bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the mGluR1-Mediated Electrical and Calcium Signaling in Purkinje Cells of Mouse Cerebellar Slices
Authors: Tempia F. , Alojado M. E. , Strata P. , Knöpfel T.
Published: December 2017

The metabotropic glutamate receptor 1 (mGluR1) plays a fundamental role in postnatal development and plasticity of ionotropic glutamate receptor-mediated synaptic excitation of cerebellar Purkinje cells. Synaptic activation of mGluR1 by brief tetanic stimulation of parallel fibers evokes a slow excitatory postsynaptic current and an elevation of intracellular calcium concentration ([Ca2+]i) in Purkinje cells. The mechanism underlying these responses has not been identified yet. Here we investigated the responses to synaptic and direct activation of mGluR1 using whole cell patch-clamp recordings in combination with microfluorometric measurements of [Ca2+]i in mouse Purkinje cells. Following pharmacological block of ionotropic glutamate receptors, two to six stimuli applied to parallel fibers at 100 Hz evoked a slow inward current that was associated with an elevation of [Ca2+]i. Both the inward current and the rise in [Ca2+]i increased in size with increasing number of pulses albeit with no clear difference between the minimal number of pulses required to evoke these responses. Application of the mGluR1 agonist ( S)-3,5-dihydroxyphenylglycine (3,5-DHPG) by means of short-lasting (5–100 ms) pressure pulses delivered through an agonist-containing pipette positioned over the Purkinje cell dendrite, evoked responses resembling the synaptically induced inward current and elevation of [Ca2+]i. No increase in [Ca2+]i was observed with inward currents of comparable amplitudes induced by the ionotropic glutamate receptor agonist AMPA. The 3,5-DHPG-induced inward current but not the associated increase in [Ca2+]i was depressed when extracellular Na+ was replaced by choline, but, surprisingly, both responses were also depressed when bathing the tissue in a low calcium (0.125 mM) or calcium-free/EGTA solution. Thapsigargin (10 μM) and cyclopiazonic acid (30 μM), inhibitors of sarco-endoplasmic reticulum Ca2+-ATPase, had little effect on either the inward current or the elevation in [Ca2+]i induced by 3,5-DHPG. Furthermore, the inward current induced by 3,5-DHPG was neither blocked by 1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy] ethyl-1H-imidazole, an inhibitor of store operated calcium influx, nor by nimodipine or omega-agatoxin, blockers of voltage-gated calcium channels. These electrophysiological and Ca2+-imaging experiments suggest that the mGluR1-mediated inward current, although mainly carried by Na+, involves influx of Ca2+ from the extracellular space.
Age-Related Changes and Condition-Dependent Modifications in Distribution of Limb Movements During Embryonic Motility
Authors: Bradley Nina S.
Published: December 2017

It has long been known that the chick initiates spontaneous motility early in embryogenesis, that the distribution of this activity is episodic, and that it varies both quantitatively and qualitatively with age. It is also well established that embryonic motility is controlled by spinal circuits and features of motility at early stages of development are likely the product of immature network properties. Over the course of embryonic development, however, the episodic distribution of motility becomes more variable. Because we are interested in determining whether movement experience in ovo is fundamental to the establishment of adaptive posthatching behaviors, this study examines the normal within-subject variability of episodic activity in embryos across ages under control and several experimental conditions. The distribution of activity, pause, and episode duration was obtained from video recordings of embryos prepared for electromyographic (EMG) and/or kinematic studies of motility in ovo at select ages (E9, E10, E12, E15, E18) under control conditions (control), acute reduction in buoyancy (ARB), ankle restraint (AR), thoracic spinal transection (spinal). Both control and ARB embryos exhibited significant age-related changes in the distribution of motility. Activity duration progressively increased with age and largely accounted for age-related increases in the variability of episodic behavior. Pause duration decreased markedly between E9 and E12 and did not appear to be a critical parameter in accounting for age-related changes in motility distribution. Activity duration was significantly lengthened in ARB embryos and decreased in spinal embryos. Pause duration was selectively lengthened in AR embryos. Collectively, age-related changes and selective effects of experimental preparations suggest that activity and pause duration are controlled by different mechanisms that operate independent of one another by E12. The results also suggest that the spinal network controlling motility becomes increasingly dependent on excitatory drive from supraspinal centers between E9 and E18. It is proposed that age-related increases in activity duration variability and condition-dependent effects on the distribution of activity are indicative of changing inputs weights for descending and sensory pathways and that they significantly impact spinal control of motility as the embryo's movement and posture are increasingly constrained by the fixed volume of the egg.
Effect of the Group I Metabotropic Glutamate Agonist DHPG on the Visual Cortex
Authors: Jin Xiao-Tao , Beaver Christopher J. , Ji Qinghua , Daw Nigel W.
Published: December 2017

