bluuebunny/crossref_metadata_2025 huggingface dataset:
Site Independence of EPSP Time Course Is Mediated by DendriticI h in Neocortical Pyramidal Neurons
Authors: Williams Stephen R. , Stuart Greg J.
Published: December 2017

Neocortical layer 5 pyramidal neurons possess long apical dendrites that receive a significant portion of the neurons excitatory synaptic input. Passive neuronal models indicate that the time course of excitatory postsynaptic potentials (EPSPs) generated in the apical dendrite will be prolonged as they propagate toward the soma. EPSP propagation may, however, be influenced by the recruitment of dendritic voltage-activated channels. Here we investigate the properties and distribution of I h channels in the axon, soma, and apical dendrites of neocortical layer 5 pyramidal neurons, and their effect on EPSP time course. We find a linear increase (9 pA/100 μm) in the density of dendritic I hchannels with distance from soma. This nonuniform distribution of I h channels generates site independence of EPSP time course, such that the half-width at the soma of distally generated EPSPs (up to 435 μm from soma) was similar to somatically generated EPSPs. As a corollary, a normalization of temporal summation of EPSPs was observed. The site independence of somatic EPSP time course was found to collapse after pharmacological blockade of I h channels, revealing pronounced temporal summation of distally generated EPSPs, which could be further enhanced by TTX-sensitive sodium channels. These data indicate that an increasing density of apical dendritic I hchannels mitigates the influence of cable filtering on somatic EPSP time course and temporal summation in neocortical layer 5 pyramidal neurons.
Modulation of Pacemaker Activity by Salmon Gonadotropin-Releasing Hormone (sGnRH) in Terminal Nerve (TN)-GnRH Neurons
Authors: Abe Hideki , Oka Yoshitaka
Published: December 2017

The terminal nerve (TN)-gonadotropin-releasing hormone (GnRH) neurons project widely in the brain instead of the pituitary and show endogenous pacemaker activity that is dependent on the physiological conditions of the animal. We suggest that the TN-GnRH system may act as a putative neuromodulator that is involved in the regulation of many long-lasting changes in the animal's behavior. In the present study, we find that the pacemaker activity of TN-GnRH neurons is modulated by salmon GnRH (sGnRH), which is the same molecular species of GnRH peptide produced by TN-GnRH neurons themselves. Bath application of sGnRH (2–200 nM) transiently decreased (early phase) and then subsequently increased (late phase) the frequency of pacemaker activity of TN-GnRH neurons in a dose-dependent manner. These biphasic changes of pacemaker activities were suppressed by intracellular application of guanosin 5′-0-(2-thiodi-phosphate) (GDP-β-S). The results suggest that G-protein coupled receptors are present on the cell surface and play a triggering role in modulating the frequency of pacemaker activities in TN-GnRH neurons. Because the TN-GnRH neurons make tight cell clusters with no intervening glial cells, it may be further suggested that GnRH released from GnRH neurons regulates the activities of their own (autocrine) and/or neighboring GnRH neurons (paracrine).
Modeling Attractor Deformation in the Rodent Head-Direction System
Authors: Goodridge Jeremy P. , Touretzky David S.
Published: December 2017

We present a model of the head-direction circuit in the rat that improves on earlier models in several respects. First, it provides an account of some of the unique characteristics of head-direction (HD) cell firing in the lateral mammillary nucleus and the anterior thalamus. Second, the model functions without making physiologically unrealistic assumptions. In particular, it implements attractor dynamics in postsubiculum and lateral mammillary nucleus without directionally tuned inhibitory neurons, which have never been observed in vivo, and it integrates angular velocity without the use of multiplicative synapses. The model allows us to examine the relationships among three HD areas and various properties of their representations. A surprising result is that certain combinations of purported HD cell properties are mutually incompatible, suggesting that the lateral mammillary nucleus may not be the primary source of head direction input to anterior thalamic HD cells.
Properties of a Calcium-Activated K+ Current on Interneurons in the Developing Rat Hippocampus
Authors: Aoki Takuya , Baraban Scott C.
Published: December 2017

