bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Outward Currents in Neurons of the Avian Nucleus Magnocellularis
Authors: Rathouz Margaret , Trussell Laurence
Published: December 2017

Rathouz, Margaret and Laurence Trussell. Characterization of outward currents in neurons of the avian nucleus magnocellularis. J. Neurophysiol. 80: 2824–2835, 1998. Neurons of the nucleus magnocellularis (NM) preserve the timing of auditory signals through the convergence of a variety of voltage- and ligand-gated ion channels. To understand better how these channels interact, we have characterized the kinetics, voltage sensitivity, and pharmacology of outward currents of NM neurons in brain slices. The reversal potential ( E rev) of outward currents varied with potassium concentration as expected for currents carried by potassium. However, E rev was consistently more positive than the Nernst potential for potassium ( E K). Deviation of E rev from the calculated E K most likely arose from potassium accumulation in extracellular spaces by potassium conductances active at rest and during depolarizing steps. Three outward potassium currents were studied that varied in voltage and pharmacological sensitivity. A tetraethylammonium (TEA)-sensitive, high-threshold current was activated within 1–5 ms of the onset of depolarization, with a half-maximal activation voltage ( V 1/2) of −19 mV. It was blocked partially by 4-aminopyridine (4-AP) and was the dominant ionic conductance of NM neurons. A dendrotoxin-I (DTX) and 4-AP-sensitive, low-threshold current had a V 1/2 of −58 mV, rapid activation kinetics, and only partial inactivation, with decay time constants between 20 and 100 ms. A rapidly inactivating current was observed that was resistant to TEA and DTX and was blocked by intracellular Cs+. The transient current was inactivated almost completely at the resting potential. The onset of inactivation was fastest at potentials negative to those that caused activation. When intracellular K+ was replaced by Cs+, large inward and outward currents were obtained that corresponded respectively to the above-mentioned DTX- and TEA-sensitive currents. Outward, TEA-sensitive current was carried by Cs+, with a P Cs/ P K of ∼0.1. In current-clamped neurons, DTX induced repetitive firing and increased membrane time constant near rest but had little effect on action potential duration. These studies indicate that a low-threshold, DTX-sensitive current plays a key role in making NM neurons highly responsive to the onset and offset of synaptic stimuli.
Cell-Specific Alterations in Synaptic Properties of Hippocampal CA1 Interneurons After Kainate Treatment
Authors: Morin F. , Beaulieu C. , Lacaille J.-C.
Published: December 2017

Morin, F., C. Beaulieu, and J.-C. Lacaille. Cell-specific alterations in synaptic properties of hippocampal CA1 interneurons after kainate treatment. J. Neurophysiol. 80: 2836–2847, 1998. Hippocampal sclerosis and hyperexcitability are neuropathological features of human temporal lobe epilepsy that are reproduced in the kainic acid (KA) model of epilepsy in rats. To assess directly the role of inhibitory interneurons in the KA model, the membrane and synaptic properties of interneurons located in 1) stratum oriens near the alveus (O/A) and 2) at the border of stratum radiatum and stratum lacunosum-moleculare (LM), as well as those of pyramidal cells, were examined with whole cell recordings in slices of control and KA-lesioned rats. In current-clamp recordings, intrinsic cell properties such as action potential amplitude and duration, amplitude of fast and medium duration afterhyperpolarizations, membrane time constant, and input resistance were generally unchanged in all cell types after KA treatment. In voltage-clamp recordings, the amplitude and conductance of pharmacologically isolated excitatory postsynaptic currents (EPSCs) were significantly reduced in LM interneurons of KA-treated animals but were not significantly changed in O/A and pyramidal cells. The rise time of EPSCs was not significantly changed in any cell type after KA treatment. In contrast, the decay time constant of EPSCs was significantly faster in O/A interneurons of KA-treated rats but was unchanged in LM and pyramidal cells. The amplitude and conductance of pharmacologically isolated γ-aminobutyric acid-A (GABAA) inhibitory postsynaptic currents (IPSCs) were not significantly changed in any cell type of KA-treated rats. The rise time and decay time constant of GABAA IPSCs were significantly faster in pyramidal cells of KA-treated rats but were not significantly changed in O/A and LM interneurons. These results suggest that complex alterations in synaptic currents occur in specific subpopulations of inhibitory interneurons in the CA1 region after KA lesions. A reduction of evoked excitatory drive onto inhibitory cells located at the border of stratum radiatum and stratum lacunosum-moleculare may contribute to disinhibition and polysynaptic epileptiform activity in the CA1 region. Compensatory changes, involving excitatory synaptic transmission on other interneuron subtypes and inhibitory synaptic transmission on pyramidal cells, may also take place and contribute to the residual, functional monosynaptic inhibition observed in principal cells after KA treatment.
