bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of ATP-Sensitive Potassium Channels to Hypoxic Hyperpolarization in Rat Hippocampal CA1 Neurons In Vitro
Authors: Fujimura N. , Tanaka E. , Yamamoto S. , Shigemori M. , Higashi H.
Published: December 2017

Fujimura, N., E. Tanaka, S. Yamamoto, M. Shigemori, and H. Higashi. Contribution of ATP-sensitive potassium channels to hypoxic hyperpolarization in rat hippocampal CA1 neurons in vitro. J. Neurophysiol. 77: 378–385, 1997. To investigate the mechanism of generation of the hypoxia-induced hyperpolarization (hypoxic hyperpolarization) in hippocampal CA1 neurons in rat tissue slices, recordings were made in current-clamp mode and single-electrode voltage-clamp mode. Superfusion with hypoxic medium produced a hyperpolarization and corresponding outward current, which were associated with an increase in membrane conductance. Reoxygenation produced a further hyperpolarization, with corresponding outward current, followed by a recovery to the preexposure level. The amplitude of the posthypoxic hyperpolarization was always greater than that of the hypoxic hyperpolarization. In single-electrode voltage-clamp mode, it was difficult to record reproducible outward currents in response to repeated hypoxic exposure with the use of electrodes with a high tip resistance. The current-clamp technique was therefore chosen to study the pharmacological characteristics of the hypoxic hyperpolarization. In 60–80% of hippocampal CA1 neurons, glibenclamide or tolbutamide (3–100 μM) reduced the amplitude of the hypoxic hyperpolarization in a concentration-dependent manner by up to ∼70%. The glibenclamide or tolbutamide concentrations producing half-maximal inhibition of the hypoxic hyperpolarization were 6 and 12 μM, respectively. The chord conductance of the membrane potential between −80 and −90 mV in the absence of glibenclamide (30 μM) or tolbutamide (100 μM) was 2–3 times greater than that in the presence of glibenclamide or tolbutamide. In contrast, the reversal potential of the hypoxic hyperpolarization was approximately −83 mV in both the absence and presence of tolbutamide or glibenclamide. In ∼40% of CA1 neurons, diazoxide (100 μM) or nicorandil (1 mM) mimicked the hypoxic hyperpolarization and pretreatment of these drugs occluded the hypoxic hyperpolarization. When ATP was injected into the impaled neuron, hypoxic exposure could not produce a hyperpolarization. The intracellular injection of the nonhydrolyzable ATP analogue 5′-adenylylimidodiphosphate lithium salt reduced the amplitude of the hypoxic hyperpolarization. Furthermore, application of dinitrophenol (10 μM) mimicked the hypoxic hyperpolarization, and the dinitrophenol-induced hyperpolarization was inhibited by either pretreatment of tolbutamide or intracellular injection of ATP, indicating that the hypoxic hyperpolarization is highly dependent on intracellular ATP. It is therefore concluded that in the majority of hippocampal CA1 neurons, exposure to hypoxic conditions resulting in a reduction in the intracellular level of ATP leads to activation of ATP-sensitive potassium channels with concomitant hyperpolarization.
Modulation of Motoneuron Excitability by Brain-Derived Neurotrophic Factor
Authors: Gonzalez Michael , Collins William F.
Published: December 2017

Gonzalez, Michael and William F. Collins, III. Modulation of motoneuron excitability by brain-derived neurotrophic factor. J. Neurophysiol. 77: 502–506, 1997. The influence of neurotrophins on motoneuron survival and development has been well documented in cell cultures and neonates. In the present study, the role of brain-derived neurotrophic factor (BDNF) in the maintenance of motoneuron electrical properties was investigated. In adult male rats, BDNF- or saline-saturated gelfoam was inserted between the medial and lateral heads of the gastrocnemius muscles. After 5 days survival, in vivo intracellular recordings were obtained, and motoneuron biophysical properties were measured. In BDNF-treated rats, significant decreases in mean rheobase and in total cell capacitance of medial gastrocnemius motoneurons were observed. In addition, a concommitant increase in input resistance and decrease in membrane time constant were noted in BDNF-treated rats but were not statistically significant. No significant treatment effect was observed in motoneuron conduction velocity, action potential amplitude, equalizing time constant, electrotonic length, afterhyperpolarization amplitude and duration, and membrane potential sag during current injection. The observed changes in motoneuron rheobase and total cell capacitance suggest that application of BDNF produces an increase in motoneuron excitability coincident with a reduction in size. These data are discussed with respect to the possible role of BDNF as a muscle-derived trophic factor for the regulation of motoneuron excitability.
Effects of 5-HT3 Receptor Antagonism on Hippocampal Cellular Activity in the Freely Moving Rat
Authors: Reznic Jeffrey , Staubli Ursula
Published: December 2017

