bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of Dendritic Calcium Signaling in Fly Neurons
Authors: Oertner Thomas G. , Brotz Tilmann M. , Borst Alexander
Published: December 2017

We examined the mechanisms underlying dendritic calcium accumulation in lobula plate tangential cells of the fly visual system using an in vitro preparation of the fly brain. Local visual stimulation evokes a localized calcium signal in the dendrites of these cells in vivo. Here we show that a similar localized calcium accumulation can be elicited in vitro by focal iontophoretic application of the cholinergic agonist carbachol. The calcium signal had at least two sources: first, voltage-dependent calcium channels contributed to the carbachol-induced signal and were concentrated on the dendrite, the soma, and the terminal ramification of the axon. However, the dendritic calcium signal induced by carbachol stimulation was only weakly dependent on membrane depolarization. The most likely explanation for the second, voltage-independent part of the dendritic calcium signal is calcium entry through nicotinic acetylcholine receptors. We found no indication of second-messenger or calcium-mediated calcium release from intracellular stores. In summary, the characteristic spatiotemporal calcium signals in the dendrites of lobula plate tangential cells can be reproduced in vitro, and result from a combination of voltage- and ligand-gated calcium influx.
Information Theoretic Analysis of Pulmonary Stretch Receptor Spike Trains
Authors: Rogers Robert F. , Runyan Jacob D. , Vaidyanathan A. Ganesh , Schwaber James S.
Published: December 2017

Primary afferent neurons transduce physical, continuous stimuli into discrete spike trains. Investigators have long been interested in interpreting the meaning of the number or pattern of action potentials in attempts to decode the spike train back into stimulus parameters. Pulmonary stretch receptors (PSRs) are visceral mechanoreceptors that respond to deformation of the lungs and pulmonary tree. They provide the brain stem with feedback that is used by cardiorespiratory control circuits. In anesthetized, paralyzed, artificially ventilated rabbits, we recorded the action potential trains of individual PSRs while continuously manipulating ventilator rate and volume. We describe an information theoretic-based analytical method for evaluating continuous stimulus and spike train data that is of general applicability to any continuous, dynamic system. After adjusting spike times for conduction velocity, we used a sliding window to discretize the stimulus (average tracheal pressure) and response (number of spikes), and constructed co-occurrence matrices. We systematically varied the number of categories into which the stimulus and response were evenly divided at 26 different sliding window widths (5, 10, 20, 30, … , 230, 240, 250 ms). Using the probability distributions defined by the co-occurrence matrices, we estimated associated stimulus, response, joint, and conditional entropies, from which we calculated information transmitted as a fraction of the maximum possible, as well as encoding and decoding efficiencies. We found that, in general, information increases rapidly as the sliding window width increases from 5 to ∼50 ms and then saturates as observation time increases. In addition, the information measures suggest that individual PSRs transmit more “when” than “what” type of information about the stimulus, based on the finding that the maximum information at a given window width was obtained when the stimulus was divided into just a few (usually <6) categories. Our results indicate that PSRs provide quite reliable information about tracheal pressure, with each PSR conveying about 31% of the maximum possible information about the dynamic stimulus, given our analytical parameters. When the stimulus and response are divided into more categories, slightly less information is transmitted, and this quantity also saturates as a function of observation time. We consider and discuss the importance of information contained in window widths on the time scales of an excitatory postsynaptic potential and Hering-Breuer reflex central delay.
Alterations in Development, Behavior, and Physiology inDrosophilaLarva That Have Reduced Ecdysone Production
Authors: Li Hao , Harrison Doug , Jones Grace , Jones Davy , Cooper Robin L.
Published: December 2017

We investigated behavior, physiology, sensitivity to exogenous application of ecdysone, and nerve terminal structure for differences between the reduced ecdysone genotype, ecd1/ecd1, and wild-type control ecd1/TM6Banimals during the early and late third instars when raised at 25°C. The ecd1mutants were able to survive through larval development and form pupae. However, the results demonstrate that the time to pupation is lengthened by about 50 h for the ecd1/ecd1as compared with the wild-type control siblings. In addition to the lengthened larval cycle in the mutant, ecd1/ecd1animals, they also display behavioral differences as compared with controls. The rate of body wall contraction and mouth hook movements are reduced in the early third instar of ecd1/ecd1as compared with controls. The physiological measure of excitatory junction potential amplitude for the combined Is and Ib terminals did not reveal any differences among the two genotypes during the early third instar but the synaptic strength is reduced in the late third instars for controls. Application of exogenous ecdysone is still effective during the late third instar for the ecd1/ecd1but not the controls. This suggests that endogenous production of ecdysone have already taken place in the wild-type but not the ecd1/ecd1larvae, thus the rapid nongenomic responses could still be observed in the late third ecd1/ecd1larvae. Structurally the number of varicosities and the terminal length showed significant differences between ecd1/ecd1and the wild-type ecd1/TM6B genotype in the late third instars.
Spinal Interneurons That Receive Input From Muscle Afferents Are Differentially Modulated by Dorsolateral Descending Systems
Authors: Chen Daofen , Theiss Renee D. , Ebersole Koji , Miller John F. , Rymer W. Zev , Heckman C. J.
Published: December 2017