Detection of Auditory Signals by Frog Inferior Collicular Neurons in the Presence of Spatially Separated Noise
Authors: Ratnam R. , Feng A. S.
Published: December 2017

Ratnam, R. and A. S. Feng. Detection of auditory signals by frog inferior collicular neurons in the presence of spatially separated noise. J. Neurophysiol. 80: 2848–2859, 1998. Psychophysical studies have shown that the ability to detect auditory signals embedded in noise improves when signal and noise sources are widely separated in space; this allows humans to analyze complex auditory scenes, as in the cocktail-part effect. Although these studies established that improvements in detection threshold (DT) are due to binaural hearing, few physiological studies were undertaken, and very little is known about the response of single neurons to spatially separated signal and noise sources. To address this issue we examined the responses of neurons in the frog inferior colliculus (IC) to a probe stimulus embedded in a spatially separated masker. Frogs perform auditory scene analysis because females select mates in dense choruses by means of auditory cues. Results of the extracellular single-unit recordings demonstrate that 22% of neurons (A-type) exhibited improvements in signal DTs when probe and masker sources were progressively separated in azimuth. In contrast, 24% of neurons (V-type) showed the opposite pattern, namely, signal DTs were lowest when probe and masker were colocalized (in many instances lower than the DT to probe alone) and increased when the two sound sources were separated. The remaining neurons demonstrated a mix of these two types of patterns. An intriguing finding was the strong correlation between A-type masking release patterns and phasic neurons and a weaker correlation between V-type patterns and tonic neurons. Although not decisive, these results suggest that phasic units may play a role in release from masking observed psychophysically. Analysis of the data also revealed a strong and nonlinear interaction among probe, masker, and masker azimuth and that signal DTs were influenced by two factors: 1) the unit's sensitivity to probe in the presence of masker and 2) the criterion level for estimating DT. For some units, it was possible to examine the interaction between these two factors and gain insights into the variation of DTs with masker azimuth. The implications of these findings are discussed in relation to signal detection in the auditory system.
Transient Neurophysiological Changes in CA3 Neurons and Dentate Granule Cells After Severe Forebrain Ischemia In Vivo
Authors: Gao T. M. , Howard E. M. , Xu Z. C.
Published: December 2017

Gao, T. M., E. M. Howard, and Z. C. Xu. Transient neurophysiological changes in CA3 neurons and dentate granule cells after severe forebrain ischemia in vivo. J. Neurophysiol. 80: 2860–2869, 1998. The spontaneous activities, evoked synaptic responses, and membrane properties of CA3 pyramidal neurons and dentate granule cells in rat hippocampus were compared before ischemia and ≤7 days after reperfusion with intracellular recording and staining techniques in vivo. A four-vessel occlusion method was used to induce ∼14 min of ischemic depolarization. No significant change in spontaneous firing rate was observed in both cell types after reperfusion. The amplitude and slope of excitatory postsynaptic potentials (EPSPs) in CA3 neurons decreased to 50% of control values during the first 12 h reperfusion and returned to preischemic levels 24 h after reperfusion. The amplitude and slope of EPSPs in granule cells slightly decreased 24–36 h after reperfusion. The amplitude of inhibitory postsynaptic potentials in CA3 neurons transiently increased 24 h after reperfusion, whereas that in granule cells showed a transient decrease 24–36 h after reperfusion. The duration of spike width of CA3 and granule cells became longer than that of control values during the first 12 h reperfusion. The spike threshold of both cell types significantly increased 24–36 h after reperfusion, whereas the frequency of repetitive firing evoked by depolarizing current pulse was decreased during this period. No significant change in rheobase and input resistance was observed in CA3 neurons. A transient increase in rheobase and a transient decrease in input resistance were detected in granule cells 24–36 h after reperfusion. The amplitude of fast afterhyperpolarization in both cell types increased for 2 days after ischemia and returned to normal values 7 days after reperfusion. The results from this study indicate that the neuronal excitability and synaptic transmission in CA3 and granule cells are transiently suppressed after severe forebrain ischemia. The depression of synaptic transmission and neuronal excitability may provide protection for neurons after ischemic insult.
