Grimm, Jan; Mueller, Anne; Hefti, Franz; Rosenthal, Arnon
Catecholaminergic neurons control diverse cognitive, motor, and endocrine functions and are associated with multiple psychiatric and neurodegenerative disorders. We present global gene-expression profiles that define the four major classes of dopaminergic (DA) and noradrenergic neurons in the brain. Hypothalamic DA neurons and noradrenergic neurons in the locus coeruleus display distinct group-specific signatures of transporters, channels, transcription, plasticity, axon-guidance, and surviva...
Full Text Available Abstract Background Deletions of the mitochondrial DNA (mtDNA accumulate to high levels in dopaminergic neurons of the substantia nigra pars compacta (SNc in normal aging and in patients with Parkinson's disease (PD. Human nigral neurons characteristically contain the pigment neuromelanin (NM, which is believed to alter the cellular redox-status. The impact of neuronal pigmentation, neurotransmitter status and brainstem location on the susceptibility to mtDNA damage remains unclear. We quantified mtDNA deletions (ΔmtDNA in single pigmented and non-pigmented catecholaminergic, as well as non-catecholaminergic neurons of the human SNc, the ventral tegmental area (VTA and the locus coeruleus (LC, using laser capture microdissection and single-cell real-time PCR. Results In healthy aged individuals, ΔmtDNA levels were highest in pigmented catecholaminergic neurons (25.2 ± 14.9%, followed by non-pigmented catecholamergic (18.0 ± 11.2% and non-catecholaminergic neurons (12.3 ± 12.3%; p Conclusions Catecholaminergic brainstem neurons are differentially susceptible to mtDNA damage. Pigmented dopaminergic neurons of the SNc show the highest ΔmtDNA levels, possibly explaining the exceptional vulnerability of the nigro-striatal system in PD and aging. Although loss of pigmented noradrenergic LC neurons also is an early feature of PD pathology, mtDNA levels are not elevated in this nucleus in healthy controls. Thus, ΔmtDNA are neither an inevitable consequence of catecholamine metabolism nor a universal explanation for the regional vulnerability seen in PD.
van der Keylen, Piet; Garreis, Fabian; Steigleder, Ruth; Sommer, Daniel; Neuhuber, Winfried L; Wörl, Jürgen
Enteric co-innervation is a peculiar innervation pattern of striated esophageal musculature. Both anatomical and functional data on enteric co-innervation related to various transmitters have been collected in different species, although its function remains enigmatic. However, it is unclear whether catecholaminergic components are involved in such a co-innervation. Thus, we examined to identify catecholaminergic neuronal elements and clarify their relationship to other innervation components in the esophagus, using immunohistochemistry with antibodies against tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT) and protein gene product 9.5 (PGP 9.5), α-bungarotoxin (α-BT) and PCR with primers for amplification of cDNA encoding TH and dopamine-β-hydroxylase (DBH). TH-positive nerve fibers were abundant throughout the myenteric plexus and localized on about 14% of α-BT-labelled motor endplates differing from VAChT-positive vagal nerve terminals. TH-positive perikarya represented a subpopulation of only about 2.8% of all PGP 9.5-positive myenteric neurons. Analysis of mRNA showed both TH and DBH transcripts in the mouse esophagus. As ChAT-positive neurons in the compact formation of the nucleus ambiguus were negative for TH, the TH-positive nerve varicosities on motor endplates are presumably of enteric origin, although a sympathetic origin cannot be excluded. In the medulla oblongata, the cholinergic ambiguus neurons were densely supplied with TH-positive varicosities. Thus, catecholamines may modulate vagal motor innervation of esophageal-striated muscles not only at the peripheral level via enteric co-innervation but also at the central level via projections to the nucleus ambiguus. As Parkinson's disease, with a loss of central dopaminergic neurons, also affects the enteric nervous system and dysphagia is prevalent in patients with this disease, investigation of intrinsic catecholamines in the esophagus may
Zhang, Shuang; Johnson, Christopher M; Cui, Ningren; Xing, Hao; Zhong, Weiwei; Wu, Yang; Jiang, Chun
Rett syndrome (RTT) is a neurodevelopmental disorder affecting multiple functions, including the norepinephrine (NE) system. In the CNS, NE is produced mostly by neurons in the locus coeruleus (LC), where defects in intrinsic neuronal properties, NE biosynthetic enzymes, neuronal CO2 sensitivity, and synaptic currents have been reported in mouse models of RTT. LC neurons in methyl-CpG-binding protein 2 gene (Mecp2) null mice show a high rate of spontaneous firing, although whether such hyperexcitability might increase or decrease the NE release from synapses is unknown. To activate the NEergic axonal terminals selectively, we generated an optogenetic mouse model of RTT in which NEergic neuronal excitability can be manipulated with light. Using commercially available mouse breeders, we produced a new strain of double-transgenic mice with Mecp2 knockout and channelrhodopsin (ChR) knockin in catecholaminergic neurons. Several RTT-like phenotypes were found in the tyrosine hydroxylase (TH)-ChR-Mecp2(-/Y) mice, including hypoactivity, low body weight, hindlimb clasping, and breathing disorders. In brain slices, optostimulation produced depolarization and an increase in the firing rate of LC neurons from TH-ChR control mice. In TH-ChR control mice, optostimulation of presynaptic NEergic neurons augmented the firing rate of hypoglossal neurons (HNs), which was blocked by the α-adrenoceptor antagonist phentolamine. Such optostimulation of NEergic terminals had almost no effect on HNs from two or three TH-ChR-Mecp2(-/Y) mice, indicating that excessive excitation of presynaptic neurons does not benefit NEergic modulation in mice with Mecp2 disruption. These results also demonstrate the feasibility of generating double-transgenic mice for studies of RTT with commercially available mice, which are inexpensive, labor/time efficient, and promising for cell-specific stimulation. © 2016 Wiley Periodicals, Inc. PMID:27317352
Nam, H; Kerman, I A
We previously characterized the organization of presympathetic-premotor neurons (PSPMNs), which send descending poly-synaptic projections with collaterals to skeletal muscle and the adrenal gland. Such neurons may play a role in shaping integrated adaptive responses, and many of them were found within well-characterized regions of noradrenergic cell populations suggesting that some of the PSPMNs are catecholaminergic. To address this issue, we used retrograde trans-synaptic tract-tracing with attenuated pseudorabies virus (PRV) recombinants combined with multi-label immunofluorescence to identify PSPMNs expressing tyrosine hydroxylase (TH). Our findings indicate that TH-immunoreactive (ir) PSPMNs are present throughout the brainstem within multiple cell populations, including the A1, C1, C2, C3, A5 and A7 cell groups along with the locus coeruleus (LC) and the nucleus subcoeruleus (SubC). The largest numbers of TH-ir PSPMNs were located within the LC and SubC. Within SubC and the A7 cell group, about 70% of TH-ir neurons were PSPMNs, which was a significantly greater fraction of neurons than in the other brain regions we examined. These findings indicate that TH-ir neurons near the pontomesencephalic junction that are distributed across the LC, SubC, and the A7 may play a prominent role in somatomotor-sympathetic integration, and that the major functional role of the A7 and SubC noradrenergic cell groups maybe in the coordination of concomitant activation of somatomotor and sympathetic outflows. These neurons may participate in mediating homeostatic adaptations that require simultaneous activation of sympathetic and somatomotor nerves in the periphery. PMID:26946268
Moon, Don-Joon; Maseko, Busisiwe C; Ihunwo, Amadi O; Fuxe, Kjell; Manger, Paul R
The distribution, morphology and nuclear subdivisions of the putative catecholaminergic and serotonergic systems within the brain of the highveld gerbil were identified following immunohistochemistry for tyrosine hydroxylase and serotonin. The aim of the present study was to investigate possible differences in the complement of nuclear subdivisions of these systems when comparing those of the highveld gerbil with those of the laboratory rat. The highveld gerbil was chosen as it is relatively closely related to the laboratory rat, but the Gerbillinae and Murinae lineages diverged over 20 million years ago. Moreover, even though brain sizes are similar, the life history and phenotypes between these two species are substantially different. The gerbils used in the present study were caught from the wild, which is again another contrast to the laboratory rat. While these differences may lead to the prediction of significant differences in the nuclear complement of these systems, we found that all nuclei identified in both systems in the laboratory rat in several earlier studies had direct homologs in the brain of the highveld gerbil. Moreover, there were no additional nuclei in the brain of the highveld gerbil that are not found in the laboratory rat. The only discernable difference between the two species was a greater density and number of catecholaminergic neurons in the olfactory bulb of the highveld gerbil. Thus, the evolution of nuclear parcellation in these systems appears to demonstrate a form of phylogenetic constraint related to the order Rodentia. PMID:17606363
Tay, Tuan Leng; Ronneberger, Olaf; Ryu, Soojin; Nitschke, Roland; Driever, Wolfgang
Essential components of animal behaviour are modulated by dopaminergic (DA) and noradrenergic circuitry. In this study, we reveal at cellular resolution the complete set of projections ('projectome') of every single type of DA and noradrenergio neurons in the central nervous system of zebrafish larvae. The most extensive DA projections are established by posterior tubercular otp-dependent neurons, with individual somata integrating the ascending DA system, the descending diencephalospinal, as...
Petersen, Christopher L; Timothy, Miky; Kim, D Spencer; Bhandiwad, Ashwin A; Mohr, Robert A; Sisneros, Joseph A; Forlano, Paul M
While the neural circuitry and physiology of the auditory system is well studied among vertebrates, far less is known about how the auditory system interacts with other neural substrates to mediate behavioral responses to social acoustic signals. One species that has been the subject of intensive neuroethological investigation with regard to the production and perception of social acoustic signals is the plainfin midshipman fish, Porichthys notatus, in part because acoustic communication is essential to their reproductive behavior. Nesting male midshipman vocally court females by producing a long duration advertisement call. Females localize males by their advertisement call, spawn and deposit all their eggs in their mate's nest. As multiple courting males establish nests in close proximity to one another, the perception of another male's call may modulate individual calling behavior in competition for females. We tested the hypothesis that nesting males exposed to advertisement calls of other males would show elevated neural activity in auditory and vocal-acoustic brain centers as well as differential activation of catecholaminergic neurons compared to males exposed only to ambient noise. Experimental brains were then double labeled by immunofluorescence (-ir) for tyrosine hydroxylase (TH), an enzyme necessary for catecholamine synthesis, and cFos, an immediate-early gene product used as a marker for neural activation. Males exposed to other advertisement calls showed a significantly greater percentage of TH-ir cells colocalized with cFos-ir in the noradrenergic locus coeruleus and the dopaminergic periventricular posterior tuberculum, as well as increased numbers of cFos-ir neurons in several levels of the auditory and vocal-acoustic pathway. Increased activation of catecholaminergic neurons may serve to coordinate appropriate behavioral responses to male competitors. Additionally, these results implicate a role for specific catecholaminergic neuronal groups in
Christopher L Petersen
Full Text Available While the neural circuitry and physiology of the auditory system is well studied among vertebrates, far less is known about how the auditory system interacts with other neural substrates to mediate behavioral responses to social acoustic signals. One species that has been the subject of intensive neuroethological investigation with regard to the production and perception of social acoustic signals is the plainfin midshipman fish, Porichthys notatus, in part because acoustic communication is essential to their reproductive behavior. Nesting male midshipman vocally court females by producing a long duration advertisement call. Females localize males by their advertisement call, spawn and deposit all their eggs in their mate's nest. As multiple courting males establish nests in close proximity to one another, the perception of another male's call may modulate individual calling behavior in competition for females. We tested the hypothesis that nesting males exposed to advertisement calls of other males would show elevated neural activity in auditory and vocal-acoustic brain centers as well as differential activation of catecholaminergic neurons compared to males exposed only to ambient noise. Experimental brains were then double labeled by immunofluorescence (-ir for tyrosine hydroxylase (TH, an enzyme necessary for catecholamine synthesis, and cFos, an immediate-early gene product used as a marker for neural activation. Males exposed to other advertisement calls showed a significantly greater percentage of TH-ir cells colocalized with cFos-ir in the noradrenergic locus coeruleus and the dopaminergic periventricular posterior tuberculum, as well as increased numbers of cFos-ir neurons in several levels of the auditory and vocal-acoustic pathway. Increased activation of catecholaminergic neurons may serve to coordinate appropriate behavioral responses to male competitors. Additionally, these results implicate a role for specific catecholaminergic
Erickson, J T; Millhorn, D E
A complete understanding of the neural mechanisms responsible for the chemoreceptor and baroreceptor reflexes requires precise knowledge of the locations and chemical phenotypes of higher-order neurons within these reflex pathways. In the present study, the protein product (Fos) of the c-fos protooncogene was used as a metabolic marker to trace central neural pathways following activation of carotid sinus nerve afferent fibers. In addition, immunohistochemical double-labeling techniques were used to define the chemical phenotypes of activated neurons. Both electrical stimulation of the carotid sinus nerve and physiological stimulation of the carotid bodies by hypoxia induced Fos-like immunoreactivity in catecholaminergic neurons containing tyrosine hydroxylase or phenylethanolamine-N-methyltransferase in the ventrolateral medulla oblongata and, to a lesser degree, in the dorsal vagal complex. Tyrosine hydroxylase/Fos colocalization was also observed in the locus coeruleus and the A5 noradrenergic cell group in pons. Many serotoninergic neurons in nucleus raphe pallidus, nucleus raphe magnus, and along the ventral medullary surface contained Fos-like immunoreactivity. In pons and midbrain, Fos-like immunoreactivity was observed in the lateral parabrachial and Kölliker-Fuse nuclei, the inferior colliculus, the cuneiform nucleus, and in the vicinity of the Edinger-Westphal nucleus, but no catecholaminergic or serotoninergic colocalization was observed in these regions. Although Fos-labeled cells were observed within and lateral to the dorsal raphe nucleus, few were catecholaminergic or serotoninergic. This study further defines a potential central neuroanatomical substrate for the chemoreceptor and/or baroreceptor reflexes. PMID:7814687
Blevins, J.E.; Chelikani, P. K.; Haver, A. C.; Reidelberger, R. D.
Peptide YY (3-36) [PYY(3-36)] inhibits feeding in rodents, nonhuman primates and humans, yet the neural circuits underlying this action remain to be determined. Here we assessed whether PYY(3-36) inhibits feeding by activating neurons in forebrain and hindbrain sites containing Y2 receptors and linked to control of food intake, or in hindbrain sites immediately downstream of vagal afferent neurons. Rats received an anorexigenic dose of PYY(3-36), and the number of neurons expressing Fos, an i...
Ceccatelli, S; Seroogy, K B; Millhorn, D E; Terenius, L
Immunofluorescence colocalization techniques were used to examine the extent of coexistence of the endogenous opioid peptide dynorphin with catecholamines and the related opioid peptide enkephalin within neurons of the rat medulla oblongata. Immunoreactivities for dynorphin and the catecholamine-synthesizing enzyme tyrosine hydroxylase were found to coexist within a limited subpopulation of A2 catecholamine cells, localized to the medial nucleus of the nucleus tractus solitarii. Colocalization of the two opioid peptides was found mainly within perikarya situated in the medial and ventrolateral nuclei of the nucleus tractus solitarii. Triple-labeling studies revealed only rare cases of catecholamine/dynorphin/enkephalin coexistence. These data demonstrate that dynorphin is present within a restricted subpopulation of catecholamine neurons in the dorsal medulla oblongata. In addition, the content of either of the opioids enkephalin or dynorphin appears to distinguish subsets of medullary catecholamine neurons. PMID:1356595
Suckow, Shelby K.; Deichsel, Emily L.; Ingram, Susan L; Morgan, Michael M; Aicher, Sue A.
The periaqueductal gray (PAG) is a critical brain region involved in opioid analgesia and provides efferents to descending pathways that modulate nociception. In addition, the PAG contains ascending pathways to regions involved in the regulation of reward, including the substantia nigra (SN) and the ventral tegmental area (VTA). SN and VTA contain dopaminergic neurons that are critical for the maintenance of positive reinforcement. Interestingly, the PAG is also reported to contain a populati...
Chandler, Daniel J.; WATERHOUSE, BARRY D.; Gao, Wen-Jun
Cognitive functions associated with prefrontal cortex (PFC), such as working memory and attention, are strongly influenced by catecholamine [dopamine (DA) and norepinephrine (NE)] release. Midbrain dopaminergic neurons in the ventral tegmental area and noradrenergic neurons in the locus coeruleus are major sources of DA and NE to the PFC. It is traditionally believed that DA and NE neurons are homogeneous with highly divergent axons innervating multiple terminal fields and once released, DA a...
Cognitive functions associated with prefrontal cortex, such as working memory and attention, are strongly influenced by catecholamine (dopamine, DA and norepinephrine, NE) release. Midbrain dopaminergic neurons in the ventral tegmental area (VTA) and noradrenergic neurons in the locus coeruleus (LC) are major sources of DA and NE to the prefrontal cortex. It is traditionally believed that DA and NE neurons are homogeneous with highly divergent axons innervating multiple terminal fields and on...
Goldstein, David S; Holmes, Courtney; Sullivan, Patti; Mash, Deborah C; Sidransky, Ellen; Stefani, Alessandro; Kopin, Irwin J; Sharabi, Yehonatan
Several neurodegenerative diseases involve loss of catecholamine neurons--Parkinson's disease (PD) is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are lost has been mysterious. Accumulating evidence supports the concept of "autotoxicity"--inherent cytotoxicity caused by catecholamine metabolites. Since vesicular sequestration limits the buildup of toxic products of enzymatic and spontaneous oxidation of catecholamines, a vesicular storage defect could play a pathogenic role in the death of catecholaminergic neurons in a variety of neurodegenerative diseases. In putamen, deficient vesicular storage is revealed in vivo by accelerated loss of (18)F-DOPA-derived radioactivity and post-mortem by decreased tissue dopamine (DA):DOPA ratios; in myocardium in vivo by accelerated loss of (18)F-dopamine-derived radioactivity and post-mortem by increased 3,4-dihydroxyphenylglycol:norepinephrine (DHPG:NE) ratios; and in sympathetic noradrenergic nerves overall in vivo by increased plasma F-dihydroxyphenylacetic acid (F-DOPAC):DHPG ratios. We retrospectively analyzed data from 20 conditions with decreased or intact catecholaminergic innervation, involving different etiologies, pathogenetic mechanisms, and lesion locations. All conditions involving parkinsonism had accelerated loss of putamen (18)F-DOPA-derived radioactivity; in those with post-mortem data there were also decreased putamen DA:DOPA ratios. All conditions involving cardiac sympathetic denervation had accelerated loss of myocardial (18)F-dopamine-derived radioactivity; in those with post-mortem data there were increased myocardial DHPG:NE ratios. All conditions involving localized loss of catecholaminergic innervation had evidence of decreased vesicular storage specifically in the denervated regions. Thus, across neurodegenerative diseases, loss of catecholaminergic neurons seems to be associated with decreased vesicular storage in the residual neurons. PMID:26255205
Full Text Available Cognitive functions associated with prefrontal cortex, such as working memory and attention, are strongly influenced by catecholamine (dopamine, DA and norepinephrine, NE release. Midbrain dopaminergic neurons in the ventral tegmental area (VTA and noradrenergic neurons in the locus coeruleus (LC are major sources of DA and NE to the prefrontal cortex. It is traditionally believed that DA and NE neurons are homogeneous with highly divergent axons innervating multiple terminal fields and once released, DA and NE individually or complementarily modulate the prefrontal functions and other brain regions. However, recent studies indicate that both DA and NE neurons in the mammalian brain are heterogeneous with a great degree of diversity, including their developmental lineages, molecular phenotypes, projection targets, afferent inputs, synaptic connectivity, physiological properties, and behavioral functions. These diverse characteristics could potentially endow DA and NE neurons with distinct roles in executive function, and alterations in their responses to genetic and epigenetic risk factors during development may contribute to distinct phenotypic and functional changes in disease states. In this review of recent literature, we discuss how these advances in DA and NE neurons change our thinking of catecholamine influences in cognitive functions in the brain, especially functions related to prefrontal cortex. We review how the projection-target specific populations of neurons in these two systems execute their functions in both normal and abnormal conditions. Additionally, we explore what open questions remain and suggest where future research needs to move in order to provide perspective insight into the cause of neuropsychiatric disorders related to DA and NE systems.
Matthews, Gillian A; Nieh, Edward H; Vander Weele, Caitlin M; Halbert, Sarah A; Pradhan, Roma V; Yosafat, Ariella S; Glober, Gordon F; Izadmehr, Ehsan M; Thomas, Rain E; Lacy, Gabrielle D; Wildes, Craig P; Ungless, Mark A; Tye, Kay M
The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PAPERCLIP. PMID:26871628
Manger, P R; Fahringer, H M; Pettigrew, J D; Siegel, J M
The present study describes the distribution and cellular morphology of catecholaminergic neurons in the CNS of two species of monotreme, the platypus (Ornithorhynchus anatinus) and the short-beaked echidna (Tachyglossus aculeatus). Tyrosine hydroxylase immunohistochemistry was used to visualize these neurons. The standard A1-A17, C1-C3 nomenclature was used for expediency, but the neuroanatomical names of the various nuclei have also been given. Monotremes exhibit catecholaminergic neurons in the diencephalon (A11, A12, A13, A14, A15), midbrain (A8, A9, A10), rostral rhombencephalon (A5, A6, A7), and medulla (A1, A2, C1, C2). The subdivisions of these neurons are in general agreement with those of other mammals, and indeed other amniotes. Apart from minor differences, those being a lack of A4, A3, and C3 groups, the catecholaminergic system of monotremes is very similar to that of other mammals. Catecholaminergic neurons outside these nuclei, such as those reported for other mammals, were not numerous with occasional cells observed in the striatum. It seems unlikely that differences in the sleep phenomenology of monotremes, as compared to other mammals, can be explained by these differences. The similarity of this system across mammalian and amniote species underlines the evolutionary conservatism of the catecholaminergic system. PMID:12476055
Matthews, Gillian A.; Nieh, Edward H.; Vander Weele, Caitlin M.; Halbert, Sarah A.; Pradhan, Roma V.; Yosafat, Ariella S.; Glober, Gordon F.; Izadmehr, Ehsan M.; Thomas, Rain E.; Lacy, Gabrielle D.; Wildes, Craig P.; Ungless, Mark A.; Tye, Kay M.
Summary The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute ...
Langer, Claus Oliver
The catecholamines norepinephrine and its biosynthetic precursor dopamine are two principal neurotransmitters in the human central nervous system (CNS). Moreover, norepinephrine is a major transmitter substance in the peripheral, autonomic nervous system. Positron emission tomography (PET) is a non-invasive imaging technique that uses positron-labeled molecules to image and measure the function of biological processes in vivo. Neuronal catecholaminergic pathways, both in CNS...
Kastenhuber, Edda; Kratochwil, Claudius F; Ryu, Soojin; Schweitzer, Jörn; Driever, Wolfgang
The catecholamines dopamine and noradrenaline provide some of the major neuromodulatory systems with far-ranging projections in the brain and spinal cord of vertebrates. However, development of these complex systems is only partially understood. Zebrafish provide an excellent model for genetic analysis of neuronal specification and axonal projections in vertebrates. Here, we analyze the ontogeny of the catecholaminergic projections in zebrafish embryos and larvae up to the fifth day of develo...