The possibility that descending systems have differential actions on the spinal interneurons that receive input from muscle afferents was investigated. Prolonged, physiological inputs were generated by stretch of the triceps surae muscles. The resulting firing patterns of 25 lumbosacral interneurons were recorded before and during a reversible cold block of the dorsolateral white matter at the thoracic level in nonparalyzed, decerebrate preparations. The strength of group I muscle afferent input was assessed from the response to sinusoidal tendon vibration, which activated muscle spindle Ia afferents directly and tendon organ Ib afferents via the resulting reflex force. The stretch-evoked responses of interneurons with strong responses to vibration were markedly suppressed by dorsal cold block, whereas the stretch-evoked responses of interneurons with weak vibration input were enhanced. The cells most strongly activated by vibration received their primary input from Ia afferents and all of these cells were inhibited by the cold block. These results suggest that a disruption of the descending system, such as occurs in spinal cord injury, will lead to a suppression of the interneuronal pathways with group Ia input while enhancing excitability within interneuronal pathways transmitting actions from higher threshold afferents. One possible consequence of this suppression would be a decreased activity among the Ia inhibitory interneurons that mediate reciprocal inhibition, resulting in abnormal reciprocal relations between antagonists and promoting anomalous muscle cocontraction.
Propofol Anesthesia and Cerebral Blood Flow Changes Elicited by Vibrotactile Stimulation: A Positron Emission Tomography Study
Authors: Bonhomme V. , Fiset P. , Meuret P. , Backman S. , Plourde G. , Paus T. , Bushnell M. C. , Evans A. C.
Published: December 2017

We investigated the effects of the general anesthetic agent propofol on cerebral structures involved in the processing of vibrotactile information. Using positron emission tomography (PET) and the H2 15O bolus technique, we measured regional distribution of cerebral blood flow (CBF) in eight healthy human volunteers. They were scanned under five different levels of propofol anesthesia. Using a computer-controlled infusion, the following plasma levels of propofol were targeted: Level W (Waking, 0 μg/ml), Level 1 (0.5 μg/ml), Level 2 (1.5 μg/ml), Level 3 (3.5 μg/ml), and Level R (Recovery). At each level of anesthesia, two 3-min scans were acquired with vibrotactile stimulation of the right forearm either on or off. The level of consciousness was evaluated before each scan by the response of the subject to a verbal command. At Level W, all volunteers were fully awake. They reported being slightly drowsy at Level 1, they had a slurred speech and slow response at Level 2, and they were not responding at all at Level 3. The following variations in regional CBF (rCBF) were observed. During the waking state (Level W), vibrotactile stimulation induced a significant rCBF increase in the left thalamus and in several cortical regions, including the left primary somatosensory cortex and the left and right secondary somatosensory cortex. During anesthesia, propofol reduced in a dose-dependent manner rCBF in the thalamus as well as in a number of visual, parietal, and prefrontal cortical regions. At Level 1 through 3, propofol also suppressed vibration-induced increases in rCBF in the primary and secondary somatosensory cortex, whereas the thalamic rCBF response was abolished only at Level 3, when volunteers lost consciousness. We conclude that propofol interferes with the processing of vibrotactile information first at the level of the cortex before attenuating its transfer through the thalamus.
Synaptically Activated Calcium Responses in Dendrites of Hippocampal Oriens-Alveus Interneurons
Authors: Gee Christine E. , Woodhall Gavin , Lacaille Jean-Claude
Published: December 2017

Activation of metabotropic glutamate receptors (mGluRs) by agonists increases intracellular calcium levels ([Ca2+]i) in interneurons of stratum oriens/alveus (OA) of the hippocampus. We examined the mechanisms that contribute to dendritic Ca2+ increases in these interneurons during agonist activation of mGluRs and during synaptically evoked burst discharges, using simultaneous whole cell recordings and confocal Ca2+ imaging in rat hippocampal slices. First, we found that the group I/II mGluR agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD; 100 μM) increased dendritic [Ca2+]i and depolarized OA interneurons. Dendritic Ca2+ responses were correlated with membrane depolarizations, but Ca2+ responses induced by ACPD were larger in amplitude than those elicited by equivalent somatic depolarization. Next, we used linescans to measure changes in dendritic [Ca2+]i during synaptically evoked burst discharges and somatically elicited repetitive firing in disinhibited slices. Dendritic Ca2+ signals and electrophysiological responses were stable over repeated trials. Peak Ca2+responses were linearly related to number and frequency of action potentials in burst discharges for both synaptic and somatic stimulation, but the slope of the relationship was steeper for responses evoked somatically. Synaptically evoked [Ca2+]i rises and excitatory postsynaptic potentials were abolished by antagonists of ionotropic glutamate receptors. The group I/II mGluR antagonist S-α-methyl-4-carboxyphenylglycine (500 μM) produced a significant partial reduction of synaptically evoked dendritic Ca2+ responses. The mGluR antagonist did not affect synaptically evoked burst discharges and did not reduce either Ca2+ responses or burst discharges evoked somatically. Therefore ionotropic glutamate receptors appear necessary for synaptically evoked dendritic Ca2+ responses, and group I/II mGluRs may contribute partially to these responses. Dendritic [Ca2+]i rises mediated by both ionotropic and metabotropic glutamate receptors may be important for synaptic plasticity and the selective vulnerability to excitotoxicity of OA interneurons.
Receptor-Stimulated Phospholipase A2Liberates Arachidonic Acid and Regulates Neuronal Excitability Through Protein Kinase C
Authors: Muzzio Isabel A. , Gandhi Chetan C. , Manyam Upendra , Pesnell Aarron , Matzel Louis D.
Published: December 2017