Functional and Immunocytochemical Identification of Glutamate Autoreceptors of an NMDA Type in Crayfish Neuromuscular Junction
Authors: Feinstein N. , Parnas D. , Parnas H. , Dudel J. , Parnas I.
Published: December 2017

Feinstein, N., D. Parnas, H. Parnas, J. Dudel, and I. Parnas. Functional and immunocytochemical identification of glutamate autoreceptors of an NMDA type in crayfish neuromuscular junction. J. Neurophysiol. 80: 2893–2899, 1998. N-Methyl-d-aspartate (NMDA) reduces release from crayfish excitatory nerve terminals. We show here that polyclonal and monoclonal antibodies raised against the mammalian postsynaptic NMDA receptor subunit 1 stain specifically the presynaptic membrane of release boutons of the crayfish neuromuscular junction. In crayfish ganglionic membranes, the polyclonal antibody recognizes a single protein band that is somewhat larger (by ∼30 kD) than the molecular weight of the rat receptor. Moreover, the monoclonal (but not the polyclonal) antibody abolishes the physiological effect of NMDA on glutamate release. The monoclonal antibody did not prevent the presynaptic effects of glutamate, which also reduces release by activation of quisqualate presynaptic receptors. Only when 6-cyano-7-nitroquinoxatine-2,3,dione (CNQX) was added together with the monoclonal antibody was the presynaptic effect of glutamate blocked. These results show that presynaptic glutamate receptors of the crayfish NMDA type are involved in the regulation of neurotransmitter release in crayfish axon terminals. Although the crayfish receptor differs in its properties from the mammalian NMDA receptor, the two receptors retained some structural similarity.
Neurotransmitter Involvement in Development and Maintenance of the Auditory Space Map in the Guinea Pig Superior Colliculus
Authors: Ingham Neil J. , Thornton Sally K. , McCrossan Damian , Withington Deborah J.
Published: December 2017

Ingham, Neil J., Sally K. Thornton, Damian McCrossan, and Deborah J. Withington. Neurotransmitter involvement in development and maintenance of the auditory space map in the guinea pig superior colliculus. J. Neurophysiol. 80: 2941–2953, 1998. The mammalian superior colliculus (SC) is a complex area of the midbrain in terms of anatomy, physiology, and neurochemistry. The SC bears representations of the major sensory modalites integrated with a motor output system. It is implicated with saccade generation, in behavioral responses to novel sensory stimuli and receives innervation from diverse regions of the brain using many neurotransmitter classes. Ethylene-vinyl acetate copolymer (Elvax-40W polymer) was used here to deliver chronically neurotransmitter receptor antagonists to the SC of the guinea pig to investigate the potential role played by the major neurotransmitter systems in the collicular representation of auditory space. Slices of polymer containing different drugs were implanted onto the SC of guinea pigs before the development of the SC azimuthal auditory space map, at ∼20 days after birth (DAB). A further group of animals was exposed to aminophosphonopentanoic acid (AP5) at ∼250 DAB. Azimuthal spatial tuning properties of deep layer multiunits of anesthetized guinea pigs were examined ∼20 days after implantation of the Elvax polymer. Broadband noise bursts were presented to the animals under anechoic, free-field conditions. Neuronal responses were used to construct polar plots representative of the auditory spatial multiunit receptive fields (MURFs). Animals exposed to control polymer could develop a map of auditory space in the SC comparable with that seen in unimplanted normal animals. Exposure of the SC of young animals to AP5, 6-cyano-7-nitroquinoxaline-2,3-dione, or atropine, resulted in a reduction in the proportion of spatially tuned responses with an increase in the proportion of broadly tuned responses and a degradation in topographic order. Thus N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors and muscarinic acetylcholine receptors appear to play vital roles in the development of the SC auditory space map. A group of animals exposed to AP5 beginning at ∼250 DAB produced results very similar to those obtained in the young group exposed to AP5. Thus NMDA glutamate receptors also seem to be involved in the maintenance of the SC representation of auditory space in the adult guinea pig. Exposure of the SC of young guinea pigs to γ-aminobutyric acid (GABA) receptor blocking agents produced some but not total disruption of the spatial tuning of auditory MURFs. Receptive fields were large compared with controls, but a significant degree of topographical organization was maintained. GABA receptors may play a role in the development of fine tuning and sharpening of auditory spatial responses in the SC but not necessarily in the generation of topographical order of the these responses.