Calcium-activated potassium currents have an essential role in regulating excitability in a variety of neurons. Although it is well established that mature CA1 pyramidal neurons possess a Ca2+-activated K+ conductance ( I K(Ca)) with early and late components, modulation by various endogenous neurotransmitters, and sensitivity to K+ channel toxins, the properties of I K(Ca) on hippocampal interneurons (or immature CA1 pyramidal neurons) are relatively unknown. To address this problem, whole-cell voltage-clamp recordings were made from visually identified interneurons in stratum lacunosum-moleculare (L-M) and CA1 pyramidal cells in hippocampal slices from immature rats (P3–P25). A biphasic calcium-activated K+ tail current was elicited following a brief depolarization from the holding potential (−50 mV). Analysis of the kinetic properties of I K(Ca)suggests that an early current component differs between these two cell types. An early I K(Ca) with a large peak current amplitude (200.8 ± 13.2 pA, mean ± SE), slow time constant of decay (70.9 ± 3.3 ms), and relatively rapid time to peak (within 15 ms) was observed on L-M interneurons ( n = 88), whereas an early I K(Ca) with a small peak current amplitude (112.5 ± 7.3 pA), a fast time constant of decay (39.4 ± 1.6 ms), and a slower time-to-peak (within 26 ms) was observed on CA1 pyramidal neurons ( n = 85). Removal of extracellular calcium or addition of inorganic Ca2+ channel blockers (cadmium, nickel, or cobalt) was used to demonstrate the calcium dependence of these currents. Addition of norepinephrine, carbachol, and a variety of channel toxins (apamin, iberiotoxin, verruculogen, paxilline, penitrem A, and charybdotoxin) were used to further distinguish between I K(Ca) on these two hippocampal cell types. Verruculogen (100 nM), carbachol (100 μM), apamin (100 nM), TEA (1 mM), and iberiotoxin (50 nM) significantly reduced early I K(Ca) on CA1 pyramidal neurons; early I K(Ca) on L-M interneurons was inhibited by apamin and TEA. Combined with previous work showing that the firing properties of hippocampal interneurons and pyramidal cells differ, our kinetic and pharmacological data provide strong support for the hypothesis that different types of Ca2+-activated K+ current are present on these two cell types.
Human Anterior Cingulate Cortex Neurons Modulated by Attention-Demanding Tasks
Authors: Davis Karen D. , Hutchison William D. , Lozano Andres M. , Tasker Ronald R. , Dostrovsky Jonathan O.
Published: December 2017

Recent imaging studies have implicated the anterior cingulate cortex (ACC) in various cognitive functions, including attention. However, until now, there was no evidence for changes in neuronal activity of individual ACC neurons during performance of tasks that require attention and effortful thought. We hypothesized these neurons must exist in the human ACC. In this study, we present electrophysiological data from microelectrode single neuron recordings in the human ACC of neuronal modulation during attention-demanding tasks in 19% of 36 neurons tested. These findings provide the first direct evidence of an influence of a cognitive state on the spontaneous neuronal activity of human ACC neurons.
Onset of Cross-Modal Synthesis in the Neonatal Superior Colliculus is Gated by the Development of Cortical Influences
Authors: Wallace M. T. , Stein B. E.
Published: December 2017

Many neurons in the superior colliculus (SC) are able to integrate combinations of visual, auditory, and somatosensory stimuli, thereby markedly affecting the vigor of their responses to external stimuli. However, this capacity for multisensory integration is not inborn. Rather, it appears comparatively late in postnatal development and is not expressed until the SC passes through several distinct developmental stages. As shown here, the final stage in this sequence is one in which a region of association cortex establishes functional control over the SC, thus enabling the multisensory integrative capabilities of its target SC neurons. The first example of this corticotectal input was seen at postnatal day 28. For any individual SC neuron, the onset of corticotectal influences appeared to be abrupt. Because this event occurred at very different times for different SC neurons, a period of 3–4 postnatal months was required before the adult-like condition was achieved. The protracted postnatal period required for the maturation of these corticotectal influences corresponded closely with estimates of the peak period of cortical plasticity, raising the possibility that the genesis of these corticotectal influences, and hence the onset of SC multisensory integration, occurs only after the cortex is capable of exerting experience-dependent control over SC neurons.
Shapes and Level Tolerances of Frequency Tuning Curves in Primary Auditory Cortex: Quantitative Measures and Population Codes
Authors: Sutter Mitchell L.
Published: December 2017

The shape and level tolerance of the excitatory frequency/intensity tuning curves (eFTCs) of 160 cat primary auditory cortical (A1) neurons were investigated. Overall, A1 cells were characterized by tremendous variety in eFTC shapes and symmetries; eFTCs were U-shaped (∼20%), V-shaped (∼20%), lower-tail-upper-sharp (∼15%), upper-tail-lower-sharp (<2%), slant-lower (∼10%), slant-upper (<3%), multipeaked (∼10%), and circumscribed (∼20%). Quantitative analysis suggests that eFTC are best thought of as forming a continuum of shapes, rather than falling into discrete categories. A1 eFTCs tended to be more level tolerant than eFTCs from earlier stations in the ascending auditory system as inferred from other studies. While individual peaks of multipeaked eFTCs were similar to single peaked eFTCs, the overall eFTC of multipeaked neurons (spanning the range of all peaks) tended to have high-frequency tails. Measurements of shape and symmetry indicate that A1 eFTCs, on average, tended to have greater area on the low-frequency side of characteristic frequency (CF) than on the high-frequency side. A1 cells showed a relationship between CF and the inverse slope of low-frequency edges of eFTCs, but not for high-frequency edges. These data demonstrate that frequency tuning, particularly along the eFTC low-frequency border, sharpens along the lemniscal pathway to A1. The results are consistent with studies in mustached bats ( Suga 1997 ) and support the idea that spectral decomposition along the ascending lemniscal pathway up to A1 is a general organizing principle of mammalian auditory systems. Altogether, these data suggest that A1 neurons' eFTCs are shaped by complex patterns of inhibition and excitation accumulating along the auditory pathways, implying that central rather than peripheral filtering properties are responsible for certain psychophysical phenomena.
Response Patterns in Second Somatosensory Cortex (SII) of Awake Monkeys to Passively Applied Tactile Gratings
Authors: Pruett J. R. , Sinclair R. J. , Burton H.
Published: December 2017

