triphosphate receptor in calcium overload and neuronal apoptosis induced by isoflurane in cultured embryonic rat hippocampal neurons. Results showed that isoflurane induced widespread neuronal apoptosis and significantly increased cytoplasmic Ca2+. Blockade of P2X7 receptors or removal of extracellular Ca2+ combined with blockade of inositol triphosphate receptors completely inhibited apoptosis or increase in cytoplasmic Ca2+. Removal of extracellular Ca2+ or blockade of inositol triphosphate receptor alone could partly inhibit these effects of isoflurane. Isoflurane could directly activate P2X7-gated channels and induce inward currents, but did not affect the expression of P2X7 receptor protein in neurons. These findings indicate that the mechanism by which isoflurane induced neuronal apoptosis in rat developing brain was mediated by intracellular calcium overload, which was caused by P2X7 receptor mediated calcium influx and inositol triphosphate receptor mediated calcium release.

  13. A neuron-benign microfluidic gradient generator for studying the response of mammalian neurons towards axon guidance factors.

    Science.gov (United States)

    Bhattacharjee, Nirveek; Li, Nianzhen; Keenan, Thomas M; Folch, Albert

    2010-11-01

    Investigation of biochemical cues in isolation or in combinations in cell culture systems is crucial for unraveling the mechanisms that govern neural development and repair. The most widely used experimental paradigms that elicit axon guidance in vitro utilize as the source of the gradient a pulsatile pipette, transfected cells, or a loaded gel, producing time-varying gradients of poor reproducibility which are not well suited for studying slow-growing mammalian cells. Although microfluidic device design have allowed for generating stable, complex gradients of diffusible molecules, the flow-induced shear forces in a microchannel has made it impossible to maintain viable mammalian neuronal cultures for sufficiently long times. In this paper, we describe axonal responses of mouse cortical neurons in a "neuron-benign" gradient-generator device based on an open chamber that can establish highly stable gradients of diffusible molecules for at least 6 h with negligible shear stress, and also allows the neurons to thrive for at least 2 weeks. Except for the period when the gradient is on, the cells in the gradient are under the same conditions as the cells on the control surfaces, which ensure a consistent set of micro-environmental variables. The gradient stability and uniformity over the cell culture surface achieved by the device, together with our software platform for acquiring, post-processing and quantitatively analyzing the large number of images allowed us to extract valuable information even from small datasets. We report a directed response of primary mammalian neurons (from E14 embryonic mice cortex) to a diffusible gradient of netrin in vitro. We infer from our studies that a large majority (∼73%) of the neurons that extend axons during the gradient application grow towards the netrin source, and our data analysis also indicates that netrin acts as a growth factor for this same population of neurons.

  14. Depolarizing actions of hydrogen sulfide on hypothalamic paraventricular nucleus neurons.

    Directory of Open Access Journals (Sweden)

    C Sahara Khademullah

    Full Text Available Hydrogen sulfide (H2S is a novel neurotransmitter that has been shown to influence cardiovascular functions as well and corticotrophin hormone (CRH secretion. Since the paraventricular nucleus of the hypothalamus (PVN is a central relay center for autonomic and endocrine functions, we sought to investigate the effects of H2S on the neuronal population of the PVN. Whole cell current clamp recordings were acquired from the PVN neurons and sodium hydrosulfide hydrate (NaHS was bath applied at various concentrations (0.1, 1, 10, and 50 mM. NaHS (1, 10, and 50 mM elicited a concentration-response relationship from the majority of recorded neurons, with almost exclusively depolarizing effects following administration. Cells responded and recovered from NaHS administration quickly and the effects were repeatable. Input differences from baseline and during the NaHS-induced depolarization uncovered a biphasic response, implicating both a potassium and non-selective cation conductance. The results from the neuronal population of the PVN shed light on the possible physiological role that H2S has in autonomic and endocrine function.

  15. Anatomical distribution of estrogen target neurons in turtle brain

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Y.S.; Stumpf, W.E.; Sar, M. (North Carolina Univ., Chapel Hill (USA))

    1981-12-28

    Autoradiographic studies with (/sup 3/H)estradiol-17..beta.. in red-eared turtle (Pseudemys scripta elegans) show concentration and retention of radioactivity in nuclei of neurons in certain regions. Accumulations of estrogen target neurons exist in the periventricular brain with relationships to ventral extensions of the forebrain ventricles, including parolfactory, amygdaloid, septal, preoptic, hypothalamic and thalamic areas, as well as the dorsal ventricular ridge, the piriform cortex, and midbrain-pontine periaqueductal structures. The general anatomical pattern of distribution of estrogen target neurons corresponds to those observed not only in another reptile (Anolis carolinensis), but also in birds and mammals, as well as in teleosts and cyclostomes. In Pseudemys, which appears to display an intermediate degree of phylogenetic differentiation, the amygdaloid-septal-preoptic groups of estrogen target neurons constitute a continuum. In phylogenetic ascendency, e.g. in mammals, these cell populations are increasingly separated and distinct, while in phylogenetic descendency, e.g. in teleosts and cyclostomes, an amygdaloid group appears to be absent or contained within the septal-preoptic target cell population.

  16. Network architecture underlying maximal separation of neuronal representations

    Directory of Open Access Journals (Sweden)

    Ron A Jortner

    2013-01-01

    Full Text Available One of the most basic and general tasks faced by all nervous systems is extracting relevant information from the organism’s surrounding world. While physical signals available to sensory systems are often continuous, variable, overlapping and noisy, high-level neuronal representations used for decision-making tend to be discrete, specific, invariant, and highly separable. This study addresses the question of how neuronal specificity is generated. Inspired by experimental findings on network architecture in the olfactory system of the locust, I construct a highly simplified theoretical framework which allows for analytic solution of its key properties. For generalized feed-forward systems, I show that an intermediate range of connectivity values between source- and target-populations leads to a combinatorial explosion of wiring possibilities, resulting in input spaces which are, by their very nature, exquisitely sparsely populated. In particular, connection probability ½, as found in the locust antennal-lobe–mushroom-body circuit, serves to maximize separation of neuronal representations across the target Kenyon-cells, and explains their specific and reliable responses. This analysis yields a function expressing response specificity in terms of lower network-parameters; together with appropriate gain control this leads to a simple neuronal algorithm for generating arbitrarily sparse and selective codes and linking network architecture and neural coding. I suggest a way to easily construct ecologically meaningful representations from this code.

  17. Persistent dynamic attractors in activity patterns of cultured neuronal networks

    Science.gov (United States)

    Wagenaar, Daniel A.; Nadasdy, Zoltan; Potter, Steve M.

    2006-05-01

    Three remarkable features of the nervous system—complex spatiotemporal patterns, oscillations, and persistent activity—are fundamental to such diverse functions as stereotypical motor behavior, working memory, and awareness. Here we report that cultured cortical networks spontaneously generate a hierarchical structure of periodic activity with a strongly stereotyped population-wide spatiotemporal structure demonstrating all three fundamental properties in a recurring pattern. During these “superbursts,” the firing sequence of the culture periodically converges to a dynamic attractor orbit. Precursors of oscillations and persistent activity have previously been reported as intrinsic properties of the neurons. However, complex spatiotemporal patterns that are coordinated in a large population of neurons and persist over several hours—and thus are capable of representing and preserving information—cannot be explained by known oscillatory properties of isolated neurons. Instead, the complexity of the observed spatiotemporal patterns implies large-scale self-organization of neurons interacting in a precise temporal order even in vitro, in cultures usually considered to have random connectivity.

  18. Long descending cervical propriospinal neurons differ from thoracic propriospinal neurons in response to low thoracic spinal injury

    Directory of Open Access Journals (Sweden)

    Stelzner Dennis J

    2010-11-01

    -regulation in the genes examined, including genes for neurotrophic/growth factor receptors as well as for several growth factors. There was a lack of a significant regenerative response, with the exception of an up-regulation of Atf3 and early up-regulation of Hspb1 (Hsp27, both involved in cell stress/neuroprotection as well as axonal regeneration. There was no indication of a cell death response over the first month post-injury. In addition, there appear to be significant phenotypic differences between uninjured TPS and LDPT neurons, which may partly account for the differences observed in their post-axotomy responses. The findings in this current study stand in stark contrast to the findings from our previous work on TPS neurons. This suggests that different approaches will be needed to enhance the capacity for each population of propriospinal neuron to survive and undergo successful axonal regeneration after SCI.

  19. Motor-Auditory-Visual Integration: The Role of the Human Mirror Neuron System in Communication and Communication Disorders

    Science.gov (United States)

    Le Bel, Ronald M.; Pineda, Jaime A.; Sharma, Anu

    2009-01-01

    The mirror neuron system (MNS) is a trimodal system composed of neuronal populations that respond to motor, visual, and auditory stimulation, such as when an action is performed, observed, heard or read about. In humans, the MNS has been identified using neuroimaging techniques (such as fMRI and mu suppression in the EEG). It reflects an…

  20. Motor-Auditory-Visual Integration: The Role of the Human Mirror Neuron System in Communication and Communication Disorders

    Science.gov (United States)

    Le Bel, Ronald M.; Pineda, Jaime A.; Sharma, Anu

    2009-01-01

    The mirror neuron system (MNS) is a trimodal system composed of neuronal populations that respond to motor, visual, and auditory stimulation, such as when an action is performed, observed, heard or read about. In humans, the MNS has been identified using neuroimaging techniques (such as fMRI and mu suppression in the EEG). It reflects an…

  1. Highly differentiated cellular and circuit properties of infralimbic pyramidal neurons projecting to the periaqueductal gray and amygdala.

    Directory of Open Access Journals (Sweden)

    Ashley N Ferreira

    2015-04-01

    Full Text Available The infralimbic (IL cortex is a key node in an inter-connected network involved in fear and emotion processing. The cellular and circuit-level mechanisms whereby IL neurons receive, filter, and modulate incoming signals they project onward to diverse downstream nodes in this complex network remain poorly understood. Using the mouse as our model, we applied anatomical labeling strategies, brain slice electrophysiology, and focal activation of caged glutamate via laser scanning photostimulation (glu-LSPS for quantitative neurophysiological analysis of projectionally defined neurons in IL. Injection of retrograde tracers into the periaqueductal grey (PAG and basolateral amygdala (BLA was used to identify cortico-PAG (CP and cortico-BLA (CA neurons in IL. CP neurons were found exclusively in layer 5 of IL whereas CA neurons were detected throughout layer 2, 3 and 5 of IL. We also identified a small percentage of IL neurons that project to both the PAG and the BLA. We found that layer 5 CP neurons have a more extensive dendritic structure compared to layer 5 CA neurons. Neurophysiological recordings performed on retrogradely labeled neurons in acute brain slice showed that CP and CA neurons in IL could be broadly classified in two groups: neuronal resonators and non-resonators. Layer 2 CA neurons were the only class that was exclusively non-resonating. CP, CA, and CP/CA neurons in layers 3 and 5 of IL consisted of heterogeneous populations of resonators and non-resonators showing that projection target is not an exclusive predictor of intrinsic physiology. Circuit mapping using glu-LSPS revealed that the strength and organization of local excitatory and inhibitory inputs were stronger to CP compared to CA neurons in IL. Together, our results establish an organizational scheme linking cellular neurophysiology with microcircuit parameters of defined neuronal subclasses in IL that send descending commands to subcortical structures involved in fear

  2. Npas1+ Pallidal Neurons Target Striatal Projection Neurons.

    Science.gov (United States)

    Glajch, Kelly E; Kelver, Daniel A; Hegeman, Daniel J; Cui, Qiaoling; Xenias, Harry S; Augustine, Elizabeth C; Hernández, Vivian M; Verma, Neha; Huang, Tina Y; Luo, Minmin; Justice, Nicholas J; Chan, C Savio

    2016-05-18

    Compelling evidence demonstrates that the external globus pallidus (GPe) plays a key role in processing sensorimotor information. An anatomical projection from the GPe to the dorsal striatum has been described for decades. However, the cellular target and functional impact of this projection remain unknown. Using cell-specific transgenic mice, modern monosynaptic tracing techniques, and optogenetics-based mapping, we discovered that GPe neurons provide inhibitory inputs to direct and indirect pathway striatal projection neurons (SPNs). Our results indicate that the GPe input to SPNs arises primarily from Npas1-expressing neurons and is strengthened in a chronic Parkinson's disease (PD) model. Alterations of the GPe-SPN input in a PD model argue for the critical position of this connection in regulating basal ganglia motor output and PD symptomatology. Finally, chemogenetic activation of Npas1-expressing GPe neurons suppresses motor output, arguing that strengthening of the GPe-SPN connection is maladaptive and may underlie the hypokinetic symptoms in PD. An anatomical projection from the pallidum to the striatum has been described for decades, but little is known about its connectivity pattern. The authors dissect the presynaptic and postsynaptic neurons involved in this projection, and show its cell-specific remodeling and strengthening in parkinsonian mice. Chemogenetic activation of Npas1(+) pallidal neurons that give rise to the principal pallidostriatal projection increases the time that the mice spend motionless. This argues that maladaptive strengthening of this connection underlies the paucity of volitional movements, which is a hallmark of Parkinson's disease. Copyright © 2016 the authors 0270-6474/16/365472-17$15.00/0.