Opioid-Activated Postsynaptic, Inward Rectifying Potassium Currents in Whole Cell Recordings in Substantia Gelatinosa Neurons
Authors: Schneider S. P. , Eckert W. A. , Light A. R.
Published: December 2017

Schneider, S. P., W. A. Eckert III, and A. R. Light. Opioid-activated postsynaptic, inward rectifying potassium currents in whole cell recordings in substantia gelatinosa neurons. J. Neurophysiol. 80: 2954–2962, 1998. Using tight-seal, whole cell recordings from isolated transverse slices of hamster and rat spinal cord, we investigated the effects of the μ-opioid agonist (d-Ala2, N-Me-Phe4,Gly5-ol)-enkephalin (DAMGO) on the membrane potential and conductance of substantia gelatinosa (SG) neurons. We observed that bath application of 1–5 μM DAMGO caused a robust and repeatable hyperpolarization in membrane potential ( V m) and decrease in neuronal input resistance ( R N) in 60% (27/45) of hamster neurons and 39% (9/23) of rat neurons, but significantly only when ATP (2 mM) and guanosine 5′-triphosphate (GTP; 100 μM) were included in the patch pipette internal solution. An ED50 of 50 nM was observed for the hyperpolarization in rat SG neurons. Because G-protein mediation of opioid effects has been shown in other systems, we tested if the nucleotide requirement for opioid hyperpolarization in SG neurons was due to G-protein activation. GTP was replaced with the nonhydrolyzable GTP analogue guanosine-5′- O-(3-thiotriphosphate) (GTP-γ-S; 100 μM), which enabled DAMGO to activate a nonreversible membrane hyperpolarization. Further, intracellular application of guanosine-5′- O-(2-thiodiphosphate) (GDP-β-S; 500 μM), which blocks G-protein activation, abolished the effects of DAMGO. We conclude that spinal SG neurons are particularly susceptible to dialysis of GTP by whole cell recording techniques. Moreover, the depletion of GTP leads to the inactivation of G-proteins that mediate μ-opioid activation of an inward-rectifying, potassium conductance in these neurons. These results explain the discrepancy between the opioid-activated hyperpolarization in SG neurons observed in previous sharp electrode experiments and the more recent failures to observe these effects with whole cell patch techniques.
Interactions of Inhibition and Excitation in the Light-Evoked Currents of X Type Retinal Ganglion Cells
Authors: Cohen Ethan D.