This experiment explored the effects of controlled manipulations of three parameters of tactile gratings, groove width (1.07–2.53 mm), contact force (30–90 g), and scanning speed (40–120 mm/s), on the responses of cells in second somatosensory cortex (SII) of awake monkeys that were performing a groove-width classification task with passively presented stimuli. A previous experiment involving an active touch paradigm demonstrated that macaque SII cells code groove-width and hand-movement parameters in their average firing rates. The present study used a passive-touch protocol to remove somatosensory activation related to hand movements that accompany haptic exploration of surfaces. Monkeys maintained a constant hand position while a robotic device delivered stimulation with tactile gratings to a single stabilized finger pad. Single-unit recordings isolated 216 neurons that were retrospectively assigned to SII on histological criteria. Firing patterns for 86 of these SII cells were characterized in detail, while monkeys classified gratings as rough (1.90 and 2.53 mm groove widths) or smooth (1.07 and 1.42 mm groove widths), with trial-wise random, parametric manipulation of force or speed; the monkeys compared 1.07 versus 1.90 mm and 1.42 versus 2.53 mm in alternating blocks of trials. We studied 33 cells with systematic variation of groove width and force, 49 with groove width and speed, and four with all three variables. Sixty-three cells were sensitive to groove width, 43 to force (effects of random force in speed experiments contributed to N), and 34 to speed. Relatively equal numbers of cells changed mean firing rates as positive or negative functions of increasing groove width, force, and/or speed. Cells typically changed mean firing rates for two or three of the independent variables. Effects of groove width, force, and speed were additive or interactive. The variety of response functions was similar to that found in a prior study of primary somatosensory cortex (SI) that used passive touch. The SII sample population showed correlated changes (both positive and negative) in firing rates with increasing groove width and force and to a lesser degree, with increasing groove width and speed. This correlation is consistent with human psychophysical studies that found increasing groove width and force increase perceived roughness magnitude, and it strengthens the argument for SII's direct involvement in roughness perception.
Role of the Cerebellar Posterior Interpositus Nucleus in Saccades I. Effect of Temporary Lesions
Authors: Robinson Farrel R.
Published: December 2017

The ventrolateral corner of the cerebellar posterior interpositus nucleus (VPIN) contains many neurons that respond during saccades. To characterize the VPIN contribution to saccades, I located this area in three monkeys with single-unit recording and injected the GABAA agonist muscimol among saccade-related neurons there to reduce or eliminate neural activity. I compared the size, direction, velocity, and duration of saccades recorded before and after a unilateral injection in all three monkeys. In two of three monkeys, I also examined saccades after bilateral injection. After unilateral VPIN inactivation, upward saccades were abnormally large (avg. across all 3 monkeys = 112% of normal) and downward saccades were abnormally small (avg. across all 3 monkeys = 94% of normal). In the two monkeys tested, bilateral inactivation increased these abnormalities. Upward saccades went from 111% of normal size in these two monkeys after unilateral inactivation to 120% after bilateral inactivation; downward saccades went from 97 to 86%. VPIN inactivation caused changes in saccade gain and did not add of a constant offset to saccades. (The 1 exception was upward saccades in 1 monkey in which both gain and offset changed.) Neither uni- nor bilateral VPIN inactivation consistently affected the size of horizontal saccades (uni- avg. = 101% normal; bi- avg. = 97% normal). In two of the three monkeys, saccades to horizontal targets angled significantly upward after VPIN inactivation (uni- avg. = 3.6° above normal, bi- avg. = 10.3° above normal). The velocities of horizontal saccades were not strongly affected, but downward saccades exhibited abnormally low peak velocities and long durations. Upward velocities were inconsistently changed. I interpret these results to mean that the activity of some VPIN neurons helps drive the eyes downward and the activity of others helps drive the eyes upward. The downward drive outweighs the upward drive. The net effect of VPIN inactivation is to deprive all saccades of a downward component and to slow downward saccades.
Hyperthermic Spreading Depressions in the Immature Rat Hippocampal Slice
Authors: Wu Jie , Fisher Robert S.
Published: December 2017

Febrile seizures are the most common seizure type in children (6 mo to 5 yr). The pathophysiology of febrile seizures is unknown. Current genetic studies show that some febrile seizures result from channelopathies. We have performed electrophysiological experiments in in vitro hippocampal slices to test a novel hypothesis that a disordered regulation of ionic homeostasis underlies the genesis of febrile seizures. In transverse hippocampal CA1 slices from 104 rats, temperature increase from 34° to 40°C produced a series of spreading depressions (SDs), called hyperthermic SDs. The hyperthermic SDs were age-dependent, occurring in only 1/17 8–16 day-old animals, 44/49 17–60 day-old animals, and 11/20 rats older than than 60 days. The hyperthermic SDs usually occurred on the rising phase of the temperature. The mean temperature to trigger a first hyperthermic SD was 38.8 ± 1.3°C (mean ± SD, n = 44). The hyperthermic SDs induced a reversible loss of evoked synaptic potentials and a dramatic decrease of input resistance. Neuronal and field epileptiform bursting occurred in the early phases of the hyperthermic SD. During hyperthermic SDs, pyramidal cell membrane potential depolarized by 38.3 ± 4.9 mV ( n = 20), extracellular field shifted negative 18.5 ± 3.9 mV ( n = 44), and extracellular K+ rose reversibly to 43.8 ± 10.9 mM ( n = 6). Similar SDs could be evoked by ouabain or transient hypoxia with normal temperature. Tetrodotoxin could block initial epileptiform bursting, without blocking SDs. Hyperthermia-induced SDs should be investigated as possible contributing factors to febrile seizures.
Development of Rat Chorda Tympani Sodium Responses: Evidence for Age-Dependent Changes in Global Amiloride-Sensitive Na+Channel Kinetics
Authors: Hendricks Susan J. , Stewart Robert E. , Heck Gerard L. , DeSimone John A. , Hill David L.
Published: December 2017