Jonathan P Wisor
Full Text Available Modafinil, in its two clinical formulations (Provigil® and Nuvigil®, is a widely prescribed wake-promoting therapeutic agent. It binds competitively to the cell membrane dopamine transporter and is dependent on catecholaminergic (dopaminergic and adrenergic signaling for its wake-promoting effects. The clinical spectrum of effects for modafinil is distinct from the effects seen with other catecholaminergic agents. Relative to other commonly used agents that act through catecholaminergic mechanisms, modafinil has a relatively low abuse potential, produces wakefulness with an attenuated compensatory sleep recovery thereafter, and does not ameliorate cataplexy in narcolepsy. These clinically relevant phenomenological differences between modafinil and agents such as amphetamines and cocaine do not eliminate catecholaminergic effects as a possible mediator of its wake-promoting action; they merely reflect its unique pharmacological profile. Modafinil is an exceptionally weak, but apparently very selective, dopamine transporter inhibitor. The pharmacodynamic response to modafinil, as measured by dopamine levels in brain microdialysate, is protracted relative to other agents that act via catecholaminergic mechanisms. The conformational constraints on the interaction of modafinil with the dopamine transporter—and probably, as a consequence, its effects on trace amine receptor signaling in the catecholaminergic cell—are unique among catecholaminergic agents. These unique pharmacological properties of modafinil should be considered both in seeking to thoroughly understand its putatively elusive mechanism of action and in the design of novel therapeutic agents.
Imberti, Jacopo F; Underwood, Katherine; Mazzanti, Andrea; Priori, Silvia G
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inheritable cardiac disorder associated with exercise- and stress-induced sudden death in young individuals. Although important steps forward have been made in the comprehension and treatment of this disease, several aspects remain unclear. Firstly, from an epidemiological standpoint the actual prevalence of CPVT is still unknown and possibly underestimated. In addition, the diagnostic process remains very challenging and can be supported by genetic analysis in only about half of the cases. Finally, up to one third of CPVT patients continue to present complex arrhythmias despite beta blocker treatment; the role of newer therapeutic options, such as flecainide and left cardiac sympathetic denervation, needs to be further elucidated. All these points constitute challenges for the cardiologist in the management of CPVT patients and fuel research into new diagnostic, prognostic and therapeutic approaches. PMID:26948768
Patzke, Nina; Bertelsen, Mads F; Fuxe, Kjell; Manger, Paul R
This study investigated the nuclear organization of four immunohistochemically identifiable neural systems (cholinergic, catecholaminergic, serotonergic and orexinergic) within the brains of three male Tasmanian devils (Sarcophilus harrisii), which had a mean brain mass of 11.6g. We found that the nuclei generally observed for these systems in other mammalian brains were present in the brain of the Tasmanian devil. Despite this, specific differences in the nuclear organization of the cholinergic, catecholaminergic and serotonergic systems appear to carry a phylogenetic signal. In the cholinergic system, only the dorsal hypothalamic cholinergic nucleus could be observed, while an extra dorsal subdivision of the laterodorsal tegmental nucleus and cholinergic neurons within the gelatinous layer of the caudal spinal trigeminal nucleus were observed. Within the catecholaminergic system the A4 nucleus of the locus coeruleus complex was absent, as was the caudal ventrolateral serotonergic group of the serotonergic system. The organization of the orexinergic system was similar to that seen in many mammals previously studied. Overall, while showing strong similarities to the organization of these systems in other mammals, the specific differences observed in the Tasmanian devil reveal either order specific, or class specific, features of these systems. Further studies will reveal the extent of change in the nuclear organization of these systems in marsupials and how these potential changes may affect functionality. PMID:25150966
Lavialle-Defaix, C.; Apaire-Marchais, V; Legros, C.; Pennetier, Cédric; Mohamed, A; P. Licznar; Corbel, Vincent; Lapied, B
To understand better the mode of action of insecticides and repellents used in vector-borne diseases control, we developed a new biological model based on mosquito neurons isolated from adults Anopheles gambiae heads. This cellular model is well adapted to multidisciplinary approaches: electrophysiology, pharmacology, molecular biology and biochemical assays. Using RT-PCR, we demonstrated that isolated neurons express the nicotinic acetylcholine receptor subunit alpha 1 (Ag alpha 1 nAchR), tw...
Yusipovich, Alexander I.; Novikov, Sergey M.; Kazakova, Tatiana A.; Erokhova, Liudmila A.; Brazhe, Nadezda A.; Lazarev, Grigory L.; Maksimov, Georgy V.
Actual aspects of using a new method of laser interference microscopy (LIM) for studying nerve cells are discussed. The peculiarities of the LIM display of neurons are demonstrated by the example of isolated neurons of a pond snail Lymnaea stagnalis. A comparative analysis of the images of the cell and subcellular structures of a neuron obtained by the methods of interference microscopy, optical transmission microscopy, and confocal microscopy is performed. Various aspects of the application of LIM for studying the lateral dimensions and internal structure of the cytoplasm and organelles of a neuron in cytology and cell physiology are discussed.
Holst, Anders Gaarsdal; Tfelt-Hansen, 1jacob; Olesen, Morten S;
Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart disease, which can lead to life-threatening ventricular arrhythmias in patients with a structurally normal heart. The age of onset is usually between two and 12 years and the initial symptom is frequently syncope or...
Talman, William T.; Dragon, Deidre Nitschke; Jones, Susan Y.; Moore, Steven A.; Lin, Li-Hsien
Lesions that remove neurons expressing neurokinin-1 (NK1) receptors from the nucleus tractus solitarii (NTS) without removing catecholaminergic neurons lead to loss of baroreflexes, labile arterial pressure, myocardial lesions and sudden death. Because destruction of NTS catecholaminergic neurons expressing tyrosine hydroxylase (TH) may also cause lability of arterial pressure and loss of baroreflexes, we sought to test the hypothesis that cardiac lesions associated with lability are not depe...
W Clay Spencer
Full Text Available The simple and well-described structure of the C. elegans nervous system offers an unprecedented opportunity to identify the genetic programs that define the connectivity and function of individual neurons and their circuits. A correspondingly precise gene expression map of C. elegans neurons would facilitate the application of genetic methods toward this goal. Here we describe a powerful new approach, SeqCeL (RNA-Seq of C. elegans cells for producing gene expression profiles of specific larval C. elegans neurons.We have exploited available GFP reporter lines for FACS isolation of specific larval C. elegans neurons for RNA-Seq analysis. Our analysis showed that diverse classes of neurons are accessible to this approach. To demonstrate the applicability of this strategy to rare neuron types, we generated RNA-Seq profiles of the NSM serotonergic neurons that occur as a single bilateral pair of cells in the C. elegans pharynx. These data detected >1,000 NSM enriched transcripts, including the majority of previously known NSM-expressed genes.This work offers a simple and robust protocol for expression profiling studies of post-embryonic C. elegans neurons and thus provides an important new method for identifying candidate genes for key roles in neuron-specific development and function.
Scott D. N. Else
Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a severe arrhythmia associated with sudden death in the young. It is caused by defective calcium handling in ventricular myocytes. The association of supraventricular tachycardia (SVT with CPVT is described in the literature, occurring in the lead-up to ventricular tachycardia during exercise testing. We describe three cases of SVT that were initiated in the recovery period of exercise testing in children with CPVT.
Shashank P Behere
Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a highly malignant inheritable cardiac channelopathy. The past decade and a half has provided exciting new discoveries elucidating the genetic etiology and pathophysiology of CPVT. This review of the current literature on CPVT aims to summarize the state of the art in our understanding of the genetic etiology and the molecular pathogenesis of CPVT, and how these relate to our current approach to diagnosis and management. We will also shed light on groundbreaking new work that will continue to refine the management of CPVT in the future. As our knowledge of CPVT continues to grow, further studies will yield a better understanding of the efficacy and pitfalls of established diagnostic approaches and therapies as well as help shape newer diagnostic and treatment strategies. Two separate searches were run on the National Center for Biotechnology Information's (NCBI website. The first used the medical subject headings (MeSH database using the term “catecholaminergic polymorphic ventricular tachycardia” that was run on the PubMed database using the age filter (birth to 18 years, and it yielded 58 results. The second search using the MeSH database with the search term “catecholaminergic polymorphic ventricular tachycardia,” applying no filters yielded 178 results. The abstracts of all these articles were studied and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles were further explored and read in full.
Kaelberer, Melanie Maya; Jordt, Sven-Eric
Somatosensory nerves transduce thermal, mechanical, chemical, and noxious stimuli caused by both endogenous and environmental agents. The cell bodies of these afferent neurons are located within the sensory ganglia. Sensory ganglia innervate a specific organ or portion of the body. For instance, the dorsal root ganglia (DRG) are located in the vertebral column and extend processes throughout the body and limbs. The trigeminal ganglia are located in the skull and innervate the face, and upper airways. Vagal afferents of the nodose ganglia extend throughout the gut, heart, and lungs. The nodose neurons control a diverse array of functions such as: respiratory rate, airway irritation, and cough reflexes. Thus, to understand and manipulate their function, it is critical to identify and isolate airway specific neuronal sub-populations. In the mouse, the airways are exposed to a fluorescent tracer dye, Fast Blue, for retrograde tracing of airway-specific nodose neurons. The nodose ganglia are dissociated and fluorescence activated cell (FAC) sorting is used to collect dye positive cells. Next, high quality ribonucleic acid (RNA) is extracted from dye positive cells for next generation sequencing. Using this method airway specific neuronal gene expression is determined. PMID:27168016
Lee, K.; McKenna, F; Rowe, I C M; Ashford, M.L.J.
The actions of several neuroleptic and tricyclic compounds were examined on the large conductance Ca2+-activated K+ (BKCa) channel present in neurones isolated from the rat motor cortex.Classical neuroleptic compounds including chlorpromazine and haloperidol applied to the intracellular surface of inside-out patches produced a concentration-dependent reduction in BKCa channel activity. Similar effects were observed when these compounds were applied to the extracellular surface of outside-out ...
Heiner, Jason D; Bullard-Berent, Jeffrey H; Inbar, Shmuel
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare adrenergically mediated arrhythmogenic disorder classically induced by exercise or emotional stress and found in structurally normal hearts. It is an important cause of cardiac syncope and sudden death in childhood. Catecholaminergic polymorphic ventricular tachycardia is a genetic cardiac channelopathy with known mutations involving genes affecting intracellular calcium regulation. We present a case of a 14-year-old boy who had cardiopulmonary arrest after an emotionally induced episode of CPVT while attempting to invite a girl to the school dance. Review of his presenting cardiac rhythm, induction of concerning ventricular arrhythmias during an exercise stress test, and genetic testing confirmed the diagnosis of CPVT. He recovered fully and was treated with β-blocker therapy and placement of an implantable cardioverter-defibrillator. In this report, we discuss this rare but important entity, including its molecular foundation, clinical presentation, basics of diagnosis, therapeutic options, and implications of genetic testing for family members. We also compare CPVT to other notable cardiomyopathic and channelopathic causes of sudden death in youth including hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, long QT syndrome, short QT syndrome, and Brugada syndrome. PMID:22068070
Filippi, Alida; Mahler, Julia; Schweitzer, Jörn; Driever, Wolfgang
The development of dopaminergic and noradrenergic neurons has received much attention based on their modulatory effect on many behavioral circuits and their involvement in neurodegenerative diseases. The zebrafish (Danio rerio) has emerged as a new model organism with which to study development and function of catecholaminergic systems. Tyrosine hydroxylase is the entry enzyme into catecholamine biosynthesis and is frequently used as a marker for catecholaminergic neurons. A genome duplicatio...
ZHANG Chaofeng; DU Huizhi; YANG Pin
Although lithium possesses neuroprotective functions, the molecular mechanism underlying its actions has not been fully elucidated. In the present paper, the effects of lithium chloride on voltage-dependent potassium currents in the CA1 pyramidal neurons acutely isolated from rat hippocampus were studied using the whole-cell patch-clamp technique. Depolarizing test pulses activated two components of outward potassium currents: a rapidly activating and inactivating component, IA and a delayed component, IK. Results showed that lithium chloride increased the amplitude of IA in a concentration-dependent manner. Half enhancement concentration (EC50) was 22.80±5.45 μmol·L-1. Lithium chloride of 25 μmol·L-1 shifted the steady-state activation curve and inactivation curve of IA to more negative potentials, but mainly affected the activation kinetics. The amplitude and the activation processes of IK were not affected by lithium chloride. The effects of lithium chloride on potassium channel appear to possess neuroprotective properties by Ca2+-lowing effects modulate neuronal excitability by activating IA in rat hippocampal neurons.
Ghahramani, Zachary N; Timothy, Miky; Kaur, Gurpreet; Gorbonosov, Michelle; Chernenko, Alena; Forlano, Paul M
Catecholamines, which include the neurotransmitters dopamine and noradrenaline, are known modulators of sensorimotor function, reproduction, and sexually motivated behaviors across vertebrates, including vocal-acoustic communication. Recently, we demonstrated robust catecholaminergic (CA) innervation throughout the vocal motor system in the plainfin midshipman fish Porichthys notatus, a seasonal breeding marine teleost that produces vocal signals for social communication. There are 2 distinct male reproductive morphs in this species: type I males establish nests and court females with a long-duration advertisement call, while type II males sneak spawn to steal fertilizations from type I males. Like females, type II males can only produce brief, agonistic, grunt type vocalizations. Here, we tested the hypothesis that intrasexual differences in the number of CA neurons and their fiber innervation patterns throughout the vocal motor pathway may provide neural substrates underlying divergence in reproductive behavior between morphs. We employed immunofluorescence (-ir) histochemistry to measure tyrosine hydroxylase (TH; a rate-limiting enzyme in catecholamine synthesis) neuron numbers in several forebrain and hindbrain nuclei as well as TH-ir fiber innervation throughout the vocal pathway in type I and type II males collected from nests during the summer reproductive season. After controlling for differences in body size, only one group of CA neurons displayed an unequivocal difference between male morphs: the extraventricular vagal-associated TH-ir neurons, located just lateral to the dimorphic vocal motor nucleus (VMN), were significantly greater in number in type II males. In addition, type II males exhibited greater TH-ir fiber density within the VMN and greater numbers of TH-ir varicosities with putative contacts on vocal motor neurons. This strong inverse relationship between the predominant vocal morphotype and the CA innervation of vocal motor neurons suggests
Yamuy, J; Sampogna, S; Morales, F R; Chase, M H
The interaction of cholinergic and catecholaminergic mechanisms in the mesopontine region has been hypothesized as being critical for the generation and maintenance of active (REM) sleep. To further examine this hypothesis, we sought to determine the pattern of neuronal activation (via c-fos expression) of catecholaminergic and cholinergic neurons in this region during active sleep induced by the pontine microapplication of carbachol (designated as active sleep-carbachol). Accordingly, we used two sets of double-labeling techniques; the first to identify tyrosine hydroxylase-containing neurons (putative catecholaminergic cells) which also express the c-fos protein product Fos, and the second to reveal choline acetyltransferase-containing neurons (putative cholinergic cells) which also express Fos. Compared to control cats, active sleep-carbachol cats exhibited a significantly greater number of Fos-expressing neurons in the dorsolateral region of the pons, which encompasses the locus coeruleus, the lateral pontine reticular formation, the peribrachial nuclei and the latero-dorsal and pedunculo-pontine tegmental nuclei. However, both control and active sleep-carbachol cats exhibited a similar number of catecholaminergic and cholinergic neurons in those regions that expressed Fos (i.e., double-labeled cells). A large number of c-fos-expressing neurons in the active sleep-carbachol cats whose neurotransmitter phenotype was not identified suggests that non-catecholaminergic, non-cholinergic neuronal populations in mesopontine regions are involved in the generation and maintenance of active sleep. The lack of increased c-fos expression in catecholaminergic neurons during active sleep-carbachol confirms and extends previous data that indicate that these cells are silent during active sleep-carbachol and naturally-occurring active sleep. The finding that cholinergic neurons of the dorsolateral pons were not activated either during wakefulness or active sleep
Gennet, Nicole; Tamburini, Claudia; Nan, Xinsheng; Li, Meng
Cell type-specific surface markers offer a powerful tool for purifying defined cell types for restorative therapies and drug screenings. Midbrain dopaminergic neurons (mesDA) are the nerve cells preferentially lost in the brains of Parkinson's disease patients. Clinical trials of transplantation of fetal neural precursors suggest that cell therapy may offer a cure for this devastating neurological disease. Many lines of preclinical studies demonstrate that neural progenitors committed to dopaminergic fate survive and integrate better than postmitotic DA neurons. We show that the folate-receptor 1 (FolR1), a GPI-anchored cell surface molecule, specifically marks mesDA neural progenitors and immature mesDA neurons. FolR1 expression superimposes with Lmx1a, a bona-fide mesDA lineage marker, during the active phase of mesDA neurogenesis from E9.5 to E14.5 during mouse development, as well as in ESC-derived mesDA lineage. FolR1(+) neural progenitors can be isolated by FACS or magnetic sorting (MAC) which give rise to dopamine neurons expressing TH and Pitx3, whilst FolR1 negative cells generate non-dopaminergic neurons and glia cells. This study identifies FolR1 as a new cell surface marker selectively expressed in mesDA progenitors in vivo and in vitro and that can be used to enrich in vitro differentiated TH neurons. PMID:27580818
De La Fuente, Sam; Van Langen, Irene M.; Postma, Alex V.; Bikker, Henni; Meijer, Albert
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon heritable disease presenting with syncope or sudden cardiac death. Two genes involved in calcium homeostasis, the ryanodine receptor gene and the calsequestrin 2 (CASQ2) gene, have been implicated in this disease. We describ
Petersen, Claus Leth; Nielsen, Jens Rokkedal; Petersen, Bodil Laub;
AIM: The study was designed to assess (1) the time course of catecholaminergic activation in acute myocardial infarction (AMI) as estimated by adrenaline (ADR) and noradrenaline (NOR) concentrations, and (2) to relate activation of these hormones to predict the outcome of cardiac performance...
Jabbari, Javad; Jabbari, Reza; Nielsen, Morten Wagner;
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal, rare hereditary disease with an estimated prevalence of 1:10 000. The genetic variants that cause CPVT are usually highly penetrant. To date, about 189 variants in 5 genes (RYR2, CASQ2, CALM1, TRND, and KCNJ2) have been...
Yakushiji, T; Fukuda, T.; Oyama, Y.; Akaike, N.
1. The effects of benzodiazepines and non-benzodiazepine compounds on the gamma-aminobutyric acid (GABA)-induced chloride current (ICl) were studied in frog isolated sensory neurones by use of a concentration-jump (termed 'concentration-clamp') technique, under single-electrode voltage-clamp conditions. The drugs used were classified into four categories as follows: full benzodiazepine receptor agonists (diazepam, clonazepam, nitrazepam, midazolam, clotiazepam and etizolam), partial agonists ...
Segmentation defines the capacity to differentiate among types of tissues. In MR. it is frequently applied to volumetric determinations. Digital images can be segmented in a number of ways; neuronal networks (NN) can be employed for this purpose. Our objective was to develop algorithms for automatic segmentation using NN and apply them to central nervous system MR images. The segmentation obtained with NN was compared with that resulting from other procedures (region-growing and K means). Each NN consisted of two layers: one based on unsupervised training, which was utilized for image segmentation in sets of K, and a second layer associating each set obtained by the preceding layer with the real set corresponding to the previously segmented objective image. This NN was trained with previously segmented images with supervised regions-growing algorithms and automatic K means. Thus, 4 different segmentation were obtained: region-growing, K means, NN with region-growing and NN with K means. The tissue volumes corresponding to cerebrospinal fluid, gray matter and white matter obtained with the 4 techniques were compared and the most representative segmented image was selected qualitatively by averaging the visual perception of 3 radiologists. The segmentation that best corresponded to the visual perception of the radiologists was that consisting of trained NN with region-growing. In comparison, the other 3 algorithms presented low percentage differences (mean, 3.44%). The mean percentage error for the 3 tissues from these algorithms was lower for region-growing segmentation (2.34%) than for trained NN with K means (3.31%) and for automatic K-means segmentation (4.66%). Thus, NN are reliable in the automation of isolated MR image segmentation. (Author) 12 refs
E. Nof; B. Belhassen; M. Arad; Z.A. Bhuiyan; C. Antzelevitch; R. Rosso; R. Fogelman; D. Luria; D. El-Ani; M.M.A.M. Mannens; S. Viskin; M. Eldar; A.A.M. Wilde; M. Glikson
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value. This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phen
Hua Mo(莫华); Ping He(何萍); Ning Mo(莫宁)
The aim of this study is to further measure the effect of 632.8-nm helium-neon laser on fast excitatory postsynaptic potential(f-EPSP)of postganglionic neurons in isolated rat superior cervical ganglia by means of intracellular recording techniques.The neurons with f-EPSP were irradiated by different power densities(1 - 5 mW/cm2)laser.Irradiated by the 2-mW/cm2 laser,the amplitude of the f-EPSP could augment(P ＜ 0.05,paired t test)and even cause action potential at the end of the first 1 - 2 minutes,the f-EPSP could descend and last for 3 - 8 minutes.But the amplitude of the f-EPSP of neurons irradiated by the 5-mW/cm2 laser could depress for the irradiating periods.The results show that:1)the variation of the amplitude of f-EPSP caused by laser is power density-dependent and time-dependent; 2)there exist the second-order phases in the interaction of the helium-neon laser with neurons.These findings may provide certain evidence in explanation of the mechanisms of clinical helium-neon laser therapy.
W Clay Spencer; Rebecca McWhirter; Tyne Miller; Pnina Strasbourger; Owen Thompson; Hillier, LaDeana W.; Waterston, Robert H.; Miller, David M.
Background The simple and well-described structure of the C. elegans nervous system offers an unprecedented opportunity to identify the genetic programs that define the connectivity and function of individual neurons and their circuits. A correspondingly precise gene expression map of C. elegans neurons would facilitate the application of genetic methods toward this goal. Here we describe a powerful new approach, SeqCeL (RNA-Seq of C. elegans cells) for producing gene expression profiles of s...
Wang, Xiaoyan; Chen, Tingfeng; Zhang, Yani; Li, Bichun; Xu, Qi; Song, Chengyi
Spermatogonial stem cells (SSCs) renew themselves throughout the life of an organism and also differentiate into sperm in the adult. They are multipopent and therefore, can be induced to differentiate into many cells types in vitro. SSCs from pigs, considered an ideal animal model, are used in studies of male infertility, regenerative medicine, and preparation of transgenic animals. Here, we report on a culture system for porcine SSCs and the differentiation of these cells into neuron-like cells and adipocytes. SSCs and Sertoli cells were isolated from neonatal piglet testis by differential adhesion and SSCs were cultured on a feeder layer of Sertoli cells. Third-generation SSCs were induced to differentiate into neuron-like cells by addition of retinoic acid, β-mercaptoethanol, and 3-isobutyl-1-methylxanthine (IBMX) to the induction media and into adipocytes by the addition of hexadecadrol, insulin, and IBMX to the induction media. The differentiated cells were characterized by biochemical staining, qRT-PCR, and immunocytochemistry. The cells were positive for SSC markers, including alkaline phosphatase and SSC-specific genes, consistent with the cells being undifferentiated. The isolated SSCs survived on the Sertoli cells for 15 generations. Karyotyping confirmed that the chromosomal number of the SSCs were normal for pig (2n = 38, n = 19). Pig SSCs were successfully induced into neuron-like cells eight days after induction and into adipocytes 22 days after induction as determined by biochemical and immunocytochemical staining. qPCR results also support this conclusion. The nervous tissue markers genes, Nestin and β-tubulin, were expressed in the neuron-like cells and the adipocyte marker genes, PPARγ and C/EBPα, were expressed in the adipocytes. PMID:26556335
Full Text Available Spermatogonial stem cells (SSCs renew themselves throughout the life of an organism and also differentiate into sperm in the adult. They are multipopent and therefore, can be induced to differentiate into many cells types in vitro. SSCs from pigs, considered an ideal animal model, are used in studies of male infertility, regenerative medicine, and preparation of transgenic animals. Here, we report on a culture system for porcine SSCs and the differentiation of these cells into neuron-like cells and adipocytes. SSCs and Sertoli cells were isolated from neonatal piglet testis by differential adhesion and SSCs were cultured on a feeder layer of Sertoli cells. Third-generation SSCs were induced to differentiate into neuron-like cells by addition of retinoic acid, β-mercaptoethanol, and 3-isobutyl-1-methylxanthine (IBMX to the induction media and into adipocytes by the addition of hexadecadrol, insulin, and IBMX to the induction media. The differentiated cells were characterized by biochemical staining, qRT-PCR, and immunocytochemistry. The cells were positive for SSC markers, including alkaline phosphatase and SSC-specific genes, consistent with the cells being undifferentiated. The isolated SSCs survived on the Sertoli cells for 15 generations. Karyotyping confirmed that the chromosomal number of the SSCs were normal for pig (2n = 38, n = 19. Pig SSCs were successfully induced into neuron-like cells eight days after induction and into adipocytes 22 days after induction as determined by biochemical and immunocytochemical staining. qPCR results also support this conclusion. The nervous tissue markers genes, Nestin and β-tubulin, were expressed in the neuron-like cells and the adipocyte marker genes, PPARγ and C/EBPα, were expressed in the adipocytes.