Metabotropic glutamate receptors have a variety of effects in visual cortex that depend on the age of the animal, the layer of the cortex, and the group of the receptor. Here we describe these effects for group I receptors, using both in vivo and in vitro preparations. The metabotropic group I glutamate receptor agonist 3,5 dihydroxyphenylglycine (DHPG) potentiates the responses to N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in slices of rat visual cortex. It also increases, initially, the visual response in the cat visual cortex. Both these effects are largest at 3–4 wk of age and decline to insignificance by 10 wk of age. Both are also largest in lower layers of cortex, which explains why the facilitatory effects found with the general metabotropic glutamate agonist 1S,3R aminocyclopentane-1,3-dicarboxylic acid (ACPD) are observed only in lower layers. Prolonged application of DHPG in the cat visual cortex, after the initial excitatory effect, produces depression. We also found that DHPG facilitates the NMDA response in fast-spiking cells, which are inhibitory, providing a partial explanation for this. Thus there are multiple effects of group I metabotropic glutamate receptors, which vary with layer and age in visual cortex.
Forward Versus Backward Walking: Transfer of Podokinetic Adaptation
Authors: Earhart Gammon M. , Melvill Jones G. , Horak F. B. , Block E. W. , Weber K. D. , Fletcher W. A.
Published: December 2017

We asked whether podokinetic adaptation to walking on a circular treadmill transfers to different forms of locomotion. Subjects were blindfolded and asked to walk straight across the floor, in the forward and backward directions, following podokinetic (PK) stimulation that consisted of 30 min of forward walking-in-place on the perimeter of a disk rotating in the clockwise direction. During both forward and backward walking following forward-walking PK stimulation, subjects involuntarily walked along curved trajectories at angular velocities well above vestibular threshold, although they perceived that they were walking along straight paths. The curved paths of forward and backward walking were indistinguishable from one another. Transfer of PK adaptations acquired during forward walking on the turntable to backward walking trials suggests that the PK system controls general locomotor trajectory. Adaptation of the system thus influences forms of locomotion other than that used during acquisition of the adaptation. This transfer also supports the concept that forward and backward walking are controlled by neural networks that share common elements. An interesting feature of the transfer of PK adaptation is that for both forward and backward walking, subjects turned in a counterclockwise direction. As such, the direction of relative rotation between the trunk and feet was maintained for both forward and backward walking. However, the relationship of the lower extremities to the center of rotation was not preserved. The left limb was the inner leg during PK stimulation and forward walking after adaptation, but the left leg was the outer leg during backward walking. These results suggest that PK adaptation affects general locomotor trajectory via a remodeling of the rotational relationship between the trunk and the feet.
Differences in Time Course of ACh and GABA Modulation of Excitatory Synaptic Potentials in Slices of Rat Hippocampus
Authors: Hasselmo Michael E. , Fehlau Brian P.
Published: December 2017

Activation of muscarinic receptors and GABABreceptors causes presynaptic inhibition of glutamatergic synaptic potentials at excitatory feedback connections in cortical structures. These effects may regulate dynamics in cortical structures, with presynaptic inhibition allowing extrinsic afferent input to dominate during encoding, while the absence of presynaptic inhibition allows stronger excitatory feedback during retrieval or consolidation. However, proposals for a functional role of such modulatory effects strongly depend on the time course of these modulatory effects; how rapidly can they turn off and on? In brain slice preparations of hippocampal region CA1, we have explored the time course of suppression of extracellularly recorded synaptic potentials after pressure pulse application of acetylcholine and GABA. Acetylcholine causes suppression of extracellular potentials with onset time constants between 1 and 2 s, and decay constants ranging between 10 and 20 s, even with very brief injection pulses. GABA causes suppression of extracellular potentials with onset time constants between 0.2 and 0.7 s, and decay time constants that decrease to values shorter than 2 s for very brief injection pulses. These techniques do not give an exact measure of the physiological time course in vivo, but they give a notion of the relative time course of the two modulators. The slow changes due to activation of muscarinic acetylcholine receptors may alter the dynamics of cortical circuits over longer intervals (e.g., between different stages of waking and sleep), setting dynamics appropriate for encoding versus consolidation processes. The faster changes in synaptic potentials caused by GABA could cause changes within each cycle of the theta rhythm, rapidly switching between encoding and retrieval dynamics during exploration.
Electrophysiological Evidence for a Chemotopy of Biologically Relevant Odors in the Olfactory Bulb of the Channel Catfish
Authors: Nikonov Alexander A. , Caprio John
Published: December 2017

Extracellular electrophysiological recordings from single olfactory bulb (OB) neurons in the channel catfish, Ictalurus punctatus, indicated that the OB is divided into different functional zones, each processing a specific class of biologically relevant odor. Different OB regions responded preferentially at slightly above threshold to either a mixture of 1) bile salts (10–7to 10−5M Na+salts of taurocholic, lithocholic, and taurolithocholic acids), 2) nucleotides [10–6to 10–4M adenosine-5′-triphosphate (ATP), inosine-5′-monophosphate (IMP), and inosine-5′-triphosphate (ITP)], or 3) amino acids (10–6to 10–4M l-alanine,l-methionine, l-arginine, andl-glutamate). Excitatory responses to bile salts were observed primarily in a thin, medial strip in both the dorsal (100–450 μm) and ventral (900–1,200 μm) OB. Excitatory responses to nucleotides were obtained primarily from dorsal, caudolateral OB, whereas excitatory responses to amino acids occurred more rostrally in the dorsolateral OB, but continued more medially in the ventral OB. The chemotopy within the channel catfish OB is more comparable to that previously described by optical imaging studies in zebrafish than by field potential studies in salmonids. The present results are consistent with recent studies, suggesting that the specific spatial organization of output neurons in the OB is necessary for the quality coding/decoding of olfactory information.
Distinguishing Subregions of the Human MT+ Complex Using Visual Fields and Pursuit Eye Movements
Authors: Dukelow Sean P. , DeSouza Joseph F. X. , Culham Jody C. , van den Berg Albert V. , Menon Ravi S. , Vilis Tutis
Published: December 2017