Type B photoreceptors in Hermissendaexhibit increased excitability (e.g., elevated membrane resistance and lowered spike thresholds) consequent to the temporal coincidence of a light-induced intracellular Ca2+increase and the release of GABA from presynaptic vestibular hair cells. Convergence of these pre- and postsynaptically stimulated biochemical cascades culminates in the activation of protein kinase C (PKC). Paradoxically, exposure of the B cell to light alone generates an inositol triphosphate-regulated rise in diacylglycerol and intracellular Ca2+, co-factors sufficient to stimulate conventional PKC isoforms, raising questions as to the unique role of synaptic stimulation in the activation of PKC. GABA receptors on the B cell are coupled to G proteins that stimulate phospholipase A2(PLA2), which is thought to regulate the liberation of arachidonic acid (AA), an “atypical” activator of PKC. Here, we directly assess whether GABA binding or PLA2stimulation liberates AA in these cells and whether free AA potentiates the stimulation of PKC. Free fatty-acid was estimated in isolated photoreceptors with the fluorescent indicator acrylodan-derivatized intestinal fatty acid-binding protein (ADIFAB). In response to 5 μM GABA, a fast and persistent increase in ADIFAB emission was observed, and this increase was blocked by the PLA2inhibitor arachidonyltrifluoromethyl ketone (50 μM). Furthermore, direct stimulation of PLA2by melittin (10 μM) increased ADIFAB emission in a manner that was kinetically analogous to GABA. In response to simultaneous exposure to the stable AA analogue oleic acid (OA, 20 μM) and light (to elevate intracellular Ca2+), B photoreceptors exhibited a sustained (>45 min) increase in excitability (membrane resistance and evoked spike rate). The excitability increase was blocked by the PKC inhibitor chelerythrine (20 μM) and was not induced by exposure of the cells to light alone. The increase in excitability in the B cell that followed exposure to light and OA persisted for ≥90 min when the pairing was conducted in the presence of the protein synthesis inhibitor anisomycin (1 μm), suggesting that the synergistic influence of these signaling agents on neuronal excitability did not require new protein synthesis. These results indicate that GABA binding to G-protein-coupled receptors on Hermissenda B cells stimulates a PLA2signaling cascade that liberates AA, and that this free AA interacts with postsynaptic Ca2+to synergistically stimulate PKC and enhance neuronal excitability. In this manner, the interaction of postsynaptic metabotropic receptors and intracellular Ca2+may serve as the catalyst for some forms of associative neuronal/synaptic plasticity.
Frequency Dependence of Spike Timing Reliability in Cortical Pyramidal Cells and Interneurons
Authors: Fellous J.-M. , Houweling A. R. , Modi R. H. , Rao R.P.N. , Tiesinga P.H.E. , Sejnowski T. J.
Published: December 2017

Pyramidal cells and interneurons in rat prefrontal cortical slices exhibit subthreshold oscillations when depolarized by constant current injection. For both types of neurons, the frequencies of these oscillations for current injection just below spike threshold were 2–10 Hz. Above spike threshold, however, the subthreshold oscillations in pyramidal cells remained low, but the frequency of oscillations in interneurons increased up to 50 Hz. To explore the interaction between these intrinsic oscillations and external inputs, the reliability of spiking in these cortical neurons was studied with sinusoidal current injection over a range of frequencies above and below the intrinsic frequency. Cortical neurons produced 1:1 phase locking for a limited range of driving frequencies for fixed amplitude. For low-input amplitude, 1:1 phase locking was obtained in the 5- to 10-Hz range. For higher-input amplitudes, pyramidal cells phase-locked in the 5- to 20-Hz range, whereas interneurons phase-locked in the 5- to 50-Hz range. For the amplitudes studied here, spike time reliability was always highest during 1:1 phase-locking, between 5 and 20 Hz for pyramidal cells and between 5 and 50 Hz for interneurons. The observed differences in the intrinsic frequency preference between pyramidal cells and interneurons have implications for rhythmogenesis and information transmission between populations of cortical neurons.
Hierarchical Equivalence of Somatosensory Areas I and II for Tactile Processing in the Cerebral Cortex of the Marmoset Monkey
Authors: Zhang H. Q. , Zachariah M. K. , Coleman G. T. , Rowe M. J.
Published: December 2017