In rat, chorda tympani nerve taste responses to Na+ salts increase between roughly 10 and 45 days of age to reach stable, mature magnitudes. Previous evidence from in vitro preparations and from taste nerve responses using Na+ channel blockers suggests that the physiological basis for this developmental increase in gustatory Na+ sensitivity is the progressive addition of functional, Na+ transduction elements (i.e., amiloride-sensitive Na+ channels) to the apical membranes of fungiform papilla taste receptor cells. To avoid potential confounding effects of pharmacological interventions and to permit quantification of aggregate Na+ channel behavior using a kinetic model, we obtained chorda tympani nerve responses to NaCl and sodium gluconate (NaGlu) during receptive field voltage clamp in rats aged from 12–14 to 60 days and older (60+ days). Significant, age-dependent increases in chorda tympani responses to these stimuli occurred as expected. Importantly, apical Na+ channel density, estimated from an apical Na+ channel kinetic model, increased monotonically with age. The maximum rate of Na+response increase occurred between postnatal days 12–14 and 29–31. In addition, estimated Na+ channel affinity increased between 12–14 and 19–23 days of age, i.e., on a time course distinct from that of the maximum rate of Na+response increase. Finally, estimates of the fraction of clamp voltage dropped across taste receptor apical membranes decreased between 19–23 and 29–31 days of age for NaCl but remained stable for NaGlu. The stimulus dependence of this change is consistent with a developmental increase in taste bud tight junctional Cl− ion permeability that lags behind the developmental increase in apical Na+ channel density. A significant, indirect anion influence on apical Na+ channel properties was present at all ages tested. This influence was evident in the higher apparent apical Na+ channel affinities obtained for NaCl relative to NaGlu. This stimulus-dependent modulation of apical Na+ channel apparent affinity relies on differences in the transepithelial potentials between NaCl and NaGlu. These originate from differences in paracellular anion permeability but act also on the driving force for Na+ through apical Na+channels. Detection of such an influence on taste depends fundamentally on the preservation of taste bud polarity and on a direct measure of sensory function, such as the response of primary afferents.
Augmentation of L-Type Calcium Current by Hypoxia in Rabbit Carotid Body Glomus Cells: Evidence for a PKC-Sensitive Pathway
Authors: Summers Beth A. , Overholt Jeffrey L. , Prabhakar Nanduri R.
Published: December 2017

Previous studies have suggested that voltage-gated Ca2+influx in glomus cells plays a critical role in sensory transduction at the carotid body chemoreceptors. The purpose of the present study was to determine the effects of hypoxia on the Ca2+current in glomus cells and to elucidate the underlying mechanism(s). Experiments were performed on freshly dissociated glomus cells from rabbit carotid bodies. Ca2+current was monitored using the whole cell configuration of the patch-clamp technique, with Ba2+as the charge carrier. Hypoxia (pO2= 40 mmHg) augmented the Ca2+current by 24 ± 3% ( n= 42, at 0 mV) in a voltage-independent manner. This effect was seen in a CO2/HCO3−-, but not in a HEPES-buffered extracellular solution at pH 7.4 ( n= 6). When the pH of a HEPES-buffered extracellular solution was lowered from 7.4 to 7.0, hypoxia augmented the Ca2+current by 20 ± 5% ( n= 4, at 0 mV). Nisoldipine, an L-type Ca2+channel blocker (2 μM, n = 6), prevented, whereas, ω-conotoxin MVIIC (2 μM, n = 6), an inhibitor of N and P/Q type Ca2+channels, did not prevent augmentation of the Ca2+current by hypoxia, implying that low oxygen affects L-type Ca2+channels in glomus cells. Protein kinase C (PKC) inhibitors, staurosporine (100 nM, n = 6) and bisindolylmaleimide (2 μM, n = 8, at 0 mV), prevented, whereas, a protein kinase A inhibitor (4 nM PKAi, n = 10) did not prevent the hypoxia-induced increase of the Ca2+current. Phorbol 12-myristate 13-acetate (PMA, 100 nM), a PKC activator, augmented the Ca2+current by 20 ± 3% ( n = 8, at 0 mV). In glomus cells treated with PMA overnight (100 nM), hypoxia did not augment the Ca2+current (−3 + 4%, n = 5, at 0 mV). Immunocytochemical analysis revealed PKCδ-like immunoreactivity in the cytosol of the glomus cells. Following hypoxia (6% O2for 5 min), PKCδ-like immunoreactivity translocated to the plasma membrane in 87 ± 3% of the cells, indicating PKC activation. These results demonstrate that hypoxia augments Ca2+current through L-type Ca2+channels via a PKC-sensitive mechanism.
Pharmacology of GABAAReceptors of Retinal Dopaminergic Neurons
Authors: Feigenspan Andreas , Gustincich Stefano , Raviola Elio
Published: December 2017