Published: December 2017

Cohen, Ethan D. Interactions of inhibition and excitation in the light-evoked currents of X type retinal ganglion cells. J. Neurophysiol. 80: 2975–2990, 1998. The excitatory and inhibitory conductances driving the light-evoked currents (LECs) of cat and ferret on- and off-center X ganglion cells were examined in sliced and isolated retina preparations using center spot stimulation in tetrodotoxin (TTX)-containing Ringer. on-center X ganglion cells showed an increase in an excitatory conductance reversed positive to +20 mV during the spot stimulus. At spot offset, a transient inhibitory conductance was activated on many cells that reversed near E Cl. off-center X ganglion cells showed increases in a sustained inhibitory conductance that reversed near E Cl during spot stimulation. At spot offset, an excitatory conductance was activated that reversed positive to +20 mV. The light-evoked current kinetics of on- and off-center X cells to spot stimulation did not significantly differ in form from their Y cell counterparts in TTX Ringer. When inhibition was blocked, current-voltage relations of the light-evoked excitatory postsynaptic currents (EPSCs) of both on- and off-X cells were L-shaped and reversed near 0 mV. The EPSCs averaged between 300 and 500 pA at −80 mV. The metabotropic glutamate receptor agonist 2-amino-4-phosphonobutyric acid (APB), was used to block on-center bipolar cell function. The LECs of on-X ganglion cells were totally blocked in APB at all holding potentials. APB caused prominent reductions in the dark holding current and synaptic noise of on-X cells. In contrast, the LECs of off-X ganglion cells remained in APB. An increase in the dark holding current was observed. The excitatory amino acid receptor antagonist combination of d-amino-5-phosphono-pentanoic acid (d-AP5) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)-quinoxalinedione (NBQX) was used to block ionotropic glutamate receptor retinal neurotransmission. The LECs of all on-X ganglion cells were totally blocked, and their holding currents were reduced similar to the actions of APB. For off-X ganglion cells, the antagonist combination always blocked the excitatory current at light-off; however, in many cells, the inhibitory current at light-on remained. on-center X ganglion cells receive active excitation during center illumination, and a transient inhibition at light-off. In contrast off-center X ganglion cells experience a sustained active inhibition during center illumination, and a shorter increase in excitation at light-offset. Cone bipolar cells provide a resting level of glutamate release on X ganglion cells on which their light-evoked currents are superimposed.
Strobe Rearing Reduces Direction Selectivity in Area 17 by Altering Spatiotemporal Receptive-Field Structure
Authors: Humphrey Allen L. , Saul Alan B.
Published: December 2017

Humphrey, Allen L. and Alan B. Saul. Strobe rearing reduces direction selectivity in area 17 by altering spatiotemporal receptive-field structure. J. Neurophysiol. 80: 2991–3004, 1998. Direction selectivity in simple cells of cat area 17 is linked to spatiotemporal (S-T) receptive-field structure. S-T inseparable receptive fields display gradients of response timing across the receptive field that confer a preferred direction of motion. Receptive fields that are not direction selective lack gradients; they are S-T separable, displaying uniform timing across the field. Here we further examine this link using a developmental paradigm that disrupts direction selectivity. Cats were reared from birth to 8 mo of age in 8-Hz stroboscopic illumination. Direction selectivity in simple cells was then measured using gratings drifting at different temporal frequencies (0.25–16 Hz). S-T structure was assessed using stationary bars presented at different receptive-field positions, with bar luminance being modulated sinusoidally at different temporal frequencies. For each cell, plots of response phase versus bar position were fit by lines to characterize S-T inseparability at each temporal frequency. Strobe rearing produced a profound loss of direction selectivity at all temporal frequencies; only 10% of cells were selective compared with 80% in normal cats. The few remaining directional cells were selective over a narrower than normal range of temporal frequencies and exhibited weaker than normal direction selectivity. Importantly, the directional loss was accompanied by a virtual elimination of S-T inseparability. Nearly all cells were S-T separable, like nondirectional cells in normal cats. The loss was clearest in layer 4. Normally, inseparability is greatest there, and it correlates well ( r = 0.77) with direction selectivity; strobe rearing reduced inseparability and direction selectivity to very low values. The few remaining directional cells were inseparable. In layer 6 of normal cats, most direction-selective cells are only weakly inseparable, and there is no consistent relationship between the two measures. However, after strobe rearing, even the weak inseparability was eliminated along with direction selectivity. The correlated changes in S-T structure and direction selectivity were confirmed using conventional linear predictions of directional tuning based on responses to counterphasing bars and white noise stimuli. The developmental changes were permanent, being observed up to 12 yr after strobe rearing. The deficits were remarkably specific; strobe rearing did not affect spatial receptive-field structure, orientation selectivity, spatial or temporal frequency tuning, or general responsiveness to visual stimuli. These results provide further support for a critical role of S-T structure in determining direction selectivity in simple cells. Strobe rearing eliminates directional tuning by altering the timing of responses within the receptive field.