In humans, functional imaging studies have demonstrated a homologue of the macaque motion complex, MT+ [suggested to contain both middle temporal (MT) and medial superior temporal (MST)], in the ascending limb of the inferior temporal sulcus. In the macaque monkey, motion-sensitive areas MT and MST are adjacent in the superior temporal sulcus. Electrophysiological research has demonstrated that while MT receptive fields primarily encode the contralateral visual field, MST dorsal (MSTd) receptive fields extend well into the ipsilateral visual field. Additionally, macaque MST has been shown to receive extraretinal smooth-pursuit eye-movement signals, whereas MT does not. We used functional magnetic resonance imaging (fMRI) and the neural properties that had been observed in monkeys to distinguish putative human areas MT from MST. Optic flow stimuli placed in the full field, or contralateral field only, produced a large cluster of functional activation in our subjects consistent with previous reports of human area MT+. Ipsilateral optic flow stimuli limited to the peripheral retina produced activation only in an anterior subsection of the MT+ complex, likely corresponding to putative MSTd. During visual pursuit of a single target, a large portion of the MT+ complex was activated. However, during nonvisual pursuit, only the anterolateral portion of the MT+ complex was activated. This subsection of the MT+ cluster could correspond to putative MSTl (lateral). In summary, we observed three distinct subregions of the human MT+ complex that were arranged in a manner similar to that seen in the monkey.
A Comparison of the Firing Properties of Putative Excitatory and Inhibitory Neurons From CA1 and the Entorhinal Cortex
Authors: Frank Loren M. , Brown Emery N. , Wilson Matthew A.
Published: December 2017

The superficial layers of the entorhinal cortex (EC) provide the majority of the neocortical input to the hippocampus, and the deep layers of the EC receive the majority of neocortically bound hippocampal outputs. To characterize information transmission through the hippocampal and EC circuitry, we recorded simultaneously from neurons in the superficial EC, the CA1 region of hippocampus, and the deep EC while rodents ran for food reward in two environments. Spike waveform analysis allowed us to classify units as fast-spiking (FS) putative inhibitory cells or putative excitatory (PE) cells. PE and FS units' firing were often strongly correlated at short time scales, suggesting the presence a monosynaptic connection from the PE to FS units. EC PE units, unlike those found in CA1, showed little or no tendency to fire in bursts. We also found that the firing of FS and PE units from all regions was modulated by the ∼8 Hz theta rhythm, although the firing of deep EC FS units tended to be less strongly modulated than that of the other types of units. When we examined the spatial specificity of FS units, we determined that FS units in all three regions showed low specificity. At the same time, retrospective coding, in which firing rates were related to past position, was present in FS units from all three regions and deep EC FS units often fired in a “path equivalent” manner in that they were active in physically different, but behaviorally related positions both within and across environments. Our results suggest that while the firing of FS units from CA1 and the EC show similarly low levels of position specificity, FS units from each region differ from one another in that they mirrored the associated PE units in terms of their tendency to show more complex positional firing properties like retrospective coding and path equivalence.
Prefrontal Cortical Representation of Visuospatial Working Memory in Monkeys Examined by Local Inactivation With Muscimol
Authors: Sawaguchi Toshiyuki , Iba Michiyo
Published: December 2017

In primates, dorsolateral areas of the prefrontal cortex (PFC) play a major role in visuospatial working memory. To examine the functional organization of the PFC for representing visuospatial working memory, we produced reversible local inactivation, with the local injection of muscimol (5 μg, 1 μl), at various sites ( n = 100) in the dorsolateral PFC of monkeys and observed the behavioral consequences in an oculomotor delayed-response task that required memory-guided saccades for locations throughout both visual fields. At 82 sites, the local injection of muscimol induced deficits in memory-guided saccades to a few specific, usually contralateral, target locations that varied with the location of the injection site. Such deficits depended on the delay length, and longer delays were associated with larger deficits in memory-guided saccades. The injection sites and affected spatial locations of the target showed a gross topographical relationship. No deficits appeared for a control task in which the subject was required to make a visually guided saccade to a visible target. These findings suggest that a specific site in the dorsolateral PFC is responsible for the working memory process for a specific visuospatial coordinate to guide goal-directed behavior. Further, memoranda for specific visuospatial coordinates appear to be represented in a topographical memory mapwithin the dorsolateral PFC to represent visuospatial working memory processes.
Direct Excitation of Mitral Cells Via Activation of α1-Noradrenergic Receptors in Rat Olfactory Bulb Slices
Authors: Hayar Abdallah , Heyward Phillip M. , Heinbockel Thomas , Shipley Michael T. , Ennis Matthew
Published: December 2017

