bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gamma Oscillation by Synaptic Inhibition in a Hippocampal Interneuronal Network Model
Authors: Wang Xiao-Jing , Buzsáki György 
Published: April 2018

Fast neuronal oscillations (gamma, 20–80 Hz) have been observed in the neocortex and hippocampus during behavioral arousal. Using computer simulations, we investigated the hypothesis that such rhythmic activity can emerge in a random network of interconnected GABAergic fast-spiking interneurons. Specific conditions for the population synchronization, on properties of single cells and the circuit, were identified. These include the following: (1) that the amplitude of spike afterhyperpolarization be above the GABAAsynaptic reversal potential; (2) that the ratio between the synaptic decay time constant and the oscillation period be sufficiently large; (3) that the effects of heterogeneities be modest because of a steep frequency–current relationship of fast-spiking neurons. Furthermore, using apopulation coherencemeasure, based on coincident firings of neural pairs, it is demonstrated that large-scale network synchronization requires a critical (minimal) average number of synaptic contacts per cell, which is not sensitive to the network size.By changing the GABAAsynaptic maximal conductance, synaptic decay time constant, or the mean external excitatory drive to the network, the neuronal firing frequencies were gradually and monotonically varied. By contrast, the network synchronization was found to be high only within a frequency band coinciding with the gamma (20–80 Hz) range. We conclude that the GABAAsynaptic transmission provides a suitable mechanism for synchronized gamma oscillations in a sparsely connected network of fast-spiking interneurons. In turn, the interneuronal network can presumably maintain subthreshold oscillations in principal cell populations and serve to synchronize discharges of spatially distributed neurons.
Differential Expression of Bone Morphogenetic Proteins in the Developing Vestibular and Auditory Sensory Organs
Authors: Oh Seung-Ha , Johnson Randy , Wu Doris K. 
Published: April 2018

The genes responsible for the formation of various sensory organs in the inner ear are not known. There are eight sensory organs in the chick inner ear, and our previous study showed that all presumptive sensory organs initially express bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor (TGF)-β gene family. To address the potential role of BMPs in the patterning of different sensory organ structures, we investigated the expression of BMP4, BMP5, and BMP7 during sensory organ differentiation in the chick inner ear. The gene expression pattern of BMP5, although similar to that of BMP4, was transient and disappeared by embryonic day 3.5 (E3.5). In contrast, BMP7 gene expression was quite extensive, starting in the otic placode. By E5, gene expression patterns of BMP4 and BMP7 differed among vestibular and auditory sensory organs. In the vestibular sensory organs, BMP7 gene expression segregated from the main sensory tissue areas at the onset of differentiation, whereas BMP4 expression concentrated in supporting cells. In the cochlea, however, BMP7 gene expression became restricted to sensory tissue over time and eventually concentrated in supporting cells, whereas BMP4 gene expression was localized to hair cells. The different BMP expression patterns in developing auditory and vestibular sensory organs may help to shape each respective sensory structure. Furthermore, the expression of BMP4 in the cochlea also revealed an interesting pattern of sensory cell differentiation: the distal portion of the cochlea differentiates first, and the tall hair cells develop before the short hair cells.
Suppression of Noxious Stimulus-Evoked Activity in the Ventral Posterolateral Nucleus of the Thalamus by a Cannabinoid Agonist: Correlation between Electrophysiological and Antinociceptive Effects
Authors: Martin William J. , Hohmann Andrea G. , Walker J. Michael 
Published: April 2018