Chronic Changes in Synaptic Responses of Entorhinal and Hippocampal Neurons After Amino-Oxyacetic Acid (AOAA)–Induced Entorhinal Cortical Neuron Loss
Authors: Scharfman H. E. , Goodman J. H. , Du F. , Schwarcz R.
Published: December 2017

Scharfman, H. E., J. H. Goodman, F. Du, and R. Schwarcz. Chronic changes in synaptic responses of entorhinal and hippocampal neurons after amino-oxyacetic acid (AOAA)–induced entorhinal neuron loss. J. Neurophysiol. 80: 3031–3046, 1998. Synaptic responses of entorhinal cortical and hippocampal neurons were examined in vivo and in vitro, 1 mo to 1.5 yr after a unilateral entorhinal lesion caused by a focal injection of amino-oxyacetic acid (AOAA). It has been shown previously that injection of AOAA into the medial entorhinal cortex produces cell loss in layer III preferentially. Although behavioral seizures stopped ∼2 h after AOAA treatment, abnormal evoked responses were recorded as long as 1.5 yr later in the entorhinal cortex and hippocampus. In the majority of slices from AOAA-treated rats, responses recorded in the superficial layers of the medial entorhinal cortex to white matter, presubiculum, or parasubiculum stimulation were abnormal. Extracellularly recorded responses to white matter stimulation were prolonged and repetitive in the superficial layers. Intracellular recordings showed that residual principal cells in superficial layers produced prolonged, repetitive excitatory postsynaptic potentials (EPSPs) and discharges in response to white matter stimulation compared with brief EPSPs and a single discharge in controls. Responses of deep layer neurons of AOAA-treated rats did not differ from controls in their initial synaptic response. However, in a some of these neurons, additional periods of excitatory activity occurred after a delay. Abnormal responses were recorded from slices ipsilateral as well as contralateral to the lesioned hemisphere. Recordings from the entorhinal cortex in vivo were abnormal also, as demonstrated by prolonged and repetitive responses to stimulation of the area CA1/subiculum border. Evoked responses of hippocampal neurons, recorded in vitro or in vivo, demonstrated abnormalities in selected pathways, such as responses of CA3 neurons to hilar stimulation in vitro. There was a deficit in the duration of potentiation of CA1 population spikes in response to repetitive CA3 stimulation in AOAA-treated rats. Theta activity was reduced in amplitude in area CA1 and the dentate gyrus of AOAA-treated rats, although evoked responses to angular bundle stimulation could not be distinguished from controls. The results demonstrate that a preferential lesion of layer III of the entorhinal cortex produces a long-lasting change in evoked and spontaneous activity in parts of the entorhinal cortex and hippocampus. Given the similarity of the lesion produced by AOAA and entorhinal lesions in temporal lobe epileptics, these data support the hypothesis that preferential damage to the entorhinal cortex contributes to long-lasting changes in excitability, which could be relevant to the etiology of temporal lobe epilepsy.
Inhibition of Calcium Currents in Rat Colon Sensory Neurons by K- But Not μ- or δ-Opioids
Authors: Su X. , Wachtel R. E. , Gebhart G. F.