The main olfactory bulb receives a significant modulatory noradrenergic input from the locus coeruleus. Previous in vivo and in vitro studies showed that norepinephrine (NE) inputs increase the sensitivity of mitral cells to weak olfactory inputs. The cellular basis for this action of NE is not understood. The goal of this study was to investigate the effect of NE and noradrenergic agonists on the excitability of mitral cells, the main output cells of the olfactory bulb, using whole cell patch-clamp recording in vitro. The noradrenergic agonists, phenylephrine (PE, 10 μM), isoproterenol (Isop, 10 μM), and clonidine (3 μM), were used to test for the functional presence of α1-, β-, and α2-receptors, respectively, on mitral cells. None of these agonists affected olfactory nerve (ON)–evoked field potentials recorded in the glomerular layer, or ON-evoked postsynaptic currents recorded in mitral cells. In whole cell voltage-clamp recordings, NE (30 μM) induced an inward current (54 ± 7 pA, n= 16) with an EC50 of 4.7 μM. Both PE and Isop also produced inward currents (22 ± 4 pA, n = 19, and 29 ± 9 pA, n = 8, respectively), while clonidine produced no effect ( n = 6). In the presence of TTX (1 μM), and blockers of excitatory and inhibitory fast synaptic transmission [gabazine 5 μM, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) 10 μM, and (±)-2-amino-5-phosphonopentanoic acid (APV) 50 μM], the inward current induced by PE persisted (EC50 = 9 μM), whereas that of Isop was absent. The effect of PE was also observed in the presence of the Ca2+ channel blockers, cadmium (100 μM) and nickel (100 μM). The inward current caused by PE was blocked when the interior of the cell was perfused with the nonhydrolyzable GDP analogue, GDPβS, indicating that the α1 effect is mediated by G-protein coupling. The current-voltage relationship in the absence and presence of PE indicated that the current induced by PE decreased near the equilibrium potential for potassium ions. In current-clamp recordings from bistable mitral cells, PE shifted the membrane potential from the downstate (−52 mV) toward the upstate (−40 mV), and significantly increased spike generation in response to perithreshold ON input. These findings indicate that NE excites mitral cells directly via α1 receptors, an effect that may underlie, at least in part, increased mitral cell responses to weak ON input during locus coeruleus activation in vivo.
Peptidergic Modulation of Insect Voltage-Gated Ca2+Currents: Role of Resting Ca2+Current and Protein Kinases A and C
Authors: Wicher Dieter
Published: December 2017

The modulation of voltage-gated Ca2+currents in isolated dorsal unpaired median (DUM) neurons of cockroach was investigated using whole cell patch clamp. The neuropeptide neurohormone D (NHD), a member of the adipokinetic hormone family, affected Ca2+currents at pico- to nanomolar concentrations. It strongly enhanced currents activating at lower depolarizations, whereas those activating at strong depolarizations were slightly attenuated. The first effect results from upregulation of a previously characterized ω-conotoxin MVIIC- and ω-agatoxin IVA-sensitive “mid/low voltage-activated” (M-LVA) Ca2+current. The cAMP-analogue 8-bromo-cAMP, forskolin, and the catalytic subunit of protein kinase A (PKA) mimicked the stimulating action of NHD. In addition, preincubation of neurons with the PKA inhibitor KT 5720 abolished the action of NHD. Thus NHD seems to upregulate the M-LVA current via channel phosphorylation by PKA. Activation of protein kinase C by oleoylacetylglycerol (OAG) mimicked the effect of NHD, and subsequent NHD application only enhanced the current to a moderate extent. On the other hand, inhibition of protein kinase C (PKC) by Gö 6976 abolished the NHD effect. These results indicate that also PKC, too, may play a role in the peptidergic modulation of the M-LVA Ca2+current. The reduction of Ca2+currents in the high-voltage-range is caused by the NHD-induced upregulation of a voltage-independent Ca2+resting current, ICa,R, which most probably leads to enhanced Ca2+-dependent inactivation of voltage-gated Ca2+currents. To assess the major consequences of the Ca2+current changes, current-clamp investigations were performed. Experiments with iberiotoxin, a specific blocker of BK-type Ca2+-dependent K+currents, and the M-LVA current-blocking ω-toxins suggested that NHD causes—via increasing Ca2+-dependent K+currents—a larger hyperpolarization of action potentials. The lowering in the action potential threshold produced by NHD, however, seems to be a direct consequence of the hyperpolarizing shift of the activation curve of total Ca2+current resulting from NHD-induced upregulation of the M-LVA current component.
Prenatal Exposure of Testosterone Prevents SDN-POA Neurons of Postnatal Male Rats From Apoptosis Through NMDA Receptor
Authors: Hsu Hseng-Kuang , Yang Rei-Cheng , Shih Huei-Chuan , Hsieh Ya-Lun , Chen U-Yang , Hsu Chin
Published: December 2017