Hay-Schmidt, Anders; Helboe, Lone; Larsen, Philip J.
Obesity, tyrosine hydroxylase, arcuate nucleus, paracentricular nucleus, raphe nuclei, leptin, serotonin, catecholamines......Obesity, tyrosine hydroxylase, arcuate nucleus, paracentricular nucleus, raphe nuclei, leptin, serotonin, catecholamines...
Soden, Marta E; Miller, Samara M; Burgeno, Lauren M; Phillips, Paul E M; Hnasko, Thomas S; Zweifel, Larry S
Nearly all animals engage in a complex assortment of social behaviors that are essential for the survival of the species. In mammals, these behaviors are regulated by sub-nuclei within the hypothalamus, but the specific cell types within these nuclei responsible for coordinating behavior in distinct contexts are only beginning to be resolved. Here, we identify a population of neurons in the ventral premammillary nucleus of the hypothalamus (PMV) that are strongly activated in male intruder mice in response to a larger resident male but that are not responsive to females. Using a combination of molecular and genetic approaches, we demonstrate that these PMV neurons regulate intruder-specific male social behavior and social novelty recognition in a manner dependent on synaptic release of the excitatory neurotransmitter glutamate. These data provide direct evidence for a unique population of neurons that regulate social behaviors in specific contexts. PMID:27346361
In this study, the effects of acute SO2 derivatives and chronic lead exposure together on sodium cur-rents （INa） were investigated in acutely isolated rat hippocampal neurons by using the whole-cell patch clamp techniques. We found that chronic lead exposure hardly reduced the amplitudes of INa. In the normal condition, sodium current started to appear at around ?70 mV, and reached the peak current at around ?40 mV. After chronic lead exposure, the data changed to ?70 and ?30 mV. After adding SO2 derivatives, the data changed to ?80 and ?40 mV, respectively. SO2 derivatives caused a significant in-crease of INa in hippocampal chronic-lead exposed neurons. Chronic lead exposure induced a right shift of the activation curve and a left shift of the inactivation curve of sodium channels. SO2 derivatives caused negative shifts of the activation and inactivation curves of INa in hippocampal chronic-lead ex-posed neurons. Lead exposure put off the time reaching the peak of INa activation. SO2 derivatives in-creased the time constants of inactivation after lead exposure. The interaction of lead and SO2 deriva-tives with voltage-dependent sodium channels may lead to changes in electrical activity and contribute to worsening the neurotoxicological damage.
Tagliafierro, Lidia; Bonawitz, Kirsten; Glenn, Omolara C; Chiba-Falek, Ornit
Different cell types and multiple cellular connections characterize the human brain. Gene expression analysis using a specific population of cells is more accurate than conducting analysis of the whole tissue homogenate, particularly in the context of neurodegenerative diseases, where a specific subset of cells is affected by the different pathology. Due to the difficulty of obtaining homogenous cell populations, gene expression in specific cell-types (neurons, astrocytes, etc.) has been understudied. To leverage the use of archive resources of frozen human brains in studies of neurodegenerative diseases, we developed and calibrated a method to quantify cell-type specific-neuronal, astrocytes-expression profiles of genes implicated in neurodegenerative diseases, including Parkinson's and Alzheimer's diseases. Archive human frozen brain tissues were used to prepare slides for rapid immunostaining using cell-specific antibodies. The immunoreactive-cells were isolated by Laser Capture Microdissection (LCM). The enrichment for a particular cell-type of interest was validated in post-analysis stage by the expression of cell-specific markers. We optimized the technique to preserve the RNA integrity, so that the RNA was suitable for downstream expression analyses. Following RNA extraction, the expression levels were determined digitally using nCounter Single Cell Gene Expression assay (NanoString Technologies®). The results demonstrated that using our optimized technique we successfully isolated single neurons and astrocytes from human frozen brain tissues and obtained RNA of a good quality that was suitable for mRNA expression analysis. We present here new advancements compared to previous reported methods, which improve the method's feasibility and its applicability for a variety of downstream molecular analyses. Our new developed method can be implemented in genetic and functional genomic research of neurodegenerative diseases and has the potential to significantly
Bagley, Elena E.; Chieng, Billy C H; Christie, MacDonald J.; Connor, Mark
The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic action, and a significant site of cellular adaptations to chronic morphine treatment (CMT). We examined μ-opioid receptor (MOP) regulation of voltage-gated calcium channel currents (ICa) and G-protein-activated K channel currents (GIRK) in PAG neurons from CMT mice.Mice were injected s.c. with 300 mg kg−1 of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). This protoc...
Charlesworth, P; Jacobson, I; Richards, C. D.
1. The action of pentobarbitone on the N-methyl-D-aspartate (NMDA) receptors of neurones freshly dissociated from the olfactory bulb and olfactory tubercle has been studied using patch-clamp techniques. 2. Pentobarbitone produced a concentration-dependent depression of the currents evoked by NMDA with an IC50 value of c. 250 microM. 3. Analysis of the NMDA-evoked noise produced power spectra that could be fitted by the sum of two Lorentzians with corner frequencies of 17 and 82 Hz. Pentobarbi...
Monoaminergic neurons in nuclei raphe dorsalis and locus coeruleus of the cat may be visualized by radioautography after local micro-instillation of tritiated serotonin and noradrenaline. The concomitant administration of the appropriate tracer with the other biogenic amine in non radioactive form permits a specific identification of serotoninergic and catecholaminergic nerve cell bodies. A small contingent of presumptive serotoninergic neurons is thus demonstrated in the region of the locus coeruleus
Full Text Available role to replace lost cells due to physiological turnover, injury, or disease and tosupport cell genesis contributing to the cell number homeostasis. Long time it wasthought that adult mammalian central nervous system doesn't possess any or fewregenerative capacity. Nowadays it was demonstrated that also in the brain thereare stem cells which have the capacity to differentiate into astocytes,oligodendrocytes and neurons.In few degenerative diseases the stem cells lose the regenerative capacity withconsequences in diminishing and loss of functional capacity. Stem cell therapyrepresents a novel and promising therapeutic approach to treatment of a variety ofdegenerative disease as multiple sclerosis. For this it is necessary that a efficientstem cell source can be found and secondary to be proven that these transplantablecells have differential potential into neural tissue.In order to be able to possess a stem cell source capable to build an implant it isnecessary to know the cultivation technology and also the instruments to prove theircapacity to differentiate into specific cells of the nervous system. These were themotives that enabled us to to try to harvest, cultivate and differentiate stem cellsfrom the murine central nervous system.
Martin, R S; Luong, L A; Welsh, N. J.; Eglen, R. M.; Martin, G R; MacLennan, S J
This study investigated the cannabinoid receptor, known to inhibit neuronally-evoked contractions of the mouse isolated urinary bladder, in bladder sections isolated from mouse, rat, dog, pig non-human primate or human.The CB1-like pharmacology of the cannabinoid receptor in mouse isolated bladder observed previously was confirmed in this study by the rank order of agonist potencies: CP 55940⩾WIN 55212-2>HU 210>JWH 015>anandamide, the high affinity of the CB1 selective antagonist, SR 141716A ...
Yakushiji, T; Fukuda, T; Oyama, Y; Akaike, N
1. The effects of benzodiazepines and non-benzodiazepine compounds on the gamma-aminobutyric acid (GABA)-induced chloride current (ICl) were studied in frog isolated sensory neurones by use of a concentration-jump (termed 'concentration-clamp') technique, under single-electrode voltage-clamp conditions. The drugs used were classified into four categories as follows: full benzodiazepine receptor agonists (diazepam, clonazepam, nitrazepam, midazolam, clotiazepam and etizolam), partial agonists (CL 218,872, Ro 16-6028, Ro 17-1812 and Ro 23-0364), inverse agonists (Ro 15-3505, FG 7142 and beta-CCE) and a benzodiazepine receptor antagonist, Ro 15-1788 (flumazenil). 2. All full agonists at concentrations of 3 x 10(-6) M or less increased dose-dependently the peak amplitude of ICl elicited by 3 x 10(-6) M GABA to twice to three times larger than the control. However, no further augmentation of the GABA response was observed at concentrations of 1 x 10(-5) M or higher. Partial agonists also showed a dose-dependent augmentation of the GABA response at concentrations ranging from 3 x 10(-8) M to 3 x 10(-5) M, but their efficacies of augmentation of the GABA response were only about half or less of those of full agonists. Of the inverse agonists, beta-CCE had a unique dose-dependent effect on the GABA response. Beta-CCE reduced dose-dependently the GABA response at concentrations of less than 3 x 10(-6) M, but augmented it at concentrations of 3 x 10(-5) M and 6 x 10(-5) M. The inverse agonists reduced dose-dependently the GABA response. The benzodiazepine antagonist, flumazenil, slightly augmented the GABA response at concentrations between 3 x 10 7M and 3 x 10 5 M. 3. These results show clear differences in the effects on the GABA response between these four categories of compounds known to affect the benzodiazepine recognition site of the GABA/ benzodiazepine receptor-chloride channel complex. Our experimental system of frog isolated sensory neurones and a 'concentration
Full Text Available A specialized population of cells residing in the hair follicle is quiescent but shows pluripotency for differentiating into epithelial-mesenchymal lineage cells. Therefore, such cells are hoped to be useful as implantable donor cells for regenerative therapy. Recently, it was reported that intracellular delivery of TAT-VHL peptide induces neuronal differentiation of skin-derived precursors. In the present study, we successfully isolated multipotent stem cells derived from the epidermis of elderly humans, characterized these cells as being capable of sphere formation and strong expression of nestin, fibronectin, and CD34 but not of keratin 15, and identified the niche of these cells as being the outer root sheath of the hair follicles. In addition, we showed that TAT-VHL peptide induced their neuronal differentiation in vitro, and confirmed by fluorescence immunohistochemistry the neuronal differentiation of such peptide-treated cells implanted into rodent brains. These multipotent nestin-expressing stem cells derived from human epidermis are easily accessible and should be useful as donor cells for neuronal regenerative cell therapy.
Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death which usually occurs during childhood. Recent studies have shown that CPVT is caused by mutations in the cardiac ryanodine receptor type 2 (RyR2 or calsequestrin 2 (CASQ2 genes. Both proteins are key contributors to the intracellular Ca2+ handling process and play a pivotal role in Ca2+ release from the sarcoplasmic reticulum to the cytosol during systole. Although the molecular pathogenesis of CPVT is not entirely clear, it was suggested that the CPVT mutations promote excessive sarcoplasmic reticulum Ca2+ leak, which initiates delayed afterdepolarizations (DADs and triggered arrhythmias in cardiac myocytes. The recent breakthrough discovery of induced pluripotent stem cells (iPSC generated from somatic cells (e.g. fibroblasts, keratinocytes now enables researches to investigate mutated cardiomyocytes generated from the patient’s iPSC. To this end, in the present article we review recent studies on CPVT iPSC-derived cardiomyocytes, thus demonstrating in the mutated cells catecholamine-induced DADs and triggered arrhythmias.
Reyes, Beverly A. S.; Van Bockstaele, Elisabeth J.
The nucleus of the solitary tract (NTS) is a critical structure involved in coordinating autonomic and visceral activities. Previous independent studies have demonstrated efferent projections from the NTS to the nucleus paragigantocellularis (PGi) and the central nucleus of the amygdala (CNA) in rat brain. To further characterize the neural circuitry originating from the NTS with postsynaptic targets in the amygdala and medullary autonomic targets, distinct green or red fluorescent latex micr...
Ian N Sabir
Full Text Available The relationship between alternans and arrhythmogenicity was studied in genetically modified murine hearts modeling catecholaminergic polymorphic ventricular tachycardia (CPVT during Langendorff perfusion, before and after treatment with catecholamines and a β-adrenergic antagonist. Heterozygous (RyR2p/s and homozygous (RyR2s/s RyR2-P2328S hearts, and wild-type (WT controls, were studied before and after treatment with epinephrine (100 nM and 1 µM and propranolol (100 nM. Monophasic action potential recordings demonstrated significantly greater incidences of arrhythmia in RyR2s/p and RyR2s/s hearts as compared to WTs. Arrhythmogenicity in RyR2s/s hearts was associated with alternans, particularly at short baseline cycle lengths. Both phenomena were significantly accentuated by treatment with epinephrine and significantly diminished by treatment with propranolol, in full agreement with clinical expectations. These changes took place, however, despite an absence of changes in action potential durations, ventricular effective refractory periods or restitution curve characteristics. Furthermore pooled data from all hearts in which arrhythmia occurred demonstrated significantly greater alternans magnitudes, but similar restitution curve slopes, to hearts that did not demonstrate arrhythmia. These findings thus further validate the RyR2-P2328S murine heart as a model for human CPVT, confirming an alternans phenotype in common with murine genetic models of the Brugada syndrome and the congenital long-QT syndrome type 3. In contrast to these latter similarities, however, this report demonstrates the dissociation of alternans from changes in the properties of restitution curves for the first time in a murine model of a human arrhythmic syndrome.
Subbarao, Raghavendra Baregundi; Ullah, Imran; Kim, Eun-Jin; Jang, Si-Jung; Lee, Won-Jae; Jeon, Ryoung Hoon; Kang, Dawon; Lee, Sung-Lim; Park, Bong-Wook; Rho, Gyu-Jin
Endometrial stromal cells (EMSCs) obtained from porcine uterus (n = 6) were positive for mesenchymal stem cell markers (CD29, CD44 and CD90), and negative for epithelial marker CD9 and hematopoietic markers CD34, CD45 analyzed by flow cytometry. Further the cells were positive for expression of mesenchymal markers, CD105, CD140b, and CD144 by PCR. Pluripotent markers OCT4, SOX2, and NANOG were positively expressed in EMSCs analyzed by Western blotting and PCR. Further, differentiation into adipocytes and osteocytes was confirmed by cytochemical staining and lineage specific gene expression by quantitative realtime-PCR. Adipocyte (FABP, LPL, AP2) and osteocyte specific genes (ON, BG, RUNX2) in differentiated EMSCs showed significant (p < 0.05) increase in expression compared to undifferentiated control cells. Neurogenic transdifferentiation of EMSCs exhibited distinctive dendritic morphology with axon projections and neuronal specific genes, NFM, NGF, MBP, NES, B3T and MAP2 and proteins, B3T, NFM, NGF, and TRKA were positively expressed in neuronal differentiated cells. Functional analysis of neuronal differentiated EMSCs displayed voltage-dependence and kinetics for transient outward K+ currents (Ito), at holding potential of -80 mV, Na+ currents and during current clamp, neuronal differentiated EMSCs was more negative than that of control EMSCs. Porcine EMSCs is a suitable model for studying molecular mechanism of transdifferentiation, assessment of electrophysiological properties and their efficiency during in vivo transplantation. PMID:26006231
Raghavendra Baregundi Subbarao
Full Text Available Endometrial stromal cells (EMSCs obtained from porcine uterus (n = 6 were positive for mesenchymal stem cell markers (CD29, CD44 and CD90, and negative for epithelial marker CD9 and hematopoietic markers CD34, CD45 analyzed by flow cytometry. Further the cells were positive for expression of mesenchymal markers, CD105, CD140b, and CD144 by PCR. Pluripotent markers OCT4, SOX2, and NANOG were positively expressed in EMSCs analyzed by Western blotting and PCR. Further, differentiation into adipocytes and osteocytes was confirmed by cytochemical staining and lineage specific gene expression by quantitative realtime-PCR. Adipocyte (FABP, LPL, AP2 and osteocyte specific genes (ON, BG, RUNX2 in differentiated EMSCs showed significant (p < 0.05 increase in expression compared to undifferentiated control cells. Neurogenic transdifferentiation of EMSCs exhibited distinctive dendritic morphology with axon projections and neuronal specific genes, NFM, NGF, MBP, NES, B3T and MAP2 and proteins, B3T, NFM, NGF, and TRKA were positively expressed in neuronal differentiated cells. Functional analysis of neuronal differentiated EMSCs displayed voltage-dependence and kinetics for transient outward K+ currents (Ito, at holding potential of −80 mV, Na+ currents and during current clamp, neuronal differentiated EMSCs was more negative than that of control EMSCs. Porcine EMSCs is a suitable model for studying molecular mechanism of transdifferentiation, assessment of electrophysiological properties and their efficiency during in vivo transplantation.
Gibbons, Chris J.; Thornton, Everard W; Ealing, John; Shaw, Pamela J; Talbot, Kevin; Tennant, Alan; Young, Carolyn A.; ,
Objective Social withdrawal is described as the condition in which an individual experiences a desire to make social contact, but is unable to satisfy that desire. It is an important issue for patients with motor neurone disease who are likely to experience severe physical impairment. This study aims to reassess the psychometric and scaling properties of the MND Social Withdrawal Scale (MND-SWS) domains and examine the feasibility of a summary scale, by applying scale data to the Rasch model....
Xiaoyan Wang; Tingfeng Chen; Yani Zhang; Bichun Li; Qi Xu; Chengyi Song
Spermatogonial stem cells (SSCs) renew themselves throughout the life of an organism and also differentiate into sperm in the adult. They are multipopent and therefore, can be induced to differentiate into many cells types in vitro. SSCs from pigs, considered an ideal animal model, are used in studies of male infertility, regenerative medicine, and preparation of transgenic animals. Here, we report on a culture system for porcine SSCs and the differentiation of these cells into neuron-like c...
Jung, Christian B; Moretti, Alessandra; Mederos y Schnitzler, Michael; Iop, Laura; Storch, Ursula; Bellin, Milena; Dorn, Tatjana; Ruppenthal, Sandra; Pfeiffer, Sarah; Goedel, Alexander; Dirschinger, Ralf J; Seyfarth, Melchior; Lam, Jason T; Sinnecker, Daniel; Gudermann, Thomas; Lipp, Peter; Laugwitz, Karl-Ludwig
Coordinated release of calcium (Ca2+) from the sarcoplasmic reticulum (SR) through cardiac ryanodine receptor (RYR2) channels is essential for cardiomyocyte function. In catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited disease characterized by stress-induced ventricular arrhythmias in young patients with structurally normal hearts, autosomal dominant mutations in RYR2 or recessive mutations in calsequestrin lead to aberrant diastolic Ca2+ release from the SR causing arrhythmogenic delayed after depolarizations (DADs). Here, we report the generation of induced pluripotent stem cells (iPSCs) from a CPVT patient carrying a novel RYR2 S406L mutation. In patient iPSC-derived cardiomyocytes, catecholaminergic stress led to elevated diastolic Ca2+ concentrations, a reduced SR Ca2+ content and an increased susceptibility to DADs and arrhythmia as compared to control myocytes. This was due to increased frequency and duration of elementary Ca2+ release events (Ca2+ sparks). Dantrolene, a drug effective on malignant hyperthermia, restored normal Ca2+ spark properties and rescued the arrhythmogenic phenotype. This suggests defective inter-domain interactions within the RYR2 channel as the pathomechanism of the S406L mutation. Our work provides a new in vitro model to study the pathogenesis of human cardiac arrhythmias and develop novel therapies for CPVT. PMID:22174035
Talani, Giuseppe; Biggio, Francesca; Licheri, Valentina; Locci, Valentina; Biggio, Giovanni; Sanna, Enrico
Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in social isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3α,5α-THP, with a parallel up-regulation of extrasynaptic GABAA receptors (GABAAR) in dentate gyrus (DG) granule cells compared to group-housed (GH) mice. In the present study, together with the SI-induced decrease in plasma concentration of both progesterone and 3α,5α-THP, and an increase in THIP-stimulated GABAergic tonic currents, patch-clamp analysis of DG granule cells revealed a significant decrease in membrane input resistance and action potential (AP) firing rate, in SI compared to GH mice, suggesting that SI exerts an inhibitory action on neuronal excitability of these neurons. Voltage-clamp recordings of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) revealed a SI-associated decrease in frequency as well as a shift from paired-pulse (PP) depression to PP facilitation (PPF) of evoked EPSCs, indicative of a reduced probability of glutamate release. Daily administration of progesterone during isolation reverted the changes in plasma 3α,5α-THP as well as in GABAergic tonic currents and neuronal excitability caused by SI, but it had only a limited effect on the changes in the probability of presynaptic glutamate release. Overall, the results obtained in this work, together with those previously published, indicate that exposure of mice to SI during adolescence reduces neuronal excitability of DG granule cells, an effect that may be linked to the increased GABAergic tonic currents as a consequence of the sustained decrease in plasma and hippocampal levels of neurosteroids. All these
Full Text Available Ethanol (EtOH–induced impairment of long-term potentiation (LTP in the rat hippocampus is prevented by the 5α-reductase inhibitor finasteride, suggesting that this effect of EtOH is dependent on the increased local release of neurosteroids such as 3α,5α-THP that promote GABA–mediated transmission. Given that social isolation (SI in rodents is associated with altered plasma and brain levels of such neurosteroids as well as with an enhanced neurosteroidogenic action of EtOH, we examined whether the inhibitory effect of EtOH on LTP at CA3-CA1 hippocampal excitatory synapses is altered in C57BL/6J mice subjected to SI for 6 weeks in comparison with group-housed (GH animals. Extracellular recording of fEPSPs as well as patch-clamp analysis were performed in hippocampal slices prepared from both SI and GH mice. Consistent with previous observations, recording of fEPSPs revealed that the extent of LTP induced in the CA1 region of SI mice was significantly reduced compared with that in GH animals. EtOH (40 mM inhibited LTP in slices from SI mice but not in those from GH mice, and this effect of EtOH was abolished by co-application of 1 µM finasteride. Current-clamp analysis of CA1 pyramidal neurons revealed a decrease in action potential frequency and an increase in the intensity of injected current required to evoke the first action potential in SI mice compared with GH mice, indicative of a decrease in neuronal excitability associated with SI. Together, our data suggest that SI results in reduced levels of neuronal excitability and synaptic plasticity in the hippocampus. Furthermore, the increased sensitivity to the neurosteroidogenic effect of EtOH associated with SI likely accounts for the greater inhibitory effect of EtOH on LTP in SI mice. The increase in EtOH sensitivity induced by SI may be important for the changes in the effects of EtOH on anxiety and on learning and memory associated with the prolonged stress attributable to social
... Prevent Painful Swimmer's Ear Additional Content Medical News Vestibular Neuronitis By Lawrence R. Lustig, MD NOTE: This ... Drugs Herpes Zoster Oticus Meniere Disease Purulent Labyrinthitis Vestibular Neuronitis Vestibular neuronitis is a disorder characterized by ...