When the vertebrate retina is stimulated by light, a class of amacrine or interplexiform cells release dopamine, a modulator responsible for neural adaptation to light. In the intact retina, dopamine release can be pharmacologically manipulated with agonists and antagonists at GABAAreceptors, and dopaminergic (DA) cells receive input from GABAergic amacrines. Because there are only 450 DA cells in each mouse retina and they cannot be distinguished in the living state from other cells on the basis of their morphology, we used transgenic technology to label DA cells with human placental alkaline phosphatase, an enzyme that resides on the outer surface of the cell membrane. We could therefore identify DA cells in vitro after dissociation of the retina and investigate their activity with whole cell voltage clamp. We describe here the pharmacological properties of the GABAAreceptors of solitary DA cells. GABA application induces a large inward current carried by chloride ions. The receptors are of the GABAAtype because the GABA-evoked current is blocked by bicuculline. Their affinity for GABA is very high with an EC50value of 7.4 μM. Co-application of benzodiazepine receptor ligands causes a strong increase in the peak current induced by GABA (maximal enhancement: CL-218872 220%; flunitrazepam 214%; zolpidem 348%) proving that DA cells express a type I benzodiazepine-receptor (BZ1). GABA-evoked currents are inhibited by Zn2+with an IC50of 58.9 ± 8.9 μM. Furthermore, these receptors are strongly potentiated by the modulator alphaxalone with an EC50of 340 ± 4 nM. The allosteric modulator loreclezole increases GABA receptor currents by 43% (1 μM) and by 107% (10 μM). Using outside-out patches, we measured in single-channel recordings a main conductance (29 pS) and two subconductance (20 and 9 pS) states. We have previously shown by single-cell RT-PCR and immunocytochemistry that DA cells express seven different GABAAreceptor subunits (α1, α3, α4, β1, β3, γ1, γ2S, and γ2L) and by immunocytochemistry that all subunits are expressed in the intact retina. We show here that at least α1, β3 and γ2 subunits are assembled into functional receptors.
Relation Between the Metrics of the Presaccadic Attention Shift and of the Saccade Before and After Saccadic Adaptation
Authors: Ditterich J. , Eggert T. , Straube A.
Published: December 2017

A shift of the visual attention focus is known to precede saccades. However, how the metrics of both this presaccadic attention shift and the saccade are coupled is still unclear. We altered the saccade size by short-term saccadic adaptation to determine whether the attention focus would still be shifted to the location of the saccade target or to the modified postsaccadic eye position. The results showed that saccadic adaptation had no influence on the presaccadic attention shift. Thus either different processes determine the metrics of the attention shift and of the saccade or saccadic adaptation causes only modifications on a lower hierarchical level of saccade programming, thereby not influencing the metrics of the attention shift.
Laminar and Temporal Heterogeneity of NMDA/Metabotropic Glutamate Receptor Binding in Posterior Cingulate Cortex
Authors: Hedberg Thomas G. , Sperber Ellen F. , Velíšková Jana , Moshé Solomon L.
Published: December 2017

Both N-methyl-d-aspartate (NMDA) and quisqualate/AMPA-insensitive metabotropic glutamate (mGlu) receptors mediate plasticity induction in neocortex, but their interlaminar distribution in cortical microcircuits is largely unknown. We used (+)3H-MK801 and3H-glutamate binding plus saturating concentrations of NMDA, AMPA, and quisqualate to autoradiographically map NMDA and mGlu receptor sites by lamina in posterior cingulate cortex in adult male rats. Specific binding at NMDA receptor sites in laminae II/III and VI was significantly reduced in comparison to other laminae. Brains prepared from rats killed during dark phase of a 12h/12h light/dark cycle showed a mean 129% increase in overall (+)3H-MK801 binding versus light phase brains but retained reduced binding densities in laminae II/III and VI. In contrast to NMDA findings, specific binding at mGlu sites was consistently elevated during light phase in both laminae II/III and VI. Specific 3H-glutamate binding in dark-phase brains showed an overall 147% increase versus light phase binding but did not retain significant interlaminar heterogeneity. Interpreted in accordance with our physiologically derived models of hippocampo-cortical microcircuitry, these results suggest that spatial and temporal variations in glutamate receptor distribution may play an important role in intracingulate neural processing of afferent input from hippocampus.
Long-Term Potentiation/Depotentiation Are Accompanied by Complex Changes in Spontaneous Unit Activity in the Hippocampus
Authors: Kimura Akihisa , Pavlides Constantine
Published: December 2017