  3. More questions for mirror neurons.

    Science.gov (United States)

    Borg, Emma

    2013-09-01

    The mirror neuron system is widely held to provide direct access to the motor goals of others. This paper critically investigates this idea, focusing on the so-called 'intentional worry'. I explore two answers to the intentional worry: first that the worry is premised on too limited an understanding of mirror neuron behaviour (Sections 2 and 3), second that the appeal made to mirror neurons can be refined in such a way as to avoid the worry (Section 4). I argue that the first response requires an account of the mechanism by which small-scale gestures are supposedly mapped to larger chains of actions but that none of the extant accounts of this mechanism are plausible. Section 4 then briefly examines refinements of the mirror neuron-mindreading hypothesis which avoid the intentional worry. I conclude that these refinements may well be plausible but that they undermine many of the claims standardly made for mirror neurons. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. [Neurons that encode sound direction].

    Science.gov (United States)

    Peña, J L

    In the auditory system, the inner ear breaks down complex signals into their spectral components, and encodes the amplitude and phase of each. In order to infer sound direction in space, a computation on each frequency component of the sound must be performed. Space specific neurons in the owl s inferior colliculus respond only to sounds coming from a particular direction and represent the results of this computation. The interaural time difference (ITD) and interaural level difference (ILD define the auditory space for the owl and are processed in separate neural pathways. The parallel pathways that process these cues merge in the external nucleus of the inferior colliculus where the space specific neurons are selective to combinations of ITD and ILD. How do inputs from the two sources interact to produce combination selectivity to ITD ILD pairs? A multiplication of postsynaptic potentials tuned to ITD and ILD can account for the subthreshold responses of these neurons to ITD ILD pairs. Examples of multiplication by neurons or neural circuits are scarce, but many computational models assume the existence of this basic operation. The owl s auditory system uses such operation to create a 2 dimensional map of auditory space. The map of space in the owl s auditory system shows important similarities with representations of space in the cerebral cortex and other sensory systems. In encoding space or other stimulus features, individual neurons appear to possess analogous functional properties related to the synthesis of high order receptive fields.

  5. Brain Neurons as Quantum Computers:

    Science.gov (United States)

    Bershadskii, A.; Dremencov, E.; Bershadskii, J.; Yadid, G.

    The question: whether quantum coherent states can sustain decoherence, heating and dissipation over time scales comparable to the dynamical timescales of brain neurons, has been actively discussed in the last years. A positive answer on this question is crucial, in particular, for consideration of brain neurons as quantum computers. This discussion was mainly based on theoretical arguments. In the present paper nonlinear statistical properties of the Ventral Tegmental Area (VTA) of genetically depressive limbic brain are studied in vivo on the Flinders Sensitive Line of rats (FSL). VTA plays a key role in the generation of pleasure and in the development of psychological drug addiction. We found that the FSL VTA (dopaminergic) neuron signals exhibit multifractal properties for interspike frequencies on the scales where healthy VTA dopaminergic neurons exhibit bursting activity. For high moments the observed multifractal (generalized dimensions) spectrum coincides with the generalized dimensions spectrum calculated for a spectral measure of a quantum system (so-called kicked Harper model, actively used as a model of quantum chaos). This observation can be considered as a first experimental (in vivo) indication in the favor of the quantum (at least partially) nature of brain neurons activity.

  6. Emerging Signaling Pathway in Arcuate Feeding-Related Neurons: Role of the Acbd7

    Directory of Open Access Journals (Sweden)

    Damien Lanfray

    2017-06-01

    Full Text Available The understanding of the mechanisms whereby energy balance is regulated is essential to the unraveling of the pathophysiology of obesity. In the last three decades, focus was put on the metabolic role played by the hypothalamic neurons expressing proopiomelanocortin (POMC and cocaine and amphetamine regulated transcript (CART and the neurons co-localizing agouti-related peptide (AgRP, neuropeptide Y (NPY, and gamma-aminobutyric acid (GABA. These neurons are part of the leptin-melanocortin pathway, whose role is key in energy balance regulation. More recently, the metabolic involvement of further hypothalamic uncharacterized neuron populations has been suggested. In this review, we discuss the potential homeostatic implication of hypothalamic GABAergic neurons that produce Acyl-Coa-binding domain containing protein 7 (ACBD7, precursor of the nonadecaneuropeptide (NDN, which has recently been characterized as a potent anorexigenic neuropeptide capable of relaying the leptin anorectic/thermogenic effect via the melanocortin system.

  7. Discovering Patterns in Multi-neuronal Spike Trains using the Frequent Episode Method

    CERN Document Server

    Unnikrishnan, K P; Sastry, P S

    2007-01-01

    Discovering the 'Neural Code' from multi-neuronal spike trains is an important task in neuroscience. For such an analysis, it is important to unearth interesting regularities in the spiking patterns. In this report, we present an efficient method for automatically discovering synchrony, synfire chains, and more general sequences of neuronal firings. We use the Frequent Episode Discovery framework of Laxman, Sastry, and Unnikrishnan (2005), in which the episodes are represented and recognized using finite-state automata. Many aspects of functional connectivity between neuronal populations can be inferred from the episodes. We demonstrate these using simulated multi-neuronal data from a Poisson model. We also present a method to assess the statistical significance of the discovered episodes. Since the Temporal Data Mining (TDM) methods used in this report can analyze data from hundreds and potentially thousands of neurons, we argue that this framework is appropriate for discovering the `Neural Code'.

  8. Citalopram increases the differentiation efifcacy of bone marrow mesenchymal stem cells into neuronal-like cells

    Institute of Scientific and Technical Information of China (English)

    Javad Verdi; Seyed Abdolreza Mortazavi-Tabatabaei; Shiva Sharif; Hadi Verdi; Alireza Shoae-Hassani

    2014-01-01

    Several studies have demonstrated that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. It is hypothesized that citalopram, a selective serotonin reuptake inhibitor, can promote the neuronal differentiation of adult bone marrow mesenchymal stem cells. Citalopram strongly enhanced neuronal characteristics of the cells derived from bone marrow mesenchymal stem cells. The rate of cell death was decreased in citalopram-treated bone marrow mesenchymal stem cells than in control cells in neurobasal medium. In addition, the cumulative population doubling level of the citalopram-treated cells was signiifcantly increased compared to that of control cells. Also BrdU incorporation was elevated in citalopram-treated cells. These ifndings suggest that citalopram can improve the neuronal-like cell differentiation of bone marrow mesenchymal stem cells by increasing cell proliferation and survival while maintaining their neuronal characteristics.

  9. Citalopram increases the differentiation efficacy of bone marrow mesenchymal stem cells into neuronal-like cells.

    Science.gov (United States)

    Verdi, Javad; Mortazavi-Tabatabaei, Seyed Abdolreza; Sharif, Shiva; Verdi, Hadi; Shoae-Hassani, Alireza

    2014-04-15

    Several studies have demonstrated that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. It is hypothesized that citalopram, a selective serotonin reuptake inhibitor, can promote the neuronal differentiation of adult bone marrow mesenchymal stem cells. Citalopram strongly enhanced neuronal characteristics of the cells derived from bone marrow mesenchymal stem cells. The rate of cell death was decreased in citalopram-treated bone marrow mesenchymal stem cells than in control cells in neurobasal medium. In addition, the cumulative population doubling level of the citalopram-treated cells was significantly increased compared to that of control cells. Also BrdU incorporation was elevated in citalopram-treated cells. These findings suggest that citalopram can improve the neuronal-like cell differentiation of bone marrow mesenchymal stem cells by increasing cell proliferation and survival while maintaining their neuronal characteristics.

  10. Neurons to algorithms LDRD final report.

    Energy Technology Data Exchange (ETDEWEB)

    Rothganger, Fredrick H.; Aimone, James Bradley; Warrender, Christina E.; Trumbo, Derek

    2013-09-01

    Over the last three years the Neurons to Algorithms (N2A) LDRD project teams has built infrastructure to discover computational structures in the brain. This consists of a modeling language, a tool that enables model development and simulation in that language, and initial connections with the Neuroinformatics community, a group working toward similar goals. The approach of N2A is to express large complex systems like the brain as populations of a discrete part types that have specific structural relationships with each other, along with internal and structural dynamics. Such an evolving mathematical system may be able to capture the essence of neural processing, and ultimately of thought itself. This final report is a cover for the actual products of the project: the N2A Language Specification, the N2A Application, and a journal paper summarizing our methods.

  11. Combining microfluidics, optogenetics and calcium imaging to study neuronal communication in vitro.

    Science.gov (United States)

    Renault, Renaud; Sukenik, Nirit; Descroix, Stéphanie; Malaquin, Laurent; Viovy, Jean-Louis; Peyrin, Jean-Michel; Bottani, Samuel; Monceau, Pascal; Moses, Elisha; Vignes, Maéva

    2015-01-01

    In this paper we report the combination of microfluidics, optogenetics and calcium imaging as a cheap and convenient platform to study synaptic communication between neuronal populations in vitro. We first show that Calcium Orange indicator is compatible in vitro with a commonly used Channelrhodopsine-2 (ChR2) variant, as standard calcium imaging conditions did not alter significantly the activity of transduced cultures of rodent primary neurons. A fast, robust and scalable process for micro-chip fabrication was developed in parallel to build micro-compartmented cultures. Coupling optical fibers to each micro-compartment allowed for the independent control of ChR2 activation in the different populations without crosstalk. By analyzing the post-stimuli activity across the different populations, we finally show how this platform can be used to evaluate quantitatively the effective connectivity between connected neuronal populations.

  12. H+-sensitivity and pattern of discharge of neurons in the chemosensitive areas of the ventral medulla oblongata of rats in vitro.

    Science.gov (United States)

    Fukuda, Y; See, W R; Honda, Y

    1980-10-01

    Effect of H+ on neuronal activity in medullary chemosensitive structures was analyzed in brain slices of the rat in vitro. Spontaneous discharges of spikes were recorded from two populations of neurons in the ventral surface layer of the medulla oblongata. Neurons located in the rostro-lateral part of the hypoglossal nerve root (area II) fired irregular phasic and/or continuous tonic discharges. More rostral and medial to it, a population of 'H+-sensitive' tonic neurons was found previously (area I). The phasic activity of neurons in area II with variable bursting and silent periods (0.1--120 s) was either increased or decreased by H+. Some neurons firing tonically in area II started to show phasic burst under low pH conditions. After cutting the slice between area I and II, the number of neurons firing phasically in area II was reduced, and the activity of area II neurons was mostly depressed by H+. An increase in activity of area I neurons by H+ was kept intact even after section. The results suggest that neurons in area I play an important role not only in the excitatory response to H+ of area II neurons but also in the initiation of phasic neuronal discharges in area II.

  13. Neuron-Based Heredity and Human Evolution

    Directory of Open Access Journals (Sweden)

    Don Marshall Gash

    2015-06-01

    Full Text Available Abstract:Abstract: It is widely recognized that human evolution has been driven by two systems of heredity: one DNA-based and the other based on the transmission of behaviorally acquired information via nervous system functions. The genetic system is ancient, going back to the appearance of life on Earth. It is responsible for the evolutionary processes described by Darwin. By comparison, the nervous system is relatively newly minted and in its highest form, responsible for ideation and mind-to-mind transmission of information. Here the informational capabilities and functions of the two systems are compared. While employing quite different mechanisms for encoding, storing and transmission of information, both systems perform these generic hereditary functions. Three additional features of neuron-based heredity in humans are identified: the ability to transfer hereditary information to other members of their population, not just progeny; a selection process for the information being transferred; and a profoundly shorter time span for creation and dissemination of survival-enhancing information in a population. The mechanisms underlying neuron-based heredity involve hippocampal neurogenesis and memory and learning processes modifying and creating new neural assemblages changing brain structure and functions. A fundamental process in rewiring brain circuitry is through increased neural activity (use strengthening and increasing the number of synaptic connections. Decreased activity in circuitry (disuse leads to loss of synapses. Use and disuse modifying an organ to bring about new modes of living, habits and functions are processes are in line with Neolamarckian concepts of evolution (Packard, 1901. Evidence is presented of bipartite evolutionary processes – Darwinian and Neolamarckian – driving human descent from a common ancestor shared with the great apes.