Reilly, Joanne M; Dharmalingam, Backialakshmi; Marsh, Stephen J; Thompson, Victoria; Goebel, Andreas; Brown, David A
Complex regional pain syndrome (CRPS) is thought to have an auto-immune component. One such target recently proposed from the effects of auto-immune IgGs on Ca(2+) transients in cardiac myocytes and cell lines is the α1-adrenoceptor. We have tested whether such IgGs exerted comparable effects on nociceptive sensory neurons isolated from rat dorsal root ganglia. Depolarisation-induced [Ca(2+)]i transients were generated by applying 30mM KCl for 2min and monitored by Fura-2 fluorescence imaging. No IgGs tested (including 3 from CRPS patients) had any significant effect on these [Ca(2+)]i transients. However, IgG from one CRPS patient consistently and significantly reduced the K(+)-induced response of cells that had been pre-incubated for 24h with a mixture of inflammatory mediators (1μM histamine, 5-hydroxytryptamine, bradykinin and PGE2). Since this pre-incubation also appeared to induce a comparable inhibitory response to the α1-agonist phenylephrine, this is compatible with the α1-adrenoceptor as a target for CRPS auto-immunity. A mechanism whereby this might enhance pain is suggested. PMID:26708558
Ceccatelli, S; Millhorn, D E; Hökfelt, T; Goldstein, M
The indirect immunofluorescence technique was used to analyze the catecholaminergic neurons in the medulla oblongata of the rat for the presence of enkephalin (ENK)- and neuropeptide Y (NPY)-like immunoreactivity (LI). In colchicine pretreated animals, using a double staining technique with mouse and rabbit antibodies against ENK and tyrosine hydroxylase (TH) or phenylethanolamine N-methyltransferase (PNMT), it was demonstrated that both TH- and ENK-LI occurred in the same neurons, particularly in many neurons of the A1 noradrenaline cell group. In the transition zone to the C1 adrenaline cell group, a proportion of PNMT-positive cells also contained ENK-LI. In the rostral and mid portion of the C1 group only few TH/PNMT-positive cells were found to be ENK-positive. In the noradrenergic A2 region, a moderate number of cell bodies also contained TH- plus ENK-LI, whereas only a few of the adrenaline cells of the C2 and C3 groups showed ENK-LI. In addition, with an elution restaining technique it was possible to demonstrate that several of the cells containing TH- and ENK-LI were also positive for NPY-LI. The present findings demonstrate that a subpopulation of the catecholaminergic neurons in the medulla oblongata of the rat is ENK-positive, thereby indicating a possible co-release of the two compounds in their projection areas, for example the paraventricular nucleus and the spinal cord. PMID:2565245
Filippi, Alida; Mueller, Thomas; Driever, Wolfgang
Throughout the vertebrate lineage, dopaminergic neurons form important neuromodulatory systems that influence motor behavior, mood, cognition, and physiology. Studies in mammals have established that dopaminergic neurons often use γ-aminobutyric acid (GABA) or glutamatergic cotransmission during development and physiological function. Here, we analyze vglut2, gad1b and gad2 expression in combination with tyrosine hydroxylase immunoreactivity in 4-day-old larval and 30-day-old juvenile zebrafish brains to determine which dopaminergic and noradrenergic groups may use GABA or glutamate as a second transmitter. Our results show that most dopaminergic neurons also express GABAergic markers, including the dopaminergic groups of the olfactory bulb (homologous to mammalian A16) and the subpallium, the hypothalamic groups (A12, A14), the prethalamic zona incerta group (A13), the preoptic groups (A15), and the pretectal group. Thus, the majority of catecholaminergic neurons are gad1b/2-positive and coexpress GABA. A very few gad1/2-negative dopaminergic groups, however, express vglut2 instead and use glutamate as a second transmitter. These glutamatergic dual transmitter phenotypes are the Orthopedia transcription factor-dependent, A11-type dopaminergic neurons of the posterior tuberculum. All together, our results demonstrate that all catecholaminergic groups in zebrafish are either GABAergic or glutamatergic. Thus, cotransmission of dopamine and noradrenaline with either GABA or glutamate appears to be a regular feature of zebrafish catecholaminergic systems. We compare our results with those that have been described for mammalian systems, discuss the phenomenon of transmitter dualism in the context of developmental specification of GABAergic and glutamatergic regions in the brain, and put this phenomenon in an evolutionary perspective. PMID:24374659
Pose, I; Sampogna, S; Chase, M H; Morales, F R
In the present study, we report that the cuneiform (Cun) nucleus, a brainstem structure that before now has not been implicated in sleep processes, exhibits a large number of neurons that express c-fos during carbachol-induced active sleep (AS-carbachol). Compared with control (awake) cats, during AS-carbachol, there was a 671% increase in the number of neurons that expressed c-fos in this structure. Within the Cun nucleus, three immunocytochemically distinct populations of neurons were observed. One group consisted of GABAergic neurons, which predominantly did not express c-fos during AS-carbachol. Two other different populations expressed c-fos during this state. One of the Fos-positive (Fos(+)) populations consisted of a distinct group of nitric oxide synthase (NOS)-NADPH-diaphorase (NADPH-d)-containing neurons; the neurotransmitter of the other Fos(+) population remains unknown. The Cun nucleus did not contain cholinergic, catecholaminergic, serotonergic, or glycinergic neurons. On the basis of neuronal activation during AS-carbachol, as indicated by c-fos expression, we suggest that the Cun nucleus is involved, in an as yet unknown manner, in the physiological expression of active sleep. The finding of a population of NOS-NADPH-d containing neurons, which were activated during AS-carbachol, suggests that nitrergic modulation of their target cell groups is likely to play a role in active sleep-related physiological processes. PMID:10777795
Torrealdea, Francisco J.; Sarasola, Cecilia; d'Anjou, Alicia; Moujahid, Abdelmalik; de Mendizábal, N. Vélez
The generation of spikes by neurons is energetically a costly process. This paper studies the consumption of energy and the information entropy in the signalling activity of a model neuron both when it is supposed isolated and when it is coupled to another neuron by an electrical synapse. The neuron has been modelled by a four dimensional Hindmarsh-Rose type kinetic model for which an energy function has been deduced. For the isolated neuron values of energy consumption and information entrop...
Gaykema, Ronald P A; Daniels, Teresa E; Shapiro, Nathan J; Thacker, Gregory C; Park, Su-Mi; Goehler, Lisa E
Caudal brainstem viscerosensory nuclei convey information about the body's internal state to forebrain regions implicated in feeding behavior and responses to immune challenge, and may modulate ingestive behavior following immune activation. Illness-induced appetite loss might be attributed to accentuated "satiety" pathways, activation of a distinct "danger channel" separate from satiety pathways, or both. To evaluate neural substrates that could mediate the effects of illness on ingestive behavior, we analyzed the pattern and phenotypes of medullary neurons responsive to consumption of a preferred food, sweetened milk, and to intraperitoneal lipopolysaccharide challenge that reduced sweetened milk intake. Brainstem sections were stained for c-Fos, dopamine beta-hydroxylase, phenylethanolamine-N-methyltransferase, and glucagon-like peptide-1 (GLP-1) immunoreactivity. Sweetened milk intake activated many neurons throughout the nucleus of the solitary tract (NTS), including A2 noradrenergic neurons in the caudal half of the NTS. LPS challenge activated a similar population of neurons in the NTS, in addition to rostral C2 adrenergic and mid-level A2 noradrenergic neurons in the NTS, many C1 and A1 neurons in the ventrolateral medulla, and in GLP-1 neurons in the dorsal medullary reticular nucleus. Increased numbers of activated GLP-1 neurons in the NTS were only associated with sweetened milk ingestion. Evidence for parallel processing was reflected in the parabrachial nucleus, where sweetened milk intake resulted in activation of the inner external lateral, ventrolateral and central medial portions, whereas LPS challenge induced c-Fos expression in the outer external lateral portions. Thus, signals generated in response to potentially dangerous physiological conditions seem to be propagated via specific populations of catecholaminergic neurons in the NTS and VLM, and likely include a pathway through the external lateral PBN. The data indicate that immune challenge
The ability of nerve growth factor to cause rapid activation of the Na+K+ pump of its responsive cells was examined by measuring the uptake of 86Rb+. A significant increase in 86Rb+ uptake in E8 chick dorsal root ganglion sensory neurons after NGF treatment was seen only if the cells had been damaged during the preparation procedure. Such damaged cells could not survive in culture in the presence of NGF, and undamaged cells that did survive in response to NGF exhibited no increased 86Rb+ uptake rate. Furthermore, cultured calf adrenal medullary cells did not show an increase in 86Rb+ uptake after treatment with NGF, although these cells respond to NGF with an increased synthesis of catecholaminergic enzymes. These results are incompatible with the hypothesis that the mechanism of action of NGF that promotes neuronal survival and enzyme induction results from an initial stimulation of the Na+K+ pump
Full Text Available Contribution of genes in attention deficit hyperactivity disorder (ADHD has been explored in various populations, and several genes were speculated to contribute small but additive effects. We have assessed variants in four genes, DDC (rs3837091 and rs3735273, DRD2 (rs1800496, rs1801028, and rs1799732, DRD4 (rs4646984 and rs4646983, and COMT (rs165599 and rs740603 in Indian ADHD subjects with comorbid attributes. Cases were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV-TR after obtaining informed written consent. DNA isolated from peripheral blood leukocytes of ADHD probands (N=170, their parents (N=310, and ethnically matched controls (n=180 was used for genotyping followed by population- and family-based analyses by the UNPHASED program. DRD4 sites showed significant difference in allelic frequencies by case-control analysis, while DDC and COMT exhibited bias in familial transmission (P<0.05. rs3837091 “AGAG,” rs3735273 “A,” rs1799732 “C,” rs740603 “G,” rs165599 “G” and single repeat alleles of rs4646984/rs4646983 showed positive correlation with co-morbid characteristics (P<0.05. Multi dimensionality reduction analysis of case-control data revealed significant interactive effects of all four genes (P<0.001, while family-based data showed interaction between DDC and DRD2 (P=0.04. This first study on these gene variants in Indo-Caucasoid ADHD probands and associated co-morbid conditions indicates altered dopaminergic neurotransmission in ADHD.
LIUYin; CHENJing-Hong; GONGZe-Hui
AIM: To establish a primary culture technique of acutely isolated dorsal root ganglion (DRG) neurons, and provide a simple & useful in vitro model for study of analgesia. Methods: Acutely isolated dorsal root ganglion (DRG) neurons were planted and cultured; the configuration and growth characters of DRG neurons were observed through inverted microscope.
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.
Llinás, R; Sugimori, M.; Lin, J. W.; Cherksey, B
A Ca2+-channel blocker derived from funnel-web spider toxin (FTX) has made it possible to define and study the ionic channels responsible for the Ca2+ conductance in mammalian Purkinje cell neurons and the preterminal in squid giant synapse. In cerebellar slices, FTX blocked Ca2+-dependent spikes in Purkinje cells, reduced the spike afterpotential hyperpolarization, and increased the Na+-dependent plateau potential. In the squid giant synapse, FTX blocked synaptic transmission without affecti...
Ji Yeon Jang
Full Text Available We identified a novel neuroprotective compound, 1-methoxyoctadecan-1-ol, from Uncaria sinensis (Oliv. Havil and investigated its effects and mechanisms in primary cortical neurons and in a photothrombotic ischemic model. In primary rat cortical neurons against glutamate-induced neurotoxicity, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced neuronal death in a dose-dependent manner. In addition, treatment with 1-methoxyoctadecan-1-ol resulted in decreased neuronal apoptotic death, as assessed by nuclear morphological approaches. To clarify the neuroprotective mechanism of 1-methoxyoctadecan-1-ol, we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR with calpain activation. Treatment with glutamate leads to early activation of NMDAR, which in turn leads to calpain-mediated cleavage of striatal-enriched protein tyrosine phosphatase (STEP and subsequent activation of p38 mitogen activated protein kinase (MAPK. However, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly attenuated activation of GluN2B-NMDAR and a decrease in calpain-mediated STEP cleavage, leading to subsequent attenuation of p38 MAPK activation. We confirmed the critical role of p38 MAPK in neuroprotective effects of 1-methoxyoctadecan-1-ol using specific inhibitor SB203580. In the photothrombotic ischemic injury in mice, treatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced infarct volume, edema size, and improved neurological function. 1-methoxyoctadecan-1-ol effectively prevents cerebral ischemic damage through down-regulation of calpain-mediated STEP cleavage and activation of p38 MAPK. These results suggest that 1-methoxyoctadecan-1-ol showed neuroprotective effects through down-regulation of calpain-mediated STEP cleavage with activation of GluN2B-NMDAR, and subsequent alleviation of p38 MAPK activation. In addition, 1-methoxyoctadecan-1-ol might be a useful therapeutic agent for
Jang, Ji Yeon; Choi, Young Whan; Kim, Ha Neui; Kim, Yu Ri; Hong, Jin Woo; Bae, Dong Won; Park, Se Jin; Shin, Hwa Kyoung; Choi, Byung Tae
We identified a novel neuroprotective compound, 1-methoxyoctadecan-1-ol, from Uncaria sinensis (Oliv.) Havil and investigated its effects and mechanisms in primary cortical neurons and in a photothrombotic ischemic model. In primary rat cortical neurons against glutamate-induced neurotoxicity, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced neuronal death in a dose-dependent manner. In addition, treatment with 1-methoxyoctadecan-1-ol resulted in decreased neuronal apoptotic death, as assessed by nuclear morphological approaches. To clarify the neuroprotective mechanism of 1-methoxyoctadecan-1-ol, we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR) with calpain activation. Treatment with glutamate leads to early activation of NMDAR, which in turn leads to calpain-mediated cleavage of striatal-enriched protein tyrosine phosphatase (STEP) and subsequent activation of p38 mitogen activated protein kinase (MAPK). However, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly attenuated activation of GluN2B-NMDAR and a decrease in calpain-mediated STEP cleavage, leading to subsequent attenuation of p38 MAPK activation. We confirmed the critical role of p38 MAPK in neuroprotective effects of 1-methoxyoctadecan-1-ol using specific inhibitor SB203580. In the photothrombotic ischemic injury in mice, treatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced infarct volume, edema size, and improved neurological function. 1-methoxyoctadecan-1-ol effectively prevents cerebral ischemic damage through down-regulation of calpain-mediated STEP cleavage and activation of p38 MAPK. These results suggest that 1-methoxyoctadecan-1-ol showed neuroprotective effects through down-regulation of calpain-mediated STEP cleavage with activation of GluN2B-NMDAR, and subsequent alleviation of p38 MAPK activation. In addition, 1-methoxyoctadecan-1-ol might be a useful therapeutic agent for brain disorder
In this study the authors have examined the uptake of tritiated dopamine into the nerve terminals of hypothalamic DA neurons, which were isolated pharmacologically from NE neurons using desmethylimipramine (DMI), an inhibitor of catecholamine uptake into NE neurons. (Auth.)
Christopher L Petersen; Miky Timothy; D Spencer Kim; Ashwin A Bhandiwad; Robert A Mohr; Sisneros, Joseph A.; Forlano, Paul M.
While the neural circuitry and physiology of the auditory system is well studied among vertebrates, far less is known about how the auditory system interacts with other neural substrates to mediate behavioral responses to social acoustic signals. One species that has been the subject of intensive neuroethological investigation with regard to the production and perception of social acoustic signals is the plainfin midshipman fish, Porichthys notatus, in part because acoustic communication is e...
Grimmelikhuijzen, C J; Ebbesen, Ditte Graff; McFarlane, I D
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......) was isolated, which also belongs to the less than Glu...Arg-X-NH2 family. Using specific antisera it was shown that all four peptides were located in neurones. Application of low doses of Antho-RFamide, or Antho-RWamide I or II induced contractions of endodermal muscles of sea anemones. This indicates...
The mammalian cortex consists of a vast network of weakly interacting excitable cells called neurons. Neurons must synchronize their activities in order to trigger activity in neighboring neurons. Moreover, interactions must be carefully regulated to remain weak (but not too weak) such that cascades of active neuronal groups avoid explosive growth yet allow for activity propagation over long-distances. Such a balance is robustly realized for neuronal avalanches, which are defined as cortical activity cascades that follow precise power laws. In experiments, scale-invariant neuronal avalanche dynamics have been observed during spontaneous cortical activity in isolated preparations in vitro as well as in the ongoing cortical activity of awake animals and in humans. Theory, models, and experiments suggest that neuronal avalanches are the signature of brain function near criticality at which the cortex optimally responds to inputs and maximizes its information capacity. Importantly, avalanche dynamics allow for the emergence of a subset of avalanches, the coherence potentials. They emerge when the synchronization of a local neuronal group exceeds a local threshold, at which the system spawns replicas of the local group activity at distant network sites. The functional importance of coherence potentials will be discussed in the context of propagating structures, such as gliders in balanced cellular automata. Gliders constitute local population dynamics that replicate in space after a finite number of generations and are thought to provide cellular automata with universal computation. Avalanches and coherence potentials are proposed to constitute a modern framework of cortical synchronization dynamics that underlies brain function.
Full Text Available Neuromelanin (NM pigment accumulates with age in catecholaminergic neurons in man, and the ventral substantia nigra dopaminergic neurons that are the most vulnerable to degeneration in Parkinson's disease (PD contain the greatest amount of this pigment. In vitro data indicate that NM pigment is formed from the excess cytosolic catecholamine that is not accumulated into synaptic vesicles via the vesicular monoamine transporter2 (VMAT2. Using semi-quantitative immunohistochemical methods in human postmortem brain, we sought to examine the relationship between the contents of VMAT2 and NM pigment. The immunostaining intensity (ISI was measured for VMAT2 in two regions of the midbrain dopaminergic cell complex. The ISI of the cells was related to the density of NM pigment within the cells. We also measured the ISI for tyrosine hydroxylase (TH and examined the noradrenergic neurons in the locus coeruleus (LC. In brains 22-65 years of age: 1 ventral substantia nigra neurons had the lowest VMAT2 ISI of all neurons in the midbrain cell complex, whereas over 2-fold higher levels are found in most ventral tegmental area neurons; 2 there was an inverse relationship between VMAT2 ISI and neuromelanin pigment in the midbrain dompaminergic neurons; 3 neurons with the highest VMAT2 ISI resided in the LC; 4 neurons with high VMAT2 ISI also had high TH ISI; and 5 in the newborn brain, which has not yet accumulated neuromelanin pigment in the aminergic neurons, the regional distribution of VMAT2 and TH-ISI was similar to that found in the adult brain. These data support the hypothesis that among the midbrain dopaminergic neurons, the ventral substantia nigra dopamine neurons accumulate the highest levels of NM pigment because they have the lowest levels of VMAT2, which thereby renders them especially vulnerable to degeneration in PD.
Full Text Available Abstract Background The homeodomain transcription factor Orthopedia (Otp is essential in restricting the fate of multiple classes of secreting neurons in the neuroendocrine hypothalamus of vertebrates. However, there is little information on the intercellular factors that regulate Otp expression during development. Results Here, we identified two otp orthologues in zebrafish (otp1 and otp2 and explored otp1 in the context of the morphogenetic pathways that specify neuroectodermal regions. During forebrain development, otp1 is expressed in anterior groups of diencephalic cells, positioned in the preoptic area (PO (anterior alar plate and the posterior tuberculum (PT (posterior basal plate. The latter structure is characterized by Tyrosine Hydroxylase (TH-positive cells, suggesting a role for otp1 in the lineage restriction of catecholaminergic (CA neurons. Disruptions of Hedgehog (HH and Fibroblast Growth Factor (FGF pathways point to the ability of SHH protein to trigger otp1 expression in PO presumptive neuroblasts, with the attenuating effect of Dzip1 and FGF8. In addition, our data disclose otp1 as a determinant of CA neurons in the PT, where otp1 activity is strictly dependent on Nodal signaling and it is not responsive to SHH and FGF. Conclusion In this study, we pinpoint the evolutionary importance of otp1 transcription factor in cell states of the diencephalon anlage and early neuronal progenitors. Furthermore, our data indicate that morphogenetic mechanisms differentially regulate otp1 expression in alar and basal plates.
Talani, Giuseppe; Biggio, Francesca; Licheri, Valentina; Locci, Valentina; Biggio, Giovanni; Sanna, Enrico
Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in social isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3α,5α-THP, with a parallel up-regulation ...
Giuseppe Talani; Francesca Biggio; Valentina Licheri; Valentina Locci; Giovanni Biggio; Enrico Sanna
Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3α,5α-THP, with a parallel up-regulation of extr...
目的 探讨儿茶酚胺敏感性室性心动过速(catecholaminergic polymorphic ventricular tachycardia,CPVT)患者的护理特点.方法 回顾性分析2005年6月至2011年6月宁波市医疗中心李惠利医院心内科收治的5例CPVT患者的临床资料,并总结其护理经验.结果 β受体阻滞剂对大多数CPVT患者效果良好,但对长期足量应用β受体阻滞剂仍不能满意控制心律失常发生的患者,需要采用植入式心律转复除颤器(implantable cardioverter defibrillator,ICD)治疗.结论 CPVT患者护理各有特点,药物治疗为主的CPVT患者应重视解释疏导和心理护理,而安装植入式心律转复除颤器(implantable cardioverter defibrillator,ICD)患者的应重视术后护理工作.%Objective To summarizes the nursing Features in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). Methods The clinical data of five CPVT patients in our hospital during June 2005 and June 2011 were analyzed retrospectivley. The nursing features were summarized according ly. Results The β-blockers are effective in the most patients but the long-term adequate doses of beta blockers are still not satisfied with the control of arrhythmia in patients. Implantable cardioverter defibril- lator (ICD) is the only option for the high risk patients. Conclusion Both treatments have different nurs ing features:one focuses on the interpretation of treatment guidelines and psychological care,and the other emphasizes the post-operative care.