Reznic, Jeffrey and Ursula Staubli. Effects of 5-HT3 receptor antagonism on hippocampal cellular activity in the freely moving rat. J. Neurophysiol. 77: 517–521, 1997. Recent physiological studies conducted in the hippocampi of freely moving rats have revealed that systemic injections of the selective serotonin-3 (5-HT3) receptor antagonist ondansetron facilitate induction of long-term potentiation (LTP), increase the frequency of the theta electroencephalogram rhythm, and enhance retention of memory in hippocampally dependent tasks. To gain insight into the cellular mechanisms underlying these observations, in the present study we examined the effects of intraperitoneal injections of ondansetron on the firing rate of CA1 interneurons and pyramidal cells in the dorsal hippocampi of freely moving rats. Mean firing rates of a substantial proportion (17 of 27) of isolated neurons were significantly different before and after ondansetron injection (500 and 1,000 μg/kg). Of the interneurons that exhibited an effect, all (11 of 11) significantly decreased their mean firing rate, with an average change of −22.4 ± 3.9% (mean ± SE) across cells. Eighty-three percent (5 of 6) of pyramidal cells showing a change in mean firing rate displayed a significant increase in activity, with an average change of 56.3 ± 25.6% across cells. Ondansetron (1.0 mg/kg ip) had no detectable effect on spontaneous behavioral activity as measured by line crossings and rearings in an open-field apparatus. The present results show that pharmacological blockade of 5-HT3 receptors causes a reduction in firing activity of a subset of CA1 hippocampal interneurons, with concomitant increases in the firing rate of pyramidal cells. These changes may be directly related to the ondansetron-induced enhancement of LTP induction and memory formation observed in previous studies.
Emergence of Radial Nerve Dominance in Median Nerve Cortex After Median Nerve Transection in an Adult Squirrel Monkey
Authors: Schroeder C. E. , Seto S. , Garraghty P. E.
Published: December 2017

Schroeder, C. E., S. Seto, and P. E. Garraghty. Emergence of radial nerve dominance in median nerve cortex after median nerve transection in an adult squirrel monkey. J. Neurophysiol. 77: 522–526, 1997. Throughout the glabrous representation in Area 3b, electrical stimulation of the dominant (median or ulnar) input produces robust, short-latency excitation, evident as a net extracellular “sink” in the Lamina 4 current source density (CSD) accompanied by action potentials. Stimulation of the collocated nondominant (radial nerve) input produces a subtle short-latency response in the Lamina 4 CSD unaccompanied by action potentials and followed by a clear excitatory response 12–15 ms later. Laminar response profiles for both inputs have a “feedforward” pattern, with initial activation in Lamina 4, followed by extragranular laminae. Such corepresentation of nondominant radial nerve inputs with the dominant (median or ulnar nerve) inputs in the glabrous hand surface representation provides a likely mechanism for reorganization after median nerve section in adult primates. To investigate this, we conducted repeated recordings using an implanted linear multi-electrode array straddling the cortical laminae at a site in “median nerve cortex” (i.e., at a site with a cutaneous receptive field on the volar surface of D2 and thus with its dominant afferent input conveyed by the median nerve) in an adult squirrel monkey. We characterized the baseline responses to median, radial, and ulnar nerve stimulation. We then cut the median nerve and semi-chronically monitored radial nerve, ulnar nerve and median nerve (proximal stump) evoked responses. The radial nerve response in median nerve cortex changed progressively during the weeks after median nerve transection, ultimately assuming the characteristics of the dominant nerve profile. During this time, median, and ulnar nerve profiles displayed little or no change.
Characterization of a P-Type Calcium Current in a Crayfish Motoneuron and Its Selective Modulation by Impulse Activity
Authors: Hong Sungwon J. , Lnenicka Gregory A.
Published: December 2017

Hong, Sungwon J. and Gregory A. Lnenicka. Characterization of a P-type calcium current in a crayfish motoneuron and its selective modulation by impulse activity. J. Neurophysiol. 77: 76–85, 1997. Previous studies have demonstrated that the voltage-dependent Ca2+current recorded from the cell body of the crayfish abdominal motoneuron, F3, undergoes a long-term reduction as a result of increased impulse activity. The properties of the Ca2+channels undergoing this long-term change were examined with the use of two-electrode voltage-clamp techniques. The Ca2+current was activated at −50 to −40 mV and its amplitude was maximal at 0 mV (−135.0 ± 25.8 nA, mean ± SE, n = 14). The current-voltage relationship and the greater sensitivity of the Ca2+channel to Cd2+than Ni2+indicated that Ca2+influx occurs through high-voltage-activated (HVA) Ca2+channels. Loose-patch recordings demonstrated that the Ca2+current was generated by the membrane of the cell body. When Ba2+was substituted for extracellular Ca2+, there was a 40% increase in the amplitude of the inward current and a negative shift of ∼10 mV in the I-V relationship. Application of the P-type Ca2+channel antagonist ω-agatoxin IVA (ω-AgTX IVA) produced a significant 33% ( n = 6) reduction in the peak amplitude of the Ba2+current, whereas neither the L-type Ca2+channel antagonist nifedipine nor the N-type channel antagonist ω-conotoxin GVIA produced a reduction in the Ba2+current. The voltage-dependent activation of this P-type (ω-AgTX-IVA-sensitive) Ca2+channel was similar to previously identified P-type channels, but different from that of the non-P-type (ω-AgTX-IVA-resistant) Ca2+channels. When Ca2+currents were measured6–7 h after an increase in impulse activity (5-Hz stimulation for45–60 min), there was a 43% reduction in the amplitude of the P-type current, but no significant changes in the non-P-type current amplitude. These results demonstrate that at least two subtypes of HVA Ca2+channels contribute to the macroscopic Ca2+current observed in the cell body of this crayfish phasic motoneuron: one belongs to the previously described P-type Ca2+channel and the other(s) does not belong to the N-, L-, or P-type Ca2+channel. The long-term, Ca2+-dependent reduction in Ca2+current previously demonstrated in motoneuron F3 is produced by the selective reduction of this P-type Ca2+current. This activity-dependent reduction in the P-type Ca2+current is likely involved in the long-term depression of transmitter release observed at the neuromuscular synapses of this motoneuron.
Modulation of K+Channels by Intracellular ATP in Human Neocortical Neurons
Authors: Jiang Chun , Haddad Gabriel G.
Published: December 2017