  14. Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura

    Directory of Open Access Journals (Sweden)

    Huang Dongyue

    2012-09-01

    Full Text Available Abstract Background Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. Methods We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir and isolectin B4 (IB4 binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. Results and conclusions We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent

  15. Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura

    Science.gov (United States)

    2012-01-01

    Background Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP) family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. Methods We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. Results and conclusions We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent neurons. Interestingly, TRPM

  16. Genomic control of neuronal demographics in the retina.

    Science.gov (United States)

    Reese, Benjamin E; Keeley, Patrick W

    2016-11-01

    The mature retinal architecture is composed of various types of neuron, each population differing in size and constrained to particular layers, wherein the cells achieve a characteristic patterning in their local organization. These demographic features of retinal nerve cell populations are each complex traits controlled by multiple genes affecting different processes during development, and their genetic determinants can be dissected by correlating variation in these traits with their genomic architecture across recombinant-inbred mouse strains. Using such a resource, we consider how the variation in the numbers of twelve different types of retinal neuron are independent of one another, including those sharing transcriptional regulation as well as those that are synaptically-connected, each mapping to distinct genomic loci. Using the populations of two retinal interneurons, the horizontal cells and the cholinergic amacrine cells, we present in further detail examples where the variation in neuronal number, as well as the variation in mosaic patterning or in laminar positioning, each maps to discrete genomic loci where allelic variants modulating these features must be present. At those loci, we identify candidate genes which, when rendered non-functional, alter those very demographic properties, and in turn, we identify candidate coding or regulatory variants that alter protein structure or gene expression, respectively, being prospective contributors to the variation in phenotype. This forward-genetic approach provides an alternative means for dissecting the molecular genetic control of neuronal population dynamics, with each genomic locus serving as a causal anchor from which we may ultimately understand the developmental principles responsible for the control of those traits.

  17. Anatomic and Molecular Development of Corticostriatal Projection Neurons in Mice

    OpenAIRE

    Macklis, Jeffrey Daniel; Sohur, Usharbudh Shivraj; Padmanabhan, Hari; Kotchetkov, Ivan S.; Menezes, Joao R.L.

    2012-01-01

    Corticostriatal projection neurons (CStrPN) project from the neocortex to ipsilateral and contralateral striata to control and coordinate motor programs and movement. They are clinically important as the predominant cortical population that degenerates in Huntington's disease and corticobasal ganglionic degeneration, and their injury contributes to multiple forms of cerebral palsy. Together with their well-studied functions in motor control, these clinical connections make them a functionally...

  18. The origin of cortical neurons

    Directory of Open Access Journals (Sweden)

    J.G. Parnavelas

    2002-12-01

    Full Text Available Neurons of the mammalian cerebral cortex comprise two broad classes: pyramidal neurons, which project to distant targets, and the inhibitory nonpyramidal cells, the cortical interneurons. Pyramidal neurons are generated in the germinal ventricular zone, which lines the lateral ventricles, and migrate along the processes of radial glial cells to their positions in the developing cortex in an `inside-out' sequence. The GABA-containing nonpyramidal cells originate for the most part in the ganglionic eminence, the primordium of the basal ganglia in the ventral telencephalon. These cells follow tangential migratory routes to enter the cortex and are in close association with the corticofugal axonal system. Once they enter the cortex, they move towards the ventricular zone, possibly to obtain positional information, before they migrate radially in the direction of the pial surface to take up their positions in the developing cortex. The mechanisms that guide interneurons throughout these long and complex migratory routes are currently under investigation.

  19. Turning skin into dopamine neurons

    Institute of Scientific and Technical Information of China (English)

    Malin Parmar; Johan Jakobsson

    2011-01-01

    The possibility to generate neurons from fibroblasts became a reality with the development of iPS technology a few years ago.By reprogramming somatic cells using transcription factor (TF) overexpression,it is possible to generate pluripotent stem cells that then can be differentiated into any somatic cell type including various subtypes of neurons.This raises the possibility of using donor-matched or even patientspecific cells for cell therapy of neurological disorders such as Parkinson's disease (PD),Huntington's disease and stroke.Supporting this idea,dopamine neurons,which are the cells dying in PD,derived from human iPS cells have been demonstrated to survive transplantation and reverse motor symptoms in animal models of PD [1].

  20. The neuronal code for number.

    Science.gov (United States)

    Nieder, Andreas

    2016-06-01

    Humans and non-human primates share an elemental quantification system that resides in a dedicated neural network in the parietal and frontal lobes. In this cortical network, 'number neurons' encode the number of elements in a set, its cardinality or numerosity, irrespective of stimulus appearance across sensory motor systems, and from both spatial and temporal presentation arrays. After numbers have been extracted from sensory input, they need to be processed to support goal-directed behaviour. Studying number neurons provides insights into how information is maintained in working memory and transformed in tasks that require rule-based decisions. Beyond an understanding of how cardinal numbers are encoded, number processing provides a window into the neuronal mechanisms of high-level brain functions.

  1. Quantitative study of NPY-expressing GABAergic neurons and axons in rat spinal dorsal horn.

    Science.gov (United States)

    Polgár, Erika; Sardella, Thomas C P; Watanabe, Masahiko; Todd, Andrew J

    2011-04-15

    Between 25-40% of neurons in laminae I-III are GABAergic, and some of these express neuropeptide Y (NPY). We previously reported that NPY-immunoreactive axons form numerous synapses on lamina III projection neurons that possess the neurokinin 1 receptor (NK1r). The aims of this study were to determine the proportion of neurons and GABAergic boutons in this region that contain NPY, and to look for evidence that they selectively innervate different neuronal populations. We found that 4-6% of neurons in laminae I-III were NPY-immunoreactive and based on the proportions of neurons that are GABAergic, we estimate that NPY is expressed by 18% of inhibitory interneurons in laminae I-II and 9% of those in lamina III. GABAergic boutons were identified by the presence of the vesicular GABA transporter (VGAT) and NPY was found in 13-15% of VGAT-immunoreactive boutons in laminae I-II, and 5% of those in lamina III. For both the lamina III NK1r-immunoreactive projection neurons and protein kinase Cγ (PKCγ)-immunoreactive interneurons in lamina II, we found that around one-third of the VGAT boutons that contacted them were NPY-immunoreactive. However, based on differences in the sizes of these boutons and the strength of their NPY-immunoreactivity, we conclude that these originate from different populations of interneurons. Only 6% of VGAT boutons presynaptic to large lamina I projection neurons that lacked NK1rs contained NPY. These results show that NPY-containing neurons make up a considerable proportion of the inhibitory interneurons in laminae I-III, and that their axons preferentially target certain classes of dorsal horn neuron.

  2. Transient activation of specific neurons in mice by selective expression of the capsaicin receptor

    Science.gov (United States)

    Güler, Ali D.; Rainwater, Aundrea; Parker, Jones G.; Jones, Graham L.; Argilli, Emanuela; Arenkiel, Benjamin R.; Ehlers, Michael D.; Bonci, Antonello; Zweifel, Larry s.; Palmiter, Richard D.

    2013-01-01

    The ability to control the electrical activity of a neuronal subtype is a valuable tool in deciphering the role of discreet cell populations in complex neural circuits. Recent techniques that allow remote control of neurons are either labor intensive and invasive or indirectly coupled to neural electrical potential with low temporal resolution. Here we show the rapid, reversible and direct activation of genetically identified neuronal subpopulations by generating two inducible transgenic mouse models. Confined expression of the capsaicin receptor, TRPV1, allows cell-specific activation after peripheral or oral delivery of ligand in freely moving mice. Capsaicin-induced activation of dopaminergic or serotonergic neurons reversibly alters both physiological and behavioural responses within minutes, and lasts ~10 min. These models showcase a robust and remotely controllable genetic tool that modulates a distinct cell population without the need for invasive and labour-intensive approaches. PMID:22434189

  3. Differential vulnerability of neurons in Huntington's disease: The role of cell type-specific features

    Science.gov (United States)

    Han, Ina; You, YiMei; Kordower, Jeffrey H.; Brady, Scott T.; Morfini, Gerardo A.

    2010-01-01

    Abnormal expansion of a polyglutamine tract in huntingtin (Htt) protein results in Huntington's disease (HD), an autosomal dominant neurodegenerative disorder involving progressive loss of motor and cognitive function. Contrasting with the ubiquitous tissue expression of polyglutamine-expanded Htt (polyQ-Htt), HD pathology is characterized by the increased vulnerability of specific neuronal populations within the striatum and the cerebral cortex. Morphological, biochemical, and functional characteristics of neurons affected in HD that might render these cells more vulnerable to the toxic effects of polyQ-Htt are covered in this review. The differential vulnerability of neurons observed in HD is discussed in the context of various major pathogenic mechanisms proposed to date, and in line with evidence showing a “dying-back” pattern of degeneration in affected neuronal populations. PMID:20236390

  4. In Vivo Profiling Reveals a Competent Heat Shock Response in Adult Neurons: Implications for Neurodegenerative Disorders.

    Directory of Open Access Journals (Sweden)

    Alisia Carnemolla

    Full Text Available The heat shock response (HSR is the main pathway used by cells to counteract proteotoxicity. The inability of differentiated neurons to induce an HSR has been documented in primary neuronal cultures and has been proposed to play a critical role in ageing and neurodegeneration. However, this accepted dogma has not been demonstrated in vivo. We used BAC transgenic mice generated by the Gene Expression Nervous System Atlas project to investigate the capacity of striatal medium sized spiny neurons to induce an HSR as compared to that of astrocytes and oligodendrocytes. We found that all cell populations were competent to induce an HSR upon HSP90 inhibition. We also show the presence and relative abundance of heat shock-related genes and proteins in these striatal cell populations. The identification of a competent HSR in adult neurons supports the development of therapeutics that target the HSR pathway as treatments for neurodegenerative disorders.

  5. Prospective Coding by Spiking Neurons.

    Directory of Open Access Journals (Sweden)

    Johanni Brea

    2016-06-01

    Full Text Available Animals learn to make predictions, such as associating the sound of a bell with upcoming feeding or predicting a movement that a motor command is eliciting. How predictions are realized on the neuronal level and what plasticity rule underlies their learning is not well understood. Here we propose a biologically plausible synaptic plasticity rule to learn predictions on a single neuron level on a timescale of seconds. The learning rule allows a spiking two-compartment neuron to match its current firing rate to its own expected future discounted firing rate. For instance, if an originally neutral event is repeatedly followed by an event that elevates the firing rate of a neuron, the originally neutral event will eventually also elevate the neuron's firing rate. The plasticity rule is a form of spike timing dependent plasticity in which a presynaptic spike followed by a postsynaptic spike leads to potentiation. Even if the plasticity window has a width of 20 milliseconds, associations on the time scale of seconds can be learned. We illustrate prospective coding with three examples: learning to predict a time varying input, learning to predict the next stimulus in a delayed paired-associate task and learning with a recurrent network to reproduce a temporally compressed version of a sequence. We discuss the potential role of the learning mechanism in classical trace conditioning. In the special case that the signal to be predicted encodes reward, the neuron learns to predict the discounted future reward and learning is closely related to the temporal difference learning algorithm TD(λ.

  6. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...... of large dorsal root ganglion cells. Motor conduction studies, autonomic function and warm and cold temperature sensation remained unchanged at all doses of cisplatin treatment. The results of these studies are consistent with degeneration of large sensory neurons whereas there was no evidence of distal...

  7. Electrodiagnosis of motor neuron disease.

    Science.gov (United States)

    Duleep, Anuradha; Shefner, Jeremy

    2013-02-01

    Electrodiagnostic testing has proved useful in helping to establish the diagnosis of amyotrophic lateral sclerosis by eliminating possible disease mimics and by demonstrating abnormalities in body areas that are clinically unaffected. Electrodiagnosis begins with an understanding of the clinical features of the disease, because clinical correlation is essential. To improve the sensitivity of the electrophysiologic evaluation, the Awaji criteria have been proposed as a modification to the revised El Escorial criteria. Although techniques to evaluate corticomotor neuron abnormalities and to quantify lower motor neuron loss have been developed, they remain primarily research techniques and have not yet influenced clinical practice.