Valle, Giorgia; Boncompagni, Simona; Sacchetto, Roberta; Protasi, Feliciano; Volpe, Pompeo
Cardiac calsequestrin (CASQ2) contributes to intracellular Ca(2+) homeostasis by virtue of its low-affinity/high-capacity Ca(2+) binding properties, maintains sarcoplasmic reticulum (SR) architecture and regulates excitation-contraction coupling, especially or exclusively upon β-adrenergic stimulation. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease associated with cardiac arrest in children or young adults. Recessive CPVT variants are due to mutations in the CASQ2 gene. Molecular and ultra-structural properties were studied in hearts of CASQ2(R33Q/R33Q) and of CASQ2(-/-) mice from post-natal day 2 to week 8. The drastic reduction of CASQ2-R33Q is an early developmental event and is accompanied by down-regulation of triadin and junctin, and morphological changes of jSR and of SR-transverse-tubule junctions. Although endoplasmic reticulum stress is activated, no signs of either apoptosis or autophagy are detected. The other model of recessive CPVT, the CASQ2(-/-) mouse, does not display the same adaptive pattern. Expression of CASQ2-R33Q influences molecular and ultra-structural heart development; post-natal, adaptive changes appear capable of ensuring until adulthood a new pathophysiological equilibrium. PMID:24370574
Full Text Available Trace amines (TAs are a class of endogenous compounds strictly related to classic monoamine neurotransmitters with regard to their structure, metabolism and tissue distribution. Although the presence of TAs in mammalian brain has been recognized for decades, until recently they were considered to be by-products of amino acid metabolism or as ‘false’ neurotransmitters. The discovery in 2001 of a new family of G protein-coupled receptors (GPCRs, namely trace amines receptors, has re-ignited interest in TAs. In particular, two members of the family, trace amine receptor 1 (TA1 and trace amine receptor 2 (TA2, were shown to be highly sensitive to these endogenous compounds. Experimental evidence suggests that TAs modulate the activity of catecholaminergic neurons and that TA dysregulation may contribute to neuropsychiatric disorders, including schizophrenia, attention deficit hyperactivity disorder, depression and Parkinson’s disease, all of which are characterised by altered monoaminergic networks. Here we review recent data concerning the electrophysiological effects of TAs on the activity of mesencephalic dopaminergic neurons. In the context of recent data obtained with TA1 receptor knockout mice, we also discuss the mechanisms by which the activation of these receptors modulates the activity of these neurons. Three important new aspects of TAs action have recently emerged: (a inhibition of firing due to increased release of dopamine; (b reduction of D2 and GABAB receptor-mediated inhibitory responses (excitatory effects due to dysinhibition; and (c a direct TA1 receptor-mediated activation of GIRK channels which produce cell membrane hyperpolarization. While the first two effects have been well documented in our laboratory, the direct activation of GIRK channels by TA1 receptors has been reported by others, but has not been seen in our laboratory (Geracitano et al., 2004. Further research is needed to address this point, and to further
Gal, Asaf; Marom, Shimon
We present experimental and theoretical arguments, at the single-neuron level, suggesting that neuronal response fluctuations reflect a process that positions the neuron near a transition point that separates excitable and unexcitable phases. This view is supported by the dynamical properties of the system as observed in experiments on isolated cultured cortical neurons, as well as by a theoretical mapping between the constructs of self-organized criticality and membrane excitability biophysics. PMID:24483496
Gal A.; Marom S.
We present experimental and theoretical arguments, at the single neuron level, suggesting that neuronal response fluctuations reflect a process that positions the neuron near a transition point that separates excitable and unexcitable phases. This view is supported by the dynamical properties of the system as observed in experiments on isolated cultured cortical neurons, as well as by a theoretical mapping between the constructs of self organized criticality and membrane excitability biophysics.
COPRAY, JCVM; LIEM, RSB
In order to study the development and functional properties of single, isolated, rat mesencephalic trigeminal neurones, a cell-culture procedure was developed for these specific primary sensory neurones. Mesencephalic trigeminal neurones were isolated from the brainstem of 16-day-old rat embryos. Va
Lihua Liu; Saiping Luo; Leping Zeng; Weihong Wang; Liming Yuan; Xiaohong Jian
Mice carrying mutant amyloid-β precursor protein and presenilin-1 genes (APP/PS1 double trans-genic mice) have frequently been used in studies of Alzheimer’s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer’s disease is known to correlate with the amount of amyloid-βprotein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age: young mice (5–6 months old) and aged mice (16–17 months old). Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase (a marker of catecholaminergic neurons in the locus coeruleus) revealed that APP/PS1 mice had 23%fewer cel s in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cel bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy-droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.
... Enhancing Diversity Find People About NINDS NINDS Neuronal Migration Disorders Information Page Table of Contents (click to ... being done? Clinical Trials Organizations What are Neuronal Migration Disorders? Neuronal migration disorders (NMDs) are a group ...
... Awards Enhancing Diversity Find People About NINDS Motor Neuron Diseases Fact Sheet See a list of all ... can I get more information? What are motor neuron diseases? The motor neuron diseases (MNDs) are a ...
Full Text Available BACKGROUND: Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. METHODS: Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22 or inclusion (SI, n = 21, respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. RESULTS: Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. CONCLUSIONS: We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological
Majocha, R.E.; Pearse, R.N.; Baldessarini, R.J.; Delong, G.R.; Walton, K.G. (Harvard Medical School, Boston, MA (USA))
Spherical aggregates formed rapidly in culture by re-aggregation of trypsin-dissociated brain cells from the 17-day-old fetal rat. Over about 10 days an initially random distribution of cells evolved into a 3-layered arrangement; cells with characteristics of neurons were found largely in the intermediate layer. The survival of neuronal and glial cell types was evaluated histologically and verified by electron microscopy, which revealed synaptic and myelin structures that rapidly increased in number after 18 days in culture. Levels of norepinephrine (NE) and dopamine (DA) reached peaks of 9.5 and 4.4 ng/mg protein, respectively, at culture day 21. Uptake of (/sup 3/H)NE paralleled these amine levels and was blocked by desipramine or pretreatment with either reserpine or 6-OH-DA. Autoradiographs of aggregates labeled with (/sup 3/H)NE showed a high density of silver grains over cells, apparently neurons, with branching processes traced for 120 ..mu..m. Previously accumulated (/sup 3/H)NE was released under depolarizing conditions (high (K/sup +/) or vertridine) only in the presence of Ca/sup 2 +/. Release was induced to a lesser extent by kainic > glutamic acid. Thus, such aggregates appear to contain catecholaminergic neurons capable of synthesis, uptake and release of NE. The time course of development of these functions supports suggestions that aggregate preparations might be useful in studying neurochemical or morphological aspects of brain development and function in vitro.
Levitas-Djerbi, Talia; Yelin-Bekerman, Laura; Lerer-Goldshtein, Tali; Appelbaum, Lior
Neurotensin (NTS) is a 13 amino acid neuropeptide that is expressed in the hypothalamus. In mammals, NTS-producing neurons that express leptin receptor (LepRb) regulate the function of hypocretin/orexin (HCRT) and dopamine neurons. Thus, the hypothalamic leptin-NTS-HCRT neuronal network orchestrates key homeostatic output, including sleep, feeding, and reward. However, the intricate mechanisms of the circuitry and the unique role of NTS-expressing neurons remain unclear. We studied the NTS neuronal networks in zebrafish and cloned the genes encoding the NTS neuropeptide and receptor (NTSR). Similar to mammals, the ligand is expressed primarily in the hypothalamus, while the receptor is expressed widely throughout the brain in zebrafish. A portion of hypothalamic nts-expressing neurons are inhibitory and some coexpress leptin receptor (lepR1). As in mammals, NTS and HCRT neurons are localized adjacently in the hypothalamus. To track the development and axonal projection of NTS neurons, the NTS promoter was isolated. Transgenesis and double labeling of NTS and HCRT neurons showed that NTS axons project toward HCRT neurons, some of which express ntsr. Moreover, another target of NTS neurons is ntsr-expressing dopaminergeric neurons. These findings suggest structural circuitry between leptin, NTS, and hypocretinergic or dopaminergic neurons and establish the zebrafish as a model to study the role of these neuronal circuits in the regulation of feeding, sleep, and reward. PMID:25421126
Proper migration of neuronal somas and axonal growth cones to designated locations in the developing brain is essential for the assembly of functional neuronal circuits.Rapid progress in research of axon guidance and neuronal migration has been made in the last twenty years.Chinese researchers began their exploration in this field ten years ago and have made significant contributions in clarifying the signal transduction of axon guidance and neuronal migration.Several unique experimental approaches,including the migration assay of single isolated neurons in response to locally delivered guidance cues,have been developed by Chinese neuroscientists to investigate the molecular machinery underlying these guidance events.
Senti, Gabriele; Ezcurra, Marina; Löbner, Jana; Schafer, William R.; Swoboda, Peter
Studying the development and mechanisms of sensory perception is challenging in organisms with complex neuronal networks. The worm Caenorhabditis elegans possesses a simple neuronal network of 302 neurons that includes 60 ciliated sensory neurons (CSNs) for detecting external sensory input. C. elegans is thus an excellent model in which to study sensory neuron development, function, and behavior. We have generated a genetic rescue system that allows in vivo analyses of isolated CSNs at both c...
Robra, Lena; Thirumalai, Vatsala
The dopamine and cAMP regulated phosphoprotein of apparent molecular weight 32 kDa (Darpp-32) is an inhibitory subunit of protein phosphatase-1 (PP-1). Darpp-32 activity is regulated by multiple ligand-activated G-protein coupled receptors (GPCRs). This protein is coded for by the protein phosphatase-1 regulatory subunit 1b (ppp1r1b) gene. Here, we provide experimental evidence for the presence of multiple isoforms of ppp1r1b in zebrafish. We show that these isoforms are differentially expressed during development with the full-length isoform being maternally deposited. Next, with a custom polyclonal antibody generated against the full-length protein, we show that in the adult, Darpp-32 is strongly expressed in principal neurons of the cerebellum and cerebellum-like circuits. These include Purkinje neurons in the cerebellum, Type-I neurons in the optic tectum, and crest cells in the medial octavolateralis nucleus (MON). We confirmed the identity of these neurons through their colocalization with Parvalbumin 7 immunoreactivity. Darpp-32 is seen in the somata and dendrites of these neurons with faint staining in the axons. In all of these regions, Darpp-32-immunoreactive cells were in close proximity to tyrosine hydroxylase (TH) immunoreactive puncta indicating the presence of direct catecholaminergic input to these neurons. Darpp-32 immunoreactivity was seen in Purkinje neurons as early as 3 days post-fertilization (dpf) when Purkinje neurons are first specified. In sum, we show that Darpp-32, a signaling integrator, is a specific marker of principal neurons in the cerebellum and cerebellum-like circuits in zebrafish. PMID:27540357
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.
Turtzo, L. Christine; Marx, Ruth; Lane, M. Daniel
White adipose tissue plays an integral role in energy metabolism and is governed by endocrine, autocrine, and neural signals. Neural control of adipose metabolism is mediated by sympathetic neurons that innervate the tissue. To investigate the effects of this innervation, an ex vivo system was developed in which 3T3-L1 adipocytes are cocultured with sympathetic neurons isolated from the superior cervical ganglia of newborn rats. In coculture, both adipocytes and neurons exhibit appropriate mo...
Full Text Available BACKGROUND: Neural activity can be affected by nitric oxide (NO produced by spiking neurons. Can neural activity also be affected by NO produced in neurons in the absence of spiking? METHODOLOGY/PRINCIPAL FINDINGS: Applying an NO scavenger to quiescent Aplysia buccal ganglia initiated fictive feeding, indicating that NO production at rest inhibits feeding. The inhibition is in part via effects on neurons B31/B32, neurons initiating food consumption. Applying NO scavengers or nitric oxide synthase (NOS blockers to B31/B32 neurons cultured in isolation caused inactive neurons to depolarize and fire, indicating that B31/B32 produce NO tonically without action potentials, and tonic NO production contributes to the B31/B32 resting potentials. Guanylyl cyclase blockers also caused depolarization and firing, indicating that the cGMP second messenger cascade, presumably activated by the tonic presence of NO, contributes to the B31/B32 resting potential. Blocking NO while voltage-clamping revealed an inward leak current, indicating that NO prevents this current from depolarizing the neuron. Blocking nitrergic transmission had no effect on a number of other cultured, isolated neurons. However, treatment with NO blockers did excite cerebral ganglion neuron C-PR, a command-like neuron initiating food-finding behavior, both in situ, and when the neuron was cultured in isolation, indicating that this neuron also inhibits itself by producing NO at rest. CONCLUSION/SIGNIFICANCE: Self-inhibitory, tonic NO production is a novel mechanism for the modulation of neural activity. Localization of this mechanism to critical neurons in different ganglia controlling different aspects of a behavior provides a mechanism by which a humeral signal affecting background NO production, such as the NO precursor L-arginine, could control multiple aspects of the behavior.
Huerta, R; Rabinovich, M I; Abarbanel, Henry D I; Abarbanel, Henry D I
Central Pattern Generators (CPGs) in invertebrates are comprised of networks of neurons in which every neuron has reciprocal connections to other members of the CPG. This is a ``closed'' network topology. An ``open'' topology, where one or more neurons receives input but does not send output to other member neurons, is not found in these CPGs. In this paper we investigate a possible reason for this topological structure using the ability to perform a biological functional task as a measure of the efficacy of the network. When the CPG is composed of model neurons which exhibit regular membrane voltage oscillations, open topologies are essentially as able to maximize this functionality as closed topologies. When we replace these models by neurons which exhibit chaotic membrane voltage oscillations, the functional criterion selects closed topologies when the demands of the task are increased, and these are the topologies observed in known CPG networks. As isolated neurons from invertebrate CPGs are known in some...
Ostergaard, J R; Hertz, Jens Michael
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...
Sarpeshkar, Rahul; Watts, Lloyd; Mead, Carver
Neural networks typically use an abstraction of the behaviour of a biological neuron, in which the continuously varying mean firing rate of the neuron is presumed to carry information about the neuron's time-varying state of excitation. However, the detailed timing of action potentials is known to be important in many biological systems. To build electronic models of such systems, one must have well-characterized neuron circuits that capture the essential behaviour of real neur...
Michael Hines; Davison, Andrew P.; Eilif Muller
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 ...
Animals use a form of sensory feedback termed proprioception to monitor their body position and modify the motor programs that control movement. In this issue of Neuron, Wen et al. (2012) provide evidence that a subset of motor neurons function as proprioceptors in C. elegans, where B-type motor neurons sense body curvature to control the bending movements that drive forward locomotion.
Narro, Martha L.; Yang, Fan; Kraft, Robert; Wenk, Carola; Efrat, Alon; Restifo, Linda L.
Using primary cell culture to screen for changes in neuronal morphology requires specialized analysis software. We developed NeuronMetrics™ for semi-automated, quantitative analysis of two-dimensional (2D) images of fluorescently labeled cultured neurons. It skeletonizes the neuron image using two complementary image-processing techniques, capturing fine terminal neurites with high fidelity. An algorithm was devised to span wide gaps in the skeleton. NeuronMetrics uses a novel strategy based on geometric features called faces to extract a branch-number estimate from complex arbors with numerous neurite-to-neurite contacts, without creating a precise, contact-free representation of the neurite arbor. It estimates total neurite length, branch number, primary neurite number, territory (the area of the convex polygon bounding the skeleton and cell body), and Polarity Index (a measure of neuronal polarity). These parameters provide fundamental information about the size and shape of neurite arbors, which are critical factors for neuronal function. NeuronMetrics streamlines optional manual tasks such as removing noise, isolating the largest primary neurite, and correcting length for self-fasciculating neurites. Numeric data are output in a single text file, readily imported into other applications for further analysis. Written as modules for ImageJ, NeuronMetrics provides practical analysis tools that are easy to use and support batch processing. Depending on the need for manual intervention, processing time for a batch of ~60 2D images is 1.0–2.5 hours, from a folder of images to a table of numeric data. NeuronMetrics’ output accelerates the quantitative detection of mutations and chemical compounds that alter neurite morphology in vitro, and will contribute to the use of cultured neurons for drug discovery. PMID:17270152
Le, Sheng; Turner, Anita J; Parker, Lindsay M; Burke, Peter G; Kumar, Natasha N; Goodchild, Ann K; McMullan, Simon
Microinjection of somatostatin (SST) causes site-specific effects on respiratory phase transition, frequency, and amplitude when microinjected into the ventrolateral medulla (VLM) of the anesthetized rat, suggesting selective expression of SST receptors on different functional classes of respiratory neurons. Of the six subtypes of SST receptor, somatostatin 2a (sst2a ) is the most prevalent in the VLM, and other investigators have suggested that glutamatergic neurons in the preBötzinger Complex (preBötC) that coexpress neurokinin-1 receptor (NK1R), SST, and sst2a are critical for the generation of respiratory rhythm. However, quantitative data describing the distribution of sst2a in respiratory compartments other than preBötC, or on functionally identified respiratory neurons, is absent. Here we examine the medullary expression of sst2a with particular reference to glycinergic/expiratory neurons in the Bötzinger Complex (BötC) and NK1R-immunoreactive/inspiratory neurons in the preBötC. We found robust sst2a expression at all rostrocaudal levels of the VLM, including a large proportion of catecholaminergic neurons, but no colocalization of sst2a and glycine transporter 2 mRNA in the BötC. In the preBötC 54% of sst2a -immunoreactive neurons were also positive for NK1R. sst2a was not observed in any of 52 dye-labeled respiratory interneurons, including seven BötC expiratory-decrementing and 11 preBötC preinspiratory neurons. We conclude that sst2a is not expressed on BötC respiratory neurons and that phasic respiratory activity is a poor predictor of sst2a expression in the preBötC. Therefore, sst2a is unlikely to underlie responses to BötC SST injection, and is sparse or absent on respiratory neurons identified by classical functional criteria. J. Comp. Neurol. 524:1384-1398, 2016. © 2015 Wiley Periodicals, Inc. PMID:26470751
The organization of neurons and glia cells on substrates composed of pristine carbon nanotube islands was investigated using high resolution scanning electron microscopy, immunostaining and confocal microscopy. Neurons were found bound and preferentially anchored to the rough surfaces; moreover, the morphology of the neuronal processes on the small, isolated islands of high density carbon nanotubes was found to be conspicuously curled and entangled. We further demonstrate that the roughness of the surface must match the diameter of the neuronal processes in order to allow them to bind. The results presented here suggest that entanglement, a mechanical effect, may constitute an additional mechanism by which neurons (and possibly other cell types) anchor themselves to rough surfaces. Understanding the nature of the interface between neurons and carbon nanotubes is essential to effectively harness carbon nanotube technology in neurological applications such as neuro-prosthetic and retinal electrodes.
Sorkin, Raya; Greenbaum, Alon; David-Pur, Moshe; Anava, Sarit; Ayali, Amir; Ben-Jacob, Eshel; Hanein, Yael
The organization of neurons and glia cells on substrates composed of pristine carbon nanotube islands was investigated using high resolution scanning electron microscopy, immunostaining and confocal microscopy. Neurons were found bound and preferentially anchored to the rough surfaces; moreover, the morphology of the neuronal processes on the small, isolated islands of high density carbon nanotubes was found to be conspicuously curled and entangled. We further demonstrate that the roughness of the surface must match the diameter of the neuronal processes in order to allow them to bind. The results presented here suggest that entanglement, a mechanical effect, may constitute an additional mechanism by which neurons (and possibly other cell types) anchor themselves to rough surfaces. Understanding the nature of the interface between neurons and carbon nanotubes is essential to effectively harness carbon nanotube technology in neurological applications such as neuro-prosthetic and retinal electrodes.
Motomura, Tamami; Hayashida, Yuki; Murayama, Nobuki
The neuromorphic device, which implements the functions of biological neural circuits by means of VLSI technology, has been collecting much attention in the engineering fields in the last decade. Concurrently, progress in neuroscience research has revealed the nonlinear computation in single neuron levels, suggesting that individual neurons are not merely the circuit elements but computational units. Thus, elucidating the properties of neuronal signal processing is thought to be an essential step for developing the next generation of neuromorphic devices. In the present study, we developed a method for dissociating single neurons from specific sublayers of mammalian retinas with using no proteolytic enzymes but rather combining tissue incubation in a low-Ca2+ medium and the vibro-dissociation technique developed for the slices of brains and spinal cords previously. Our method took shorter time of the procedure, and required less elaborated skill, than the conventional enzymatic method did; nevertheless it yielded enough number of the cells available for acute electrophysiological experiments. The isolated retinal neurons were useful for measuring the nonlinear membrane conductances as well as the spike firing properties under the perforated-patch whole-cell configuration. These neurons also enabled us to examine the effects of proteolytic enzymes on the membrane excitability in those cells.
Adler, S. L.; Bhanot, G. V.; Weckel, J. D.
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 mod...
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. PMID:20167276
Murase, Haruhiko; KOYAMA, Shuhei; HONAMI, Nobuo; Kuwabara, Takao
An attempt of implementing Kalman filter algorithm in the procedure for training the neural network was made and evaluated. The Kalman filter neuron training program (KNT) was coded. The performance of Kalman filter in KNT was compared to commonly used neuron training algorithm. The study revealed that KNT requires much less calculation time to accomplish neuron training than commonly used other algorithms do. KNT also gave much smaller final error than any other algorithms tested in this study.
Oh, Yohan; Cho, Gun-Sik; Li, Zhe; Hong, Ingie; Zhu, Renjun; Kim, Min-Jeong; Kim, Yong Jun; Tampakakis, Emmanouil; Tung, Leslie; Huganir, Richard; Dong, Xinzhong; Kwon, Chulan; Lee, Gabsang
Summary Neurons derived from human pluripotent stem cells (hPSCs) are powerful tools for studying human neural development and diseases. Robust functional coupling of hPSC-derived neurons with target tissues in vitro is essential for modeling intercellular physiology in a dish and to further translational studies, but has proven difficult to achieve. Here, we derive sympathetic neurons from hPSCs and show they can form physical and functional connections with cardiac muscle cells. Using multiple hPSC reporter lines, we recapitulated human autonomic neuron development in vitro and successfully isolated PHOX2B:eGFP+ neurons that exhibit sympathetic marker expression and electrophysiological properties, and norepinephrine secretion. Upon pharmacologic and optogenetic manipulation, PHOX:eGFP+ neurons controlled beating rates of cardiomyocytes, and the physical interactions between these cells increased neuronal maturation. This study provides a foundation for human sympathetic neuron specification and for hPSC-based neuronal control of organs in a dish. PMID:27320040
Torrealdea, Francisco J; d'Anjou, Alicia; Moujahid, Abdelmalik; de Mendizábal, N Vélez; 10.1016/j.biosystems.2009.04.004
The generation of spikes by neurons is energetically a costly process. This paper studies the consumption of energy and the information entropy in the signalling activity of a model neuron both when it is supposed isolated and when it is coupled to another neuron by an electrical synapse. The neuron has been modelled by a four dimensional Hindmarsh-Rose type kinetic model for which an energy function has been deduced. For the isolated neuron values of energy consumption and information entropy at different signalling regimes have been computed. For two neurons coupled by a gap junction we have analyzed the roles of the membrane and synapse in the contribution of the energy that is required for their organized signalling. Computational results are provided for cases of identical and nonidentical neurons coupled by unidirectional and bidirectional gap junctions. One relevant result is that there are values of the coupling strength at which the organized signalling of two neurons induced by the gap junction take...
Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.
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 ar...
Fullerene, the third allotrope of carbon, has been referred to as a "radical sponge" because of its powerful radical scavenging activities. However, the hydrophobicity and toxicity associated with fullerene limits its application as a therapeutic antioxidant. In the present study, we sought to overcome these limitations by generating water-soluble nanoformulations of fullerene (C(60)). Fullerene (C(60)) was formulated with poly(N-vinyl pyrrolidine) (PVP) or poly(2-alkyl-2-oxazoline)s (POx) homopolymer and random copolymer to form nano-complexes. These C(60)-polymer complexes were characterized by UV-vis spectroscopy, infrared spectroscopy (IR), dynamic light scattering (DLS), atomic force microscopy (AFM) and transmission electron microscopy (TEM). Cellular uptake and intracellular distribution of the selected formulations in catecholaminergic (CATH.a) neurons were examined by UV-vis spectroscopy, immunofluorescence and immunogold labeling. Electron paramagnetic resonance (EPR) spectroscopy was used to determine the ability of these C(60)-polymer complexes to scavenge superoxide. Their cytotoxicity was evaluated in three different cell lines. C(60)-POx and C(60)-PVP complexes exhibited similar physicochemical properties and antioxidant activities. C(60)-poly(2-ethyl-2-oxazoline) (PEtOx) complex, but not C(60)-PVP complex, were efficiently taken up by CATH.a neurons and attenuated the increase in intra-neuronal superoxide induced by angiotensin II (Ang II) stimulation. These results show that C(60)-POx complexes are non-toxic, neuronal cell permeable, superoxide scavenging antioxidants that might be promising candidates for the treatment of brain-related diseases associated with increased levels of superoxide.