Typically, long-term potentiation (LTP) has been assessed as long-lasting changes in field potentials or intracellularly recorded postsynaptic potentials evoked by activation of a set of afferents. In the present experiment, we determined changes in spontaneous unit activity in the dentate gyrus (DG) following high-frequency (HFS) or low-frequency stimulation (LFS) of the medial perforant pathway. Experiments were performed in anesthetized rats. Field potentials and unit recordings were obtained alternatively from the same recording electrode. Of 39 single units isolated (from 25 independent sessions), the spontaneous discharges of 13 units (33%) increased, while 7 units (18%) decreased their discharges following HFS that induced significant LTP of the field potentials. Such opposing modulations of unit discharges following HFS were observed on simultaneously recorded units. LFS applied following HFS also induced bi-directional effects on unit discharges. Of 20 single units isolated from a subset of recordings (12 experiments) to which LFS was applied, 6 units increased and 4 units decreased their discharges. LFS produced a long-lasting (>20 min) depotentiation, to the baseline level, on field potentials in four recording cases. The autocorrelation functions indicated that the isolated unit discharges were comparable to those of the putative DG granule cells and interneurons, shown in previous studies. The results suggest that changes in synaptic efficacy following HFS or LFS produce rather dynamic changes in cell activity in the DG.
Optical Monitoring of Neuronal Activity During Spontaneous Sharp Waves in Chronically Epileptic Human Neocortical Tissue
Authors: Köhling Rüdiger , Höhling Jörg-Michael , Straub Heidrun , Kuhlmann Dieter , Kuhnt Ulrich , Tuxhorn Ingrid , Ebner Alois , Wolf Peter , Pannek Heinz-Wolfgang , Gorji Ali , Speckmann Erwin-Josef
Published: December 2017

Functional changes in neuronal circuitry reflected in spontaneously occurring synchronous sharp field potentials (SSFP) have been reported to occur in human brain suffering from chronic epileptogenicity but not in primary nonepileptic tissue from peritumoral resectates. Voltage sensitive dyes and fast imaging were used to visualize spontaneously occurring rhythmic depolarizations correlated to SSFP in chronically epileptic human neocortical slices obtained during epilepsy surgery. Localized and spatially inhomogeneous neuronal depolarizations were found to underlie spontaneous SSFP, which remained unchanged and spatially restricted to foci <750 μm diam even under epileptogenic (low-Mg2+) conditions. In cases where ictaform paroxysmal activity occurred in low-Mg2+medium, neuronal depolarizations were wide-spread but still spatially inhomogeneous, and the events were preferentially initiated at distinct foci. The findings suggest that small neuronal networks are able to establish and maintain synchronous rhythmic and epileptiform activity.
Vestibulospinal and Reticulospinal Neuronal Activity During Locomotion in the Intact Cat. II. Walking on an Inclined Plane
Authors: Matsuyama Kiyoji , Drew Trevor
Published: December 2017

The experiments described in this report were designed to determine the contribution of vestibulospinal neurons (VSNs) in Deiters' nucleus and of reticulospinal neurons (RSNs) in the medullary reticular formation to the modifications of the walking pattern that are associated with locomotion on an inclined plane. Neuronal discharge patterns were recorded from 44 VSNs and 63 RSNs in cats trained to walk on a treadmill whose orientation was varied from +20° (uphill) to −10° (downhill), referred to as pitch tilt, and from 20° roll tilt left to 20° roll tilt right. During uphill locomotion, a majority of VSNs (25/44) and rhythmically active RSNs (24/39) showed an increase in peak discharge frequency, above that observed during locomotion on a level surface. VSNs, unlike some of the RSNs, exhibited no major deviations from the overall pattern of the activity recorded during level walking. The relative increase in discharge frequency of the RSNs (on average, 31.8%) was slightly more than twice that observed in the VSNs (on average, 14.4%), although the average absolute change in discharge frequency was similar (18.2 Hz in VSNs and 21.6 Hz in RSNs). Changes in discharge frequency during roll tilt were generally more modest and were more variable, than those observed during uphill locomotion as were the relative changes in the different limb muscle electromyograms that we recorded. In general, discharge frequency in VSNs was more frequently increased when the treadmill was rolled to the right (ear down contralateral to the recording site) than when it was rolled to the left. Most VSNs that showed significant linear relationships with treadmill orientation in the roll plane increased their activity during right roll and decreased activity during left roll. Discharge activity in phasically modulated RSNs was also modified by roll tilt of the treadmill. Modulation of activity in RSNs that discharged twice in each step cycle was frequently reciprocal in that one burst of activity would increase during left roll and the other during right roll. The overall results indicate that each system contributes to the changes in postural tone that are required to adapt the gait for modification on an inclined surface. The characteristics of the discharge activity of the VSNs suggest a role primarily in the overall control of the level of electromyographic activity, while the characteristics of the RSNs suggest an additional role in determining the relative level of different muscles, particularly when the pattern is asymmetric.
Effect of Extracellular HCO3 − on Na+Channel Characteristics in Hippocampal CA1 Neurons
Authors: Gu Xiang Q. , Yao Hang , Haddad Gabriel G.
Published: December 2017