Jiang, Chun and Gabriel G. Haddad. Modulation of K+channels by intracellular ATP in human neocortical neurons. J. Neurophysiol. 77: 93–102, 1997. ATP-modulated K+channels play an important role in regulating membrane excitability during metabolic stress. To characterize such K+channels from the human brain, single channel currents were studied in excised inside-out patches from freshly dissociated human neocortical neurons. Three currents that were sensitive to physiological concentrations of ATP and selectively permeable to K+were identified. One of these currents had a unitary conductance of ∼47 pS and showed a strong inward rectification with symmetric K+concentrations across the membrane. This K+current was inhibited by ATP in a concentration-dependent manner with an IC50(half-inhibition of channel activity) of ∼130 μM. Channel activity also was suppressed by ADP, nonhydrolyzable ATP analogue AMP-PNP, and sulfonylurea receptor/channel blocker glibenclamide. The second K+current had a unitary conductance of ∼200 pS and showed a weak inward rectification. Similarly, this current was inhibited by ATP (IC50= 350 μM), AMP-PNP, and glibenclamide. Unlike the small-conductance ATP-inhibitable K+channel (S-KATP), activation of this large-conductance K+channel (L-KATP) required the presence of micromolar concentration of Ca2+in the internal solution, but charybdotoxin did not inhibit this channel. The third K+current was also Ca2+dependent and had a large conductance (∼280 pS). It was inhibited by external charybdotoxin, iberiotoxin, and tetraethylammonium. In contrast to the other two KATPchannels, ATP enhanced channel open-state probability and unitary conductance, and glibenclamide at concentration of 10–20 μM had no inhibitory effect on this current. K+channels that have single-channel and pharmacological properties similar to these three human ATP-modulated K+channels also were observed in experiments on rat neocortical neurons. These results therefore indicate that KATPchannels are expressed in human neocortical neurons, and two distinct KATPchannels (S-KATPand L-KATP) exist in the human and rat neurons. The observation that ATP at different concentrations modulates different K+channels suggests that metabolic rate may be continuously sensed in neurons with resulting alterations in neuronal membrane excitability.
D2Dopamine Receptors Reduce N-Type Ca2+Currents in Rat Neostriatal Cholinergic Interneurons Through a Membrane-Delimited, Protein-Kinase-C-Insensitive Pathway
Authors: Yan Zhen , Song Wen-Jie , Surmeier D. James
Published: December 2017

Yan, Zhen, Wen-Jie Song, and D. James Surmeier. D2dopamine receptors reduce N-type Ca2+currents in rat neostriatal cholinergic interneurons through a membrane-delimited, protein-kinase-C-insensitive pathway. J. Neurophysiol. 77: 1003–1015, 1997. Dopamine has long been known to regulate the activity of striatal cholinergic interneurons and the release of acetylcholine. Yet, the cellular mechanisms by which this regulation occurs have not been elucidated. One way in which dopamine might act is by modulating voltage-dependent Ca2+channels. To test this hypothesis, the impact of dopaminergic agonists on Ca2+channels in neostriatal cholinergic interneurons was studied by combined whole cell voltage-clamp recording and single-cell reverse transcription–polymerase chain reactions. Cholinergic interneurons were identified by the presence of choline acetyltransferase mRNA. Nearly all interneurons tested (90%, n = 17) coexpressed D2(short and long isoforms) and D1b(D5) dopamine receptor mRNAs. D1areceptor mRNA was found in only a small subset (20%) of the sample and D3and D4receptor mRNAs were undetectable. D2receptor agonists rapidly and reversibly reduced N-type Ca2+currents. D1b/D1areceptor activation had little or no effect on Ca2+currents. The D2receptor antagonist sulpiride blocked the effect of D2agonists. Dialysis with guanosine-5′-O-(2-thiodiphosphate) or brief exposure to the G protein (Gi/o) alkylating agent N-ethylmaleimide also blocked the D2modulation. The reduction in N-type currents was neither accompanied by kinetic slowing nor significantly reversed by depolarizing prepulses. The D2receptor effects were mediated by a membrane-delimited pathway, because the modulation was not seen in cell-attached patches when agonist was applied to the bath and was not disrupted by perturbations in cytosolic signaling pathways known to be linked to D2receptors. Activation of M2 muscarinic receptors occluded the D2modulation, suggesting a shared signaling element. However, activation of protein kinase C attenuated the M2 modulation without significantly affecting the D2modulation. Taken together, our results suggest that activation of D2dopamine receptors in cholinergic interneurons reduces N-type Ca2+currents via a membrane-delimited, Gi/oclass G protein pathway that is not regulated by protein kinase C. This signaling pathway may underlie the ability of D2receptors to reduce striatal acetylcholine release.
GABAA Mediated Afterdepolarization in Pyramidal Neurons From Rat Neocortex
Authors: Cerne R. , Spain W. J.
Published: December 2017