Full Text Available Responses of individual neurons to ongoing input are highly variable, reflecting complex threshold dynamics. Experimental access to this threshold dynamics is required in order to fully characterize neuronal input-output relationships. The challenge is practically intractable using present day experimental paradigms due to the cumulative, nonlinear interactions involved. Here we introduce the Neuronal Response Clamp, a closed-loop technique enabling control over the instantaneous response probability of the neuron. The potential of the technique is demonstrated by showing direct access to threshold dynamics of cortical neuron in-vitro using extracellular recording and stimulation, over timescales ranging from seconds to many hours. Moreover, the method allowed us to expose the sensitivity of threshold dynamics to spontaneous input from the network in which the neuron is embedded. The Response Clamp technique follows the rationale of the voltage-clamp and dynamic-clamp approaches, extending it to the neuron's spiking behavior. The general framework offered here is applicable in the study of other neural systems, beyond the single neuron level.
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.
Corey J Keller
Full Text Available To date, single neuron recordings remain the gold standard for monitoring the activity of neuronal populations. Since obtaining single neuron recordings is not always possible, high frequency or 'multiunit activity' (MUA is often used as a surrogate. Although MUA recordings allow one to monitor the activity of a large number of neurons, they do not allow identification of specific neuronal subtypes, the knowledge of which is often critical for understanding electrophysiological processes. Here, we explored whether prior knowledge of the single unit waveform of specific neuron types is sufficient to permit the use of MUA to monitor and distinguish differential activity of individual neuron types. We used an experimental and modeling approach to determine if components of the MUA can monitor medium spiny neurons (MSNs and fast-spiking interneurons (FSIs in the mouse dorsal striatum. We demonstrate that when well-isolated spikes are recorded, the MUA at frequencies greater than 100Hz is correlated with single unit spiking, highly dependent on the waveform of each neuron type, and accurately reflects the timing and spectral signature of each neuron. However, in the absence of well-isolated spikes (the norm in most MUA recordings, the MUA did not typically contain sufficient information to permit accurate prediction of the respective population activity of MSNs and FSIs. Thus, even under ideal conditions for the MUA to reliably predict the moment-to-moment activity of specific local neuronal ensembles, knowledge of the spike waveform of the underlying neuronal populations is necessary, but not sufficient.
Brown, Guy C; Vilalta, Anna
Microglia are resident brain macrophages that become inflammatory activated in most brain pathologies. Microglia normally protect neurons, but may accidentally kill neurons when attempting to limit infections or damage, and this may be more common with degenerative disease as there was no significant selection pressure on the aged brain in the past. A number of mechanisms by which activated microglia kill neurons have been identified, including: (i) stimulation of the phagocyte NADPH oxidase (PHOX) to produce superoxide and derivative oxidants, (ii) expression of inducible nitric oxide synthase (iNOS) producing NO and derivative oxidants, (iii) release of glutamate and glutaminase, (iv) release of TNFα, (v) release of cathepsin B, (vi) phagocytosis of stressed neurons, and (vii) decreased release of nutritive BDNF and IGF-1. PHOX stimulation contributes to microglial activation, but is not directly neurotoxic unless NO is present. NO is normally neuroprotective, but can react with superoxide to produce neurotoxic peroxynitrite, or in the presence of hypoxia inhibit mitochondrial respiration. Glutamate can be released by glia or neurons, but is neurotoxic only if the neurons are depolarised, for example as a result of mitochondrial inhibition. TNFα is normally neuroprotective, but can become toxic if caspase-8 or NF-κB activation are inhibited. If the above mechanisms do not kill neurons, they may still stress the neurons sufficiently to make them susceptible to phagocytosis by activated microglia. We review here whether microglial killing of neurons is an artefact, makes evolutionary sense or contributes in common neuropathologies and by what mechanisms. This article is part of a Special Issue entitled SI: Neuroprotection. PMID:26341532
NAKAMURA, SHIRO; Bradley, Robert M.
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...
McKenna, Thomas M; Zornetzer, Steven F
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
Biswas, Ayan K.; Atulasimha, Jayasimha; Bandyopadhyay, Supriyo
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. Here, we propose and analyze a different type of spin-neuron in which t...
Responses of electrophysiologically identified tuberohypophysial paraventricular nucleus (PVN) neurons were examined following electrical stimulation of the A1, A2, A6, and C2 catecholaminergic cell groups and of the ventral noradrenergic ascending bundle (VNAB). A1, A2, and A6 stimulation evoked primarily excitatory responses from the cells recorded, but C2 stimulation yielded a greater proportion of inhibitory responses. VNAB stimulation at low frequencies (0.5/5 Hz) excited the majority of cells tested, but high-frequency (50 Hz) trains of stimulation reversed the direction of response to inhibition for approximately half of the cells excited by single-shock stimulation. Only 5-Hz stimulation had any affect on blood pressure, causing a slight increase. Treatment with alpha-methylparatyrosine, to inhibit (nor) epinephrine synthesis, reduced the proportion of excitatory responses and prevented the response reversals following 50-Hz VNAB stimulation. Treatment with 6-hydroxydopamine also reduced the proportion of cells excited by VNAB stimulation. Iontophoresis of either norepinephrine or the alpha 1-adrenoceptor agonist l-phenylephrine increased the activity of most cells tested whilst the alpha 1-antagonist ergotamine reduced the activity of most cells tested and prevented excitation elicited by VNAB stimulation. The alpha 2-agonist clonidine excited all cells tested. The beta-antagonist propranolol increased the activity of the majority of cells and prevented inhibitory responses following 50-Hz VNAB stimulation. The results confirm a role for brain stem projections in regulating PVN neuronal activity and demonstrate for the first time that the VNAB provides excitatory input to the PVN, primarily regulated by alpha 1-adrenoceptors. The effects of propranolol on spontaneous activity, and on the inhibitory responses following high-frequency VNAB stimulation, indicate the presence of an inhibitory counterbalancing beta-adrenoceptor mechanism. PMID:8388662
Cholecystokinin (CCK) is a peptide, which is present in the gastrointestinat tract in endocrine cells and in the enteric nervous system (ENS). A possible function in the control of motility of the small intestine has been attributed to neuronal CCK. The aim of this thesis was to obtain a fundamental insight into the action and effects of CCK on enteric neurons. Therefore, intracelluiar recordings were made of myenteric neurons in an isolated preparation of the guinea-pig ileum. Two types of ...
Hines, Michael L.; Carnevale, Nicholas T.
We describe four recent additions to NEURON's suite of graphical tools that make it easier for users to create and manage models: an enhancement to the Channel Builder that facilitates the specification and efficient simulation of stochastic channel models
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.
Barber, Michael J.; Ristig, Manfred L.
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 network...
Crotty, Patrick; Schult, Daniel; Segall, Ken
With the goal of understanding the intricate behavior and dynamics of collections of neurons, we present superconducting circuits containing Josephson junctions that model biologically realistic neurons. These "Josephson junction neurons" reproduce many characteristic behaviors of biological neurons such as action potentials, refractory periods, and firing thresholds. They can be coupled together in ways that mimic electrical and chemical synapses. Using existing fabrication technologies, lar...
Park, Kyoung Ho [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Yeo, Sang Won, E-mail: email@example.com [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Troy, Frederic A., E-mail: firstname.lastname@example.org [Department of Biochemistry and Molecular Medicine, University of California, School of Medicine, Davis, CA 95616 (United States); Xiamen University, School of Medicine, Xiamen City (China)
Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.
Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders
Dan Dan Xu
Full Text Available Rhynchophylline (Rhy is an active component isolated from species of the genus Uncaria which has been used for the treatment of ailments to the central nervous system in traditional Chinese medicine. Besides acting as a calcium channel blocker, Rhy was also reported to be able to protect against glutamate-induced neuronal death. We thus hypothesize that Rhy may have neuroprotective activity against methamphetamine (MA. The primary neurons were cultured directly from the cerebral cortex of neonatal rats, acting as in vitro model in the present study. The neurotoxicity of MA and the protective effect of Rhy were evaluated by MTT assay. The effects of MA, Rhy or their combination on intracellular free calcium concentration ([Ca2+]i were determined in individual neocortical neurons by the Fluo-3/AM tracing method. The MTT assay demonstrated that MA has a dose-dependent neurotoxicity in neuronal cultures. The addition of Rhy prior to the exposure to MA prevented neuronal death. Time course studies with the Fluo-3/AM probe showed that Rhy significantly decreased neuronal [Ca2+]i which was elevated by the exposure to MA. Our results suggested that Rhy can protect the neuronal cultures against MA exposure and promptly attenuate intracellular calcium overload triggered by MA challenge. This is the first report demonstrating an inhibitory effect of Rhy against MA impairment in cultured neurons in vitro.
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.
Cullen, D. Kacy; Gilroy, Meghan; Irons, Hillary R.; LaPlaca, Michelle C.
Synapse formation is a fundamental process in neurons that occurs throughout development, maturity, and aging. Although these stages contain disparate and fluctuating numbers of mature neurons, tactics employed by neuronal networks to modulate synapse number as a function of neuronal density are not well understood. The goal of this study was to utilize an in vitro model to assess the influence of cell density and neuronal maturity on synapse number and distribution. Specifically, cerebral co...
Onesto, Valentina; Cosentino, Carlo; Di Fabrizio, Enzo; Cesarelli, Mario; Amato, Francesco; Gentile, Francesco
Neurons are specialized, electrically excitable cells which use electrical to chemical signals to transmit and elaborate information. Understanding how the cooperation of a great many of neurons in a grid may modify and perhaps improve the information quality, in contrast to few neurons in isolation, is critical for the rational design of cell-materials interfaces for applications in regenerative medicine, tissue engineering, and personalized lab-on-a-chips. In the present paper, we couple an...
Rollenhagen, Astrid; Bischof, Hans-Joachim
An area of the caudal forebrain of male zebra finches, the Archi-Neostriatum caudale (ANC), which is active during arousal (Bischof and Herrmann, 1986, 1988), shows rearing-dependent changes in neuron morphology (Rollenhagen and Bischof, 1991). We demonstrate here that rearing conditions also affect the shape of spines of one of the four ANC neuron types. This neuron type was examined in birds reared under five different conditions - in isolation (1), caged (2), in the aviary (3), and with so...
Yuan Liu; Li Wang; Zaiyun Long; Lin Zeng; Yamin Wu
Protoplasmic astrocytes have been reported to exhibit neuroprotective effects on neurons, but there has been no direct evidence for a functional relationship between protoplasmic astrocytes and neural stem cells (NSCs). In this study, we examined neuronal differentiation of NSCs induced by protoplasmic astrocytes in a co-culture model. Protoplasmic astrocytes were isolated from new-born and NSCs from the E13-15 cortex of rats respectively. The differentiated cells labeled with neuron-specific...
Greenwood, Priscilla E
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...
Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders.
Bistra B Nankova
Full Text Available Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA like propionic (PPA, and butyric acid (BA, which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD. Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals
Sgro, Allyson E.; Nowak, Amy L.; Austin, Naola S.; Custer, Kenneth L.; Allen, Peter B.; Chiu, Daniel T.; Bajjalieh, Sandra M.
Generating microislands of culture substrate on coverslips by spray application of poly-D lysine is a commonly used method for culturing isolated neurons that form self (autaptic) synapses. This preparation has multiple advantages for studying synaptic transmission in isolation; however, generating microislands by spraying produces islands of non-uniform size and thus cultures vary widely in the number of islands containing single neurons. To address these problems, we developed a high-throug...
@@ 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.
Highlights: → A chaotic model of spontaneous neuron firing. → Mapping the irregular spiking time-series into telegraph signals. → Fundamental frequency of the Rossler attractor provides periodic component. → Spiking time-series from spontaneous activity of hippocampal neurons. → Comparison shows good agreement between the model and the experiment. - Abstract: A chaotic model of spontaneous (without external stimulus) neuron firing has been analyzed by mapping the irregular spiking time-series into telegraph signals. In this model the fundamental frequency of chaotic Roessler attractor provides (with a period doubling) the strong periodic component of the generated irregular signal. The exponentially decaying broad-band part of the spectrum of the Roessler attractor has been transformed by the threshold firing mechanism into a scaling tale. These results are compared with irregular spiking time-series obtained in vitro from a spontaneous activity of hippocampal (CA3) singular neurons (rat's brain slice culture). The comparison shows good agreement between the model and experimentally obtained spectra.
The paper gives a generic idea of the solutions that the neuronal nets contribute to the robotics. The advantages and the inconveniences are exposed that have regarding the conventional techniques. It also describe the more excellent applications as the pursuit of trajectories, the positioning based on images, the force control or of the mobile robots management, among others
Girish Baburao Kulkarni
Full Text Available With advances in the neuro-imaging modalities, diverse manifestations of the cerebral venous sinus thrombosis (CVT are being recognized. There are very few reports of isolated cranial nerve palsies in CVT. In this case report, we describe a patient of lower motor neuron facial palsy with CVT who was successfully treated with anticoagulation, highlighting the atypical manifestation of the disease.
Authors: Parizad M. Bilimoria and Azad Bonni1 Corresponding author (()) ### INTRODUCTION Primary cultures of granule neurons from the post-natal rat cerebellum provide an excellent model system for molecular and cell biological studies of neuronal development and function. The cerebellar cortex, with its highly organized structure and few neuronal subtypes, offers a well-characterized neural circuitry. Many fundamental insight...
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. (general)
Lü Yong-Bing; Shi Xia; Zheng Yan-Hong
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.
MA Bei; NI Xin; HAN Hong; BURNSTOCK Geoffrey
Objective:To investigate the expression of P2X receptors on rat intracardiac and paratracheal ganglion neurons. Methods: For preparation of intracardiac neurons, hearts were excised, the atria were separated and the medial region containing intracardiac ganglia was isolated and cut into pieces. For preparation of paratracheal neurons, the tracheas were removed and the superficial membranous layer containing paratracheal ganglia was rapidly isolated. Intracardiac and paratracheal ganglion neurons were dissociated after digestion by collagenase and trypsin. Whole-cell patch clamp recording was used to identify the pharmacological properties of P2X receptors in cultured neurons. Results:Neurons from these two ganglia responded to ATP with a rapidly activating, sustained inward current. Αβ-meATP failed to evoke any responses in paratracheal ganglion neurons while a few of intracardiac ganglion neurons responded to αβ-meATP with a tiny sustained inward current. ADP and UTP had no effect on intracardiac neurons. Lowering pH potentiated ATP responses in neurons from these two ganglia whereas increasing pH inhibited ATP responses. Co-application of Zn2+ potentiated ATP responses in intracardiac and paratracheal ganglion neurons. Conclusion: The receptor subtypes involved in intracardiac and paratracheal ganglia appear to be homomeric P2X2, while heteromeric P2X2/3 could not be completely excluded from intracardiac neurons.
Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary neurons mediating pain and itch. A large number of cell surface receptors in these neurons couple to phospholipase C (PLC) enzymes leading to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and the generation of downstream signaling molecules. These neurons also express many different ion channels, several of which are regulated by phosphoinositides. This review will summarize the knowledge on phosphoinositide signaling in DRG neurons, with special focus on effects on sensory and other ion channels. PMID:26724974
Motor neurone disease (MND), or amyotrophic lateral sclerosis (ALS), is a neurodegenerative disorder of unknown aetiology. Progressive motor weakness and bulbar dysfunction lead to premature death, usually from respiratory failure. Confirming the diagnosis may initially be difficult until the full clinical features are manifest. For all forms of the disease there is a significant differential diagnosis to consider, including treatable conditions, and therefore specialist neurological opinion ...
Bota, Mihail; Swanson, Larry W.
A systematic account of neuron cell types is a basic prerequisite for determining the vertebrate nervous system global wiring diagram. With comprehensive lineage and phylogenetic information unavailable, a general ontology based on structure-function taxonomy is proposed and implemented in a knowledge management system, and a prototype analysis of select regions (including retina, cerebellum, and hypothalamus) presented. The supporting Brain Architecture Knowledge Management System (BAMS) Neu...
John R. Skoyles
Full Text Available Commonsense says we are isolated. After all, our bodies are physically separate. But Seneca’s colamus humanitatem, and John Donne’s observation that “no man is an island” suggests we are neither entirely isolated nor separate. A recent discovery in neuroscience—that of mirror neurons—argues that the brain and the mind is neither built nor functions remote from what happens in other individuals. What are mirror neurons? They are brain cells that process both what happens to or is done by an individual, and, as it were, its perceived “refl ection,” when that same thing happens or is done by another individual. Thus, mirror neurons are both activated when an individual does a particular action, and when that individual perceives that same action done by another. The discovery of mirror neurons suggests we need to radically revise our notions of human nature since they offer a means by which we may not be so separated as we think. Humans unlike other apes are adapted to mirror interact nonverbally when together. Notably, our faces have been evolved to display agile and nimble movements. While this is usually explained as enabling nonverbal communication, a better description would be nonverbal commune based upon mirror neurons. I argue we cherish humanity, colamus humanitatem, because mirror neurons and our adapted mirror interpersonal interface blur the physical boundaries that separate us.
We investigate the properties of recently proposed "shotgun" sampling approach for the common inputs problem in the functional estimation of neuronal connectivity. We study the asymptotic correctness, the speed of convergence, and the data size requirements of such an approach. We show that the shotgun approach can be expected to allow the inference of complete connectivity matrix in large neuronal populations under some rather general conditions. However, we find that the posterior error of the shotgun connectivity estimator grows quickly with the size of unobserved neuronal populations, the square of average connectivity strength, and the square of observation sparseness. This implies that the shotgun connectivity estimation will require significantly larger amounts of neuronal activity data whenever the number of neurons in observed neuronal populations remains small. We present a numerical approach for solving the shotgun estimation problem in general settings and use it to demonstrate the shotgun connectivity inference in the examples of simulated synfire and weakly coupled cortical neuronal networks. PMID:27515518
Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G
Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation. PMID:27058317
Xiaojing Xu; Min Wang; Jing Liu; Jingya Lv; Yanan Hu; Huanxiang Zhang
As supportive cells for neuronal growth and development, much effort has been devoted to the role of astrocytes in the normal state. However, the effect of the astrocytes after injury remains elusive. In the present study, neurons isolated from the subventricular zone of injured neonatal rat brains were co-cultured with astrocytes. After 6 days, these astrocytes showed a mature neuron-like appearance and the number of survivingneurons, primary dendrites and total branches was significantly higher than those at 3 days. The neurons began to shrink at 9 days after co-culture with shorter and thinner processes and the number of primary dendrites and total branches was significantly reduced. These experimental findings indicate that astrocytes in the injured brain promote the development of neurons in the early stages of co-culture while these cells reversely inhibit neuronal growth and development at the later states.
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 gangli...
Gavello, Daniela; Rojo-Ruiz, Jonathan; Marcantoni, Andrea; Franchino, Claudio; Carbone, Emilio; Carabelli, Valentina
Besides regulating energy balance and reducing body-weight, the adipokine leptin has been recently shown to be neuroprotective and antiapoptotic by promoting neuronal survival after excitotoxic and oxidative insults. Here, we investigated the firing properties of mouse hippocampal neurons and the effects of leptin pretreatment on hypoxic damage (2 hours, 3% O(2)). Experiments were carried out by means of the microelectrode array (MEA) technology, monitoring hippocampal neurons activity from 11 to 18 days in vitro (DIV). Under normoxic conditions, hippocampal neurons were spontaneously firing, either with prevailing isolated and randomly distributed spikes (11 DIV), or with patterns characterized by synchronized bursts (18 DIV). Exposure to hypoxia severely impaired the spontaneous activity of hippocampal neurons, reducing their firing frequency by 54% and 69%, at 11 and 18 DIV respectively, and synchronized their firing activity. Pretreatment with 50 nM leptin reduced the firing frequency of normoxic neurons and contrasted the hypoxia-induced depressive action, either by limiting the firing frequency reduction (at both ages) or by increasing it to 126% (in younger neurons). In order to find out whether leptin exerts its effect by activating large conductance Ca(2+)-activated K(+) channels (BK), as shown on rat hippocampal neurons, we applied the BK channel blocker paxilline (1 µM). Our data show that paxilline reversed the effects of leptin, both on normoxic and hypoxic neurons, suggesting that the adipokine counteracts hypoxia through BK channels activation in mouse hippocampal neurons. PMID:22848520
Bupesh, Munisamy; Vicario, Alba; Abellán, Antonio; Desfilis, Ester; Medina, Loreta
Emotional and motivational dysfunctions observed in Parkinson's disease, schizophrenia, and drug addiction are associated to an alteration of the mesocortical and mesolimbic dopaminergic pathways, which include axons projecting to the prefrontal cortex, the ventral striatum, and the amygdala. Subpopulations of catecholaminergic neurons have been described in the cortex and striatum of several mammals, but the presence of such cells in the adult amygdala is unclear in murine rodents, and in other rodents appears to show variations depending on the species. Moreover, the embryonic origin of telencephalic tyrosine hydroxylase (TH) cells is unknown, which is essential for trying to understand aspects of their evolution, distribution and function. Herein we investigated the expression of TH mRNA and protein in cells of the striatum and amygdala of developing and adult mice, and analyzed the embryonic origin of such cells using in vitro migration assays. Our results showed the presence of TH mRNA and protein expressing cells in the striatum (including nucleus accumbens), central and medial extended amygdala during development, which are persistent in adulthood although they are less numerous, generally show weak mRNA expression, and some appear to lack the protein. Fate mapping analysis showed that these cells include at least two subpopulations with different embryonic origin in either the commissural preoptic area of the subpallium or the supraopto-paraventricular domain of the alar hypothalamus. These data are important for future studies trying to understand the role of catecholamines in modulation of emotion, motivation, and reward. PMID:23479178
Full Text Available Fine-tuning of neuronal activity was thought to be a neuron-autonomous mechanism until the discovery that astrocytes are active players of synaptic transmission. The involvement of astrocytes has changed our understanding of the roles of non-neuronal cells and shed new light on the regulation of neuronal activity. Microglial cells are the macrophages of the brain and they have been mostly investigated as immune cells. However recent data discussed in this review support the notion that, similarly to astrocytes, microglia are involved in the regulation of neuronal activity. For instance, in most, if not all, brain pathologies a strong temporal correlation has long been known to exist between the pathological activation of microglia and dysfunction of neuronal activity. Recent studies have convincingly shown that alteration of microglial function is responsible for pathological neuronal activity. This causal relationship has also been demonstrated in mice bearing loss-of-function mutations in genes specifically expressed by microglia. In addition to these long-term regulations of neuronal activity, recent data show that microglia can also rapidly regulate neuronal activity, thereby acting as partners of neurotransmission.
Franze, Kristian; Guck, Jochen
For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.
Biswas, Ayan K; Atulasimha, Jayasimha; Bandyopadhyay, Supriyo
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. PMID:26112081
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.
Hoshimaru, M; Ray, J.; Sah, D W; Gage, F.H.
A regulatable retroviral vector in which the v-myc oncogene is driven by a tetracycline-controlled transactivator and a human cytomegalovirus minimal promoter fused to a tet operator sequence was used for conditional immortalization of adult rat neuronal progenitor cells. A single clone, HC2S2, was isolated and characterized. Two days after the addition of tetracycline, the HC2S2 cells stopped proliferating, began to extend neurites, and expressed the neuronal markers tau, NeuN, neurofilament...