  8. Amyloid β Protein Aggravates Neuronal Senescence and Cognitive Deficits in 5XFAD Mouse Model of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Zhen Wei

    2016-01-01

    Conclusions: oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for AD population.

  9. Zebrafish Müller glia-derived progenitors are multipotent, exhibit proliferative biases and regenerate excess neurons

    National Research Council Canada - National Science Library

    Powell, Curtis; Cornblath, Eli; Elsaeidi, Fairouz; Wan, Jin; Goldman, Daniel

    2016-01-01

    ...) that respond to injury by reprogramming and adopting retinal stem cell properties. These reprogrammed MG divide to produce a proliferating population of retinal progenitors that migrate to areas of retinal damage and regenerate lost neurons...

  10. Human motor neuron progenitor transplantation leads to endogenous neuronal sparing in 3 models of motor neuron loss.

    Science.gov (United States)

    Wyatt, Tanya J; Rossi, Sharyn L; Siegenthaler, Monica M; Frame, Jennifer; Robles, Rockelle; Nistor, Gabriel; Keirstead, Hans S

    2011-01-01

    Motor neuron loss is characteristic of many neurodegenerative disorders and results in rapid loss of muscle control, paralysis, and eventual death in severe cases. In order to investigate the neurotrophic effects of a motor neuron lineage graft, we transplanted human embryonic stem cell-derived motor neuron progenitors (hMNPs) and examined their histopathological effect in three animal models of motor neuron loss. Specifically, we transplanted hMNPs into rodent models of SMA (Δ7SMN), ALS (SOD1 G93A), and spinal cord injury (SCI). The transplanted cells survived and differentiated in all models. In addition, we have also found that hMNPs secrete physiologically active growth factors in vivo, including NGF and NT-3, which significantly enhanced the number of spared endogenous neurons in all three animal models. The ability to maintain dying motor neurons by delivering motor neuron-specific neurotrophic support represents a powerful treatment strategy for diseases characterized by motor neuron loss.

  11. Adult axolotls can regenerate original neuronal diversity in response to brain injury

    OpenAIRE

    Amamoto, Ryoji; Huerta, Violeta Gisselle Lopez; Takahashi, Emi; Dai, Guangping; Grant, Aaron K.; Fu, Zhanyan; Arlotta, Paola

    2016-01-01

    The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notabl...

  12. Simultaneous whole-animal 3D-imaging of neuronal activity using light field microscopy

    CERN Document Server

    Prevedel, R; Hoffmann, M; Pak, N; Wetzstein, G; Kato, S; Schrödel, T; Raskar, R; Zimmer, M; Boyden, E S; Vaziri, A

    2014-01-01

    3D functional imaging of neuronal activity in entire organisms at single cell level and physiologically relevant time scales faces major obstacles due to trade-offs between the size of the imaged volumes, and spatial and temporal resolution. Here, using light-field microscopy in combination with 3D deconvolution, we demonstrate intrinsically simultaneous volumetric functional imaging of neuronal population activity at single neuron resolution for an entire organism, the nematode Caenorhabditis elegans. The simplicity of our technique and possibility of the integration into epi-fluoresence microscopes makes it an attractive tool for high-speed volumetric calcium imaging.

  13. Spatial learning depends on both the addition and removal of new hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    David Dupret

    2007-08-01

    Full Text Available The role of adult hippocampal neurogenesis in spatial learning remains a matter of debate. Here, we show that spatial learning modifies neurogenesis by inducing a cascade of events that resembles the selective stabilization process characterizing development. Learning promotes survival of relatively mature neurons, apoptosis of more immature cells, and finally, proliferation of neural precursors. These are three interrelated events mediating learning. Thus, blocking apoptosis impairs memory and inhibits learning-induced cell survival and cell proliferation. In conclusion, during learning, similar to the selective stabilization process, neuronal networks are sculpted by a tightly regulated selection and suppression of different populations of newly born neurons.

  14. Intrinsic cholinergic neurons in the hippocampus: fact or artefact?

    Directory of Open Access Journals (Sweden)

    Jan Krzysztof Blusztajn

    2016-03-01

    Full Text Available It is generally agreed that hippocampal acetylcholine (ACh is synthesized and released exclusively from the terminals of the long-axon afferents whose cell bodies reside in the medial septum and diagonal band. The search for intrinsic cholinergic neurons in the hippocampus has a long history; however evidence for the existence of these neurons has been inconsistent, with most investigators failing to detect them using in situ hybridization or immunohistochemical staining of the cholinergic markers, choline acetyltransferase (CHAT or vesicular acetylcholine transporter (VACHT. Advances in the use of bacterial artificial chromosome (BAC transgenic mice expressing a reporter protein under the control of the genomic elements of the Chat gene (Chat-BAC mice have facilitated studies of cholinergic neurons. Such mice show robust and faithful expression of the reporter proteins in all known cholinergic cell populations. The availability of the Chat-BAC mice re-ignited interest in hippocampal cholinergic interneurons, because a small number of such reporter-expressing cells is frequently observed in the hippocampus of these mice. However, to date, attempts to confirm that these neurons co-express the endogenous cholinergic markers CHAT or VACHT, or release ACh, have been unsuccessful. Without such confirmatory evidence it is best to conclude that there are no cholinergic neurons in the hippocampus. Similar considerations apply to other BAC transgenic lines, whose utility as a discovery tool for cell populations heretofore not known to express the genes of interest encoded by the BACs, must be validated by methods that detect expression of the endogenous genes.

  15. [What mirror neurons have revealed: revisited].

    Science.gov (United States)

    Murata, Akira; Maeda, Kazutaka

    2014-06-01

    The first paper on mirror neurons was published in 1992. In the span of over two decades since then, much knowledge about the relationship between social cognitive function and the motor control system has been accumulated. Direct matching of visual actions and their corresponding motor representations is the most important functional property of mirror neuron. Many studies have emphasized intrinsic simulation as a core concept for mirror neurons. Mirror neurons are thought to play a role in social cognitive function. However, the function of mirror neurons in the macaque remains unclear, because such cognitive functions are limited or lacking in macaque monkeys. It is therefore important to discuss these neurons in the context of motor function. Rizzolatti and colleagues have stressed that the most important function of mirror neurons in macaques is recognition of actions performed by other individuals. I suggest that mirror neurons in the Macaque inferior pariental lobule might be correlated with body schema. In the parieto-premotor network, matching of corollary discharge and actual sensory feedback is an essential neuronal operation. Recently, neurons showing mirror properties were found in some cortical areas outside the mirror neuron system. The current work would revisit the outcomes of mirror neuron studies to discuss the function of mirror neurons in the monkey.

  16. Genetically-directed, cell type-specific sparse labeling for the analysis of neuronal morphology.

    Directory of Open Access Journals (Sweden)

    Thomas Rotolo

    Full Text Available BACKGROUND: In mammals, genetically-directed cell labeling technologies have not yet been applied to the morphologic analysis of neurons with very large and complex arbors, an application that requires extremely sparse labeling and that is only rendered practical by limiting the labeled population to one or a few predetermined neuronal subtypes. METHODS AND FINDINGS: In the present study we have addressed this application by using CreER technology to non-invasively label very small numbers of neurons so that their morphologies can be fully visualized. Four lines of IRES-CreER knock-in mice were constructed to permit labeling selectively in cholinergic or catecholaminergic neurons [choline acetyltransferase (ChAT-IRES-CreER or tyrosine hydroxylase (TH-IRES-CreER], predominantly in projection neurons [neurofilament light chain (NFL-IRES-CreER], or broadly in neurons and some glia [vesicle-associated membrane protein2 (VAMP2-IRES-CreER]. When crossed to the Z/AP reporter and exposed to 4-hydroxytamoxifen in the early postnatal period, the number of neurons expressing the human placental alkaline phosphatase reporter can be reproducibly lowered to fewer than 50 per brain. Sparse Cre-mediated recombination in ChAT-IRES-CreER;Z/AP mice shows the full axonal and dendritic arbors of individual forebrain cholinergic neurons, the first time that the complete morphologies of these very large neurons have been revealed in any species. CONCLUSIONS: Sparse genetically-directed, cell type-specific neuronal labeling with IRES-creER lines should prove useful for studying a wide variety of questions in neuronal development and disease.

  17. Intrinsic neuronal properties switch the mode of information transmission in networks.

    Directory of Open Access Journals (Sweden)

    Julijana Gjorgjieva

    2014-12-01

    Full Text Available Diverse ion channels and their dynamics endow single neurons with complex biophysical properties. These properties determine the heterogeneity of cell types that make up the brain, as constituents of neural circuits tuned to perform highly specific computations. How do biophysical properties of single neurons impact network function? We study a set of biophysical properties that emerge in cortical neurons during the first week of development, eventually allowing these neurons to adaptively scale the gain of their response to the amplitude of the fluctuations they encounter. During the same time period, these same neurons participate in large-scale waves of spontaneously generated electrical activity. We investigate the potential role of experimentally observed changes in intrinsic neuronal properties in determining the ability of cortical networks to propagate waves of activity. We show that such changes can strongly affect the ability of multi-layered feedforward networks to represent and transmit information on multiple timescales. With properties modeled on those observed at early stages of development, neurons are relatively insensitive to rapid fluctuations and tend to fire synchronously in response to wave-like events of large amplitude. Following developmental changes in voltage-dependent conductances, these same neurons become efficient encoders of fast input fluctuations over few layers, but lose the ability to transmit slower, population-wide input variations across many layers. Depending on the neurons' intrinsic properties, noise plays different roles in modulating neuronal input-output curves, which can dramatically impact network transmission. The developmental change in intrinsic properties supports a transformation of a networks function from the propagation of network-wide information to one in which computations are scaled to local activity. This work underscores the significance of simple changes in conductance parameters in

  18. Intrinsic neuronal properties switch the mode of information transmission in networks.

    Science.gov (United States)

    Gjorgjieva, Julijana; Mease, Rebecca A; Moody, William J; Fairhall, Adrienne L

    2014-12-01

    Diverse ion channels and their dynamics endow single neurons with complex biophysical properties. These properties determine the heterogeneity of cell types that make up the brain, as constituents of neural circuits tuned to perform highly specific computations. How do biophysical properties of single neurons impact network function? We study a set of biophysical properties that emerge in cortical neurons during the first week of development, eventually allowing these neurons to adaptively scale the gain of their response to the amplitude of the fluctuations they encounter. During the same time period, these same neurons participate in large-scale waves of spontaneously generated electrical activity. We investigate the potential role of experimentally observed changes in intrinsic neuronal properties in determining the ability of cortical networks to propagate waves of activity. We show that such changes can strongly affect the ability of multi-layered feedforward networks to represent and transmit information on multiple timescales. With properties modeled on those observed at early stages of development, neurons are relatively insensitive to rapid fluctuations and tend to fire synchronously in response to wave-like events of large amplitude. Following developmental changes in voltage-dependent conductances, these same neurons become efficient encoders of fast input fluctuations over few layers, but lose the ability to transmit slower, population-wide input variations across many layers. Depending on the neurons' intrinsic properties, noise plays different roles in modulating neuronal input-output curves, which can dramatically impact network transmission. The developmental change in intrinsic properties supports a transformation of a networks function from the propagation of network-wide information to one in which computations are scaled to local activity. This work underscores the significance of simple changes in conductance parameters in governing how neurons

  19. Do premotor interneurons act in parallel on spinal motoneurons and on dorsal horn spinocerebellar and spinocervical tract neurons in the cat?

    Science.gov (United States)

    Krutki, Piotr; Jelen, Sabina; Jankowska, Elzbieta

    2011-04-01

    It has previously been established that ventral spinocerebellar tract (VSCT) neurons and dorsal spinocerebellar tract neurons located in Clarke's column (CC DSCT neurons) forward information on actions of premotor interneurons in reflex pathways from muscle afferents on α-motoneurons. Whether DSCT neurons located in the dorsal horn (dh DSCT neurons) and spinocervical tract (SCT) neurons are involved in forwarding similar feedback information has not yet been investigated. The aim of the present study was therefore to examine the input from premotor interneurons to these neurons. Electrical stimuli were applied within major hindlimb motor nuclei to activate axon-collaterals of interneurons projecting to these nuclei, and intracellular records were obtained from dh DSCT and SCT neurons. Direct actions of the stimulated interneurons were differentiated from indirect actions by latencies of postsynaptic potentials evoked by intraspinal stimuli and by the absence or presence of temporal facilitation. Direct actions of premotor interneurons were found in a smaller proportion of dh DSCT than of CC DSCT neurons. However, they were evoked by both excitatory and inhibitory interneurons, whereas only inhibitory premotor interneurons were previously found to affect CC DSCT neurons [as indicated by monosynaptic excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) in dh DSCT and only IPSPs in CC DSCT neurons]. No effects of premotor interneurons were found in SCT neurons, since monosynaptic EPSPs or IPSPs were only evoked in them by stimuli applied outside motor nuclei. The study thus reveals a considerable differentiation of feedback information provided by different populations of ascending tract neurons.