The CNS contains a putative cannabinergic neurotransmitter and an abundance of G-protein-coupled cannabinoid receptors. However, little is known about the function of this novel neurochemical system. Cannabinoid agonists produce antinociception in behavioral tests, suggesting the possibility that this system serves in part to modulate pain sensitivity. To explore this possibility, the effects of the cannabinoid agonist WIN 55,212-2 on nociceptive neurons in the ventroposterolateral (VPL) nucleus of the thalamus were examined in urethane-anesthetized rats. After identification of a nociresponsive neuron, a computer-controlled device delivered graded pressure stimuli to the contralateral hindpaw. WIN 55,212-2 (0.0625, 0.125, and 0.25 mg/kg, i.v.) suppressed noxious stimulus-evoked activity of VPL neurons in a dose-dependent and reversible manner. Noxious stimulus-evoked firing was affected more than spontaneous firing. These effects were apparently mediated by cannabinoid receptors, because the cannabinoid receptor-inactive enantiomer of the drug (WIN 55,212–3, 0.25 mg/kg) failed to alter the activity of this population of cells. Administration of morphine (0.5 mg/kg, i.v.) produced effects that were very similar to those produced by the cannabinoid. WIN 55,212-2 (0.25 mg/kg, i.v.) failed to alter the responses of non-nociceptive low-threshold mechanosensitive neurons in the VPL. WIN 55,212-2 produced antinociceptive effects with a potency and time course similar to that observed in the electrophysiological experiments, despite the differences in the anesthetic states of the animals used in these experiments. The antinociceptive and electrophysiological effects on VPL neurons outlasted the motor effects of the drug. Furthermore, the changes in nociceptive responding could not be attributed to changes in skin temperature. Taken together, these findings suggest that cannabinoids decrease nociceptive neurotransmission at the level of the thalamus and that one function of endogenous cannabinoids may be to modulate pain sensitivity.
Plastic Neuronal Remodeling Is Impaired in Patients with Alzheimer’s Disease Carrying Apolipoprotein ε4 Allele
Authors: Arendt Thomas , Schindler Cornelia , Brückner Martina K. , Eschrich Klaus , Bigl Volker , Zedlick Dyrk , Marcova Lena 
Published: April 2018

A relationship between the apolipoprotein E (apoE) genotype and the risk to develop Alzheimer’s disease has been established recently. Apolipoprotein synthesis is implicated in developmental processes and in neuronal repair of the adult nervous system.In the present study, we investigated the influence of the apolipoprotein polymorphism on the severity of neuronal degeneration and the extent of plastic dendritic remodeling in Alzheimer’s disease. Changes in length and arborization of dendrites of Golgi-impregnated neurons in the basal nucleus of Meynert, locus coeruleus, raphe magnus nucleus, medial amygdaloid nucleus, pedunculopontine tegmental nucleus, and substantia nigra were analyzed after three-dimensional reconstruction. Patients with either one or two apoE ε4 alleles not only showed a more severe degeneration in all areas investigated than in patients lacking the apoE 4 allele but also revealed significantly less plastic dendritic changes. ApoE ε4 allele copy number, furthermore, had a significant effect on the pattern of dendritic arborization. Moreover, the relationship between the intensity of dendritic growth and both the extent of neuronal degeneration and the stage of the disease seen in patients lacking the apoE ε4 allele was very weak in the presence of one ε4 allele and completely lost in patients homozygous for the ε4 allele.The results provide direct evidence that neuronal reorganization is affected severely in patients with Alzheimer’s disease carrying the apoE ε4 allele. This impairment of neuronal repair might lead to a more rapid functional decompensation, thereby contributing to an earlier onset and more rapid progression of the disease.
A Test of the Excitability-Gradient Hypothesis in the Swimmeret System of Crayfish
Authors: Mulloney Brian 
Published: April 2018

The motor pattern that drives coordinated movements of swimmerets in different segments during forward swimming characteristically begins with a power-stroke by the most posterior limbs, followed progressively by power-strokes of each of the more anterior limbs. To explain this caudal-to-rostral progression, the hypothesis was proposed that the neurons that drive the most posterior swimmerets are more excitable than their more anterior counterparts, and so reach threshold first.To test this excitability-gradient hypothesis, I used carbachol to excite expression of the swimmeret motor pattern and used tetrodotoxin (TTX), sucrose solutions, and cutting to block the flow of information between anterior and posterior segments. I showed that the swimmeret activity elicited by carbachol is like that produced when the swimmeret system is spontaneously active and that blocking an intersegmental connective uncoupled swimmeret activity on opposite sides of the block.When anterior and posterior segments were isolated from each other, the frequencies of the motor patterns expressed by anterior segments were not slower than those expressed by posterior segments exposed to the same concentrations of carbachol. This result was independent of the concentration of carbachol applied and of the number of segmental ganglia that remained connected. When TTX was used to block information flow, the motor patterns produced in segments anterior to the block were significantly faster than those from segments posterior to the block.These observations contradict the predictions of the excitability-gradient hypothesis and lead to the conclusion that the hypothesis is incorrect.
Temporal Integration and Duration Tuning in the Dorsal Zone of Cat Auditory Cortex
Authors: He Jufang , Hashikawa Tsutomu , Ojima Hisayuki , Kinouchi Yohsuke 
Published: April 2018