Target-derived influences of nerve growth factor on neuronal survival and differentiation are well documented, though effects of other neurotrophins are less clear. To examine the influence of NT-3 neurotrophin overexpression in a target tissue of sensory and sympathetic neurons, transgenic mice were isolated that overexpress NT- 3 in the epidermis. Overexpression of NT-3 led to a 42% increase in the number of dorsal root ganglia sensory neurons, a 70% increase in the number of trigeminal sen...
Liu, Dong; Croteau, Deborah L; Souza-Pinto, Nadja; Pitta, Michael; Tian, Jingyan; Wu, Christopher; Jiang, Haiyang; Mustafa, Khadija; Keijzers, Guido; Bohr, Vilhelm; Mattson, Mark P
. Cortical neurons isolated from OGG1(-/-) mice were more vulnerable to oxidative insults than were OGG1(+/+) neurons, and OGG1(-/-) mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1(+/+) mice. Accumulations of oxidative DNA...
Christensen-Dalsgaard, J; Walkowiak, W
We present results from in vitro and in vivo studies of response properties of neurons in the saccular and caudal nuclei in the frog. In the in vitro studies the saccular nerve of the isolated brain was stimulated with electrical pulses. In the in vivo experiments, the neurons were stimulated...
Grant D. Nicol
@@ Because nerve growth factor (NGF) is elevated during inflammation, plays a causal role in the initiation of hyperalgesia, and is known to activate the sphingomyelin signalling pathway, we examined whether NGF and its putative second messenger, ceramide, could modulate the excitability of capsaicin-sensitive adult sensory neurons.Using the whole-cell patch-clamp recording technique,exposure of isolated sensory neurons to either 100 ng/mL NGF or 1 mmol/L N-acetyl sphingosine (C2-ceramide) produced a 3-4 fold increase in the number of action po-tentials (APs) evoked by a ramp of depolarizing current in a time-dependent manner. Intracellular perfusion with bac- terial sphingomyelinase (SMase) also increased the num- ber of APs suggesting that the release of native ceramide enhanced neuronal excitability.
Vardi, Roni; Timor, Reut; Marom, Shimon; Abeles, Moshe; Kanter, Ido
Psychological and physiological considerations entail that formation and functionality of neuronal cell assemblies depend upon synchronized repeated activation such as zero-lag synchronization. Several mechanisms for the emergence of this phenomenon have been suggested, including the global network quantity, the greatest common divisor of neuronal circuit delay loops. However, they require strict biological prerequisites such as precisely matched delays and connectivity, and synchronization is represented as a stationary mode of activity instead of a transient phenomenon. Here we show that the unavoidable increase in neuronal response latency to ongoing stimulation serves as a nonuniform gradual stretching of neuronal circuit delay loops. This apparent nuisance is revealed to be an essential mechanism in various types of neuronal time controllers, where synchronization emerges as a transient phenomenon and without predefined precisely matched synaptic delays. These findings are described in an experimental procedure where conditioned stimulations were enforced on a circuit of neurons embedded within a large-scale network of cortical cells in vitro, and are corroborated and extended by simulations of circuits composed of Hodgkin-Huxley neurons with time-dependent latencies. These findings announce a cortical time scale for time controllers based on tens of microseconds stretching of neuronal circuit delay loops per spike. They call for a reexamination of the role of the temporal periodic mode in brain functionality using advanced in vitro and in vivo experiments.
Bennett, Michael J.; Rakheja, Dinesh
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…
Manzini, Ivan; Peters, Florian; Schild, Detlev
We used a slice preparation of the olfactory epithelium of Xenopus laevis tadpoles to record odorant responses of olfactory receptor neurons (ORNs) and compared these to odorant responses recorded in isolated ORNs. The maximum recording time in the slice was considerably longer than in isolated ORNs, which is essential when many odorants are to be tested. No odorant-induced responses could be obtained from isolated ORNs recorded in the on-cell mode, while recordings in the slice (on-cell and ...
Mandel, P; Ledig, M; M'Paria, J R
The effect of ethanol on membrane enzymes (Na+, K+ and Mg2+ ATPases, 5'-nucleotidase, adenylate cyclase) alcohol dehydrogenase, aldehyde dehydrogenase and superoxide dismutase were studied in nerve cells (established cell lines, primary cultures of chick and rat brain) cultured in the presence of 100 mM ethanol, and in total rat brain, following various ethanol treatments of the rats (20% ethanol as the sole liquid source, intraperitoneal injection). The results show a difference between neuronal and glial cells. Most of the observed changes in enzymatic activities returned rapidly to control values when ethanol was withdrawn from the culture medium or from the diet. Alcohol dehydrogenase was more stimulated by ethanol than aldehyde dehydrogenase; therefore acetaldehyde may be accumulated. The inhibition of superoxide dismutase activity may allow an accumulation of cytotoxic O2- radicals in nervous tissue and may explain the polymorphism of lesions brought about by alcohol intoxication. PMID:6264495
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.
Collin J Lobb
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.
Bergheim, Thomas Stian; Skogvold, Arve Aleksander Nymo
Neurons communicate through electrophysiological signals, which may be recorded using electrodes inserted into living tissue.When a neuron emits a signal, it is referred to as a spike, and an electrode can detect these from multiple neurons.Neuronal spike sorting is the process of classifying the spike activity based on which neuron each spike signal is emitted from.Advances in technology have introduced better recording equipment, which allows the recording of many neurons at the same time.H...
Full Text Available Insulin and related peptides play important and conserved functions in growth and metabolism. Although Drosophila has proved useful for the genetic analysis of insulin functions, little is known about the transcription factors and cell lineages involved in insulin production. Within the embryonic central nervous system, the MP2 neuroblast divides once to generate a dMP2 neuron that initially functions as a pioneer, guiding the axons of other later-born embryonic neurons. Later during development, dMP2 neurons in anterior segments undergo apoptosis but their posterior counterparts persist. We show here that surviving posterior dMP2 neurons no longer function in axonal scaffolding but differentiate into neuroendocrine cells that express insulin-like peptide 7 (Ilp7 and innervate the hindgut. We find that the postmitotic transition from pioneer to insulin-producing neuron is a multistep process requiring retrograde bone morphogenetic protein (BMP signalling and four transcription factors: Abdominal-B, Hb9, Fork Head, and Dimmed. These five inputs contribute in a partially overlapping manner to combinatorial codes for dMP2 apoptosis, survival, and insulinergic differentiation. Ectopic reconstitution of this code is sufficient to activate Ilp7 expression in other postmitotic neurons. These studies reveal striking similarities between the transcription factors regulating insulin expression in insect neurons and mammalian pancreatic beta-cells.
YANG Xiao-feng; CAO Fei; PAN De-sheng; LIU Wei-guo; HU Wei-wei; ZHENG Xiu-jue; ZHAO Xue-qun; L(U) Shi-ting
Objective:To establish a simple, reproducible, and practical mechanical injury model of hippocampal neurons of Sprague-Dawley rats in vitro.Methods: Hippocampal neurons isolated from1-2-day old rats were cultured in vitro. Mild, moderate and severe mechanical injuries were delivered to the neurons by syringe needle tearing, respectively. The control neurons were treated identically with the exception of trauma. Cell damage was assessed by measuring the Propidium Iodide(PI) uptaking at different time points (0.5, 1, 6, 12 and24 hours) after injury. The concentration of neuron specific enolase was also measured at some time points.Results: Pathological examination showed that degeneration, degradation and necrosis occurred in the injured cultured neurons. Compared with the control group, the ratio of PI-positive cells in the injured groups increased significantly after 30 minutes of injury (P ＜0.05). More severe the damage was, more PI-positive neurons were detected. Compared with the control group,the concentration of neuron specific enolase in the injured culture increased significantly after 1 hour of injury (P ＜0.05).Conclusions: The established model of hippocampal neuron injury in vitro can be repeated easily and can simulate the damage mechanism of traumatic brain injury,which can be used in the future research of traumatic brain injury.
Spaethling, Jennifer M; Piel, David; Dueck, Hannah; Buckley, Peter T; Morris, Jacqueline F; Fisher, Stephen A; Lee, Jaehee; Sul, Jai-Yoon; Kim, Junhyong; Bartfai, Tamas; Beck, Sheryl G; Eberwine, James H
Despite the recognized importance of the dorsal raphe (DR) serotonergic (5-HT) nuclei in the pathophysiology of depression and anxiety, the molecular components/putative drug targets expressed by these neurons are poorly characterized. Utilizing the promoter of an ETS domain transcription factor that is a stable marker of 5-HT neurons (Pet-1) to drive 5-HT neuronal expression of YFP, we identified 5-HT neurons in live acute slices. We isolated RNA from single 5-HT neurons in the ventromedial and lateral wings of the DR and performed single-cell RNA-Seq analysis identifying >500 G-protein coupled receptors (GPCRs) including receptors for classical transmitters, lipid signals, and peptides as well as dozens of orphan-GPCRs. Using these data to inform our selection of receptors to assess, we found that oxytocin and lysophosphatidic acid 1 receptors are translated and active in costimulating, with the α1-adrenergic receptor, the firing of DR 5-HT neurons, while the effects of histamine are inhibitory and exerted at H3 histamine receptors. The inhibitory histamine response provides evidence for tonic in vivo histamine inhibition of 5-HT neurons. This study illustrates that unbiased single-cell transcriptomics coupled with functional analyses provides novel insights into how neurons and neuronal systems are regulated. PMID:24192459
Starich, T. A.; Herman, R. K.; Kari, C. K.; Yeh, W. H.; Schackwitz, W. S.; Schuyler, M. W.; Collet, J.; Thomas, J. H.; Riddle, D L
We have identified and characterized 95 mutations that reduce or abolish dye filling of amphid and phasmid neurons and that have little effect on viability, fertility or movement. Twenty-seven mutations occurred spontaneously in strains with a high frequency of transposon insertion. Sixty-eight were isolated after treatment with EMS. All of the mutations result in defects in one or more chemosensory responses, such as chemotaxis to ammonium chloride or formation of dauer larvae under conditio...
Cha, Kyung Soo; Kim, Soo Ryun; Lee, Yong Chul; Park, Soo Soung [Chung Ang University College of Medicine, Seoul (Korea, Republic of); Sim, Young Soo [Seoul National University College of Medicine, Seoul (Korea, Republic of)
Isolated situs inversus of the stomach with otherwise normal position of the thoracic and abdominal viscera is an extremely rare anomaly occurring in two district forms. Majority of cases are associated with eventration of the diphragm and are reported as being confused with spontaneous pneumothorax or pyopneumothorax at base of the right lung. The right sided stomach may produce interesting and confusing changes in liver scan. We have experienced 2 cases of the isolated dextrogastria.
Isolated situs inversus of the stomach with otherwise normal position of the thoracic and abdominal viscera is an extremely rare anomaly occurring in two district forms. Majority of cases are associated with eventration of the diphragm and are reported as being confused with spontaneous pneumothorax or pyopneumothorax at base of the right lung. The right sided stomach may produce interesting and confusing changes in liver scan. We have experienced 2 cases of the isolated dextrogastria
Mammalian Mueller cells have been reported to possess retinal progenitor cell properties and generate new neurons after injury. This study investigates murine Mueller cells under in vitro conditions for their capability of dedifferentiation into retinal progenitor cells. Mueller cells were isolated from mouse retina, and proliferating cells were expanded in serum-containing medium. For dedifferentiation, the cultured cells were transferred to serum-replacement medium (SRM) at different points in time after their isolation. Interestingly, early cell passages produced fibrous tissue in which extracellular matrix proteins and connective tissue markers were differentially expressed. In contrast, aged Mueller cell cultures formed neurospheres in SRM that are characteristic for neuronal progenitor cells. These neurospheres differentiated into neuron-like cells after cultivation on laminin/ornithine cell culture substrate. Here, we report for the first time that murine Mueller cells can be progenitors for both, fibrous tissue cells and neuronal cells, depending on the age of the cell culture
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.
Connor, Mark; Bagley, Elena E.; Mitchell, Vanessa A; Ingram, Susan L; Christie, MacDonald J.; Humphrey, Patrick P A; Vaughan, Christopher W
Functional studies indicate that the midbrain periaqueductal grey (PAG) is involved in the analgesic actions of somatostatin; however, the cellular actions of somatostatin in this brain region are unknown. In the present study, whole-cell patch clamp recordings were made from rat PAG neurons in vitro. In 93% of acutely isolated neurons, somatostatin inhibited Ca2+-channel currents. This effect was mimicked by the sst-2 selective agonist BIM-23027, but not by the sst-1 and sst-5 selective agon...
Lake, Blue B; Ai, Rizi; Kaeser, Gwendolyn E; Salathia, Neeraj S; Yung, Yun C; Liu, Rui; Wildberg, Andre; Gao, Derek; Fung, Ho-Lim; Chen, Song; Vijayaraghavan, Raakhee; Wong, Julian; Chen, Allison; Sheng, Xiaoyan; Kaper, Fiona; Shen, Richard; Ronaghi, Mostafa; Fan, Jian-Bing; Wang, Wei; Chun, Jerold; Zhang, Kun
The human brain has enormously complex cellular diversity and connectivities fundamental to our neural functions, yet difficulties in interrogating individual neurons has impeded understanding of the underlying transcriptional landscape. We developed a scalable approach to sequence and quantify RNA molecules in isolated neuronal nuclei from a postmortem brain, generating 3227 sets of single-neuron data from six distinct regions of the cerebral cortex. Using an iterative clustering and classification approach, we identified 16 neuronal subtypes that were further annotated on the basis of known markers and cortical cytoarchitecture. These data demonstrate a robust and scalable method for identifying and categorizing single nuclear transcriptomes, revealing shared genes sufficient to distinguish previously unknown and orthologous neuronal subtypes as well as regional identity and transcriptomic heterogeneity within the human brain. PMID:27339989
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.
Emily A Gomme
Full Text Available Rabies virus (RABV is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Analysis of human brains post-mortem reveals surprisingly little tissue damage and neuropathology considering the dramatic clinical symptomology, supporting the neuronal dysfunction model. However, whether or not neurons survive infection and clearance and, provided they do, whether they are functionally restored to their pre-infection phenotype has not been determined in vivo for RABV, or any neurotropic virus. This is due, in part, to the absence of a permanent "mark" on once-infected cells that allow their identification long after viral clearance. Our approach to study the survival and integrity of RABV-infected neurons was to infect Cre reporter mice with recombinant RABV expressing Cre-recombinase (RABV-Cre to switch neurons constitutively expressing tdTomato (red to expression of a Cre-inducible EGFP (green, permanently marking neurons that had been infected in vivo. We used fluorescence microscopy and quantitative real-time PCR to measure the survival of neurons after viral clearance; we found that the vast majority of RABV-infected neurons survive both infection and immunological clearance. We were able to isolate these previously infected neurons by flow cytometry and assay their gene expression profiles compared to uninfected cells. We observed transcriptional changes in these "cured" neurons, predictive of decreased neurite growth and dysregulated microtubule dynamics. This suggests that viral clearance, though allowing for survival of neurons, may not restore them to their pre-infection functionality. Our data provide a proof-of-principle foundation to re-evaluate the etiology of human central nervous system diseases of unknown etiology: viruses may trigger permanent neuronal
Cynthia M. Hingtgen
Neurofibromatosis type 1 (NF1) is a common autosomal dominant disease characterized by formation of multiple benign and malignant tumors. People with this disorder also experience chronic pain, which can be disabling. Neurofibromin, the protein product of the Nfl gene, is a gnanosine triphosphatase activating protein (GAP) for p21Ras (Ras). Loss of Nfl results in an increase in activity of the Ras transduction cascade. Because of the growing evidence suggesting involvement of downstream components of the Ras transduction cascade in the sensitization of nociceptive sensory neurons, we examined the stimulus-evoked release of the neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP), from primary sensory neurons of mice with a mutation of the Nfl gene (NfI+1-). Measuring the levels of SP and CGRP by radioimmunoassay, we demonstrated that capsaicin-stimulated release of neuropep-tides is 3-5 folds higher in spinal cord slices from Nfl+1-mice than that from wildtype mouse tissue. In addition, the potassium- and capsaicin-stimulated release of CGRP from the culture of sensory neurons isolated from Nfl+1- mice was more than double that from the culture of wildtype neurons. Using patch-clamp electrophysiological techniques, we also examined the excitability of capsaicin-sensitive sensory neurons. It was found that the number of action potentials generated by the neurons from Nfl+1- mice, responsing to a ramp of depolarizing current, was more than three times of that generated by wildtype neurons. Consistent with that observation, neurons from Nfl+1- mice had lower firing thresholds, lower rheobase currents and shorter firing latencies compared with wildtype neurons. These data clearly demonstrate that GAPs, such as neurofihromin, can alter the excitability of nociceptive sensory neurons. The augmented response of sensory neurons with altered Ras signaling may explain the abnormal pain sensations experienced by people with NFI and suggests an important
Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger David John
damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses...... include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review...... the responses of neurons to various physiological stressors at the molecular and cellular level....
Fink, Christian G.
We discuss several techniques used in simulating neuronal networks by exploring how a network's connectivity structure affects its propensity for synchronous spiking. Network connectivity is generated using the Watts-Strogatz small-world algorithm, and two key measures of network structure are described. These measures quantify structural characteristics that influence collective neuronal spiking, which is simulated using the leaky integrate-and-fire model. Simulations show that adding a small number of random connections to an otherwise lattice-like connectivity structure leads to a dramatic increase in neuronal synchronization.
Corcelli, Angela; Lobasso, Simona; Lopalco, Patrizia; Dibattista, Michele; Araneda, Ricardo; Peterlin, Zita; Firestein, Stuart
The response of olfactory sensory neurons to TNT and RDX as well as to some volatile organic compounds present in the vapors of antipersonnel landmines has been studied both in the pig and in the rat. GC/MS analyses of different plastic components of six different kinds of landmines were performed in order to identify the components of the "perfume" of mines. Studies on rat olfactory mucosa were carried out with electro-olfactogram and calcium imaging techniques, while changes in the cyclic adenosine monophosphate (cAMP) levels following exposure to odorants and explosives were used as a criterion to evaluate the interaction of TNT and RDX with olfactory receptors in a preparation of isolated pig olfactory cilia. These studies indicate that chemical compounds associated with explosives and explosive devices can activate mammalian olfactory receptors. PMID:19913995
de Jaeger, T
The behaviour of neurons under the influence of periodic external input has been modelled very successfully by circle maps. The aim of this note is to extend certain aspects of this analysis to a much more general class of forcing processes. We apply results on the fibred rotation number of randomly forced circle maps to show the uniqueness of the asymptotic firing frequency of ergodically forced pacemaker neurons. The details of the analysis are carried out for the forced leaky integrate-and...
Moroz, Leonid L.; Edwards, John R.; Puthanveettil, Sathyanarayanan V.; Kohn, Andrea B.; Ha, Thomas; Heyland, Andreas; Knudsen, Bjarne; Sahni, Anuj; Yu, Fahong; Liu, Li; Jezzini, Sami; LOVELL, PETER; Iannucculli, William; Chen, Minchen; Nguyen, Tuan
Molecular analyses of Aplysia, a well-established model organism for cellular and systems neural science, have been seriously handicapped by a lack of adequate genomic information. By sequencing cDNA libraries from the central nervous system (CNS), we have identified over 175,000 expressed sequence tags (ESTs), of which 19,814 are unique neuronal gene products and represent 50%–70% of the total Aplysia neuronal transcriptome. We have characterized the transcriptome at three levels: (1) the ce...
Segev, Ronen; Ben-Jacob, Eshel
During embryonic morpho-genesis, a collection of individual neurons turns into a functioning network with unique capabilities. Only recently has this most staggering example of emergent process in the natural world, began to be studied. Here we propose a navigational strategy for neurites growth cones, based on sophisticated chemical signaling. We further propose that the embryonic environment (the neurons and the glia cells) acts as an excitable media in which concentric and spiral chemical ...
de Vladar, Harold P.; Szathmáry, Eörs
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
Armañanzas, Rubén; Ascoli, Giorgio A.
The classification of neurons into types has been much debated since the inception of modern neuroscience. Recent experimental advances are accelerating the pace of data collection. The resulting information growth of morphological, physiological, and molecular properties encourages efforts to automate neuronal classification by powerful machine learning techniques. We review state-of-the-art analysis approaches and availability of suitable data and resources, highlighting prominent challenge...
Mohamed BEN MESSAOUD
Motivation. In medical field, particularly the cardiology, the diagnosis systems constitute the essential domain of research. In some applications, the traditional methods of classification present some limitations. The neuronal technique is considered as one of the promising algorithms to resolve such problem.Method. In this paper, two approaches of the Artificial Neuronal Network (ANN) technique are investigated to classify the heart beats which are Multi Layer Perception (MLP) and Radial B...
Paugam-Moisy, H.; Bohte, Sander; Rozenberg, G.; Baeck, Thomas; Kok, Joost
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 neurons, taking into account the time of spike firing. SNNs overcome the computational power of neural networks made of threshold or sigmoidal units. Based on dynamic event-driven processing, they ope...
First, it is not clear from Gold and Stoljar's definition of biological neuroscience whether it includes computational and representational concepts. If so, then their evaluation of Kandel's theory is problematic. If not, then a more direct refutation of the radical neuron doctrine is available. Second, objections to the psychological sciences might derive not just from the conflation of the radical and the trivial neuron doctrines. There might also be the implicit belief that, for many menta...
Bera, Bidesh K.; Ghosh, Dibakar; Lakshmanan, M.
We study the existence of chimera states in pulse-coupled networks of bursting Hindmarsh-Rose neurons with nonlocal, global and local (nearest neighbor) couplings. Through a linear stability analysis, we discuss the behavior of stability function in the incoherent (i.e. disorder), coherent, chimera and multi-chimera states. Surprisingly, we find that chimera and multi-chimera states occur even using local nearest neighbor interaction in a network of identical bursting neurons alone. This is i...
Bak, Lasse Kristoffer; Obel, Linea Lykke Frimodt; Walls, Anne B;
We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N-methyl-d-aspartate)-ind......We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N...... an ionomycin-induced increase in intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose...... utilization is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based...
Rose, G; Siebler, M
Electrophysiological properties of neurons as the basic cellular elements of the central nervous system and their synaptic connections are well characterized down to a molecular level. However, the behavior of complex noisy networks formed by these constituents usually cannot simply be derived from the knowledge of its microscopic parameters. As a consequence, cooperative phenomena based on the interaction of neurons were postulated. This is a report on a study of global network spike activity as a function of synaptic interaction. We performed experiments in dissociated cultured hippocampal neurons and, for comparison, simulations of a mathematical model closely related to electrophysiology. Numeric analyses revealed that at a critical level of synaptic connectivity the firing behavior undergoes a phase transition. This cooperative effect depends crucially on the interaction of numerous cells and cannot be attributed to the spike threshold of individual neurons. In the experiment a drastic increase in the firing level was observed upon increase of synaptic efficacy by lowering of the extracellular magnesium concentration, which is compatible with our theoretical predictions. This "on-off" phenomenon demonstrates that even in small neuronal ensembles collective behavior can emerge which is not explained by the characteristics of single neurons. PMID:8542966
Inglis, Andrew; Roe, Dan L; Stanley, H E; Rosene, Douglas L; Urbanc, Brigita
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 ...
The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are
Andersen, N.E.; Ankerstjerne, P.; Jørgensen, B.;
Omfattende vejledning, der angiver, hvordan energiforbruget i eksisterende huse kan nedbringes ved isolering, tætning og forbedring af varmeanlægget, og hvor meget det koster. Anvisningen indeholder detaljerede eksempler på efterisolering af ydervægge, tage, gulve og vinduer. Henvender sig til ej...