  20. Role of immediate-early genes in synaptic plasticity and neuronal ensembles underlying the memory trace

    Directory of Open Access Journals (Sweden)

    Keiichiro eMinatohara

    2016-01-01

    Full Text Available In the brain, neuronal gene expression is dynamically changed in response to neuronal activity. In particular, the expression of immediate-early genes (IEGs such as egr-1, c-fos, and Arc is rapidly and selectively upregulated in subsets of neurons in specific brain regions associated with learning and memory formation. IEG expression has therefore been widely used as a molecular marker for neuronal populations that undergo plastic changes underlying formation of long-term memory. In recent years, optogenetic and pharmacogenetic studies of neurons expressing c-fos or Arc have revealed that, during learning, IEG-positive neurons encode and store information that is required for memory recall, suggesting that they may be involved in formation of the memory trace. However, despite accumulating evidence for the role of IEGs in synaptic plasticity, the molecular and cellular mechanisms associated with this process remain unclear. In this review, we first summarize recent literature concerning the role of IEG-expressing neuronal ensembles in organizing the memory trace. We then focus on the physiological significance of IEGs, especially Arc, in synaptic plasticity, and describe our hypotheses about the importance of Arc expression in various types of input-specific circuit reorganization. Finally, we offer perspectives on Arc function that would unveil the role of IEG-expressing neurons in the formation of memory traces in the hippocampus and other brain areas.

  1. Arcuate AgRP neurons and the regulation of energy balance

    Directory of Open Access Journals (Sweden)

    Céline eCansell

    2012-12-01

    Full Text Available The arcuate nucleus of the hypothalamus contains at least two crucial populations of neurons that continuously monitor signals reflecting energy status and promote the appropriate behavioral and metabolic responses to changes in energy demand. Neurons making pro-opiomelanocortin (POMC decrease food intake and increase energy expenditure through activation of G protein-coupled receptors melanocortin receptors (MCR via the release of a-melanocyte stimulating hormone. A prevailing idea until recently was that the neighboring neurons expressing the orexigenic neuropeptides, agouti-related protein (AgRP and neuropeptide Y (NPY (AgRP neurons increased feeding by opposing the anorexigenic actions of the POMC neurons. AgRP neurons activation but not POMC neurons inhibition was recently demonstrated to be necessary and sufficient to promote feeding. AgRP expressing axons were identified in mesolimbic, midbrain and pontine structure where they regulate feeding but also feeding-independent functions such as reward or peripheral nutrient partitioning. Post-synaptic Gamma aminobutyric acid (GABA, lasting in a timeline similar to neuromodulation, was identified as the core mechanism by which hunger-activated neurons regulate feeding and non-food related processes in a melanocortin independent manner.

  2. Antipsychotic drugs alter neuronal development including ALM neuroblast migration and PLM axonal outgrowth in Caenorhabditis elegans.

    Science.gov (United States)

    Donohoe, Dallas R; Weeks, Kathrine; Aamodt, Eric J; Dwyer, Donard S

    2008-01-01

    Antipsychotic drugs are increasingly being prescribed for children and adolescents, and are used in pregnant women without a clear demonstration of safety in these populations. Global effects of these drugs on neurodevelopment (e.g., decreased brain size) have been reported in rats, but detailed knowledge about neuronal effects and mechanisms of action are lacking. Here we report on the evaluation of a comprehensive panel of antipsychotic drugs in a model organism (Caenorhabditis elegans) that is widely used to study neuronal development. Specifically, we examined the effects of the drugs on neuronal migration and axonal outgrowth in mechanosensory neurons visualized with green fluorescent protein expressed from the mec-3 promoter. Clozapine, fluphenazine, and haloperidol produced deficits in the development and migration of ALM neurons and axonal outgrowth in PLM neurons. The defects included failure of neuroblasts to migrate to the proper location, and excessive growth of axons past their normal termination point, together with abnormal morphological features of the processes. Although the antipsychotic drugs are potent antagonists of dopamine and serotonin receptors, the neurodevelopmental deficits were not rescued by co-incubation with serotonin or the dopaminergic agonist, quinpirole. Other antipsychotic drugs, risperidone, aripiprazole, quetiapine, trifluoperazine and olanzapine, also produced modest, but detectable, effects on neuronal development. This is the first report that antipsychotic drugs interfere with neuronal migration and axonal outgrowth in a developing nervous system.

  3. Tumor necrosis factor alpha is toxic to embryonic mesencephalic dopamine neurons.

    Science.gov (United States)

    McGuire, S O; Ling, Z D; Lipton, J W; Sortwell, C E; Collier, T J; Carvey, P M

    2001-06-01

    Levels of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) are increased in postmortem brain and cerebral spinal fluid from patients with Parkinson's disease (PD). This observation provides a basis for associating TNFalpha with neurodegeneration, but a specific toxicity in dopamine (DA) neurons has not been firmly established. Therefore, we investigated TNFalpha-induced toxicity in DA neurons by utilizing primary cultures of embryonic rat mesencephalon. Exposure to TNFalpha resulted in a dose-dependent decrease in DA neurons as evidenced by decreased numbers of tyrosine hydroxylase-immunoreactive (THir) cells. TNFalpha toxicity was selective for DA neurons in that neither glial cell counts nor the total number of neurons was decreased and no general cytotoxicity was evidenced by lactate dehydrogenase assay. Many of the cells which remained immunoreactive for TH had shrunken and rounded cell bodies with broken, blunted, or absent processes. However, TNFalpha-treated cultures also contained some THir cells which appeared to be undamaged and possibly resistant to TNFalpha-induced toxicity. Additionally, immunocytochemistry revealed basal expression of TNFalpha receptor 1 (p55, R1) and TNFalpha receptor 2 (p75, R2) on all cells within the mesencephalic cultures to some degree, even though only DA neurons were affected by TNFalpha treatment. These data strongly suggest that TNFalpha mediates cell death in a sensitive population of DA neurons and support the potential involvement of proinflammatory cytokines in the degeneration of DA neurons in PD.

  4. Activity of protease-activated receptors in primary cultured human myenteric neurons

    Directory of Open Access Journals (Sweden)

    Eva Maria Kugler

    2012-09-01

    Full Text Available Activity of the four known protease-activated receptors (PARs has been well studied in rodent enteric nervous system and results in animal models established an important role for neuronal PAR2. We recently demonstrated that, unlike in rodents, PAR1 is the dominant neuronal protease receptor in the human submucous plexus. With this study we investigated whether this also applies to the human myenteric plexus. We used voltage sensitive dye recordings to detect action potential discharge in primary cultures of human myenteric neurons in response to PAR activating peptides (AP. Application of the PAR1-AP (TFLLR or PAR4-AP (GYPGQV evoked spike discharge in 79% or 23% of myenteric neurons, respectively. The PAR1-AP response was mimicked by the endogenous PAR1 activator thrombin and blocked by the PAR1 antagonists SCH79797. Human myenteric neurons did not respond to PAR2-AP. This was not due to culture conditions because all three PAR-APs evoked action potentials in cultured guinea pig myenteric neurons. Consecutive application of PAR-APs revealed coexpression (relative to the population responding to PAR-APs of PAR1/PAR2 in 51%, PAR1/PAR4 in 43% and of PAR2/PAR4 in 29% of guinea pig myenteric neurons. Our study provided further evidence for the prominent role of neuronal PAR1 in the human enteric nervous system.

  5. Temporally matched subpopulations of selectively interconnected principal neurons in the hippocampus.

    Science.gov (United States)

    Deguchi, Yuichi; Donato, Flavio; Galimberti, Ivan; Cabuy, Erik; Caroni, Pico

    2011-04-01

    The extent to which individual neurons are interconnected selectively within brain circuits is an unresolved problem in neuroscience. Neurons can be organized into preferentially interconnected microcircuits, but whether this reflects genetically defined subpopulations is unclear. We found that the principal neurons in the main subdivisions of the hippocampus consist of distinct subpopulations that are generated during distinct time windows and that interconnect selectively across subdivisions. In two mouse lines in which transgene expression was driven by the neuron-specific Thy1 promoter, transgene expression allowed us to visualize distinct populations of principal neurons with unique and matched patterns of gene expression, shared distinct neurogenesis and synaptogenesis time windows, and selective connectivity at dentate gyrus-CA3 and CA3-CA1 synapses. Matched subpopulation marker genes and neuronal subtype markers mapped near clusters of olfactory receptor genes. The nonoverlapping matched timings of synaptogenesis accounted for the selective connectivities of these neurons in CA3. Therefore, the hippocampus contains parallel connectivity channels assembled from distinct principal neuron subpopulations through matched schedules of synaptogenesis.

  6. Role of Immediate-Early Genes in Synaptic Plasticity and Neuronal Ensembles Underlying the Memory Trace.

    Science.gov (United States)

    Minatohara, Keiichiro; Akiyoshi, Mika; Okuno, Hiroyuki

    2015-01-01

    In the brain, neuronal gene expression is dynamically changed in response to neuronal activity. In particular, the expression of immediate-early genes (IEGs) such as egr-1, c-fos, and Arc is rapidly and selectively upregulated in subsets of neurons in specific brain regions associated with learning and memory formation. IEG expression has therefore been widely used as a molecular marker for neuronal populations that undergo plastic changes underlying formation of long-term memory. In recent years, optogenetic and pharmacogenetic studies of neurons expressing c-fos or Arc have revealed that, during learning, IEG-positive neurons encode and store information that is required for memory recall, suggesting that they may be involved in formation of the memory trace. However, despite accumulating evidence for the role of IEGs in synaptic plasticity, the molecular and cellular mechanisms associated with this process remain unclear. In this review, we first summarize recent literature concerning the role of IEG-expressing neuronal ensembles in organizing the memory trace. We then focus on the physiological significance of IEGs, especially Arc, in synaptic plasticity, and describe our hypotheses about the importance of Arc expression in various types of input-specific circuit reorganization. Finally, we offer perspectives on Arc function that would unveil the role of IEG-expressing neurons in the formation of memory traces in the hippocampus and other brain areas.

  7. The molecular signature and cis-regulatory architecture of a C. elegans gustatory neuron

    Science.gov (United States)

    Etchberger, John F.; Lorch, Adam; Sleumer, Monica C.; Zapf, Richard; Jones, Steven J.; Marra, Marco A.; Holt, Robert A.; Moerman, Donald G.; Hobert, Oliver

    2007-01-01

    Taste receptor cells constitute a highly specialized cell type that perceives and conveys specific sensory information to the brain. The detailed molecular composition of these cells and the mechanisms that program their fate are, in general, poorly understood. We have generated serial analysis of gene expression (SAGE) libraries from two distinct populations of single, isolated sensory neuron classes, the gustatory neuron class ASE and the thermosensory neuron class AFD, from the nematode Caenorhabditis elegans. By comparing these two libraries, we have identified >1000 genes that define the ASE gustatory neuron class on a molecular level. This set of genes contains determinants of the differentiated state of the ASE neuron, such as a surprisingly complex repertoire of transcription factors (TFs), ion channels, neurotransmitters, and receptors, as well as seven-transmembrane receptor (7TMR)-type putative gustatory receptor genes. Through the in vivo dissection of the cis-regulatory regions of several ASE-expressed genes, we identified a small cis-regulatory motif, the “ASE motif,” that is required for the expression of many ASE-expressed genes. We demonstrate that the ASE motif is a binding site for the C2H2 zinc finger TF CHE-1, which is essential for the correct differentiation of the ASE gustatory neuron. Taken together, our results provide a unique view of the molecular landscape of a single neuron type and reveal an important aspect of the regulatory logic for gustatory neuron specification in C. elegans. PMID:17606643

  8. Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions.