The effect of HCO3 −/CO2 on membrane properties of isolated hippocampal CA1 neurons was studied with the use of the whole cell configuration of the patch-clamp technique. Neurons were acutely dissociated from 21- to 30-day-old mice. In the current-clamp mode, HCO3 −/CO2significantly hyperpolarized CA1 neurons by more than 10 mV and decreased their input resistance. In addition, the overall excitability of these neurons was lower in the presence of HCO3 −/CO2 than in HEPES. Spontaneous and evoked action potential firing frequency was lower in the presence of HCO3 −/CO2 than in its absence. In the voltage-clamp mode, both activation and steady-state inactivation of a fast Na+ current were shifted in the hyperpolarized direction in such a way that the window currents were smaller in HCO3 −/CO2 than in HEPES. Recovery from inactivation and deactivation from the open state of the fast Na+ current was slower in HCO3 −/CO2 than in HEPES. We conclude that HCO3 −/CO2decreases the intrinsic excitability of CA1 neurons by altering not only the passive properties of the neuronal membranes but also by changing several characteristics of the fast Na+current, including activation and inactivation kinetics as well as the recovery from inactivation and deactivation.
Spatiotemporal Properties of Fast and Slow Neurons in the Pretectal Nucleus Lentiformis Mesencephali in Pigeons
Authors: Wylie Douglas R. W. , Crowder Nathan A.
Published: December 2017

Neurons in the pretectal nucleus lentiformis mesencephali (LM) are involved in the analysis of optic flow that results from self-motion. Previous studies have shown that LM neurons have large receptive fields in the contralateral eye, are excited in response to largefield stimuli moving in a particular (preferred) direction, and are inhibited in response to motion in the opposite (anti-preferred) direction. We investigated the responses of LM neurons to sine wave gratings of varying spatial and temporal frequency drifting in the preferred and anti-preferred directions. The LM neurons fell into two categories. “Fast” neurons were maximally excited by gratings of low spatial [0.03–0.25 cycles/° (cpd)] and mid-high temporal frequencies (0.5–16 Hz). “Slow” neurons were maximally excited by gratings of high spatial (0.35–2 cpd) and low-mid temporal frequencies (0.125–2 Hz). Of the slow neurons, all but one preferred forward (temporal to nasal) motion. The fast group included neurons that preferred forward, backward, upward, and downward motion. For most cells (81%), the spatial and temporal frequency that elicited maximal excitation to motion in the preferred direction did not coincide with the spatial and temporal frequency that elicited maximal inhibition to gratings moving in the anti-preferred direction. With respect to motion in the anti-preferred direction, a substantial proportion of the LM neurons (32%) showed bi-directional responses. That is, the spatiotemporal plots contained domains of excitation in addition to the region of inhibition. Neurons tuned to stimulus velocity across different spatial frequency were rare (5%), but some neurons (39%) were tuned to temporal frequency. These results are discussed in relation to previous studies of the responses of neurons in the accessory optic system and pretectum to drifting gratings and other largefield stimuli.
Voltage-Dependent Na+ Currents in Mammalian Retinal Cone Bipolar Cells
Authors: Pan Zhuo-Hua , Hu Hui-Juan
Published: December 2017

Voltage-dependent Na+ channels are usually expressed in neurons that use spikes as a means of signal coding. Retinal bipolar cells are commonly thought to be nonspiking neurons, a category of neurons in the CNS that uses graded potential for signal transmission. Here we report for the first time voltage-dependent Na+ currents in acutely isolated mammalian retinal bipolar cells with whole cell patch-clamp recordings. Na+ currents were observed in ∼45% of recorded cone bipolar cells but not in rod bipolar cells. Both on and off cone bipolar cells were found to express Na+ channels. The Na+ currents were activated at membrane potentials around −50 to −40 mV and reached their peak around −20 to 0 mV. The half-maximal activation and steady-state inactivation potentials were −24.7 and −68.0 mV, respectively. The time course of recovery from inactivation could be fitted by two time constants of 6.2 and 81 ms. The amplitude of the Na+ currents ranged from a few to >300 pA with the current density in some cells close or comparable to that of retinal third neurons. In current-clamp recordings, Na+-dependent action potentials were evoked in Na+-current-bearing bipolar cells by current injections. These findings raise the possibility that voltage-dependent Na+ currents may play a role in bipolar cell function.
Hypoxic Augmentation of Fast-Inactivating and Persistent Sodium Currents in Rat Caudal Hypothalamic Neurons
Authors: Horn Eric M. , Waldrop Tony G.
Published: December 2017

Previous work from this laboratory has indicated that TTX-sensitive sodium channels are involved in the hypoxia-induced inward current response of caudal hypothalamic neurons. Since this inward current underlies the depolarization and increased firing frequency observed in these cells during hypoxia, the present study utilized more detailed biophysical methods to specifically determine which sodium currents are responsible for this hypoxic activation. Caudal hypothalamic neurons from ∼3-wk-old Sprague-Dawley rats were acutely dissociated and patch-clamped in the voltage-clamp mode to obtain recordings from fast-inactivating and persistent (noninactivating) whole cell sodium currents. Using computer-generated activation and inactivation voltage protocols, rapidly inactivating sodium currents were analyzed during normal conditions and during a brief (3–6 min) period of severe hypoxia. In addition, voltage-ramp and extended-voltage-activation protocols were used to analyze persistent sodium currents during normal conditions and during hypoxia. A polarographic oxygen electrode determined that the level of oxygen in this preparation quickly dropped to 10 Torr within 2 min of initiation of hypoxia and stabilized at <0.5 Torr within 4 min. During hypoxia, the peak fast-inactivating sodium current was significantly increased throughout the entire activation range, and both the activation and inactivation values ( V 1/2) were negatively shifted. Furthermore both the voltage-ramp and extended-activation protocols demonstrated a significant increase in the persistent sodium current during hypoxia when compared with normoxia. These results demonstrate that both rapidly inactivating and persistent sodium currents are significantly enhanced by a brief hypoxic stimulus. Furthermore the hypoxic-induced increase in these currents most likely is the primary mechanism for the depolarization and increased firing frequency observed in caudal hypothalamic neurons during hypoxia. Since these neurons are important in modulating cardiorespiratory activity, the oxygen responsiveness of these sodium currents may play a significant role in the centrally mediated cardiorespiratory response to hypoxia.
Characterization of Ca2+ Channels in Rat Subthalamic Nucleus Neurons
Authors: Song Wen-Jie , Baba Yosuke , Otsuka Takeshi , Murakami Fujio
Published: December 2017