The role of N-methyl-d-aspartate (NMDA) receptor in mediating the effect of testosterone exposure prenatally on neuronal apoptosis in the sexual dimorphic nucleus of the preoptic area (SDN-POA) of rats was studied. The endogenous testosterone was diminished by prenatal stress (PNS) or simulated by testosterone exposure (TE) to understand the effect of testosterone on NR1(a functional subunit protein of NMDA receptor) expression and neuronal apoptosis. To further study whether the testosterone, after being converted into estradiol, modulates NR1expression, 4-androstein-4-ol-3,17-dione (ATD; an aromatase inhibitor) was used to block the conversion of estradiol from testosterone. The expressions of the NR1mRNA and NR1subunit protein were quantified by RT-PCR and western blotting analysis, respectively. In addition, a noncompetitive antagonist of NMDA receptor, MK-801, was used to find out whether blockage of NMDA receptor affects the naturally occurring apoptosis in SDN-POA. The results showed the following. 1) Expression of perinatal NR1subunit protein in the central part of the medial preoptic area of male rats was significantly higher than that of females, especially on postnatal days 1 and 3. 2) The testosterone level of male fetuses on embryonic day 18 was significantly higher than that of females, while the testosterone level of TE females or PNS males was similar to that of intact males or intact females, respectively. 3) The apoptotic incidence of intact male rats was significantly less than that of females, and the apoptosis was stimulated by PNS in male or inhibited by TE in female. 4) The expression of NR1subunit protein could be inhibited by PNS or ATD-treatment in male, while stimulated by TE in female. 5) NR1mRNA showed no significant difference among intact male, PNS male, ATD-treated male, TE female and intact female rats. 6) The low apoptotic incidence of male rats was significantly increased when NMDA receptor was blocked by MK-801. These results suggest that testosterone, after being converted to estradiol, may prevent the SDN-POA neurons of male rats from apoptosis through enhancing the expression of NR1at the posttranscriptional level.
Epileptiform Discharges With In-Vivo-Like Features in Slices of Rat Piriform Cortex With Longitudinal Association Fibers
Authors: Demir Rezan , Haberly Lewis B. , Jackson Meyer B.
Published: December 2017

Brain slices serve as useful models for the investigation of epilepsy. However, the preparation of brain slices disrupts circuitry and severs axons, thus complicating efforts to relate epileptiform activity in vitro to seizure activity in vivo. This issue is relevant to studies in transverse slices of the piriform cortex (PC), the preparation of which disrupts extensive rostrocaudal fiber systems. In these slices, epileptiform discharges propagate slowly and in a wavelike manner, whereas such discharges in vivo propagate more rapidly and jump abruptly between layers. The objective of the present study was to identify fiber systems responsible for these differences. PC slices were prepared by cutting along three different nearly orthogonal planes (transverse, parasagittal, and longitudinal), and epileptiform discharges were imaged with a voltage-sensitive fluorescent dye. Interictal-like epileptiform activity was enabled by either a kindling-like induction process or disinhibition with bicuculline. The pattern of discharge onset was very similar in slices cut in different planes. As described previously in transverse PC slices, discharges were initiated in the endopiriform nucleus (En) and adjoining regions in a two-stage process, starting with low-amplitude “plateau activity” at one site and leading to an accelerating depolarization and discharge onset at another nearby site. The similar pattern of onset in slices of various orientations indicates that the local circuitry and neuronal properties in and around the En, rather than long-range fibers, assume dominant roles in the initiation of epileptiform activity. Subtle variations in the onset site indicate that interneurons can fine tune the site of discharge onset. In contrast to the mode of onset, discharge propagation showed striking variations. In longitudinal slices, where rostrocaudal association fibers are best preserved, discharge propagation resembled in vivo seizure activity in the following respects: propagation was as rapid as in vivo and about two to three times faster than in other slices; discharges jumped abruptly between the En and PC; and discharges had large amplitudes in superficial layers of the PC. Cuts in longitudinal slices that partially separated the PC from the En eliminated these unique features. These results help clarify why epileptiform activity differs between in vitro and in vivo experiments and suggest that rostrocaudal pyramidal cell association fibers play a major role in the propagation of discharges in the intact brain. The longitudinal PC slice, which best preserves these fibers, is ideally suited for the study their role.
Dynamic Modulation of Mossy Fiber System Throughput by Inferior Olive Synchrony: A Multielectrode Study of Cerebellar Cortex Activated by Motor Cortex
Authors: Schwarz Cornelius , Welsh John P.
Published: December 2017

We investigated the effects of climbing fiber synchrony on the temporal dynamics of mossy fiber system throughput in populations of cerebellar Purkinje cells (PCs). A multielectrode technique was used in ketamine-anesthetized rats that allowed both complex and simple spikes (CSs and SSs) to be recorded from multiple PCs simultaneously in lobule crus IIa. Stimulation of the tongue area of the primary motor cortex (TM1) was used to evoke cerebro-cerebellar interaction. At the single PC level, robust short-term interactions of CSs and SSs were observed after TM1 stimulation that typically consisted of an immediate depression and subsequent enhancement of SS firing after the occurrence of a CS. Such modulations of SS rate in a given PC were as robustly correlated to the CSs of simultaneously recorded PCs as they were to the CS on its own membrane—and did not require a CS on its own membrane—indicating a network basis for the interaction. Analyses of simultaneously recorded PCs using the normalized joint perievent time histogram demonstrated that CS and SS firing were dynamically correlated after TM1 stimulation in a manner that indicated strong control of mossy fiber system throughput by CS synchrony. For ≤300 ms after TM1 stimulation, most PCs showed episodic modulations in SS rate that appeared to be entrained by the population rhythm of climbing fiber synchrony. SS rhythmicity also was modulated dynamically by CSs, such that it was depressed by CSs and facilitated by their absence. Like the modulations in SS rate, a given PC's modulation in SS rhythmicity did not require it to fire a CS but was, on those instances, equally correlated to the synchronous CSs of other PCs. The data indicate that the climbing fiber system controls the temporal dynamics of SS firing in populations of PCs by using synchrony to engage intracerebellar circuitry and modulate mossy fiber system throughput.
Sodium Influx Blockade and Hypoxic Damage to CA1 Pyramidal Neurons in Rat Hippocampal Slices
Authors: Raley-Susman K. M. , Kass I. S. , Cottrell J. E. , Newman R. B. , Chambers G. , Wang J.
Published: December 2017