The present study examined auditory cortical neurons, the responses of which depended on the duration of noise bursts. We recorded from 150 neurons with response latencies exceeding 30 msec and from 28 neurons with OFF responses to auditory stimuli in the dorsal zone of cat auditory cortex. Of 150 long-latency neurons, 132 displayed some form of duration selectivity. Seventy-eight were classified as selective for long durations. Among the long-duration-selective neurons, 30 responded only to noise burst stimuli with durations longer than a minimal threshold and were classified further as duration threshold neurons. Of 132 duration-selective neurons, 41 responded selectively to noise bursts of short duration; 13 showed maximal responses to noise bursts of a particular duration and could be regarded as duration-tuned neurons. OFF-response neurons included ones that were long-duration-selective, duration-tuned, and nonduration-selective.Duration tuning has been described previously only at the midbrain level in amphibians and bats. The present finding of sensitivity to sound duration in at least one region of cat auditory cortex indicates that this form of neural tuning may be important for hearing in all vertebrates, and for processing of sound at multiple levels in the auditory pathway. The duration tuning in the cat auditory cortex was much broader, and the best duration was distributed over a wider range than in the bat inferior colliculus. We suggest that the duration selectivity of the long-latency neurons results from integration along the time domain of a stimulus during the latent period.
An Antibody to the Tetraspan Membrane Protein CD9 Promotes Neurite Formation in a Partially α3β1 Integrin-Dependent Manner
Authors: Banerjee Shilpi A. , Hadjiargyrou Michael , Patterson Paul H. 
Published: April 2018

The tetraspan cell surface glycoprotein, CD9, has been implicated in cellular signaling during growth and differentiation in the hematopoietic and nervous systems. Because CD9 expression is induced early in development in sensory and sympathetic neuroblasts, we investigated the role of CD9 in neurite outgrowth. We plated dissociated cells from neonatal sympathetic ganglia on immobilized anti-CD9 antibodies or antibodies against other cell surface molecules. We show here that B2C11, an anti-CD9 antibody that has been shown previously to activate Schwann cellsin vitro, promotes robust neurite outgrowth from sympathetic neurons that is greater than that on other antibody surfaces and is comparable to neurite outgrowth on a collagen substratum. In addition, B2C11 causes dramatic morphological changes in neurons and glia from dissociated ganglia, including a flattening of these cells.Because CD9 interacts with integrins in many cell types including Schwann cells, and specifically with the α3β1 integrin in some cells, we tested whether the effect of B2C11 on neurite outgrowth is mediated by this integrin. An anti-α3β1 antibody, Ralph 3–1, attenuates the extent of neurite outgrowth on B2C11 and collagen, but not on laminin. Because the α3β1 integrin has been shown to mediate neurite outgrowth on different substrates, these results provide a functional significance for the CD9-α3β1 interaction; downstream signaling may be activated by thiscisinteraction on the cell surface in response to external cues that promote neurite outgrowth.
Presynaptic Control of Subunit Composition of NMDA Receptors Mediating Synaptic Plasticity
Authors: Gottmann Kurt , Mehrle Alexander , Gisselmann Günter , Hatt Hanns 
Published: April 2018