Published: December 2017

Su, Xin, R. E. Wachtel, and G. F. Gebhart. Inhibition of calcium currents in rat colon sensory neurons by κ- but not μ- or δ-opioids. J. Neurophysiol. 80: 3112–3119, 1998. We previously reported that κ-, but not μ- or δ-opioid receptor agonists (ORAs) have selective, potentially useful peripheral analgesic effects in visceral pain. To evaluate one potential site and mechanism by which these effects are produced, we studied opioid effects on high-voltage activated (HVA) Ca2+currents in identified (Di-I) pelvic nerve sensory neurons from the S1 dorsal root ganglion (DRG). Results were compared with opioid effects on cutaneous neurons from L5 or L6 DRG. Di-I–labeled DRG cells were voltage clamped (perforated whole cell patch clamp), and HVA Ca2+currents were evoked by depolarizing 240-ms test pulses to +10 mV from a holding potential of −60 mV. Neither μ-ORAs (morphine, 10−6M, n = 16; [D-Ala2, N-Me-Phe4, Gly-ol5] enkephalin, 10−6M, n = 12) nor δ-ORAs ([D-Pen2, D-Pen5] enkephalin, 10−7M, n = 16; SNC-80, 10−7M, n = 7) affected HVA Ca2+currents in colon sensory neurons. In contrast, the κ-ORAs U50,488 (10−6M), bremazocine (10−6M), and nalBzoH (10−6M) significantly attenuated HVA Ca2+currents in colon sensory neurons; effects on cutaneous sensory neurons were variable. A nonreceptor selective concentration of naloxone (10−5M) and nor-BNI (10−6M), a selective κ-opioid receptor antagonist, reversed the inhibitory effect of κ-ORAs. In the presence of N-, P-, or Q-, but not L-type Ca2+channel antagonists, the effect of U50,488 on HVA Ca2+currents was significantly reduced. Pretreatment with pertussis toxin (PTX) prevented the inhibition by U50,488. These results suggest that κ-opioid receptors are coupled to multiple HVA Ca2+channels in colon sensory neurons by a PTX-sensitive G protein pathway. We conclude that inhibition of Ca2+channel function likely contributes in part to the peripheral analgesic action of κ-ORAs in visceral nociception.
Large-Scale Functional Connectivity in Associative Learning: Interrelations of the Rat Auditory, Visual, and Limbic Systems
Authors: Mcintosh A. R. , Gonzalez-Lima F.
Published: December 2017

McIntosh, A. R. and F. Gonzalez-Lima. Large-scale functional connectivity in associative learning: interrelations of the rat auditory, visual, and limbic systems. J. Neurophysiol. 80: 3148–3162, 1998. Functional relations between specialized parts of the brain may be important determinants of learned behaviors. To study this, we examined the interrelations of the auditory system with several extraauditory structures in two groups of rats having different behavioral histories. Both groups were trained to associate a tone conditional stimulus (CS) with an aversive unconditional stimulus (US). For one group, a light presented with the tone predicted the absence of the US ( group TL−). In the other group, the light was a neutral stimulus ( group TL0). Fluorodeoxyglucose (FDG) incorporation was measured in the presence of the tone-light compound. Because the tone-light compound was physically identical for both groups, neural differences between groups reflected differences in the learned associative properties of the stimuli. Covariances of FDG uptake in the auditory system and extraauditory structures were examined using partial least squares. Three strong covariance or functional connectivity patterns were identified. The first pattern mainly reflected similarities between groups, with strong interrelations between the subcortical auditory system and the thalamocortical visual system, cerebellum, deep cerebellar nuclei, and midline thalamus. This pattern of interactions may represent part of a common circuit for relaying the associative value of the tone CS to the cerebellum and the midline thalamus. The external nucleus of the inferior colliculus and medial division of the medial geniculate nucleus were associated more strongly with this pattern for group TL−, which was interpreted as representing the change of the associative value of the tone by the light, mediated through extraauditory influences on these two regions. A second pattern involved midbrain auditory regions, superior colliculus, zona incerta, and subiculum and was stronger for group TL0. The relations between midbrain structures may represent the excitatory conditioned response (CR) evoked by the tone in this group. The final pattern was strongest in group TL−and involved interrelations of the thalamocortical auditory system with hippocampus, basolateral amygdala, and hypothalamus. This pattern may represent the learned inhibition of the CR to the tone in the presence of the light. These findings are consistent with behavioral studies suggesting that at least two types of associations are formed during associative learning. One is the sensory relation of the stimuli and another is the relation between the CS and the affective components of the US. These behavioral associations are mapped to the patterns of functional connectivity between auditory and extraauditory regions.