Olfactory sensory neurons, located in the nasal epithelium, detect and transmit odorant information to the central nervous system. This requires that these neurons form specific neuronal connections within the olfactory bulb and express receptors and signaling molecules specific for these functions. This protocol describes a primary olfactory sensory neuron culture technique that allows in vitro investigation of olfactory sensory neuron differentiation, axon outgrowth, odorant receptor expres...
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 sclerosis (ALS; both lower and upper motor neuron affected) and progressive muscular atrophy (PMA; only lower motor neuron affected) are recognized. There is no cure, despite numerous pharmaceutical tria...
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.; Chan, C. Savio
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,...
Lu, Yun-Bi; Franze, Kristian; Seifert, Gerald; Steinhäuser, Christian; Kirchhoff, Frank; Wolburg, Hartwig; Guck, Jochen; Janmey, Paul; Wei, Er-Qing; Käs, Josef; Reichenbach, Andreas
One hundred fifty years ago glial cells were discovered as a second, non-neuronal, cell type in the central nervous system. To ascribe a function to these new, enigmatic cells, it was suggested that they either glue the neurons together (the Greek word "gammalambdaiotaalpha" means "glue") or provide a robust scaffold for them ("support cells"). Although both speculations are still widely accepted, they would actually require quite different mechanical cell properties, and neither one has ever been confirmed experimentally. We investigated the biomechanics of CNS tissue and acutely isolated individual neurons and glial cells from mammalian brain (hippocampus) and retina. Scanning force microscopy, bulk rheology, and optically induced deformation were used to determine their viscoelastic characteristics. We found that (i) in all CNS cells the elastic behavior dominates over the viscous behavior, (ii) in distinct cell compartments, such as soma and cell processes, the mechanical properties differ, most likely because of the unequal local distribution of cell organelles, (iii) in comparison to most other eukaryotic cells, both neurons and glial cells are very soft ("rubber elastic"), and (iv) intriguingly, glial cells are even softer than their neighboring neurons. Our results indicate that glial cells can neither serve as structural support cells (as they are too soft) nor as glue (because restoring forces are dominant) for neurons. Nevertheless, from a structural perspective they might act as soft, compliant embedding for neurons, protecting them in case of mechanical trauma, and also as a soft substrate required for neurite growth and facilitating neuronal plasticity. PMID:17093050
Hongliang Liu; Tijun Dai; Weitao Guo
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.
A model neuron with delayline feedback connections can learn a time series generated by another model neuron. It has been known that some student neurons that have completed such learning under the instruction of a teacher's quasi-periodic sequence mimic the teacher's time series over a long interval, even after instruction has ceased. We found that in addition to such faithful students, there are unfaithful students whose time series eventually diverge exponentially from that of the teacher. In order to understand the circumstances that allow for such a variety of students, the orbit dimension was estimated numerically. The quasi-periodic orbits in question were found to be confined in spaces with dimensions significantly smaller than that of the full phase space
Dallas C Kinch
Full Text Available Cholecystokinin (CCK facilitates the process of satiation via activation of vagal afferent neurons innervating the upper gastrointestinal tract. Recent findings indicate CCK acts on these neurons via a ruthenium red (RuR sensitive pathway that involves members of the vanilloid (V subfamily of transient receptor potential (TRP channels. To further test this mechanism, the mouse provides an ideal model in which genetic tools could be applied. However, whether CCK acts by similar mechanism(s in mice has not been determined. In the present study we explored the actions of CCK on nodose neurons isolated from Sprague Dawley (SD rat and two strains of mice; C57BL/6 and BalbC using fluorescence-based calcium imaging. With minor exceptions nodose neurons isolated from all species/strains behaved similarly. They all respond to brief depolarization with a large calcium transient. A significant subset of neurons responded to capsaicin (CAP, a TRPV1 agonist, although neurons from C57BL/6 were 10-fold more sensitive to CAP than SD rats or BalbC mice, and a significantly smaller fraction of neurons from BalbC mice responded to CAP. CCK-8 dose-dependently activated a subpopulation of neurons with similar dose dependency, percent responders, and overlap between CCK and CAP responsiveness. In all species/strains CCK-8 induced activation was significantly attenuated (but not completely blocked by pretreatment with the TRPV channel blocker RuR. Surprisingly, the CCK analogue JMV-180, which is reported to have pure antagonistic properties in rat but mixed agonist/antagonist properties in mice, behaved as a pure antagonist to CCK in both rat and mouse neurons. The pure antagonistic action of JMV-180 in this in vitro preparation suggests that prior reported differential effects of JMV-180 on satiation in rats versus mouse must be mediated by a site other than vagal afferent activation.
Full Text Available The electrochemical processes that underlie neural function manifest themselves in ceaseless spatial and temporal fluctuations in the extracellular electric field. The local field potential (LFP, used to study neural interactions during various brain states, is regarded as an epiphenomenon of coordinated neural activity. Yet the extracellular field activity feeds back onto the electrical potential across the neuronal membrane via ephaptic coupling (Jefferys et al, Physiol Rev, 1995. The extent to which such ephaptic coupling alters the functioning of individual neurons and neural assemblies under physiological conditions has remained largely speculative despite recent advances (Ozen et al, JNeurosci, 2010; Fröhlich & McCormick, Neuron, 2010, Anastassiou et al, JNeurosci, 2010. To address this question we use a 12-pipette setup that allows independent positioning of each pipette under visual control with μm accuracy, with the flexibility of using an arbitrary number of these as patching, extracellularly stimulating or extracellular recording pipettes only a few μm away from the cell body of patched neurons (Anastassiou et al, Nat Neurosci, 2011. We stimulated in rat somatosensory cortical slices a variety of layer 5 neural types and recorded inside and outside their cell bodies while pharmacologically silencing synaptic transmission. Pyramidal cells couple to the extracellular field distinctly different from interneurons. Ephaptic coupling strength depends both on the field strength (as measured at the neuron soma as well as the spike-history of neurons. In particular, we find that ephaptic coupling strength depends both on the field strength (as measured at the cell body as well as the spike-history of neurons. How do such effects manifest themselves in vivo? We address this question through detailed large-scale simulations from thousands of biophysically realistic and interconnected neurons (Reimann, Anastassiou et al, Neuron, 2013 emulating
Dicke, Ursula; Roth, Gerhard
Many attempts have been made to correlate degrees of both animal and human intelligence with brain properties. With respect to mammals, a much-discussed trait concerns absolute and relative brain size, either uncorrected or corrected for body size. However, the correlation of both with degrees of intelligence yields large inconsistencies, because although they are regarded as the most intelligent mammals, monkeys and apes, including humans, have neither the absolutely nor the relatively largest brains. The best fit between brain traits and degrees of intelligence among mammals is reached by a combination of the number of cortical neurons, neuron packing density, interneuronal distance and axonal conduction velocity--factors that determine general information processing capacity (IPC), as reflected by general intelligence. The highest IPC is found in humans, followed by the great apes, Old World and New World monkeys. The IPC of cetaceans and elephants is much lower because of a thin cortex, low neuron packing density and low axonal conduction velocity. By contrast, corvid and psittacid birds have very small and densely packed pallial neurons and relatively many neurons, which, despite very small brain volumes, might explain their high intelligence. The evolution of a syntactical and grammatical language in humans most probably has served as an additional intelligence amplifier, which may have happened in songbirds and psittacids in a convergent manner. PMID:26598734
Tuma, Tomas; Pantazi, Angeliki; Le Gallo, Manuel; Sebastian, Abu; Eleftheriou, Evangelos
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.
Matynia, Anna; Nguyen, Eileen; Sun, Xiaoping; Blixt, Frank W.; Parikh, Sachin; Kessler, Jason; Pérez de Sevilla Müller, Luis; Habib, Samer; Kim, Paul; Wang, Zhe Z.; Rodriguez, Allen; Charles, Andrew; Nusinowitz, Steven; Edvinsson, Lars; Barnes, Steven; Brecha, Nicholas C.; Gorin, Michael B.
The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior.
Matynia, Anna; Nguyen, Eileen; Sun, Xiaoping; Blixt, Frank W; Parikh, Sachin; Kessler, Jason; Pérez de Sevilla Müller, Luis; Habib, Samer; Kim, Paul; Wang, Zhe Z; Rodriguez, Allen; Charles, Andrew; Nusinowitz, Steven; Edvinsson, Lars; Barnes, Steven; Brecha, Nicholas C; Gorin, Michael B
The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior. PMID:27559310
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
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
Matikainen, Oliver Albert; Andersen, Kian Alexander; Thorup, Johannes Hoff; Slotsager, Christian Knud; Jensen, Mette Ingersholm; Bachmann, Zenia Gruhl; Razga, Pauline Marie
This study examines whether or not isolation can lead to personal growth. In order to answer this question we distinguish between loneliness and aloneness. We explain the theory of existential psychotherapist Irvin D. Yalom and on the basis of this examination, we analyze a conducted interview through the theory. Based on the theory, interview and analysis, we discuss the validity of Yalom’s theory. Considering the examination, the analysis and the distinction between the two types of isolati...
Bera, Bidesh K.; Ghosh, Dibakar; Lakshmanan, M.
We study the existence of chimera states in pulse-coupled networks of bursting Hindmarsh-Rose neurons with nonlocal, global, and local (nearest neighbor) couplings. Through a linear stability analysis, we discuss the behavior of the stability function in the incoherent (i.e., disorder), coherent, chimera, and multichimera states. Surprisingly, we find that chimera and multichimera states occur even using local nearest neighbor interaction in a network of identical bursting neurons alone. This is in contrast with the existence of chimera states in populations of nonlocally or globally coupled oscillators. A chemical synaptic coupling function is used which plays a key role in the emergence of chimera states in bursting neurons. The existence of chimera, multichimera, coherent, and disordered states is confirmed by means of the recently introduced statistical measures and mean phase velocity.
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. PMID:27150407
Malin Parmar; Johan Jakobsson
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 .
Ivanova, J L; Leonova, O G; Popenko, V I; Ierusalimsky, V N; Korshunova, T A; Boguslavsky, D V; Malyshev, A Y; Balaban, P M; Belyavsky, A V
1. The HCS2 (Helix command specific 2) gene expressed in giant command neurons for withdrawal behavior of the terrestrial snail Helix lucorum encodes a unique hybrid precursor protein that contains a Ca-binding (EF-hand motif) protein and four small peptides (CNP1-CNP4) with similar Tyr-Pro-Arg-X aminoacid sequence at the C terminus. Previous studies suggest that under conditions of increased intracellular Ca(2+) concentration the HCS2 peptide precursor may be cleaved, and small physiologically active peptides transported to the release sites. In the present paper, intracellular localization of putative peptide products of the HCS2-encoded precursor was studied immunocytochemically by means of light and electron microscopy. 2. Polyclonal antibodies against the CNP3 neuropeptide and a Ca-binding domain of the precursor protein were used for gold labeling of ultrathin sections of identified isolated neurons maintained in culture for several days, and in same identified neurons freshly isolated from the central nervous system. 3. In freshly isolated neurons, the gold particles were mainly localized over the cytoplasmic secretory granules, with the density of labeling for the CNP3 neuropeptide being two-fold higher than for the calcium-binding domain. In cultured neurons, both antibodies mostly labeled clusters of secretory granules in growth cones and neurites of the neuron. The density of labeling for cultured neurons was the same for both antibodies, and was two-fold higher than for the freshly isolated from the central nervous system neurons. 4. The immunogold particles were practically absent in the bodies of cultured neurons. 5. The data obtained conform to the suggestion that the HCS2 gene products are transported from the cell body to the regions of growth or release sites. PMID:16763780
Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H;
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...... processes 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...
Wu, Shaw-Wen; Lindberg, Jonathan E M; Peters, James H
Primary vagal afferent neurons express a multitude of thermosensitive ion channels. Within this family of ion channels, the heat-sensitive capsaicin receptor (TRPV1) greatly influences vagal afferent signaling by determining the threshold for action-potential initiation at the peripheral endings, while controlling temperature-sensitive forms of glutamate release at central vagal terminals. Genetic deletion of TRPV1 does not completely eliminate these temperature-dependent effects, suggesting involvement of additional thermosensitive ion channels. The warm-sensitive, calcium-permeable, ion channel TRPV3 is commonly expressed with TRPV1; however, the extent to which TRPV3 is found in vagal afferent neurons is unknown. Here, we begin to characterize the genetic and functional expression of TRPV3 in vagal afferent neurons using molecular biology (RT-PCR and RT-quantitative PCR) in whole nodose and isolated neurons and fluorescent calcium imaging on primary cultures of nodose ganglia neurons. We confirmed low-level TRPV3 expression in vagal afferent neurons and observed direct activation with putative TRPV3 agonists eugenol, ethyl vanillin (EVA), and farnesyl pyrophosphate (FPP). Agonist activation stimulated neurons also containing TRPV1 and was blocked by ruthenium red. FPP sensitivity overlapped with EVA and eugenol but represented the smallest percentage of vagal afferent neurons, and it was the only agonist that did not stimulate neurons from TRPV3(-/-1) mice, suggesting FPP has the highest selectivity. Further, FPP was predictive of enhanced responses to capsaicin, EVA, and eugenol in rats. From our results, we conclude TRPV3 is expressed in a discrete subpopulation of vagal afferent neurons and may contribute to vagal afferent signaling either directly or in combination with TRPV1. PMID:26843581
Full Text Available Decision making in invertebrates often relies on simple neural circuits composed of only a few identified neurons. The relative simplicity of these circuits makes it possible to identify the key computation and neural properties underlying decisions. In this review, we summarize recent research on the neural basis of ultrasound avoidance in crickets, a response that allows escape from echolocating bats. The key neural property shaping behavioral output is high-frequency bursting of an identified interneuron, AN2, which carries information about ultrasound stimuli from receptor neurons to the brain. AN2's spike train consists of clusters of spikes –bursts– that may be interspersed with isolated, non-burst spikes. AN2 firing is necessary and sufficient to trigger avoidance steering but only high-rate firing, such as occurs in bursts, evokes this response. AN2 bursts are therefore at the core of the computation involved in deciding whether or not to steer away from ultrasound. Bursts in AN2 are triggered by synaptic input from nearly synchronous bursts in ultrasound receptors. Thus the population response at the very first stage of sensory processing –the auditory receptor- already differentiates the features of the stimulus that will trigger a behavioral response from those that will not. Adaptation, both intrinsic to AN2 and within ultrasound receptors, scales the burst-generating features according to the stimulus statistics, thus filtering out background noise and ensuring that bursts occur selectively in response to salient peaks in ultrasound intensity. Furthermore AN2’s sensitivity to ultrasound varies adaptively with predation pressure, through both developmental and evolutionary mechanisms. We discuss how this key relationship between bursting and the triggering of avoidance behavior is also observed in other invertebrate systems such as the avoidance of looming visual stimuli in locusts or heat avoidance in beetles.
Intrinsic excitabilities of acutely isolated medial vestibular nucleus (MVN) neurons of rats with normal labyrinth and with undergoingvestibular compensation from 30 min to 24 h after unilateral vestibular deafferentation (UVD) were compared. In control rats, proportions of type A andB cells were 30 and 70%, respectively, however, the proportion of type A cells increased following UVD. Bursting discharge and irregular firingpatterns were recorded from 2 to 12 h post UVD. The spontaneous discharge rate of neurons in the ipsilesional MVN increased significantly at 2 hpost-UVD and remained high until 12 h post-UVD in both type A and type B cells. Mter-hyperpolarization (AHP) of the MVN neurons decreasedsignificantly from 2 h post-UVD in both types of cells. These results suggest that the early stage of vestibular compensation after peripheralneurectomy is associated with an increase in intrinsic excitability due to reduction of AHP in MVN neurons.
LIFei; ZHAOShengmei; ZHENGBaoyu
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.
Volkow, Nora D; Wang, Gen-Jack; Tomasi, Dardo; Baler, Ruben D.
Through sequential waves of drug-induced neurochemical stimulation, addiction co-opts the brain's neuronal circuits that mediate reward, motivation, , to behavioral inflexibility and a severe disruption of self-control and compulsive drug intake. Brain imaging technologies have allowed neuroscientists to map out the neural landscape of addiction in the human brain and to understand how drugs modify it.
Nehlig, Astrid; Coles, Jonathan A
Most techniques presently available to measure cerebral activity in humans and animals, i.e. positron emission tomography (PET), autoradiography, and functional magnetic resonance imaging, do not record the activity of neurons directly. Furthermore, they do not allow the investigator to discriminate which cell type is using glucose, the predominant fuel provided to the brain by the blood. Here, we review the experimental approaches aimed at determining the percentage of glucose that is taken up by neurons and by astrocytes. This review is integrated in an overview of the current concepts on compartmentation and substrate trafficking between astrocytes and neurons. In the brain in vivo, about half of the glucose leaving the capillaries crosses the extracellular space and directly enters neurons. The other half is taken up by astrocytes. Calculations suggest that neurons consume more energy than do astrocytes, implying that astrocytes transfer an intermediate substrate to neurons. Experimental approaches in vitro on the honeybee drone retina and on the isolated vagus nerve also point to a continuous transfer of intermediate metabolites from glial cells to neurons in these tissues. Solid direct evidence of such transfer in the mammalian brain in vivo is still lacking. PET using [(18)F]fluorodeoxyglucose reflects in part glucose uptake by astrocytes but does not indicate to which step the glucose taken up is metabolized within this cell type. Finally, the sequence of metabolic changes occurring during a transient increase of electrical activity in specific regions of the brain remains to be clarified. PMID:17659529
Jang, Jae Myung; Lee, Jeonghyeon; Kim, Hyeongeun; Jeon, Noo Li; Jung, Woonggyu
In this study, we demonstrate a novel platform for optical stimulation of neural circuits combined with a microfluidic culture method and microelectrode array measurements. Neuron-on-a-chip was designed and fabricated to isolate axons without a soma or dendrite. Thus, it is readily able to manipulate the neuronal alignment and to investigate the neuronal activity at the locations we want to observe. We adapted the optical stimulation technique to the arranged neurons to generate the neuronal signals in a non-invasive fashion. A blue light-emitting diode and a femtosecond laser with 780 nm center wavelength were used for neuronal activation and the corresponding neuronal signals were measured by MEAs at the same time. We found that one-photon light via caged glutamate provoked periodic spiking. In contrast, the femtosecond pulse irradiation generated repetitive firing at constant rates. Response times of one-photon and two-photon stimulation were around 200 ms and 50 ms, respectively. We also quantified neural responses, by varying optical parameters such as exposure time and irradiation power. PMID:27053163
Hubscher, C H; Johnson, R D
1. The medullary reticular formation (MRF) is known to be involved in the modulation of certain reproductive behaviors. Ejaculation in the male, disrupted after spinal transection, may depend on a spinal-bulbo-spinal connection. To determine whether single neurons in the MRF receive sensory input from the male genitalia, the present study was undertaken using electrophysiological techniques. 2. The MRF of 14 urethan-anesthetized mature male rats was searched for single neurons responsive to bilateral electrical stimulation of the dorsal nerve of the penis (DNP). In addition, each DNP-responsive neuron was tested for responsiveness to bilateral electrical stimulation of the pelvic nerve (PN) and to mechanical stimulation (gentle touch, pressure, pinch) of the external genitalia, anus, urethra, and skin over most regions of the body. 3. A total of 165 single neurons responsive to bilateral electrical stimulation of the DNP were isolated and characterized throughout the MRF. All neurons responded to both ipsilateral and contralateral DNP stimulation. The majority of responses were excitatory, and most neurons had no background activity. Some neurons required wind-up with bilateral electrical stimulation of the DNP to respond. 4. About half of the neurons were located in the nucleus reticularis gigantocellularis (Gi); the remainder were located in surrounding (dorsal, ventral, lateral) regions of the MRF. Variations in response properties were found among neurons located in different MRF regions. 5. Eighty-eight DNP-responsive neurons were additionally responsive to bilateral electrical stimulation of the PN. None of the responses to bilateral PN were stronger than those for bilateral DNP and many (48%) were weaker. 6. Of the 165 DNP-responsive neurons, all were responsive to pressure/pinching of the penis; 16% responded to gentle stroking of the glans. Most of these neurons were additionally responsive (bilaterally) to pinching more than one (often all) of the
Rui-Long LIU; Ke WANG; Jian-Jun MENG; Tian-Miao HUA; Zhen LIANG; Min-Min XI
The mean firing rate of visual cortical neurons is reduced after prolonged visual stimulation,but the underlying process by which this occurs as well as the biological significance of this phenomenon remains unknown.Computational neuroscience studies indicate that high-frequency bursts in stimulus-driven responses can be transmitted across synapses more reliably than isolated spikes,and thus may carry accurate stimulus-related information.Our research examined whether or not adaptation affects the burst firing property of visual cortical neurons by examining changes in the burst firing changes of V1 neurons during adaptation to the preferred visual stimulus.The results show that adaptation to prolonged visual stimulation significantly decreased burst frequency (bursts/s) and burst length (spikes/burst),but increased burst duration and the interspike interval within bursts.These results suggest that the adaptation of V1 neurons to visual stimulation may result in a decrease of feedforward response gain but an increase of functional activities from lateral and/or feedback connections,which could lead to a reduction in the effectiveness of adapted neurons in transmitting information to its driven neurons.
Inglis, A.; Cruz, L; Roe, D L; H. E. Stanley; Rosene, D.L.; Urbanc, B.
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 ...
van Spronsen, C.S.A.M.
Human thoughts and behavior are the outcome of communication between neurons in our brains. There is an entire world inside each of these neurons where transactions are established and meeting points are set. By using molecular motors to transport proteins and organelles along cytoskeletal tracks, neurons create the internal order of the bustling community of macromolecules. Given the challenging geometry of the neuron, the mechanisms that deliver fuel and materials to sustain the distant syn...
Wallach, Gilad; Lallouette, Jules; Herzog, Nitzan; De Pittà, Maurizio; Ben Jacob, Eshel; Berry, Hugues; Hanein, Yael
Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocyt...
Campbell, Jacob; Singh, Dipika; Hollett, Geoffrey; Dravid, Shashank M; Sailor, Michael J.; Arikkath, Jyothi
Synaptic activity is intimately linked to neuronal structure and function. Stimulation of live cultured primary neurons, coupled with fluorescent indicator imaging, is a powerful technique to assess the impact of synaptic activity on neuronal protein trafficking and function. Current technology for neuronal stimulation in culture include chemical techniques or microelectrode or optogenetic based techniques. While technically powerful, chemical stimulation has limited spatial resolution and mi...
Kohring, G. A.
Artificial neurons with arbitrarily complex internal structure are introduced. The neurons can be described in terms of a set of internal variables, a set activation functions which describe the time evolution of these variables and a set of characteristic functions which control how the neurons interact with one another. The information capacity of attractor networks composed of these generalized neurons is shown to reach the maximum allowed bound. A simple example taken from the domain of p...
da Silva Serra, I.; Husson, Z.; Bartlett, J.D.; Smith, E.S.J.
Background A wide range of stimuli can activate sensory neurons and neurons innervating specific tissues often have distinct properties. Here, we used retrograde tracing to identify sensory neurons innervating the hind paw skin (cutaneous) and ankle/knee joints (articular), and combined immunohistochemistry and electrophysiology analysis to determine the neurochemical phenotype of cutaneous and articular neurons, as well as their electrical and chemical excitability. Results Immunohistoche...