Responsiveness of the first somatosensory area (SI) of the cerebral cortex was investigated in the marmoset monkey ( Callithrix jacchus) in association with cooling-induced, reversible inactivation of the second somatosensory area, SII. The aim was to determine whether SI responsiveness to peripheral tactile stimulation depends on SII and therefore whether SI and SII in the marmoset occupy hierarchically equivalent positions in a parallel organizational scheme for thalamocortical tactile processing as appears to be the case in nonprimate mammals. Inactivation of SII was achieved when the temperature over SII was lowered to ≤12°C, as indicated by abolition of the SII-evoked potentials generated by brief tap stimuli to the hand or foot, and by abolition of tactile responses in single SII neurons located at the margin beneath the block. The effect of SII inactivation on SI-evoked potentials was examined in 16 experiments by simultaneous recording of the SI- and SII-evoked potentials. SI-evoked potentials were never abolished and remained unaffected in 11 cases. In three experiments there was a small reduction in amplitude and inconsistent effects in the remaining two. Responsiveness to controlled tactile stimuli was examined quantitatively in 31 individual SI neurons of different functional classes before, during, and after the inactivation of SII. Tactile responsiveness in individual SI neurons was never abolished by SII inactivation, remaining unchanged in 20 neurons (65%) while undergoing some reduction in the remaining 11 SI neurons (35%). This reduction of tactile responsiveness in one-third of SI neurons is most likely attributable to a removal of a facilitatory influence emanating from SII, based on the observation that background activity of the affected neurons was also reduced. Furthermore, phase locking of SI responses to vibrotactile stimulation was unchanged when SII was inactivated. The retention of responsiveness in SI neurons when SII was inactivated by cooling in the marmoset demonstrates that tactile inputs can reach SI without traversing an indirect, serially organized path through SII. The present results, together with our previous observations that responsiveness in the majority of SII neurons survived SI inactivation, demonstrate that there is a parallel organization of the SI and SII areas for tactile processing in the marmoset monkey and that SI and SII occupy hierarchically equivalent positions in a parallel processing network. There is therefore no longer justification for the view that there are fundamental differences in the organization of thalamocortical tactile processing for SI and SII between simian primates, in general, and other mammals.
Visual Spatial Characterization of Macaque V1 Neurons
Authors: Sceniak Michael P. , Hawken Michael J. , Shapley Robert
Published: December 2017

This study characterizes the spatial organization of excitation and inhibition that influences the visual responses of neurons in macaque monkey's primary visual cortex (V1). To understand the spatial extent of excitatory and inhibitory influences on V1 neurons, we performed area-summation experiments with suprathreshold contrast stimulation. The extent of spatial summation and the magnitude of surround suppression were estimated quantitatively by analyzing the spatial summation experiments with a difference of Gaussians (DOG) model. The average extent of spatial summation is approximately the same across layers except for layer 6 cells, which tend to sum more extensively than cells in the other layers. On average, the extent of length and width summation is approximately equal. Across the population, surround suppression is greatest in layer 4B and weakest in layer 6. Estimates of summation and suppression are compared for the DOG (subtractive) model and a normalization (divisive) model. The two models yield quantitatively similar estimates of the extent of excitation and inhibition. However, the normalization (divisive) model predicts weaker surround strength than the DOG model.
Age-Related Changes in Lower Trunk Coordination and Energy Transfer During Gait
Authors: McGibbon Chris A. , Krebs David E.
Published: December 2017

The effects of aging on lower trunk ( trunk–low-back joint–pelvis) coordination and energy transfer during locomotion has received little attention; consequently, there are scant biomechanical data available for comparison with patient populations whose upper body movements may be impaired by orthopaedic or neurologic disorders. To address this problem, we analyzed gait data from a cross-sectional sample of healthy adults ( n = 93) between 20 and 90 yr old ( n = 44 elderly, >50 yr old; n = 49 young, <50 yr old). Gait characteristics of elders were mostly typical: gait speed of elders (1.13 ± 0.20 m/s) was significantly ( P = 0.007) lower than gait speed of young subjects (1.20 ± 0.18 m/s). Although elders had less low-back (trunk relative to pelvis) range of motion (ROM; P = 0.013) during gait than young subjects, no age-related differences were detected in absolute trunk and pelvis ROM or peak pitch angles during gait. Despite similar upper body postures, there was a strong association between age and pelvis-trunk angular velocity phase angle ( r = 0.48, P < 0.001) with zero phase occurring at approximately 55 yr of age; young subjects lead with the pelvis while elderly subjects lead with the trunk. Age related changes in gait speed and low-back ROM were unable to explain the above findings. The trunk-leading strategy used by elders resulted in a sense reversal of the low-back joint power curve and increased ( P = 0.013) the mechanical energy expenditure required for eccentric control of the lower trunk musculature during stance phase of gait. These data suggest an age-related change in the control of lower trunk movements during gait that preserves upper body posture and walking speed but requires a leading trunk and higher mechanical energy demands of lower trunk musculature—two factors that may reduce the ability to recover from dynamic instabilities. The behavioral and motor control aspects of these findings may be important for understanding locomotor impairment compensations in aging humans and in quantifying falls risk.
Medium Afterhyperpolarization and Firing Pattern Modulation in Interneurons of Stratum Radiatum in the CA3 Hippocampal Region
Authors: Savić Natas̆a , Pedarzani Paola , Sciancalepore Marina
Published: December 2017