We studied the effects of lidocaine and tetrodotoxin (TTX) on hypoxic changes in CA1 pyramidal neurons to examine the ionic basis of neuronal damage. Lidocaine (10 and 100 μM) and TTX (6 and 63 nM) delayed and attenuated the hypoxic depolarization and improved recovery of the resting and action potentials after 10 min of hypoxia. Lidocaine (10 and 100 μM) and TTX (63 nM) reduced the number of morphologically damaged CA1 cells and improved protein synthesis measured after 10 min hypoxia. Lidocaine (10 μM) attenuated the increase in intracellular sodium (181 vs. 218%) and the depolarization (−21 vs. −1 mV) during hypoxia but did not significantly attenuate the changes in ATP, potassium, or calcium measured at 10 min of hypoxia. Lidocaine (100 μM) attenuated the changes in membrane potential, sodium, potassium, ATP, and calcium during hypoxia. TTX (63 nM) attenuated the changes in membrane potential (−36 vs. −1 mV), sodium (179 vs. 226%), potassium (78 vs. 50%), and ATP (24 vs. 11%) but did not significantly attenuate the increase in calcium during hypoxia. These data indicate that the primary blockade of sodium channels can secondarily alter other cellular parameters. The hypoxic depolarization and the increase in intracellular sodium appear to be important triggers of hypoxic damage independent of their effect on cytosolic calcium; a treatment that selectively blocked sodium influx (lidocaine 10 μM) improved recovery. Our data indicate that selective blockade of sodium channels with a low concentration of lidocaine or TTX improves recovery after hypoxia by attenuating the rise in cellular sodium and the hypoxic depolarization. This blockade improves the resting and action potentials, histologic state, and protein synthesis of CA1 pyramidal neurons after 10 min of hypoxia to rat hippocampal slices. A higher concentration of lidocaine, which also improved ATP, potassium, and calcium concentrations during hypoxia was more potent. In conclusion, the depolarization and increased sodium concentration during hypoxia account for a portion of the neuronal damage after hypoxia independent of changes in calcium.
Variability and Information in a Neural Code of the Cat Lateral Geniculate Nucleus
Authors: Liu Robert C. , Tzonev Svilen , Rebrik Sergei , Miller Kenneth D.
Published: December 2017

A central theme in neural coding concerns the role of response variability and noise in determining the information transmission of neurons. This issue was investigated in single cells of the lateral geniculate nucleus of barbiturate-anesthetized cats by quantifying the degree of precision in and the information transmission properties of individual spike train responses to full field, binary (bright or dark), flashing stimuli. We found that neuronal responses could be highly reproducible in their spike timing (∼1–2 ms standard deviation) and spike count (∼0.3 ratio of variance/mean, compared with 1.0 expected for a Poisson process). This degree of precision only became apparent when an adequate length of the stimulus sequence was specified to determine the neural response, emphasizing that the variables relevant to a cell's response must be controlled to observe the cell's intrinsic response precision. Responses could carry as much as 3.5 bits/spike of information about the stimulus, a rate that was within a factor of two of the limit the spike train could transmit. Moreover, there appeared to be little sign of redundancy in coding: on average, longer response sequences carried at least as much information about the stimulus as would be obtained by adding together the information carried by shorter response sequences considered independently. There also was no direct evidence found for synergy between response sequences. These results could largely, but not entirely, be explained by a simple model of the response in which one filters the stimulus by the cell's impulse response kernel, thresholds the result at a fairly high level, and incorporates a postspike refractory period.
Postnatal Changes in Membrane Properties of Mice Trigeminal Ganglion Neurons
Authors: Cabanes Carmen , López de Armentia Mikel , Viana Félix , Belmonte Carlos
Published: December 2017