Cerne, R. and W. J. Spain. A GABAA mediated afterdepolarization in pyramidal neurons from rat neocortex. J. Neurophysiol. 77: 1039–1045, 1997. We report a novel slow afterdepolarization (sADP) in layer V pyramidal neurons when brain slices from somatosensory cortex are perfused with γ-aminobutyric acid (GABA). Whole cell recordings were made from visually identified neurons in slices from 3- to 5-wk-old rats. The firing of action potentials at 100 Hz for 1 s, evoked by a train of brief current pulses, typically is followed by a slow afterhyperpolarization (sAHP). When GABA (1 mM) was applied to the perfusate, the sAHP was replaced by a sADP of ≈18 mV in amplitude, which on average lasted for 26 s. The sADP was not evoked or terminated as an all-or-none event: it grew in amplitude and duration as the number of evoked action potentials was increased; and when the sADP was interrupted with hyperpolarizing current steps, its amplitude and duration were graded in a time- and voltage-dependent manner. The sADP did not depend on Ca2+ entry into the cell: it could be evoked when bath Ca2+ was replaced by Mn2+ or in neurons dialyzed with 20 mM bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid. We hypothesized that the sADP was generated predominantly in the dendrites because it was associated with the firing of small-amplitude action potentials that continued after the somatic membrane potential was repolarized to −70 mV by steady current injection. We tested this hypothesis by evoking the sADP in neurons with surgically amputated apical dendrites. In those neurons, the average duration of the sADP was 78% shorter than in neurons with an intact apical dendrite and there were no associated small action potentials. The sADP also was evoked by muscimol, but not by baclofen, and was blocked by bicuculline or picrotoxin but not by CGP 35348, indicating that it is mediated through the activation of GABAA receptors. Our results suggest that intense activity in the presence of GABA results in a long-lasting enhancement of excitability in the apical dendrite that in turn could lead to amplification of distal excitatory synaptic potentials.
Heterosynaptic LTD and Depotentiation in the Medial Perforant Path of the Dentate Gyrus in the Freely Moving Rat
Authors: Doyère Valérie , Srebro Bolek , Laroche Serge
Published: December 2017

Doyère, Valérie, Bolek Srebro, and Serge Laroche. Heterosynaptic LTD and depotentiation in the medial perforant path of the dentate gyrus in the freely moving rat. J. Neurophysiol. 77: 571–578, 1997. We examined the characteristics of heterosynaptic long-term depression (LTD) and depotentiation of previously established long-term potentiation (LTP) in the medial and lateral entorhinal afferents to the dentate gyrus in the awake rat. Rats were prepared for chronic recording of dentate gyrus evoked potentials to activation of the medial and lateral perforant paths. This study in awake rats confirms that heterosynaptic LTD can be induced at inactive medial perforant path synapses in conjunction with the induction of LTP produced by high-frequency stimulation of the lateral perforant path. This form of LTD was long lasting and reversible by tetanic stimulation delivered to the depressed pathway. In contrast, tetanic stimulation of the medial perforant path had only a small heterosynaptic effect on the lateral pathway, suggesting that the two input pathways to the dentate gyrus are not symmetrical in their ability to induce heterosynaptic LTD. We also examined the ability of high-frequency stimulation of one pathway to produce depotentiation of the other pathway. We found that when LTP was first induced in the medial perforant path, depotentiation was induced heterosynaptically by tetanization of the lateral pathway. Both newly established LTP (30 min) and LTP induced and saturated by repeated tetanic stimulation over several days can be depotentiated heterosynaptically. Moreover, depotentiation of the medial perforant path synapses was found to be linearly correlated with the magnitude of LTP induced in the lateral perforant path synapses, and subsequent tetanic stimulation of the depotentiated medial perforant path restored LTP to an extent that counterbalanced depotentiation. The saturation and repotentiation experiments provide clear support for the conclusion that the rapid reversal of LTP reflects true depotentiation of the medial input. Again, as with heterosynaptic LTD, tetanization of the medial perforant path had little effect on previously induced LTP in the lateral path. These results provide evidence that medial perforant path synapses can be depressed and depotentiated heterosynaptically. They suggest that in the intact rat synaptic changes in the afferents to the dentate gyrus from the lateral entorhinal cortex exert powerful control over ongoing or recent synaptic plasticity in the medial entorhinal afferents.
Normal and Adapted Visuooculomotor Reflexes in Goldfish
Authors: Marsh Eric , Baker Robert
Published: December 2017

Marsh, Eric and Robert Baker. Normal and adapted visuooculomotor reflexes in goldfish. J. Neurophysiol. 77: 1099–1118. Under normal physiological conditions, whole field visual motion generally occurs in response to either active or passive self-motion. In the laboratory, selective movement of the visual surround produces an optokinetic response (OKR) that acts primarily to support the vestibuloocular reflex (VOR). During visual world motion, however, the OKR can be viewed as operating independently over frequency and amplitude ranges insufficient for vestibular activation. The goal of the present study was to characterize this isolated behavior of the OKR in goldfish as an essential step for studying central neuronal correlates of visual-vestibular interactions and the mechanisms underlying oculomotor adaptation. After presentation of either binocular sinusoidal or step visual stimuli, conjugate eye movements were elicited with an amplitude and phase profile similar to that of other vertebrates. An early and a delayed component were measured with different dynamics that could be altered independently by visual training. The ensuing visuomotor plasticity was robust and exhibited five major characteristics. First, the gain of both early and delayed components of the OKR increased >100%. Second, eye velocity decreased 0.5–2.0 s before the change in direction of stimulus velocity. Third, on lengthening the duration of a constant velocity visual stimulus (e.g., from 8 to 16 s), eye velocity decreased toward 0°/s. This behavior was correlated with the direction and period as opposed to the frequency of the visual stimulus (“period tuning”). Fourth, visual stimulus training increased VOR eye velocity with a ratio of 0.6 to 1 to that measured for the OKR. Fifth, after OKR adaptation, eye velocity consistently oscillated in a conjugate, symmetrical fashion at 2.4 Hz in the light, whereas in the dark, a rhythmical low-amplitude eye velocity occurred at the visual training frequency. We conclude that the frequency and amplitude of visual stimuli for eliciting the goldfish OKR are well suited for complementing the VOR. Unlike most mammals, OKR adaptive modifications significantly alter VOR gain, whereas the effects of VOR training are much less on OKR gain. These observations suggest that both distributed circuits and discrete neuronal populations control visuo- and vestibulomotor performance. Finally, the existence of a rhythmic, “period tuned” visuomotor behavior provides a unique opportunity to examine the neuronal mechanisms of adaptive plasticity.
Role of Intrinsic Burst Firing, Potassium Accumulation, and Electrical Coupling in the Elevated Potassium Model of Hippocampal Epilepsy
Authors: Jensen Morten S. , Yaari Yoel
Published: December 2017