Stratum (st.) radiatum interneurons represent a heterogeneous class of hippocampal cells with as yet poorly characterized physiological properties. Intracellular staining with biocytin, in situ hybridization, and patch-clamp recording have been combined to investigate the morphological and electrophysiological properties of these cells in the CA3 hippocampal region in young rats [ postnatal days 10 to 21 ( P10–21)]. Labeled cells presented a heterogeneous morphology with various soma shapes, often found multipolar, and dendritic arborizations confined to st. radiatum. The passive membrane properties of these st. radiatum interneurons showed instead no significant differences between P10 and P21. Low resting potential, high-input resistance, and short time constants characterized CA3 st. radiatum interneurons, which were silent at rest. Action potentials, elicited by brief current pulses, were lower and shorter than in pyramidal cells and followed by a Ca2+-dependent medium-duration afterhyperpolarizing potential (mAHP). Prolonged depolarizing current injection generated trains of action potentials that fired at constant frequency after a slight accommodation. The maximum steady-state firing rate was 31 ± 4 (SD) Hz. Hyperpolarizing current pulses revealed a prominent inward rectification characterized by a “sag,” followed by a depolarizing rebound that triggered action potentials. Sag and anodal brake excitation were blocked by Cs+, suggesting that they were mediated by a hyperpolarization-activated cation conductance ( I h). In the presence of tetrodotoxin and tetraethylammonium, biphasic tail currents were elicited in voltage clamp after a depolarizing step inducing Ca2+influx. Tail currents presented a fast Ca2+-activated and apamin-sensitive component ( I AHP) and were further reduced by carbachol. The presence of I AHP was consistent with the high expression level of the apamin-sensitive SK2 subunit transcript in CA3 st. radiatum interneurons as detected by in situ hybridization. Different pharmacological agents were shown to affect the afterhyperpolarizing potential as well as the firing properties of st. radiatum interneurons. Exposure to Ca2+-free solutions mainly affected the late phase of repolarization and strongly reduced the mAHP. The mAHP was also attenuated by carbachol and by apamin, suggesting it to be partly mediated by I AHP. Reduction of the mAHP increased the interneuron firing frequency. In conclusion, st. radiatum interneurons of CA3 hippocampal region represent a class of nonpyramidal cells with action potentials followed by an AHP of relatively short duration, partially generated by apamin and carbachol-sensitive conductances involved in the regulation of the cell firing rate.
Mixtures of Octopamine and Serotonin Have Nonadditive Effects on the CNS of the Medicinal Leech
Authors: Mesce Karen A. , Crisp Kevin M. , Gilchrist Laura S.
Published: December 2017

It is well established that neural networks respond to a wide variety of modulatory substances by which they can become reconfigured, yet few studies have examined the effects of neurotransmitter mixtures on such networks. In a previous study of the medicinal leech using triple intracellular recordings, we found that stimulation of identified mechanosensory neurons activated both the serotonergic cell 21 (a swimgating neuron) and the dorsal lateral octopamine (DLO) cell. Because these findings suggested that serotonin (5-HT) and octopamine (OA) may be released together, we investigated the effects of 5-HT and OA mixtures on isolated nerve cords of Hirudo medicinalis (which contained both head and tail brains). Fifty micromolar OA, 50 μM 5-HT, or a mixture of 50 μM OA and 50 μM 5-HT was bath applied to the nerve cord under constant perfusion conditions. Additional experiments were performed with combinations of either 25 or 100 μM OA and 5-HT. Neural activity was examined specifically in the segmentally repeated dorsal posterior (DP) nerve because it has been shown to contain identified swim motor units. Nonadditive effects of amine combinations were most apparent in their ability to decrease overall activity in the DP nerve and to alter patterned motor activity in the form of fictive swimming. Whereas swim burst activity has been previously shown to increase in nerve cords bathed in either 5-HT or OA solutions alone, we demonstrated that a mixture of the two amines resulted in a robust decrease in the number of swim bursts expressed and an inhibition of swim activity in preparations already swimming. Most compelling was the observation that when the amine mixture was replaced with normal saline, swim burst activity increased dramatically. We discuss that the effects of amine mixtures may be due to their interaction with descending interneurons known to trigger and inhibit swimming as the mixture-induced effects were not observed in nerve cords lacking the head and tail brains. Because the net effect of the two amines was not simply additive (i.e., 5-HT or OA is known to activate swimming, yet the mix inhibits swimming), this result reveals yet another layer of complexity inherent in “simpler” invertebrate nervous systems.
Short-Term Synaptic Depression in the Neonatal Mouse Spinal Cord: Effects of Calcium and Temperature
Authors: Li Yan , Burke R. E.
Published: December 2017