Intracellular recordings from neurons in the mouse trigeminal ganglion (TG) in vitro were used to characterize changes in membrane properties that take place from early postnatal stages (P0–P7) to adulthood (>P21). All neonatal TG neurons had uniformly slow conduction velocities, whereas adult neurons could be separated according to their conduction velocity into Aδ and C neurons. Based on the presence or absence of a marked inflection or hump in the repolarization phase of the action potential (AP), neonatal neurons were divided into S- (slow) and F-type (fast) neurons. Their passive and subthreshold properties (resting membrane potential, input resistance, membrane capacitance, and inward rectification) were nearly identical, but they showed marked differences in AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and afterhyperpolarization (AHP) duration. Adult TG neurons also segregated into S- and F-type groups. Differences in their mean AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and AHP duration were also prominent. In addition, axons of 90% of F-type neurons and 60% of S-type neurons became faster conducting in their central and peripheral branch, suggestive of axonal myelination. The proportion of S- and F-type neurons did not vary during postnatal development, suggesting that these phenotypes were established early in development. Membrane properties of both types of TG neurons evolved differently during postnatal development. The nature of many of these changes was linked to the process of myelination. Thus myelination was accompanied by a decrease in AP duration, input resistance ( R in), and increase in membrane capacitance (C). These properties remained constant in unmyelinated neurons (both F- and S-type). In adult TG, all F-type neurons with inward rectification were also fast-conducting Aδ, suggesting that those F-type neurons showing inward rectification at birth will evolve to F-type Aδ neurons with age. The percentage of F-type neurons showing inward rectification also increased with age. Both F- and S-type neurons displayed changes in the sensitivity of the AP to reductions in extracellular Ca2+ or substitution with Co2+ during the process of maturation.
Controlling the Statistics of Action: Obstacle Avoidance
Authors: Hamilton Antonia F. de C. , Wolpert Daniel M.
Published: December 2017

Task optimization in the presence of signal-dependent noise (TOPS) has been proposed as a general framework for planning goal-directed movements. Within this framework, the motor command is assumed to be corrupted by signal-dependent noise, which leads to a distribution of possible movements. A task can then be equated with optimizing some function of the statistics of this distribution. We found the optimal trajectory for obstacle avoidance by minimizing the mean-squared error at the end of the movement while keeping the probability of collision with the obstacle below a fixed limit. The optimal paths accurately predicted the empirical trajectories. This demonstrates that controlling the statistics of movements in the presence of signal-dependent noise may be a fundamental and unifying principle of goal-directed movements.
Role for G Protein Gβγ Isoform Specificity in Synaptic Signal Processing: A Computational Study
Authors: Bertram Richard , Arnot Michelle I. , Zamponi Gerald W.
Published: December 2017

Computational modeling is used to investigate the functional impact of G protein–mediated presynaptic autoinhibition on synaptic filtering properties. It is demonstrated that this form of autoinhibition, which is relieved by depolarization, acts as a high-pass filter. This contrasts with vesicle depletion, which acts as a low-pass filter. Model parameters are adjusted to reproduce kinetic slowing data from different Gβγ dimeric isoforms, which produce different degrees of slowing. With these sets of parameter values, we demonstrate that the range of frequencies filtered out by the autoinhibition varies greatly depending on the Gβγ isoform activated by the autoreceptors. It is shown that G protein autoinhibition can enhance the spatial contrast between a spatially distributed high-frequency signal and surrounding low-frequency noise, providing an alternate mechanism to lateral inhibition. It is also shown that autoinhibition can increase the fidelity of coincidence detection by increasing the signal-to-noise ratio in the postsynaptic cell. The filter cut, the input frequency below which signals are filtered, depends on several biophysical parameters in addition to those related to Gβγ binding and unbinding. By varying one such parameter, the rate at which transmitter unbinds from autoreceptors, we show that the filter cut can be adjusted up or down for several of the Gβγ isoforms. This allows for great synapse-to-synapse variability in the distinction between signal and noise.
Evidence Against a Moving Hill in the Superior Colliculus During Saccadic Eye Movements in the Monkey
Authors: Soetedjo Robijanto , Kaneko Chris R. S. , Fuchs Albert F.
Published: December 2017

Saccadic eye movements of different sizes and directions are represented in an orderly topographic map across the intermediate and deep layers of the superior colliculus (SC), where large saccades are encoded caudally and small saccades rostrally. Based on experiments in the cat, it has been suggested that saccades are initiated by a hill of activity at the caudal site appropriate for a particular saccade. As the saccade evolves and the remaining distance to the target, the motor error, decreases, the hill moves rostrally across successive SC sites responsible for saccades of increasingly smaller amplitudes. When the hill reaches the “fixation zone” in the rostral SC, the saccade is terminated. A moving hill of activity has also been posited for the monkey, in which it is supposed to be transported via so-called build-up neurons (BUNs), which have a prelude of activity that culminates in a burst for saccades. However, several studies using a variety of approaches have yet to provide conclusive evidence for or against a moving hill. The moving hill scenario predicts that during a large saccade the burst of a BUN in the rostral SC will be delayed until the motor error remaining in the evolving saccade is equal to the saccadic amplitude for which that BUN discharges best, i.e., its optimal amplitude. Therefore a plot of the burst lead preceding the “optimal” motor error against the time of occurrence of the optimal motor error should have a slope of zero. A slope of −1 indicates no moving hill. For our 20 BUNs, we used three measures of burst timing: the leads to the onset, peak, and center of the burst. The average slopes of these relations were −1.09, −0.79, and −0.58, respectively. For individual BUNs, the slopes of all three relations always differed significantly from zero. Although the peak and center leads fall between −1 and 0, a hill of activity moving rostrally at a rate indicated by either of these slopes would arrive at the fixation zone much too late to terminate the saccade at the appropriate time. Calculating our same three timing measures from averaged data leads us to the same conclusion. Thus our data do not support the moving hill model. However, we argue in the discussion that the constant lead of the burst onset relative to saccade onset (∼27 ms) suggests that the BUNs may help to trigger the saccade.
Voluntary Control of Static Endpoint Stiffness During Force Regulation Tasks
Authors: Perreault Eric J. , Kirsch Robert F. , Crago Patrick E.
Published: December 2017