Jensen, Morten S. and Yoel Yaari. Role of intrinsic burst firing, potassium accumulation, and electrical coupling in the elevated potassium model of hippocampal epilepsy. J. Neurophysiol. 77: 1224–1233, 1997. Perfusing rat hippocampal slices with high-K+ (7.5 mM) saline induced brief population bursts originating in CA3 at 0.5–1 Hz and spreading synaptically into CA1. In 42% of the slices the brief bursts evoked in CA1 gave way every 0.5–2 s to sustained ictal (or seizure) episodes with tonic and clonic components. Paired intra- and extracellular recordings in the CA1 pyramidal layer were used to characterize the synaptic and nonsynaptic mechanisms generating the brief and sustained epileptiform events. The interictal, tonic, or clonic primary burst response in CA1 comprised a spindle-shaped, tight cluster (170–180 Hz) of five to seven population spikes. Bursts evoked between sequential seizures (interictal bursts) were initially small and progressively increased in size. Concurrently, basal extracellular K+ concentration ([K+]o) increased from 6.5 to 7.5 mM. The tonic event emanated from a large primary burst and comprised prolonged (>1 s), self-sustained afterdischarge, associated with a rise in [K+]o to 12 mM. Bursts generated during the subsequent [K+]o decline (clonic bursts) also were large and followed by some afterdischarge. They became small during [K+]o undershoot to 6.5 mM. Intrinsically burst firing pyramidal cells (PCs) were recruited before or at the very onset of the primary population burst and fired repetitively during its course. Nonbursters were recruited ≥10 ms after the beginning of the primary burst and fired, on average, only one spike. The PCs depolarized during the primary burst and subsequent afterdischarge. The primary depolarizing shift was larger in bursters than in nonbursters. Both bursters and nonbursters fired repetitively, albeit intermittently, during tonic and clonic afterdischarge. Throughout the interictal-ictal cycle intracellular spikes were time-locked to population spikes, indicating that PCs fire in tight synchrony. Differential recording of transmembrane potentials unmasked rapid (4–7 ms) transmembrane depolarizing potentials of up to 10 mV, coincident with population spikes. We conclude that in the high-K+ model of hippocampal epilepsy, the local generation of population bursts in CA1 is led by intrinsic bursters, which recruit and synchronize other PCs by synaptic, electrical, and K+-mediated excitatory interactions. The cycling between interictal, tonic, and clonic events appears to result from feedback interactions between neuronal discharge and [K+]o.
Transient Synaptic Potentiation in the Visual Cortex. II. Developmental Regulation
Authors: Harsanyi Krisztina , Friedlander Michael J.
Published: December 2017

Harsanyi, Krisztina and Michael J. Friedlander. Transient synaptic potentiation in the visual cortex. II. Developmental regulation. J. Neurophysiol. 77: 1284–1293, 1997. In our previous study, pairing-induced transient synaptic potentiation in supragranular layers of the visual cortex was described in mature guinea pigs. In the present study, the development of this type of synaptic plasticity and the underlying cellular mechanisms that mediate it were evaluated in animals from postnatal day (PND) 5 to 180. Potentiation is more reliably evoked in younger animals (likelihood: 75%, PND 5–30; 51%, PND ≥34), and the magnitude of the effect is greater (+40 ± 3%, mean ± SE, PND 5–30; +26 ± 3%, PND ≥34). Similar to data obtained from the mature animals, visual cortical transient synaptic potentiation in the immature cortex occurs at excitatory synaptic sites directly activated by the stimulation, and activation by local recurrent cortical circuits is not necessary for the induction of this potentiation. This is demonstrated by 1) experiments in which action potential output from the paired neuron was blocked by Lidocaine, N-ethyl bromide quaternary salt applied into the neuron (5 of 5), and 2) experiments in which the contribution to the compound postsynaptic potential by inhibitory synapses was eliminated by selective, intracellular blockade of γ-aminobutyric acid-mediated inhibitory postsynaptic potentials only onto the recorded neuron (7 of 11). Thus these perturbations do not reduce the likelihood or magnitude of this synaptic potentiation. In contrast to the N-methyl-d-aspartate (NMDA) receptor dependence for induction of this synaptic potentiation in the cortex of mature animals, in the young animals' cortices (PND 11–27) potentiation is readily induced during blockade of NMDA receptors (72%, 13 of 18, not different from control: 75%, 40 of 53). Thus the NMDA receptor becomes functionally linked to a synaptic potentiation cascade during development, replacing another 2-amino-5-phosphonovaleric acid (APV)-insensitive potentiation process in the neonatal cortex. Postsynaptic intracellular calcium has a critical role in the induction of this form of synaptic potentiation in all ages studied. Synaptic potentiation was prevented (8 of 11 cases) or was replaced by synaptic depression (3 of 11 cells) in experiments in which postsynaptic calcium levels were reduced by intracellular application of 1,2-bis-2-aminophenoxy ethane- N,N,N′,N′-tetraacetic acid (BAPTA) in the cortex of young (PND 7–14) animals, or in which the extracellular calcium concentration was lowered. Inhibition of postsynaptic calcium-induced calcium release blocked synaptic potentiation (4 of 4 cells). Prolonged superfusion (3 h) of the nitric oxide synthase inhibitor l-nitro-arginine (LNA) did not significantly affect the likelihood (in LNA, 81%; 13 of 16 cells), or the magnitude (+38 ± 7% increase in LNA vs. +40 ± 3% in control cases) of potentiation, in contrast to its effects in the mature cortex.
Anatomy of Motor Learning. II. Subcortical Structures and Learning by Trial and Error
Authors: Jueptner M. , Frith C. D. , Brooks D. J. , Frackowiak R.S.J. , Passingham R. E.
Published: December 2017