We have studied short-term synaptic depression of excitatory postsynaptic potentials (EPSPs) in lumbosacral motoneurons in the isolated, in vitro spinal cord of neonatal mice at 2–4 days postnatal age. We used 2-amino-5-phosphonovaleric acid (AP5; 100 μM) to suppress spontaneous and stimulus-evoked polysynaptic activity. Monosynaptic EPSPs were generated by trains of 10 pulses stimuli delivered to a dorsal root at eight frequencies between 0.125 and 16 Hz. The amplitudes of the second (R2), third (R3), and the average of R8, R9, and R10 (tail) EPSPs, normalized by the first EPSP (R1), defined the shapes of synaptic depression curves. Tail responses were increasingly depressed as stimulation frequency increased but R2 and R3 exhibited relative facilitation at frequencies >1 Hz. Control experiments indicated that the depression curves were not explained by presynaptic activation failure. Lowering external Ca2+ concentration ([Ca2+]o) from 2.0 to 0.8 mM without changing [Mg2+]o reduced average R1 amplitudes and R2 depression with little change in tail depression. Conversely, increasing [Ca2+]o to 4.0 mM increased average R1 amplitude and R2 depression but again did not change tail depression. Increasing the bath temperature from 24 to 32°C produced little change in R1 amplitudes but markedly reduced the depression of all responses at most frequencies. We developed an empirical model, based on mechanisms described in more accessible synaptic systems, that assumes: transmitter is released from a constant fraction, f, of release-ready elements in two presynaptic compartments ( N and S) that are subsequently renewed by independent processes with exponential time constants (τ N and τ S ); an activation-dependent facilitation of transmitter release with constant increment and fast exponential decay; and a more slowly decaying, activation-dependent augmentation of the rate of renewal (τ N ) of N. The model gave satisfactory fits to data from all [Ca2+]o conditions and implied that f and the increments of the facilitation and augmentation processes were all changed in the same direction as [Ca2+]o, without changing the time constants. In contrast, model fits to the 32°C data implied that the process time constants all decreased by 40–45% while the presumably Ca2+-related weighting factors were unchanged. The model also successfully matched the normalized amplitudes of EPSPs during trains with irregular intervals.
Visual Response Properties of Neurons in the LGN of Normally Reared and Visually Deprived Macaque Monkeys
Authors: Levitt Jonathan B. , Schumer Robert A. , Sherman S. Murray , Spear Peter D. , Movshon J. Anthony
Published: December 2017

It is now well appreciated that parallel retino-geniculo-cortical pathways exist in the monkey as in the cat, the species in which parallel visual pathways were first and most thoroughly documented. What remains unclear is precisely how many separate pathways pass through the parvo- and magnocellular divisions of the macaque lateral geniculate nucleus (LGN), what relationships—homologous or otherwise—these pathways have to the cat's X, Y, and W pathways, and whether these are affected by visual deprivation. To address these issues of classification and trans-species comparison, we used achromatic stimuli to obtain an extensive set of quantitative measurements of receptive field properties in the parvo- and magnocellular laminae of the LGN of nine macaque monkeys: four normally reared and five monocularly deprived of vision by lid suture near the time of birth. In agreement with previous studies, we find that on average magnocellular neurons differ from parvocellular neurons by having shorter response latencies to optic chiasm stimulation, greater sensitivity to luminance contrast, and better temporal resolution. Magnocellular laminae are also distinguished by containing neurons that summate luminance over their receptive fields nonlinearly (Y cells) and whose temporal response phases decrease with increasing stimulus contrast (indicative of a contrast gain control mechanism). We found little evidence for major differences between magno- and parvocellular neurons on the basis of most spatial parameters except that at any eccentricity, the neurons with the smallest receptive field centers tended to be parvocellular. All parameters were distributed unimodally and continuously through the parvo- and magnocellular populations, giving no indications of subpopulations within each division. Monocular deprivation led to clear anatomical effects: cells in deprived-eye laminae were pale and shrunken compared with those in nondeprived eye laminae, and Cat-301 immunoreactivity in deprived laminae was essentially uniformly abolished. However, deprivation had only subtle effects on the response properties of LGN neurons. Neurons driven by the deprived eye in both magno- and parvocellular laminae had lower nonlinearity indices (i.e., summed signals across their receptive fields more linearly) and were somewhat less responsive. In magnocellular laminae driven by the deprived eye, neuronal response latencies to stimulation of the optic chiasm were slightly shorter than those in the nondeprived laminae, and receptive field surrounds were a bit stronger. No other response parameters were affected by deprivation, and there was no evidence for loss of a specific cell class as in the cat.
Properties of Synchronous and Asynchronous Release During Pulse Train Depression in Cultured Hippocampal Neurons
Authors: Hagler Donald J. , Goda Yukiko
Published: December 2017

Neurotransmitter release displays at least two kinetically distinct components in response to a single action potential. The majority of release occurs synchronously with action-potential-triggered Ca2+ influx; however, delayed release—also called asynchronous release—persists for tens of milliseconds following the peak Ca2+ transient. In response to trains of action potentials, synchronous release eventually declines, whereas asynchronous release often progressively increases, an effect that is primarily attributed to the buildup of intracellular Ca2+ during repetitive stimulation. The precise relationship between synchronous and asynchronous release remains unclear at central synapses. To gain better insight into the mechanisms that regulate neurotransmitter release, we systematically characterized the two components of release during repetitive stimulation at excitatory autaptic hippocampal synapses formed in culture. Manipulations that increase the Ca2+ influx triggered by an action potential—elevation of extracellular Ca2+ or bath application of tetraethylammonium (TEA)—accelerated the progressive decrease in synchronous release (peak excitatory postsynaptic current amplitude) and concomitantly increased asynchronous release. When intracellular Ca2+ was buffered by extracellular application of EGTA-AM, initial depression of synchronous release was equal to or greater than control; however, it quickly reached a plateau without further depression. In contrast, asynchronous release was largely abolished in EGTA-AM. The total charge transfer following each pulse—accounting for both synchronous and asynchronous release—reached a steady-state level that was similar between control and EGTA-AM. A portion of the decreased synchronous release in control conditions therefore was matched by a higher level of asynchronous release. We also examined the relative changes in synchronous and asynchronous release during repetitive stimulation under conditions that highly favor asynchronous release by substituting extracellular Ca2+ with Sr2+. Initially, asynchronous release was twofold greater in Sr2+. By the end of the train, the difference was ∼50%; consequently, the total release per pulse during the plateau phase was slightly larger in Sr2+ compared with Ca2+. We thus conclude that while asynchronous release—like synchronous release—is limited by vesicle availability, it may be able to access a slightly larger subset of the readily releasable pool. Our results are consistent with the view that during repetitive stimulation, the elevation of asynchronous release depletes the vesicles immediately available for release, resulting in depression of synchronous release. This implies that both forms of release share a small pool of immediately releasable vesicles, which is being constantly depleted and refilled during repetitive stimulation.
Mechanisms Underlying Regulation of Respiratory Pattern by Nicotine in PreBötzinger Complex
Authors: Shao Xuesi M. , Feldman Jack L.
Published: December 2017