The goals of this study were to determine the degree to which subjects could voluntarily modulate static endpoint stiffness orientation and to quantify the effects of simultaneously generated voluntary endpoint forces on this ability. Static endpoint stiffness, which characterizes the relationship between externally imposed displacements of the hand and the elastic forces generated in response, was estimated in real time during the application of planar, stochastic perturbations of endpoint position. This estimation was accomplished using a real-time parametric identification algorithm on measured force and position data. Subjects were provided with real-time visual feedback of endpoint stiffness, and their ability to modulate the orientation of maximum static stiffness was measured for different endpoint force magnitudes and directions. We found that individuals can voluntarily change stiffness orientation but that the magnitude of these changes is small, the range of available stiffness orientations decreases as endpoint force exertion increases, and endpoint force direction significantly constrains direction and magnitude of the stiffness orientations that can be achieved. Given these findings it appears unlikely that static endpoint stiffness orientation is controlled independently of force by voluntary neural mechanisms during postural tasks.
DRASIC Contributes to pH-Gated Currents in Large Dorsal Root Ganglion Sensory Neurons by Forming Heteromultimeric Channels
Authors: Xie Jinghui , Price Margaret P. , Berger Allan L. , Welsh Michael J.
Published: December 2017

For many years it has been observed that extracellular acid activates transient cation currents in large-diameter mechanosensory dorsal root ganglion (DRG) neurons. However, the molecular basis of these currents has not been known. Large DRG neurons express the dorsal root acid sensing ion channel (DRASIC), suggesting that DRASIC might contribute to H+-gated DRG currents. To test this, we examined whole cell currents in large DRG neurons from mice in which the DRASIC gene had been disrupted. We found that DRASIC null neurons retained H+-gated currents, indicating that DRASIC alone was not required for the currents. However, without DRASIC, the properties of the currents changed substantially as compared with wild-type neurons. In DRASIC –/– neurons, the rate of current desensitization in the continued presence of an acid stimulus slowed dramatically. H+-gated currents in DRASIC null neurons showed a decreased sensitivity to pH and an enhanced sensitivity to amiloride. The loss of DRASIC also altered but did not abolish the current potentiation generated by FMRF-related peptides. These data indicate that the DRASIC subunit makes an important contribution to H+-gated currents in large DRG sensory neurons. The results also suggest that related acid-activated DEG/ENaC channel subunits contribute with DRASIC to form heteromultimeric acid-activated channels.
Identification of T-Type α1H Ca2+ Channels (Cav3.2) in Major Pelvic Ganglion Neurons
Authors: Lee Jung-Ha , Kim Eun-Gi , Park Byong-Gon , Kim Kyoung-Han , Cha Seung-Kyu , Kong In Deok , Lee Joong-Woo , Jeong Seong-Woo
Published: December 2017

Among autonomic neurons, sympathetic neurons of the major pelvic ganglia (MPG) are unique by expressing low-voltage–activated T-type Ca2+ channels. To date, the T-type Ca2+ channels have been poorly characterized, although they are believed to be potentially important for functions of the MPG neurons. In the present study, thus we investigated characteristics and molecular identity of the T-type Ca2+ channels using patch-clamp and RT-PCR techniques. When the external solution contained 10 mM Ca2+ as a charge carrier, T-type Ca2+ currents were first activated at −50 mV and peaked around −20 mV. Besides the low-voltage activation, T-type Ca2+ currents displayed typical characteristics including transient activation/inactivation and voltage-dependent slow deactivation. Overlap of the activation and inactivation curves generated a prominent window current around resting membrane potentials. Replacement of the external Ca2+ with 10 mM Ba2+ did not affect the amplitudes of T-type Ca2+ currents. Mibefradil, a known T-type Ca2+ channel antagonist, depressed T-type Ca2+ currents in a concentration-dependent manner (IC50 = 3 μM). Application of Ni2+ also produced a concentration-dependent blockade of T-type Ca2+ currents with an IC50 of 10 μM. The high sensitivity to Ni2+ implicates α1H in generating the T-type Ca2+ currents in MPG neurons. RT-PCR experiments showed that MPG neurons predominantly express mRNAs encoding splicing variants of α1H (called pelvic Ta and Tb, short and long forms of α1H, respectively). Finally, we tested whether the low-threshold spikes could be generated in sympathetic MPG neurons expressing T-type Ca2+ channels. When hyperpolarizing currents were injected under a current-clamp mode, sympathetic neurons produced postanodal rebound spikes, while parasympathetic neurons were silent. The number of the rebound spikes was reduced by 10 μM Ni2+ that blocked 50% of T-type Ca2+ currents and had a little effect on HVA Ca2+ currents in sympathetic MPG neurons. Furthermore, generation of the rebound spikes was completely prevented by 100 μM Ni2+ that blocked most of the T-type Ca2+ currents. In conclusions, T-type Ca2+ currents in MPG neurons mainly arise from α1H among the three isoforms (α1G, α1H, and α1I) and may contribute to generation of low-threshold spikes in sympathetic MPG neurons.