Jueptner, M., C. D. Frith, D. J. Brooks, R.S.J. Frackowiak, and R. E. Passingham. Anatomy of motor learning. II. Subcortical structures and learning by trial and error. J. Neurophysiol. 77: 1325–1337, 1997. We used positron emission tomography to study motor learning by trial and error. Subjects learned sequences of eight finger movements. Tones generated by a computer told the subjects whether any particular move was correct or incorrect. A control condition was used in which the subjects generated moves, but there was no feeback to indicate success or failure, and so no learning occured. In this condition (free selection) the subjects were required to make a finger movement on each trial and to vary the movements randomly over trials. The subjects had a free choice of which finger to move on any one trial. On this task there was no systematic change in responses over trials and no change in the response times. Two other conditions were included. In one the subjects repetitively moved the same finger on all trials and in a baseline condition the subjects heard the pacing tones and auditory feedback but made no movements. Comparing new learning with the free selection task, there was a small activation in the right prefrontal cortex. This may reflect the fact that in new learning, but not free selection, the subjects rehearse past moves and adapt their responses accordingly. The caudate nucleus was strongly activated during new learning. It is suggested that this activity may be related either to mental rehearsal or to reinforcement of the movements as a consequence of the outcomes. The putamen was activated anteriorly on the free selection task and more posteriorly when the subjects repetitively made the same movement. It is suggested that the differences in the location of the peak activation in the striatum may represent the operation of different corticostriatal loops. The cerebellar nuclei (bilaterally) and vermis were more active in the new learning condition than during the performance of the free selection task. There was no difference in the activation of the cerebellum when the free selection task was compared with repetitive performance of the same movement. We tentatively suggest that the basal ganglia may be involved in the specification of movement on the basis of memory of either the movements or the outcomes, but that the cerebellum may be more directly involved in changes in the parameters of movement execution.
Chorda Tympani Responses Under Lingual Voltage Clamp: Implications for NH4Salt Taste Transduction
Authors: Kloub Mamoun A. , Heck Gerard L. , Desimone John A.
Published: December 2017

Kloub, Mamoun A., Gerard L. Heck, and John A. DeSimone. Chorda tympani responses under lingual voltage clamp: implications for NH4salt taste transduction. J. Neurophysiol. 77: 1393–1406, 1997. Rat chorda tympani (CT) responses to NH4Cl, ammonium acetate (NH4Ac), and ammonium hippurate (NH4Hp) were obtained during simultaneous current and voltage clamping of the lingual field potential. Although functional and developmental similarities for gustation have been reported for NH+4and K+salts, we report here that significant differences are discernible in the CT responses to both salts. Unlike neural responses to KCl, those to NH4Cl are voltage sensitive, enhanced by submucosa negative and suppressed by positive voltage clamp. In this regard, NH4Cl responses are qualitatively similar to NaCl responses; however, the magnitude of NH4Cl voltage sensitivity is significantly less than that of NaCl. The concentration dependence of the CT response to NH4Cl manifests a biphasic nonlinear relationship not observed with KCl or NaCl. Below 0.3 M, the CT response increases as if to approach a saturation value. However, beyond 0.3 M an inflection appears in the CT-concentration curve because of an abrupt increase in CT responses. This kinetic profile is Cl−dependent and is correlated with an increase in transepithelial conductance that displays similar NH4Cl concentration dependence. The biphasic relation to salt concentration is not observed when acetate or hippurate is substituted for Cl−. As with Na+and K+salts, less mobile anions than Cl−(Ac−and Hp−) lower the CT responses. However, like Na+salts, but in contrast to K+salts, the onset kinetics of CT responses to NH4Ac or NH4Hp remain rapid, even under positive voltage-clamp conditions. Amiloride (100 μM) partially suppresses CT responses within the concentration range of 0.05–0.3 M (48–20% suppression). Amiloride also suppresses the voltage sensitivity of NH4Cl CT responses, but does not eliminate that sensitivity as it does for Na+salts. In conclusion, the data suggest that taste transduction for NH4salts is mediated over two NH+4conduction pathways in the taste bud. This is especially evident with NH4Cl, where the CT-concentration curves show two distinct kinetic regimes. Below 0.3 M the saturation with increasing concentration, clamp voltage response dependence, and amiloride sensitivity suggest an apical membrane transduction conductance. Above 0.3 M, the high anion dependence of the response and its amiloride insensitivity indicate participation of the paracellular pathway in transduction.
Rostral Fastigial Nucleus Activity in the Alert Monkey During Three-Dimensional Passive Head Movements
Authors: Siebold C. , Glonti L. , Glasauer S. , Büttner U.
Published: December 2017