    Science.gov (United States)

    Luhmann, Heiko J; Sinning, Anne; Yang, Jenq-Wei; Reyes-Puerta, Vicente; Stüttgen, Maik C; Kirischuk, Sergei; Kilb, Werner

    2016-01-01

    Neuronal activity has been shown to be essential for the proper formation of neuronal circuits, affecting developmental processes like neurogenesis, migration, programmed cell death, cellular differentiation, formation of local and long-range axonal connections, synaptic plasticity or myelination. Accordingly, neocortical areas reveal distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, when immature neurons start to develop voltage-dependent channels, spontaneous activity is highly synchronized within small neuronal networks and governed by electrical synaptic transmission. Subsequently, spontaneous activity patterns become more complex, involve larger networks and propagate over several neocortical areas. The developmental shift from local to large-scale network activity is accompanied by a gradual shift from electrical to chemical synaptic transmission with an initial excitatory action of chloride-gated channels activated by GABA, glycine and taurine. Transient neuronal populations in the subplate (SP) support temporary circuits that play an important role in tuning early neocortical activity and the formation of mature neuronal networks. Thus, early spontaneous activity patterns control the formation of developing networks in sensory cortices, and disturbances of these activity patterns may lead to long-lasting neuronal deficits.

  9. Estimate of size and total number of neurons in superior cervical ganglion of rat, capybara and horse.

    Science.gov (United States)

    Ribeiro, Antonio Augusto Coppi Maciel; Davis, Christine; Gabella, Giorgio

    2004-08-01

    The superior (cranial) cervical ganglion was investigated by light microscopy in adult rats, capybaras (Hydrochaeris hydrochaeris) and horses. The ganglia were vascularly perfused, embedded in resin and cut into semi-thin sections. An unbiased stereological procedure (disector method) was used to estimate ganglion neuron size, total number of ganglion neurons, neuronal density. The volume of the ganglion was 0.5 mm3 in rats, 226 mm3 in capybaras and 412 mm3 in horses. The total number of neurons per ganglion was 18,800, 1,520,000 and 3,390,000 and the number of neurons per cubic millimetre was 36,700, 7,000 and 8,250 in rats, capybaras and horses, respectively. The average neuronal size (area of the largest sectional profile of a neuron) was 358, 982 and 800 microm2, and the percentage of volume occupied by neurons was 33, 21 and 17% in rats, capybaras and horses, respectively. When comparing the three species (average body weight: 200 g, 40 kg and 200 kg), most of the neuronal quantitative parameters change in line with the variation of body weight. However, the average neuronal size in the capybara deviates from this pattern in being larger than that of in the horse. The rat presented great interindividual variability in all the neuronal parameters. From the data in the literature and our new findings in the capybara and horse, we conclude that some correlations exist between average size of neurons and body size and between total number of neurons and body size. However, these correlations are only approximate and are based on averaged parameters for large populations of neurons: they are less likely to be valid if one considers a single quantitative parameter. Several quantitative features of the nervous tissue have to be taken into account together, rather than individually, when evolutionary trends related to size are considered.

  10. Co-localization of Gamma-Aminobutyric Acid and Glutamate in Neurons of the Spider Central Nervous System.

    Science.gov (United States)

    Fabian-Fine, Ruth; Meisner, Shannon; Torkkeli, Päivi H; Meinertzhagen, Ian A

    2015-12-01

    Spider sensory neurons with cell bodies close to various sensory organs are innervated by putative efferent axons from the central nervous system (CNS). Light and electronmicroscopic imaging of immunolabeled neurons has demonstrated that neurotransmitters present at peripheral synapses include γ-aminobutyric acid (GABA), glutamate and octopamine. Moreover, electrophysiological studies show that these neurotransmitters modulate the sensitivity of peripheral sensory neurons. Here, we undertook immunocytochemical investigations to characterize GABA and glutamate-immunoreactive neurons in three-dimensional reconstructions of the spider CNS. We document that both neurotransmitters are abundant in morphologically distinct neurons throughout the CNS. Labeling for the vesicular transporters, VGAT for GABA and VGLUT for glutamate, showed corresponding patterns, supporting the specificity of antibody binding. Whereas some neurons displayed strong immunolabeling, others were only weakly labeled. Double labeling showed that a subpopulation of weakly labeled neurons present in all ganglia expresses both GABA and glutamate. Double labeled, strongly and weakly labeled GABA and glutamate immunoreactive axons were also observed in the periphery along muscle fibers and peripheral sensory neurons. Electron microscopic investigations showed presynaptic profiles of various diameters with mixed vesicle populations innervating muscle tissue as well as sensory neurons. Our findings provide evidence that: (1) sensory neurons and muscle fibers are innervated by morphologically distinct, centrally located GABA- and glutamate immunoreactive neurons; (2) a subpopulation of these neurons may co-release both neurotransmitters; and (3) sensory neurons and muscles are innervated by all of these neurochemically and morphologically distinct types of neurons. The biochemical diversity of presynaptic innervation may contribute to how spiders filter natural stimuli and coordinate appropriate response

  11. The isotropic fractionator provides evidence for differential loss of hippocampal neurons in two mouse models of Alzheimer's disease.

    Science.gov (United States)

    Brautigam, Hannah; Steele, John W; Westaway, David; Fraser, Paul E; St George-Hyslop, Peter H; Gandy, Sam; Hof, Patrick R; Dickstein, Dara L

    2012-11-22

    The accumulation of amyloid beta (Aβ) oligomers or fibrils is thought to be one of the main causes of synaptic and neuron loss, believed to underlie cognitive dysfunction in Alzheimer's disease (AD). Neuron loss has rarely been documented in amyloid precursor protein (APP) transgenic mouse models. We investigated whether two APP mouse models characterized by different folding states of amyloid showed different neuronal densities using an accurate method of cell counting. We examined total cell and neuronal populations in Swedish/Indiana APP mutant mice (TgCRND8) with severe Aβ pathology that includes fibrils, plaques, and oligomers, and Dutch APP mutant mice with only Aβ oligomer pathology. Using the isotropic fractionator, we found no differences from control mice in regional total cell populations in either TgCRND8 or Dutch mice. However, there were 31.8% fewer hippocampal neurons in TgCRND8 compared to controls, while no such changes were observed in Dutch mice. We show that the isotropic fractionator is a convenient method for estimating neuronal content in milligram quantities of brain tissue and represents a useful tool to assess cell loss efficiently in transgenic models with different types of neuropathology. Our data support the hypothesis that TgCRND8 mice with a spectrum of Aβ plaque, fibril, and oligomer pathology exhibit neuronal loss whereas Dutch mice with only oligomers, showed no evidence for neuronal loss. This suggests that the combination of plaques, fibrils, and oligomers causes more damage to mouse hippocampal neurons than Aβ oligomers alone.

  12. Reorganization of cortical population activity imaged throughout long-term sensory deprivation.

    Science.gov (United States)

    Margolis, David J; Lütcke, Henry; Schulz, Kristina; Haiss, Florent; Weber, Bruno; Kügler, Sebastian; Hasan, Mazahir T; Helmchen, Fritjof

    2012-11-01

    Sensory maps are reshaped by experience. It is unknown how map plasticity occurs in vivo in functionally diverse neuronal populations because activity of the same cells has not been tracked over long time periods. Here we used repeated two-photon imaging of a genetic calcium indicator to measure whisker-evoked responsiveness of the same layer 2/3 neurons in adult mouse barrel cortex over weeks, first with whiskers intact, then during continued trimming of all but one whisker. Across the baseline period, neurons displayed heterogeneous yet stable responsiveness. During sensory deprivation, responses to trimmed whisker stimulation globally decreased, whereas responses to spared whisker stimulation increased for the least active neurons and decreased for the most active neurons. These findings suggest that recruitment of inactive, 'silent' neurons is part of a convergent redistribution of population activity underlying sensory map plasticity. Sensory-driven responsiveness is a key property controlling experience-dependent activity changes in individual neurons.

  13. Counting Populations

    Science.gov (United States)

    Damonte, Kathleen

    2004-01-01

    Scientists use sampling to get an estimate of things they cannot easily count. A population is made up of all the organisms of one species living together in one place at the same time. All of the people living together in one town are considered a population. All of the grasshoppers living in a field are a population. Scientists keep track of the…

  14. Computing with Spiking Neuron Networks

    NARCIS (Netherlands)

    Paugam-Moisy, H.; Bohte, S.M.; Rozenberg, G.; Baeck, T.H.W.; Kok, J.N.

    2012-01-01

    Abstract Spiking Neuron Networks (SNNs) are often referred to as the 3rd gener- ation of neural networks. Highly inspired from natural computing in the brain and recent advances in neurosciences, they derive their strength and interest from an ac- curate modeling of synaptic interactions between neu

  15. Motor neurone disease: an overview.

    Science.gov (United States)

    Kent, Anna

    Motor neurone disease (MND) is a relatively rare, progressive and incurable neurological condition affecting patients' speech, mobility and respiratory function. Care of patients with MND is complex and involves various healthcare professionals and services. There is a need to discuss symptom management and promote palliative and end of life care from the point of diagnosis to ensure appropriate holistic care is provided.

  16. Neuronal circuits of fear extinction.

    Science.gov (United States)

    Herry, Cyril; Ferraguti, Francesco; Singewald, Nicolas; Letzkus, Johannes J; Ehrlich, Ingrid; Lüthi, Andreas

    2010-02-01

    Fear extinction is a form of inhibitory learning that allows for the adaptive control of conditioned fear responses. Although fear extinction is an active learning process that eventually leads to the formation of a consolidated extinction memory, it is a fragile behavioural state. Fear responses can recover spontaneously or subsequent to environmental influences, such as context changes or stress. Understanding the neuronal substrates of fear extinction is of tremendous clinical relevance, as extinction is the cornerstone of psychological therapy of several anxiety disorders and because the relapse of maladaptative fear and anxiety is a major clinical problem. Recent research has begun to shed light on the molecular and cellular processes underlying fear extinction. In particular, the acquisition, consolidation and expression of extinction memories are thought to be mediated by highly specific neuronal circuits embedded in a large-scale brain network including the amygdala, prefrontal cortex, hippocampus and brain stem. Moreover, recent findings indicate that the neuronal circuitry of extinction is developmentally regulated. Here, we review emerging concepts of the neuronal circuitry of fear extinction, and highlight novel findings suggesting that the fragile phenomenon of extinction can be converted into a permanent erasure of fear memories. Finally, we discuss how research on genetic animal models of impaired extinction can further our understanding of the molecular and genetic bases of human anxiety disorders.

  17. What do mirror neurons mirror?

    NARCIS (Netherlands)

    Uithol, S.; Rooij, I.J.E.I. van; Bekkering, H.; Haselager, W.F.G.

    2011-01-01

    Single cell recordings in monkeys provide strong evidence for an important role of the motor system in action understanding. This evidence is backed up by data from studies of the (human) mirror neuron system using neuroimaging or TMS techniques, and behavioral experiments. Although the data acquire

  18. What do mirror neurons mirror?

    NARCIS (Netherlands)

    Uithol, S.; Rooij, I.J.E.I. van; Bekkering, H.; Haselager, W.F.G.

    2011-01-01

    Single cell recordings in monkeys provide strong evidence for an important role of the motor system in action understanding. This evidence is backed up by data from studies of the (human) mirror neuron system using neuroimaging or TMS techniques, and behavioral experiments. Although the data

  19. Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

    Energy Technology Data Exchange (ETDEWEB)

    Greene, Carol Ann, E-mail: carol.greene@auckland.ac.nz; Chang, Chuan-Yuan; Fraser, Cameron J.; Nelidova, Dasha E.; Chen, Jing A.; Lim, Angela; Brebner, Alex; McGhee, Jennifer; Sherwin, Trevor; Green, Colin R.

    2014-03-10

    Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors.

  20. [The ontogeny of the mirror neuron system].

    Science.gov (United States)

    Myowa-Yamakoshi, Masako

    2014-06-01

    Abstract Humans utilize the mirror neuron system to understand and predict others' actions. However, the ontogeny of the mirror neuron system remains unknown. Whether mirror neuron function is an innate trait or whether mirror neurons acquire their sensorimotor matching properties ontogenetically remains to be clarified. In this paper, I review the ontogenetic theory of the mirror neuron system. I then discuss the functioning of the mirror neuron system in the context of social cognitive abilities, which are unique to humans. Recently, some researchers argue that it is too early to interpret the function of mirror neurons as an understanding of the underlying psychological states of others. They imply that such functioning would require inferential cognitive processes that are known to involve areas outside the mirror neuron system. Filling in this missing link may be the key to elucidating the unique ability of humans to understand others' actions.