Cholinergic neurotransmission plays a role in regulation of respiratory pattern. Nicotine from cigarette smoke affects respiration and is a risk factor for sudden infant death syndrome (SIDS) and sleep-disordered breathing. The cellular and synaptic mechanisms underlying this regulation are not understood. Using a medullary slice preparation from neonatal rat that contains the preBötzinger Complex (preBötC), the hypothesized site for respiratory rhythm generation, and generates respiratory-related rhythm in vitro, we examined the effects of nicotine on excitatory neurotransmission affecting inspiratory neurons in preBötC and on the respiratory-related motor activity from hypoglossal nerve (XIIn). Microinjection of nicotine into preBötC increased respiratory frequency and decreased the amplitude of inspiratory bursts, whereas when injected into XII nucleus induced a tonic activity and an increase in amplitude but not in frequency of inspiratory bursts from XIIn. Bath application of nicotine (0.2–0.5 μM, approximately the arterial blood nicotine concentration immediately after smoking a cigarette) increased respiratory frequency up to 280% of control in a concentration-dependent manner. Nicotine decreased the amplitude to 82% and increased the duration to 124% of XIIn inspiratory bursts. In voltage-clamped preBötC inspiratory neurons (including neurons with pacemaker properties), nicotine induced a tonic inward current of −19.4 ± 13.4 pA associated with an increase in baseline noise. Spontaneous excitatory postsynaptic currents (sEPSCs) present during the expiratory period increased in frequency to 176% and in amplitude to 117% of control values; the phasic inspiratory drive inward currents decreased in amplitude to 66% and in duration to 89% of control values. The effects of nicotine were blocked by mecamylamine (Meca). The inspiratory drive current and sEPSCs were completely eliminated by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the presence or absence of nicotine. In the presence of tetrodotoxin (TTX), low concentrations of nicotine did not induce any tonic current or any increase in baseline noise, nor affect the input resistance in inspiratory neurons. In this study, we demonstrated that nicotine increased respiratory frequency and regulated respiratory pattern by modulating the excitatory neurotransmission in preBötC. Activation of nicotinic acetylcholine receptors (nAChRs) enhanced the tonic excitatory synaptic input to inspiratory neurons including pacemaker neurons and at the same time, inhibited the phasic excitatory coupling between these neurons. These mechanisms may account for the cholinergic regulation of respiratory frequency and pattern.
Serotonin and NO Complementarily Regulate Generation of Oscillatory Activity in the Olfactory CNS of a Terrestrial Mollusk
Authors: Inoue Tsuyoshi , Watanabe Satoshi , Kirino Yutaka
Published: December 2017

Synchronous oscillation of membrane potentials, generated by assemblies of neurons, is a prominent feature in the olfactory systems of many vertebrate and invertebrate species. However, its generation mechanism is still controversial. Biogenic amines play important roles for mammalian olfactory learning and are also implicated in molluscan olfactory learning. Here, we investigated the role of serotonin, a biogenic amine, in the oscillatory dynamics in the procerebrum (PC), the molluscan olfactory center. Serotonin receptor blockers inhibited the spontaneous synchronous oscillatory activity of low frequency (approximately 0.5 Hz) in the PC. This was due to diminishing the periodic slow oscillation of membrane potential in bursting (B) neurons, which are essential neuronal elements for the synchronous oscillation in the PC. On the other hand, serotonin enhanced the amplitude of the slow oscillation in B neurons and subsequently increased the number of spikes in each oscillatory cycle. These results show that the extracellular serotonin level regulates the oscillation amplitude in B neurons and thus serotonin may be called an oscillation generator in the PC. Although nitric oxide (NO) is known to also be a crucial factor for generating the PC oscillatory activity and setting the PC oscillation frequency, the present study showed that NO only regulates the oscillation frequency in B neurons but could not increase the spikes in each oscillatory cycle. These results suggest complementary regulation of the PC oscillatory activity: NO determines the probability of occurrence of slow potentials in B neurons, whereas serotonin regulates the amplitude in each cycle of the oscillatory activity in B neurons.
Comparison of the Effects of Stimulating Groups of Static γ Axons With Different Conduction Velocity Ranges on Cat Spindles
Authors: Emonet-Dénand Françoise , Laporte Yves , Petit Julien
Published: December 2017