Subunit composition of subsynaptic transmitter receptors is controlled presynaptically in the developing neuromuscular junction. To investigate presynaptic regulation of NMDA receptor subunit composition in the CNS, we co-cultured different types of hippocampal explants with dissociated target neurons. Postsynaptic NMDA receptors were studied using whole-cell patch-clamp recordings.After 1 week in culture with innervation by dentate gyrus (dg) explants, the kinetic and pharmacological properties of postsynaptic NMDA receptors indicated the expression of NMDA receptor subtypes containing NR2B subunits (NR1/NR2A/NR2B or NR1/NR2B or both). The properties of NMDA receptors in noninnervated neurons were similar to those of neurons innervated by dg explants. In contrast, after innervation by explants from the cornu ammonis (CA) region, we found an additional NMDA receptor subtype with properties consistent with the subunit composition NR1/NR2A. These findings indicate that presynaptic signals determine NMDA receptor subunit composition.After prolonged cultivation (11–12 d) the properties of synaptic NMDA receptors in the majority of dg-innervated neurons also indicated the expression of NR1/NR2A receptors. This suggests a delayed developmental maturation of NMDA receptors in dg-innervated neurons.Long-term plasticity of central glutamatergic synapses is critically influenced by the subunit composition of NMDA receptors, and thus presynaptic control of NMDA receptor subunit composition might regulate synaptic plasticity.
Functional Neuroanatomy of Human Slow Wave Sleep
Authors: Maquet Pierre , Degueldre Christian , Delfiore Guy , Aerts Joël , Péters Jean-Marie , Luxen André , Franck Georges 
Published: April 2018

The distribution of regional cerebral blood flow (rCBF) was estimated during sleep and wakefulness by using H215O positron emission tomography (PET) and statistical parametric mapping. A group analysis on 11 good sleepers (8 with steady slow wave sleep, SWS) showed a significant negative correlation between the occurrence of SWS and rCBF in dorsal pons and mesencephalon, thalami, basal ganglia, basal forebrain/hypothalamus, orbitofrontal cortex, anterior cingulate cortex, precuneus, and, on the right side, in a region that follows the medial aspect of the temporal lobe. Given the known decrease in global cerebral blood flow levels during SWS, these negative correlations suggest that rCBF is decreased significantly more in these cerebral areas than in the rest of the brain.The marked rCBF decreases in the pons, mesencephalon, thalamic nuclei, and basal forebrain reflect their close implication in the generation of SWS rhythms. The influence of these rhythms on the telencephalon usually are thought to be global and homogeneous. In contrast, our results show that rCBF is decreased more in some cortical areas (especially in orbitofrontal cortex) than in the rest of the cortex. We hypothesize that cellular processes taking place during SWS might be modulated differently in these regions.Given the functions of the ventromedial frontal areas, we surmise that SWS might be particularly critical for the adaptation of behavior to environmental pressures. This hypothesis is supported indirectly by results of sleep deprivation experiments.
Differential Roles of Apamin- and Charybdotoxin-Sensitive K+Conductances in the Generation of Inferior Olive RhythmicityIn Vivo
Authors: Lang E. J. , Sugihara I. , Llinás R. 
Published: April 2018

The basic electrical rhythmicity of the olivocerebellar system was investigatedin vivousing multiple electrode recordings of Purkinje cell (PC) complex spike (CS) activity. CSs demonstrate a 10 Hz rhythmicity, thought to result from the interaction of Ca2+and Ca2+-dependent K+conductances present in inferior olivary (IO) neurons. To assess the roles of different K+channels in generating this rhythmicity, intraolivary microinjections of charybdotoxin (CTX) and apamin were used. Both K+channel blockers increased average CS spike-firing rates. However, apamin produced a tonic increase in firing with a decrement in the CS rhythmicity. In contrast, after CTX administration, highly rhythmic CS discharges were interleaved with silent periods, suggesting that apamin- and CTX-sensitive K+channels have distinct rhythmogenic roles in IO neurons. CTX-sensitive channels seem to be functionally coupled to low threshold Ca2+channels, whereas the apamin-sensitive channels relate to high threshold Ca2+channels.Blocking intraolivary GABAAreceptors increases IO excitability and the spatial distribution of synchronized CS activity while disrupting its rostrocaudal banding pattern (Lang et al., 1996). The present experiments show that K+channel blockers increase IO excitability without causing widespread synchronization of CS activity. Thus, changes in the IO excitability have relatively little effect in determining the spatial organization of CS synchrony. In contrast, the degree of CS rhythmicity seemed to influence the patterns of CS synchrony. Thus, after CTX, increased CS rhythmicity was associated with increased intraband synchrony and decreased interband synchrony, whereas apamin had the opposite effects on intra- and interband synchronization.
Comparison of N- and P/Q-Type Voltage-Gated Calcium Channel Current Inhibition
Authors: Currie Kevin P. M. , Fox Aaron P. 
Published: April 2018