  1. Performance of a Single Quantum Neuron

    Institute of Scientific and Technical Information of China (English)

    LIFei; ZHAOShengmei; ZHENGBaoyu

    2005-01-01

    Quantum neural network (QNN) is a promising area in the field of quantum computing and quantum information processing. A novel model for quantum neuron is described, a quantum learning algorithm is proposed and its convergence property is investigated. It has been shown, Quantum neuron (QN) has the same convergence property as Conventional neuron (CN) but can attain faster training than Conventional neuron. The computational power of the quantum neuron is also explored.Numerical and graphical results show that this single quantum neuron can implement the Walsh-Hadamard transformation, perform the XOR function unrealizable with a classical neuron and can eliminate the necessity of building a network of neurons to obtain nonlinear mapping.

  2. Effect of Methamidophos on cerebellar neuronal cells

    African Journals Online (AJOL)

    olayemitoyin

    TH-mediated cerebellar neuronal cell development and function, and consequently could interfere with TH-regulated neuronal ... 1972), decreased number of synapses between the. Purkinje .... 0.008%DNase and triturated in same solution to ...

  3. In vitro differentiation of bone marrow stromal cells into neurons and glial cells and differential protein expression in a two-compartment bone marrow stromal cell/neuron co-culture system.

    Science.gov (United States)

    Qi, Xu; Shao, Ming; Peng, Haisheng; Bi, Zhenggang; Su, Zhiqiang; Li, Hulun

    2010-07-01

    This study was performed to establish a bone marrow stromal cell (BMSC)/neuron two-compartment co-culture model in which differentiation of BMSCs into neurons could occur without direct contact between the two cell types, and to investigate protein expression changes during differentiation of this entirely BMSC-derived population. Cultured BMSCs isolated from Wistar rats were divided into three groups: BMSC culture, BMSC/neuron co-culture and BMSC/neuron two-compartment co-culture. Cells were examined for neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) expression. The electrophysiological behavior of the BMSCs was examined using patch clamping. Proteins that had significantly different expression levels in BMSCs cultured alone and co-cultured with neurons were studied using a protein chip-mass spectroscopy technique. Expression of NSE and GFAP were significantly higher in co-culture cells than in two-compartment co-culture cells, and significantly higher in both co-culture groups than in BMSCs cultured alone. Five proteins showed significant changes in expression during differentiation: TIP39_RAT and CALC_RAT underwent increases, and INSL6_RAT, PNOC_RAT and PCSK1_RAT underwent decreases in expression. We conclude that BMSCs can differentiate into neurons during both contact co-culture with neurons and two-compartment co-culture with neurons. The rate at which BMSCs differentiated into neurons was higher in contact co-culture than in non-contact co-culture.

  4. CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin

    Directory of Open Access Journals (Sweden)

    Pierre Cardinal

    2014-10-01

    Full Text Available Metabolic flexibility allows rapid adaptation to dietary change, however, little is known about the CNS mechanisms regulating this process. Neurons in the hypothalamic ventromedial nucleus (VMN participate in energy balance and are the target of the metabolically relevant hormone leptin. Cannabinoid type-1 (CB1 receptors are expressed in VMN neurons, but the specific contribution of endocannabinoid signaling in this neuronal population to energy balance regulation is unknown. Here we demonstrate that VMN CB1 receptors regulate metabolic flexibility and actions of leptin. In chow-fed mice, conditional deletion of CB1 in VMN neurons (expressing the steroidogenic factor 1, SF1 decreases adiposity by increasing sympathetic activity and lipolysis, and facilitates metabolic effects of leptin. Conversely, under high-fat diet, lack of CB1 in VMN neurons produces leptin resistance, blunts peripheral use of lipid substrates and increases adiposity. Thus, CB1 receptors in VMN neurons provide a molecular switch adapting the organism to dietary change.

  5. CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin.

    Science.gov (United States)

    Cardinal, Pierre; André, Caroline; Quarta, Carmelo; Bellocchio, Luigi; Clark, Samantha; Elie, Melissa; Leste-Lasserre, Thierry; Maitre, Marlene; Gonzales, Delphine; Cannich, Astrid; Pagotto, Uberto; Marsicano, Giovanni; Cota, Daniela

    2014-10-01

    Metabolic flexibility allows rapid adaptation to dietary change, however, little is known about the CNS mechanisms regulating this process. Neurons in the hypothalamic ventromedial nucleus (VMN) participate in energy balance and are the target of the metabolically relevant hormone leptin. Cannabinoid type-1 (CB1) receptors are expressed in VMN neurons, but the specific contribution of endocannabinoid signaling in this neuronal population to energy balance regulation is unknown. Here we demonstrate that VMN CB1 receptors regulate metabolic flexibility and actions of leptin. In chow-fed mice, conditional deletion of CB1 in VMN neurons (expressing the steroidogenic factor 1, SF1) decreases adiposity by increasing sympathetic activity and lipolysis, and facilitates metabolic effects of leptin. Conversely, under high-fat diet, lack of CB1 in VMN neurons produces leptin resistance, blunts peripheral use of lipid substrates and increases adiposity. Thus, CB1 receptors in VMN neurons provide a molecular switch adapting the organism to dietary change.

  6. Hypoglycemia-activated GLUT2 neurons of the nucleus tractus solitarius stimulate vagal activity and glucagon secretion.

    Science.gov (United States)

    Lamy, Christophe M; Sanno, Hitomi; Labouèbe, Gwenaël; Picard, Alexandre; Magnan, Christophe; Chatton, Jean-Yves; Thorens, Bernard

    2014-03-04

    Glucose-sensing neurons in the brainstem participate in the regulation of energy homeostasis but have been poorly characterized because of the lack of specific markers to identify them. Here we show that GLUT2-expressing neurons of the nucleus of the tractus solitarius form a distinct population of hypoglycemia-activated neurons. Their response to low glucose is mediated by reduced intracellular glucose metabolism, increased AMP-activated protein kinase activity, and closure of leak K(+) channels. These are GABAergic neurons that send projections to the vagal motor nucleus. Light-induced stimulation of channelrhodospin-expressing GLUT2 neurons in vivo led to increased parasympathetic nerve firing and glucagon secretion. Thus GLUT2 neurons of the nucleus tractus solitarius link hypoglycemia detection to counterregulatory response. These results may help identify the cause of hypoglycemia-associated autonomic failure, a major threat in the insulin treatment of diabetes.

  7. Toward on-chip functional neuronal networks: computational study on the effect of synaptic connectivity on neural activity.

    Science.gov (United States)

    Foroushani, Armin Najarpour; Ghafar-Zadeh, Ebrahim

    2014-01-01

    This paper presents a new unified computational-experimental approach to study the role of the synaptic activity on the activity of neurons in the small neuronal networks (NNs). In a neuronal tissue/organ, this question is investigated with higher complexities by recording action potentials from population of neurons in order to find the relationship between connectivity and the recorded activities. In this approach, we study the dynamics of very small cortical neuronal networks, which can be experimentally synthesized on chip with constrained connectivity. Multi-compartmental Hodgkin-Huxley model is used in NEURON software to reproduce cells by extracting the experimental data from the synthesized NNs. We thereafter demonstrate how the type of synaptic activity affects the network response to specific spike train using the simulation results.

  8. Spiking neuron network Helmholtz machine.

    Science.gov (United States)

    Sountsov, Pavel; Miller, Paul

    2015-01-01

    An increasing amount of behavioral and neurophysiological data suggests that the brain performs optimal (or near-optimal) probabilistic inference and learning during perception and other tasks. Although many machine learning algorithms exist that perform inference and learning in an optimal way, the complete description of how one of those algorithms (or a novel algorithm) can be implemented in the brain is currently incomplete. There have been many proposed solutions that address how neurons can perform optimal inference but the question of how synaptic plasticity can implement optimal learning is rarely addressed. This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well-studied computational model called the Helmholtz Machine. The Helmholtz Machine is amenable to neural implementation as the algorithm it uses to learn its parameters, called the wake-sleep algorithm, uses a local delta learning rule. Our spiking-neuron network implements both the delta rule and a small example of a Helmholtz machine. This neuronal network can learn an internal model of continuous-valued training data sets without supervision. The network can also perform inference on the learned internal models. We show how various biophysical features of the neural implementation constrain the parameters of the wake-sleep algorithm, such as the duration of the wake and sleep phases of learning and the minimal sample duration. We examine the deviations from optimal performance and tie them to the properties of the synaptic plasticity rule.

  9. Properties of bilateral spinocerebellar activation of cerebellar cortical neurons

    Directory of Open Access Journals (Sweden)

    Pontus eGeborek

    2014-10-01

    Full Text Available We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT and the dorsal spinocerebellar tract (DSCT, respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF and the ipsilateral LF (iLF at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e. that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.

  10. BlastNeuron for Automated Comparison, Retrieval and Clustering of 3D Neuron Morphologies.

    Science.gov (United States)

    Wan, Yinan; Long, Fuhui; Qu, Lei; Xiao, Hang; Hawrylycz, Michael; Myers, Eugene W; Peng, Hanchuan

    2015-10-01

    Characterizing the identity and types of neurons in the brain, as well as their associated function, requires a means of quantifying and comparing 3D neuron morphology. Presently, neuron comparison methods are based on statistics from neuronal morphology such as size and number of branches, which are not fully suitable for detecting local similarities and differences in the detailed structure. We developed BlastNeuron to compare neurons in terms of their global appearance, detailed arborization patterns, and topological similarity. BlastNeuron first compares and clusters 3D neuron reconstructions based on global morphology features and moment invariants, independent of their orientations, sizes, level of reconstruction and other variations. Subsequently, BlastNeuron performs local alignment between any pair of retrieved neurons via a tree-topology driven dynamic programming method. A 3D correspondence map can thus be generated at the resolution of single reconstruction nodes. We applied BlastNeuron to three datasets: (1) 10,000+ neuron reconstructions from a public morphology database, (2) 681 newly and manually reconstructed neurons, and (3) neurons reconstructions produced using several independent reconstruction methods. Our approach was able to accurately and efficiently retrieve morphologically and functionally similar neuron structures from large morphology database, identify the local common structures, and find clusters of neurons that share similarities in both morphology and molecular profiles.

  11. Spontaneous Calcium Changes in Micro Neuronal Networks

    Science.gov (United States)

    Saito, Aki; Moriguchi, Hiroyuki; Iwabuchi, Shin; Goto, Miho; Takayama, Yuzo; Kotani, Kiyoshi; Jimbo, Yasuhiko

    We have developed a practical experimental method to mass-produce and maintain a variation of minimal neuronal networks (“micro neuronal networks”) consisted of a single to several neurons in culture using spray-patterning technique. In this paper, we could maintain the micro-cultures for one month or more by adding conditioned medium and carried out optical recording of spontaneous activity in micro neuronal networks and considered the interactions between them. To determine the interactions between micro neuronal networks, fluorescence changes in several small networks were simultaneously measured using calcium indicator dye fluo-4 AM, and time-series analysis was carried out using surrogate arrangements. By using the spray-patterning method, a large number of cell-adhesive micro regions were formed. Neurons extended neurites along the edge of the cell-adhesive micro regions and form micro neuronal networks. In part of micro regions, some neurite was protruded from the region, and thus micro neuronal networks were connected with synapses. In these networks, a single neuron-induced network activity was observed. On the other hand, even in morphologically non-connected micro neuronal networks, synchronous oscillations between micro neuronal networks were observed. Our micro-patterning methods and results provide the possibility that synchronous activity is occurred between morphologically non-connected neuronal networks. This suggest that the humoral factor is also a important component for network-wide dynamics.

  12. Studies Gain Insight into Neuronal Polarity

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ A typical matured nerve cell (or neuron) has one axon and multiple dendrites. It receives information at the dendrites and sending signals to other neurons via the axon. Although scientists have discovered that this axon-dendrite polarity is a cardinal feature of neuronal morphology essential for information flow, they are still in the dark about the cause of this polarization.

  13. Oscillating from Neurosecretion to Multitasking Dopamine Neurons

    Directory of Open Access Journals (Sweden)

    David R. Grattan

    2016-04-01

    Full Text Available In this issue of Cell Reports, Stagkourakis et al. (2016 report that oscillating hypothalamic TIDA neurons, previously thought to be simple neurosecretory neurons controlling pituitary prolactin secretion, control dopamine output via autoregulatory mechanisms and thus could potentially regulate other physiologically important hypothalamic neuronal circuits.

  14. Cognition and behavior in motor neuron disease

    NARCIS (Netherlands)

    Raaphorst, J.