In cat peroneus tertius muscles, static γ axons were prepared in groups of three to four according to the conduction velocity of their axons (fast, intermediate, or slow). Effects of stimulating these groups (at 20, 30, and 50 Hz) on spindle ensemble discharges during sinusoidal stretch (peak-to-peak amplitude, 0.5 mm; frequency linearly increasing from 0.5 to 8 Hz in 10 s) were compared. Ensemble discharges were obtained by digital treatment of the discharges in afferent fibers from all the spindles in peroneus tertius as recorded from the muscle nerve. Stimulation of each group prevented ensemble discharges from falling to very low levels during shortening phases. However, this effect was clearly larger when the group of fast-conducting axons was stimulated. In view of the known effects of the activation of bag2 and chain fibers (either separately or together) on single primary ending discharges during comparable sinusoidal stretches, this stronger effect supports the view that static γ axons with faster conduction velocities are more likely to supply more bag2 fibers than slower ones. Possibly the proportions of bag2 and chain fibers activated during motor activity are determined by a recruitment of static γ motoneurons related to their size.
Nerve Growth Factor Regulates Sodium But Not Potassium Channel Currents in Sympathetic B Neurons of Adult Bullfrogs
Authors: Lei Saobo , Dryden William F. , Smith Peter A.
Published: December 2017

The TTX-sensitive and -resistant components of the voltage-gated Na+current (TTX-s INaand TTX-r INa) are increased within 2 wk of cutting the axons of B-cells in bullfrog paravertebral sympathetic ganglia (BFSG). Axotomy also increases the noninactivating, voltage-activated K+current (M current IM), whereas delayed rectifier K+current ( IK) is reduced. We found that similar effects were produced when BFSG B cells were dissociated from adult bullfrogs and maintained in a defined-medium, neuron-enriched, low-density, serum-free culture. Thus the density of TTX-s INa, TTX-r INa, and IMwere transiently increased, whereas IKdensity was decreased. Reduction in voltage-sensitive, Ca2+-dependent K+current ( IC) was attributed to previously documented decreases in Ca2+channel current ( ICa). To test whether axotomy- or culture-induced changes in ion channel function reflect loss of retrograde influence of nerve growth factor (NGF), we examined the effect of murine β-NGF on TTX-s INa, TTX-r INa, IK, and IM. Culture of neurons for 15 days in the presence of NGF (200 ng/ml), more than doubled total INadensity but did not enhance neurite outgrowth. The TTX-r INadensity was increased about threefold and the TTX-s INadensity increased 2.4-fold. NGF did not affect the activation or inactivation kinetics of the total Na+conductance. Effects of NGF were blocked by the transcription inhibitors, cordycepin (20 μM) and actinomycin D (0.01 μg/ml). IKand IMwere unaffected by NGF, and although ICwas enhanced, this likely reflected the known effect of NGF on ICain BFSG neurons. Na+channel synthesis and/or expression in adult sympathetic neurons is therefore subject to selective regulation by NGF. Despite this, the increase in INaand IMas well as the decrease in IKseen in BFSG neurons in culture or after axotomy cannot readily be explained in terms of alterations in the availability of target-derived NGF.
Gaze-Stabilizing Deficits and Latent Nystagmus in Monkeys With Brief, Early-Onset Visual Deprivation: Eye Movement Recordings
Authors: Tusa Ronald J. , Mustari Michael J. , Burrows Andrew F. , Fuchs Albert F.
Published: December 2017

The normal development and the capacity to calibrate gaze-stabilizing systems may depend on normal vision during infancy. At the end of 1 yr of dark rearing, cats have gaze-stabilizing deficits similar to that of the newborn human infant including decreased monocular optokinetic nystagmus (OKN) in the nasal to temporal (N-T) direction and decreased velocity storage in the vestibuloocular reflex (VOR). The purpose of this study is to determine to what extent restricted vision during the first 2 mo of life in monkeys affects the development of gaze-stabilizing systems. The eyelids of both eyes were sutured closed in three rhesus monkeys ( Macaca mulatta) at birth. Eyelids were opened at 25 days in one monkey and 40 and 55 days in the other two animals. Eye movements were recorded from each eye using scleral search coils. The VOR, OKN, and fixation were examined at 6 and 12 mo of age. We also examined ocular alignment, refraction, and visual acuity in these animals. At 1 yr of age, visual acuity ranged from 0.3 to 0.6 LogMAR (20/40–20/80). All animals showed a defect in monocular OKN in the N-T direction. The velocity-storage component of OKN (i.e., OKAN) was the most impaired. All animals had a mild reduction in VOR gain but had a normal time constant. The animals deprived for 40 and 55 days had a persistent strabismus. All animals showed a nystagmus similar to latent nystagmus (LN) in human subjects. The amount of LN and OKN defect correlated positively with the duration of deprivation. In addition, the animal deprived for 55 days demonstrated a pattern of nystagmus similar to congenital nystagmus in human subjects. We found that restricted visual input during the first 2 mo of life impairs certain gaze-stabilizing systems and causes LN in primates.