The subthalamic nucleus (STN) plays a key role in motor control. Although previous studies have suggested that Ca2+ conductances may be involved in regulating the activity of STN neurons, Ca2+ channels in this region have not yet been characterized. We have therefore investigated the subtypes and functional characteristics of Ca2+ conductances in STN neurons, in both acutely isolated and slice preparations. Acutely isolated STN cells were identified by retrograde filling with the fluorescent dye, Fluoro-Gold. In acutely isolated STN neurons, Cd2+-sensitive, depolarization-activated Ba2+ currents were observed in all cells studied. The current-voltage relationship and current kinetics were characteristic of high-voltage–activated Ca2+channels. The steady-state voltage-dependent activation curves and inactivation curves could both be fitted with a single Boltzmann function. Currents evoked with a prolonged pulse, however, inactivated with multiple time constants, suggesting either the presence of more than one Ca2+ channel subtype or multiple inactivation processes with a single channel type in STN neurons. Experiments using organic Ca2+ channel blockers revealed that on average, 21% of the current was nifedipine sensitive, 52% was sensitive to ω-conotoxin GVIA, 16% was blocked by a high concentration of ω-agatoxin IVA (200 nM), and the remainder of the current (9%) was resistant to the co-application of all blockers. These currents had similar voltage dependencies, but the nifedipine-sensitive current and the resistant current activated at slightly lower voltages. ω-Agatoxin IVA at 20 nM was ineffective in blocking the current. Together, the above results suggest that acutely isolated STN neurons have all subtypes of high-voltage–activated Ca2+ channels except for P-type, but have no low-voltage–activated channels. Although acutely isolated neurons provide a good preparation for whole cell voltage-clamp study, dendritic processes are lost during dissociation. To gain information on Ca2+ channels in dendrites, we thus studied Ca2+ channels of STN neurons in a slice preparation, focusing on low-voltage–activated channels. In current-clamp recordings, a slow spike was always observed following termination of an injected hyperpolarizing current. The slow spike occurred at resting membrane potentials and was sensitive to micromolar concentrations of Ni2+, suggesting that it is a low-threshold Ca2+ spike. Together, our results suggest that STN neurons express low-voltage–activated Ca2+ channels and several high-voltage–activated subtypes. Our results also suggest the possibility that the low-voltage–activated channels have a preferential distribution to the dendritic processes.
End Points of Planar Reaching Movements Are Disrupted by Small Force Pulses: An Evaluation of the Hypothesis of Equifinality
Authors: Popescu Florin C. , Rymer W. Zev
Published: December 2017

A single force pulse was applied unexpectedly to the arms of five normal human subjects during nonvisually guided planar reaching movements of 10-cm amplitude. The pulse was applied by a powered manipulandum in a direction perpendicular to the motion of the hand, which gripped the manipulandum via a handle at the beginning, at the middle, or toward the end the movement. It was small and brief (10 N, 10 ms), so that it was barely perceptible. We found that the end points of the perturbed motions were systematically different from those of the unperturbed movements. This difference, dubbed “terminal error,” averaged 14.4 ± 9.8% (mean ± SD) of the movement distance. The terminal error was not necessarily in the direction of the perturbation, although it was affected by it, and it did not decrease significantly with practice. For example, while perturbations involving elbow extension resulted in a statistically significant shift in mean end-point and target-acquisition frequency, the flexion perturbations were not clearly affected. We argue that this error distribution is inconsistent with the “equilibrium point hypothesis” (EPH), which predicts minimal terminal error is determined primarily by the variance in the command signal itself, a property referred to as “equifinality.” This property reputedly derives from the “spring-like” properties of muscle and is enhanced by reflexes. To ensure that terminal errors were not due to mid-course voluntary corrections, we only accepted trials in which the final position was already established before such a voluntary response to the perturbation could have begun, that is, in a time interval shorter than the minimum reaction time (RT) for that subject. This RT was estimated for each subject in supplementary experiments in which the subject was instructed to move to a new target if perturbed and to the old target if no perturbation was detected. These RT movements were found to either stop or slow greatly at the original target, then re-accelerate to the new one. The average latency of this second motion was used to estimate the voluntary RT for each subject (316 ms mean). Additionally, we found that the hand neither exerted target-oriented force against the handle nor drifted toward the desired end point just before coming to rest, making it unlikely that the mechanical properties of the manipulandum prevented the hand from reaching its intended target.