Siebold, C., L. Glonti, S. Glasauer, and U. Büttner. Rostral fastigial nucleus activity in the alert monkey during three-dimensional passive head movements. J. Neurophysiol. 77: 1432–1446, 1997. The fastigial nucleus (FN) receives vestibular information predominantly from Purkinje cells of the vermis. FN in the monkey can be divided in a rostral part, related to spinal mechanisms, and a caudal part with oculomotor functions. To understand the role of FN during movements in space, single-unit activity in alert monkeys was recorded during passive three-dimensional head movements from rostral FN. Seated monkeys were rotated sinusoidally around a horizontal earth-fixed axis (vertical stimulation) at different orientations 15° apart (including roll, pitch, vertical canal plane and intermediate planes). In addition, sinusoidal rotations around an earth-vertical axis (yaw stimulus) included different roll and pitch positions (±10°, ±20°). The latter positions were also used for static stimulation. One hundred fifty-eight neurons in two monkeys were modulated during the sinusoidal vertical search stimulation. The vast majority showed a uniform response pattern: a maximum at a specific head orientation (response vector orientation) and a null response 90° apart. Detailed analysis was obtained from 111 neurons. On the basis of their phase relation during dynamic stimulation and their response to static tilt, these neurons were classified as vertical semicircular canal related ( n = 79, 71.2%) or otolith related ( n = 25; 22.5%). Only seven neurons did not follow the usual response pattern and were classified as complex neurons. For the vertical canal-related neurons ( n = 79) all eight major response vector orientations (ipsilateral or contralateral anterior canal, posterior canal, roll, and nose-down and nose-up pitch) were found in FN on one side. Neurons with ipsilateral orientations were more numerous and on average more sensitive than those with contralateral orientations. Twenty-eight percent of the vertical canal-related neurons also responded to horizontal canal stimulation. None of the vertical canal-related neurons responded to static tilt. Otolith-related neurons ( n = 25) had a phase relation close to head position and were considerably less numerous than canal-related neurons. Except for pitch, all other response vector orientations were found. Seventy percent of these neurons responding during dynamic stimulation also responded during static tilt. The sensitivity during dynamic stimulation was always higher than during static stimulation. Sixty-one percent of the otolith-related neurons responded also to horizontal canal stimulation. These results show that in FN, robust vestibular signals are abundant. Canal-related responses are much more common than otolith-related responses. Although for many canal neurons the responses can be related to single canal planes, convergence between vertical canals but also with horizontal canals is common.
Contribution of Voltage-Dependent Potassium Channels to the Somatic Shunt in Neck Motoneurons of the Cat
Authors: Campbell D. M. , Rose P. K.
Published: December 2017

Campbell, D. M. and P. K. Rose. Contribution of voltage-dependent potassium channels to the somatic shunt in neck motoneurons of the cat. J. Neurophysiol. 77: 1470–1486, 1997. The specific membrane resistivity of motoneurons at or near the soma ( R ms) is much lower than the specific membrane resistivity of the dendritic tree ( R md). The goal of the present experiments was to investigate the contribution of tonically active voltage-dependent potassium channels at or near the soma to the low R ms. These channels were blocked with the use of intracellular injections of cesium. Input resistance ( R N), R ms/ R md, a conductance representing voltage-dependent potassium channels on the soma, G K, and a conductance attributed to damage caused by electrode impalement, G Da, were estimated from voltage responses to a step of current. The effect of intracellular injections of cesium on electrotonic structure was determined with the use of two strategies: 1) a population analysis that compared data from two groups of motoneurons, those recorded with potassium acetate electrodes (control group) and those recorded with cesium acetate electrodes after the motoneurons were loaded with cesium; and 2) an analysis of changes in electrotonic structure that occurred over the course of multiple injections of cesium or during similar periods of time in control cells. R N of control and cesium-loaded motoneurons was similar. Over the course of the recordings, R N of control cells usually increased and this increase was associated with a hyperpolarization. In contrast, increases in R N after successive injections of cesium were closely linked to a depolarization. At corresponding membrane potentials, R ms/ R md of cesium-loaded motoneurons was greater than R ms/ R md of control motoneurons. Over the course of cesium injections, R ms/ R md increased and the membrane potential depolarized. In contrast, increases in R ms/ R md observed during the course of recordings from control cells were associated with a hyperpolarization. Compared with control cells at corresponding membrane potentials, G K was less in cesium-loaded cells. Increases in G K that occurred over the course of recordings in control cells were closely coupled to a depolarization. In cesium-loaded cells, G K usually decreased as the cell depolarized during the injections. In control cells, increases in G Da that occurred during the recording period were closely coupled to a depolarization. In contrast, changes in G Da that occurred during cesium injections were not related to the change in membrane potential and did not explain the corresponding changes in R ms/ R md and membrane potential. The results of this study indicate that voltage-dependent potassium channels contribute to the somatic shunt (low R ms) in neck motoneurons and provide a voltage-dependent mechanism for the dynamic regulation of motoneuron electrotonic properties.
Visual Acuity for Moving Objects in First- and Second-Order Neurons of the Fly Compound Eye
Authors: Juusola Mikko , French Andrew S.
Published: December 2017