Activation of N- and P/Q-type voltage-gated calcium channels triggers neurotransmitter release at central and peripheral synapses. These channels are targets for regulatory mechanisms, including inhibition by G-protein-linked receptors. Inhibition of P/Q-type channels has been less well studied than the extensively characterized inhibition of N-type channels, but it is thought that they are inhibited by similar mechanisms although possibly to a lesser extent than N-type channels. The aim of this study was to compare the inhibition of the two channel types.Calcium currents were recorded from adrenal chromaffin cells and isolated by the selective blockers ω-conotoxin GVIA (1 μm) and ω-agatoxin IVA (400 nm). The inhibition was elicited by ATP (100 μm) or intracellular application of GTP-γ-S. It was classified as voltage-sensitive (relieved by a conditioning prepulse) or voltage-insensitive (present after a conditioning prepulse). The voltage-insensitive inhibition accounted for a 20% reduction of both currents, whereas the voltage-sensitive inhibition reduced the N-type current by 45% but the P/Q-type current by 18%. However, the voltage dependence of the inhibition, the time course of relief from inhibition during a conditioning prepulse, and the time course of reinhibition after such a prepulse showed few differences between the N- and P/Q-type channels. Assuming a simple bimolecular reaction, our data suggest that changes in the kinetics of the G-protein/channel interaction alone cannot explain the differences in the inhibition of the N- and P/Q-type calcium channels. The subtle differences in inhibition may facilitate the selective regulation of neurotransmitter release.
GABA Activity Mediating Cytosolic Ca2+Rises in Developing Neurons Is Modulated by cAMP-Dependent Signal Transduction
Authors: Obrietan Karl , van den Pol Anthony N. 
Published: April 2018

In the majority of developing neurons, GABA can exert depolarizing actions, thereby raising neuronal Ca2+. Ca2+elevations can have broad consequences during development, inducing gene expression, altering neurite outgrowth and growth cone turning, activating enzyme pathways, and influencing neuronal survival. We used fura-2 and fluo-3 Ca2+digital imaging to assess the effects of inhibiting or activating the cAMP signal transduction pathway on GABA activity mediating Ca2+rises during the early stages ofin vitrohypothalamic neural development. Our experiments stemmed from the finding that stimulation of transmitter receptors shown to either activate or inhibit adenylyl cyclase activity caused a rapid decrease in Ca2+rises mediated by synaptically released GABA.Both the adenylyl cyclase activator forskolin and the inhibitor SQ-22,536 reduced the Ca2+rise elicited by the synaptic release of GABA. Bath application of the membrane-permeable cAMP analogs 8-bromo-cAMP (8-Br-cAMP) or 8-(4-chlorophenylthio)-cAMP (0.2–5 mm) produced a rapid, reversible, dose-dependent inhibition of Ca2+rises triggered by synaptic GABA release. Potentiation of GABAergic activity mediating Ca2+rises was observed in some neurons at relatively low concentrations of the membrane-permeable cAMP analogs (20–50 μm). In the presence of tetrodotoxin (TTX), postsynaptic Ca2+rises triggered by the bath application of GABA were only moderately depressed (13%) by 8-Br-cAMP (1 mm), suggesting that the inhibitory effects of 8-Br-cAMP were largely the result of a presynaptic mechanism.The protein kinase A (PKA) inhibitors H89 and Rp-3′,5′-cyclic monophosphothioate triethylamine also caused a large reduction (>70%) in Ca2+rises triggered by synaptic GABA release. Unlike the short-term depression elicited by activation of the cAMP signal transduction pathway, Ca2+depression elicited by PKA inhibition persisted for an extended period (>30 min) after PKA inhibitor washout. Postsynaptic depression of GABA-evoked Ca2+rises triggered by H89 (in the presence of TTX) recovered rapidly, suggesting that the extended depression observed during synaptic GABA release was largely through a presynaptic mechanism. Long-term Ca2+modulation by cAMP-regulating hypothalamic peptides may be mediated through a parallel mechanism.Together, these results suggest that GABAergic activity mediating Ca2+rises is dependent on ongoing PKA activity that is maintained within a narrow zone for GABA to elicit a maximal Ca2+elevation. Thus, neuromodulator-mediated changes in the cAMP-dependent signal transduction pathway (activation or inhibition) could lead to a substantial decrease in GABA-mediated Ca2+rises during early development.