    2015-01-01

    Motor neuron disease (MND) is a devastating neurodegenerative disorder characterized by progressive motor neuron loss, leading to weakness of the muscles of arms and legs, bulbar and respiratory muscles. Depending on the involvement of the lower and the upper motor neuron, amyotrophic lateral sclero

  15. Neuronal networks: enhanced feedback feeds forward.

    Science.gov (United States)

    Calabrese, Ronald L

    2012-09-25

    Modulatory projection neurons gate neuronal networks, such as those comprising motor central pattern generators; in turn, they receive feedback from the networks they gate. A recent study has shown that, in the crab stomatogastric ganglion, this feedback is also subject to modulation: the enhanced feedback feeds forward through the projection neurons to modify circuit output.

  16. Astrocytic modulation of neuronal excitability through K(+) spatial buffering.

    Science.gov (United States)

    Bellot-Saez, Alba; Kékesi, Orsolya; Morley, John W; Buskila, Yossi

    2017-03-06

    The human brain contains two major cell populations, neurons and glia. While neurons are electrically excitable and capable of discharging short voltage pulses known as action potentials, glial cells are not. However, astrocytes, the prevailing subtype of glia in the cortex, are highly connected and can modulate the excitability of neurons by changing the concentration of potassium ions in the extracellular environment, a process called K(+) clearance. During the past decade, astrocytes have been the focus of much research, mainly due to their close association with synapses and their modulatory impact on neuronal activity. It has been shown that astrocytes play an essential role in normal brain function including: nitrosative regulation of synaptic release in the neocortex, synaptogenesis, synaptic transmission and plasticity. Here, we discuss the role of astrocytes in network modulation through their K(+) clearance capabilities, a theory that was first raised 50 years ago by Orkand and Kuffler. We will discuss the functional alterations in astrocytic activity that leads to aberrant modulation of network oscillations and synchronous activity.

  17. fMRI repetition suppression: neuronal adaptation or stimulus expectation?

    Science.gov (United States)

    Larsson, Jonas; Smith, Andrew T

    2012-03-01

    Measurements of repetition suppression with functional magnetic resonance imaging (fMRI adaptation) have been used widely to probe neuronal population response properties in human cerebral cortex. fMRI adaptation techniques assume that fMRI repetition suppression reflects neuronal adaptation, an assumption that has been challenged on the basis of evidence that repetition-related response changes may reflect unrelated factors, such as attention and stimulus expectation. Specifically, Summerfield et al. (Summerfield C, Trittschuh EH, Monti JM, Mesulam MM, Egner T. 2008. Neural repetition suppression reflects fulfilled perceptual expectations. Nat Neurosci. 11:1004-1006) reported that the relative frequency of stimulus repetitions and non-repetitions influenced the magnitude of repetition suppression in the fusiform face area, suggesting that stimulus expectation accounted for most of the effect of repetition. We confirm that stimulus expectation can significantly influence fMRI repetition suppression throughout visual cortex and show that it occurs with long as well as short adaptation durations. However, the effect was attention dependent: When attention was diverted away from the stimuli, the effects of stimulus expectation completely disappeared. Nonetheless, robust and significant repetition suppression was still evident. These results suggest that fMRI repetition suppression reflects a combination of neuronal adaptation and attention-dependent expectation effects that can be experimentally dissociated. This implies that with an appropriate experimental design, fMRI adaptation can provide valid measures of neuronal adaptation and hence response specificity.

  18. Magnetosensitive neurons mediate geomagnetic orientation in Caenorhabditis elegans

    Science.gov (United States)

    Vidal-Gadea, Andrés; Ward, Kristi; Beron, Celia; Ghorashian, Navid; Gokce, Sertan; Russell, Joshua; Truong, Nicholas; Parikh, Adhishri; Gadea, Otilia; Ben-Yakar, Adela; Pierce-Shimomura, Jonathan

    2015-01-01

    Many organisms spanning from bacteria to mammals orient to the earth's magnetic field. For a few animals, central neurons responsive to earth-strength magnetic fields have been identified; however, magnetosensory neurons have yet to be identified in any animal. We show that the nematode Caenorhabditis elegans orients to the earth's magnetic field during vertical burrowing migrations. Well-fed worms migrated up, while starved worms migrated down. Populations isolated from around the world, migrated at angles to the magnetic vector that would optimize vertical translation in their native soil, with northern- and southern-hemisphere worms displaying opposite migratory preferences. Magnetic orientation and vertical migrations required the TAX-4 cyclic nucleotide-gated ion channel in the AFD sensory neuron pair. Calcium imaging showed that these neurons respond to magnetic fields even without synaptic input. C. elegans may have adapted magnetic orientation to simplify their vertical burrowing migration by reducing the orientation task from three dimensions to one. DOI: http://dx.doi.org/10.7554/eLife.07493.001 PMID:26083711

  19. Functionalized anatomical models for EM-neuron Interaction modeling

    Science.gov (United States)

    Neufeld, Esra; Cassará, Antonino Mario; Montanaro, Hazael; Kuster, Niels; Kainz, Wolfgang

    2016-06-01

    The understanding of interactions between electromagnetic (EM) fields and nerves are crucial in contexts ranging from therapeutic neurostimulation to low frequency EM exposure safety. To properly consider the impact of in vivo induced field inhomogeneity on non-linear neuronal dynamics, coupled EM-neuronal dynamics modeling is required. For that purpose, novel functionalized computable human phantoms have been developed. Their implementation and the systematic verification of the integrated anisotropic quasi-static EM solver and neuronal dynamics modeling functionality, based on the method of manufactured solutions and numerical reference data, is described. Electric and magnetic stimulation of the ulnar and sciatic nerve were modeled to help understanding a range of controversial issues related to the magnitude and optimal determination of strength-duration (SD) time constants. The results indicate the importance of considering the stimulation-specific inhomogeneous field distributions (especially at tissue interfaces), realistic models of non-linear neuronal dynamics, very short pulses, and suitable SD extrapolation models. These results and the functionalized computable phantom will influence and support the development of safe and effective neuroprosthetic devices and novel electroceuticals. Furthermore they will assist the evaluation of existing low frequency exposure standards for the entire population under all exposure conditions.

  20. Interleukin-3 prevents neuronal death induced by amyloid peptide

    Directory of Open Access Journals (Sweden)

    Otth Carola

    2007-10-01

    Full Text Available Abstract Background Interleukin-3 (IL-3 is an important glycoprotein involved in regulating biological responses such as cell proliferation, survival and differentiation. Its effects are mediated via interaction with cell surface receptors. Several studies have demonstrated the expression of IL-3 in neurons and astrocytes of the hippocampus and cortices in normal mouse brain, suggesting a physiological role of IL-3 in the central nervous system. Although there is evidence indicating that IL-3 is expressed in some neuronal populations, its physiological role in these cells is poorly known. Results In this study, we demonstrated the expression of IL-3 receptor in cortical neurons, and analyzed its influence on amyloid β (Aβ-treated cells. In these cells, IL-3 can activate at least three classical signalling pathways, Jak/STAT, Ras/MAP kinase and the PI 3-kinase. Viability assays indicated that IL-3 might play a neuroprotective role in cells treated with Aβ fibrils. It is of interest to note that our results suggest that cell survival induced by IL-3 required PI 3-kinase and Jak/STAT pathway activation, but not MAP kinase. In addition, IL-3 induced an increase of the anti-apoptotic protein Bcl-2. Conclusion Altogether these data strongly suggest that IL-3 neuroprotects neuronal cells against neurodegenerative agents like Aβ.

  1. Epileptic syndrome in systemic lupus erythematosus and neuronal autoantibody associations.

    Science.gov (United States)

    Kampylafka, E I; Alexopoulos, H; Fouka, P; Moutsopoulos, H M; Dalakas, M C; Tzioufas, A G

    2016-10-01

    We investigated systemic lupus erythematosus (SLE) patients with epilepsy, a major and organic neurological symptom. Our aim was to test patients for the autoimmune epilepsy-associated antibodies anti-GAD, anti-NMDAR, anti-AMPAR1/2, anti-GABABR and anti-VGKC. We tested sera from ten SLE patients with current or previous episodes of epileptic seizures. In addition, sera were tested for staining on primary hippocampal neurons. The patients' clinical and neuroimaging profile, disease activity and accumulated damage scores and therapeutic regimens administered were recorded, and correlations were evaluated. Patients were negative for all anti-neuronal autoantibodies tested, and showed no staining on primary hippocampal cells, which suggests the absence of autoantibodies against neuronal cell surface antigens. Epileptic seizures were all tonic-clonic, and all patients had high disease activity (mean SLE Damage Acticity Index score 19.3 ± 7.3). Six patients had minor or no brain magnetic resonance imaging findings, and three had major findings. 9/10 patients received immunosuppression for 5 ± 4 months, while anti-convulsive treatment was administered to all patients (4.2 ± 3 years). Our results suggest that the majority of SLE-related epileptic seizures cannot be attributed to the action of a single antibody against neuronal antigens. Studies with larger neuropsychiatric SLE populations and stricter inclusion criteria are necessary to verify these findings. © The Author(s) 2016.

  2. Timing intervals using population synchrony and spike timing dependent plasticity

    Directory of Open Access Journals (Sweden)

    Wei Xu

    2016-12-01

    Full Text Available We present a computational model by which ensembles of regularly spiking neurons can encode different time intervals through synchronous firing. We show that a neuron responding to a large population of convergent inputs has the potential to learn to produce an appropriately-timed output via spike-time dependent plasticity. We explain why temporal variability of this population synchrony increases with increasing time intervals. We also show that the scalar property of timing and its violation at short intervals can be explained by the spike-wise accumulation of jitter in the inter-spike intervals of timing neurons. We explore how the challenge of encoding longer time intervals can be overcome and conclude that this may involve a switch to a different population of neurons with lower firing rate, with the added effect of producing an earlier bias in response. Experimental data on human timing performance show features in agreement with the model’s output.

  3. Transgenic Mouse Lines Subdivide External Segment of the Globus Pallidus (GPe) Neurons and Reveal Distinct GPe Output Pathways

    Science.gov (United States)

    Mastro, Kevin J.; Bouchard, Rachel S.; Holt, Hiromi A. K.

    2014-01-01

    Cell-type diversity in the brain enables the assembly of complex neural circuits, whose organization and patterns of activity give rise to brain function. However, the identification of distinct neuronal populations within a given brain region is often complicated by a lack of objective criteria to distinguish one neuronal population from another. In the external segment of the globus pallidus (GPe), neuronal populations have been defined using molecular, anatomical, and electrophysiological criteria, but these classification schemes are often not generalizable across preparations and lack consistency even within the same preparation. Here, we present a novel use of existing transgenic mouse lines, Lim homeobox 6 (Lhx6)–Cre and parvalbumin (PV)–Cre, to define genetically distinct cell populations in the GPe that differ molecularly, anatomically, and electrophysiologically. Lhx6–GPe neurons, which do not express PV, are concentrated in the medial portion of the GPe. They have lower spontaneous firing rates, narrower dynamic ranges, and make stronger projections to the striatum and substantia nigra pars compacta compared with PV–GPe neurons. In contrast, PV–GPe neurons are more concentrated in the lateral portions of the GPe. They have narrower action potentials, deeper afterhyperpolarizations, and make stronger projections to the subthalamic nucleus and parafascicular nucleus of the thalamus. These electrophysiological and anatomical differences suggest that Lhx6–GPe and PV–GPe neurons participate in different circuits with the potential to contribute to different aspects of motor function and dysfunction in disease. PMID:24501350

  4. Coherence resonance in globally coupled neuronal networks with different neuron numbers

    Institute of Scientific and Technical Information of China (English)

    Ning Wei-Lian; Zhang Zheng-Zhen; Zeng Shang-You; Luo Xiao-Shu; Hu Jin-Lin; Zeng Shao-Wen; Qiu Yi; Wu Hui-Si

    2012-01-01

    Because a brain consists of tremendous neuronal networks with different neuron numbers ranging from tens to tens of thousands,we study the coherence resonance due to ion channel noises in globally coupled neuronal networks with different neuron numbers.We confirm that for all neuronal networks with different neuron numbers there exist the array enhanced coherence resonance and the optimal synaptic conductance to cause the maximal spiking coherence.Furthermoremore,the enhancement effects of coupling on spiking coherence and on optimal synaptic conductance are almost the same,regardless of the neuron numbers in the neuronal networks.Therefore for all the neuronal networks with different neuron numbers in the brain,relative weak synaptic conductance (0.1 mS/cm2) is sufficient to induce the maximal spiking coherence and the best sub-threshold signal encoding.

  5. Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

    Science.gov (United States)

    Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

    2017-01-01

    The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.