Juusola, Mikko and Andrew S. French. Visual acuity for moving objects in first- and second-order neurons of the fly compound eye. J. Neurophysiol. 77: 1487–1495, 1997. The early stages of visual systems contain a variety of components that limit both the spatial resolution and the temporal resolution of vision. When an animal sees a moving object, or moves relative to its environment, both spatial and temporal factors contribute to its ability to resolve the movement. In the present work we have combined currently available knowledge about the early stages of fly vision (optical system, photoreceptors, and large monopolar cells) to predict the resolution of the first two cell layers to moving point objects. These calculations included recent measurements of nonlinear light responses. Because background light level has a strong effect on the temporal behavior of these early visual layers, we examined the effects of light level on motion resolution. We also studied the effect of position within the eye, which is known to affect the static resolution of vision. Our results indicate that responses in large monopolar cells to moving point objects are maximal at angular velocities of 100–200°/s. The resolution of point objects by both these early stages of the visual system is similar from stationary to an angular velocity of ∼200°/s. Above this, resolution deteriorates approximately linearly with velocity.
Low-Threshold, Persistent Sodium Current in Rat Large Dorsal Root Ganglion Neurons in Culture
Authors: Baker Mark D. , Bostock Hugh
Published: December 2017

Baker, Mark D. and Hugh Bostock. Low-threshold, persistent sodium current in rat large dorsal root ganglion neurons in culture. J. Neurophysiol. 77: 1503–1513, 1997. Dorsal root ganglion neurons from adult rats (≥200 g) were maintained in culture for between 1 and 3 days. Membrane currents generated by large neurons (50–75 μm apparent diameter) were recorded with the whole cell patch-clamp technique. Large neurons generated transient Na+ currents and at least two types of inward current that persisted throughout 200-ms voltage-clamp steps to +20 mV. One persistent current activated close to −35 mV (high threshold), whereas in about half of the cells another persistent current began to activate negative to −70 mV (low threshold). The high-threshold persistent current was identified as a Ca2+ current, as previously described in these neurons. The low-threshold current was reversibly suppressed either by replacing external Na+ with tetramethylammonium ions or by reducing external Na+ concentration ([Na+]) and simultaneously raising external [Ca2+]. It was blocked by tetrodotoxin (TTX) with an apparent equilibrium dissociation constant in the single nanomolar range. We conclude that the low-threshold current is a TTX-sensitive, persistent Na+ current. The persistent TTX-sensitive current contributed to steady-state membrane current from at least −70 mV to 0 mV, a wider potential range than predicted by activation-inactivation gating overlap for transient Na+ current. Because of its low threshold and fast activation kinetics, the persistent Na+ current is expected to play an important role in determining membrane excitability.
Ionic Mechanisms of Muscarinic Depolarization in Entorhinal Cortex Layer II Neurons
Authors: Klink Ruby , Alonso Angel
Published: December 2017

Klink, Ruby and Angel Alonso. Ionic mechanisms of muscarinic depolarization in entorhinal cortex layer II neurons. J. Neurophysiol. 77: 1829–1843, 1997. The mechanisms underlying direct muscarinic depolarizing responses in the stellate cells (SCs) and non-SCs of medial entorhinal cortex layer II were investigated in tissue slices by intracellular recording and pressure-pulse applications of carbachol (CCh). Subthreshold CCh depolarizations were largely potentiated in amplitude and duration when paired with a short DC depolarization that triggered cell firing. During Na+ conductance block, CCh depolarizations were also potentiated by a brief DC depolarization that allowed Ca2+ influx and the potentiation was more robust in non-SCs than in SCs. Also, in non-SCs, CCh depolarizations could be accompanied by spikelike voltage oscillations at a slow frequency. In both SCs and non-SCs, the voltage-current ( V-I) relations were similarly affected by CCh, which caused a shift to the left of the steady-state V-I relations over the entire voltage range and an increase in apparent slope input resistance at potentials positive to about −70 mV. CCh responses potentiated by Ca2+ influx demonstrated a selective increase in slope input resistance at potentials positive to about −75 mV in relation to the nonpotentiated responses. K+ conductance block with intracellular injection of Cs+ (3 M) and extracellular Ba2+ (1 mM) neither abolished CCh depolarizations nor resulted in any qualitatively distinct effect of CCh on the V-I relations. CCh depolarizations were also undiminished by block of the time-dependent inward rectifier I h with extracellular Cs+. However, CCh depolarizations were abolished during Ca2+ conductance block with low-Ca2+ (0.5 mM) solutions containing Cd2+, Co2+, or Mn2+, as well asby intracellular Ca2+ chelation with bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid. Inhibition of the Na+-K+ ATPase with strophanthidin resulted in larger CCh depolarizations. On the other hand, when NaCl was replaced by N-methyl-d-glucamine, CCh depolarizations were largely diminished. CCh responses were blocked by 0.8 μM pirenzepine, whereas hexahydro-sila-difenidolhydrochloride,p-fluoroanalog (p-F-HHSiD) and himbacine were only effective antagonists at 5- to 10-fold larger concentrations. Our data are consistent with CCh depolarizations being mediated in both SCs and non-SCs by m1 receptor activation of a Ca2+-dependent cationic conductance largely permeable to Na+. Activation of this conductance is potentiated in a voltage-dependent manner by activity triggering Ca2+ influx. This property implements a Hebbian-like mechanism whereby muscarinic receptor activation may only be translated into substantial membrane depolarization if coupled to postsynaptic cell activity. Such a mechanism could be highly significant in light of the role of the entorhinal cortex in learning and memory as well as in pathologies such as temporal lobe epilepsy.