Interaction of GABAB-Mediated Inhibition With Voltage-Gated Currents of Pyramidal Cells: Computational Mechanism of a Sensory Searchlight
Authors: Berman Neil J. , Maler Leonard
Published: December 2017

Berman, Neil J. and Leonard Maler. Interaction of GABAB-mediated inhibition with voltage-gated currents of pyramidal cells: computational mechanism of a sensory searchlight. J. Neurophysiol. 80: 3197–3213, 1998. This study examines, in the in vitro electrosensory lateral line lobe (ELL) slice preparation, mono- and disynaptic inhibition in pyramidal cells evoked by stimulation of the direct descending pathway from nucleus praeminentialis (Pd). The pathway forms the stratum fibrosum (StF) in the ELL and consists of excitatory fibers from Pd stellate cells that make monosynaptic contact with pyramidal cells and disynaptic inhibitory contacts via local interneurons and of GABAergic inhibitory fibers from Pd bipolar cells. Single or tetanic stimulation (physiological rates of 100–200 Hz) of the StF produced excitatory postsynaptic potentials (EPSPs) or compound EPSPs in ELL pyramidal cells. Slow (>600 ms) and fast inhibitory postsynaptic potentials (IPSPs; 5–50 ms) also were evoked. Application of γ-aminobutyric acid-A (GABAA) antagonists blocked the fast inhibition and dramatically increased the firing rate response to StF tetanic stimuli. GABAA antagonists also increased the amplitude of the slow IPSP. The slow IPSP was reduced by GABAB antagonists. Blockade of excitatory amino acid (EAA) synaptic transmission allowed the monosynaptic bipolar-cell-mediated inhibition to be studied in isolation: EAA antagonists blocked most of the EPSP response to StF stimulation leaving fast and (an increased amplitude) slow IPSP components. The bipolar-cell IPSPs were mediated by GABAA and GABAB receptors as they were sensitive to GABAA and GABAB antagonists. The bipolar-cell IPSPs scaled with stimulation rate (20–400 Hz), reaching a maximum amplitude at 200 Hz. Inhibitory efficacy of bipolar-cell slow IPSPs were tested by their ability to reduce spiking in the face of sustained or brief current pulses. Established spike trains (by sustained injected current) were little affected by the onset of the slow IPSP. Weak brief currents injected during the slow IPSP were strongly inhibited. Strong brief currents could overcome the slow IPSP inhibitory effect. Inhibition was observed to interact with the intrinsic I A-like K+ currents to produce a complex control of cell spiking. Hyperpolarizing inhibition removes inactivation of I A to prevent subsequent inputs from driving the cell to threshold. Established depolarizing inputs, having allowed I A to inactivate, enable the cell to be highly sensitive to further depolarizing input. The term “conditional inhibition” is proposed to describe the general phenomenon where synaptic inhibition interacts with voltage-sensitive intrinsic currents.
Functional Reorganization of the Rat Motor Cortex Following Motor Skill Learning
Authors: Kleim Jeffrey A. , Barbay Scott , Nudo Randolph J.
Published: December 2017

Kleim, Jeffrey A., Scott Barbay, and Randolph J. Nudo. Functional reorganization of the rat motor cortex following motor skill learning. J. Neurophysiol. 80: 3321–3325, 1998. Adult rats were allocated to either a skilled or unskilled reaching condition (SRC and URC, respectively). SRC animals were trained for 10 days on a skilled reaching task while URC animals were trained on a simple bar pressing task. After training, microelectrode stimulation was used to derive high resolution maps of the forelimb and hindlimb representations within the motor cortex. In comparison with URC animals, SRC animals exhibited a significant increase in mean area of the wrist and digit representations but a decrease in elbow/shoulder representation within the caudal forelimb area. No between-group differences in areal representation were found in either the hindlimb or rostral forelimb areas. These results demonstrate that motor skill learning is associated with a reorganization of movement representations within the rodent motor cortex.
Glycine Uptake Governs Glycine Site Occupancy at NMDA Receptors of Excitatory Synapses
Authors: Berger Albert J. , Dieudonné Stéphane , Ascher Philippe
Published: December 2017

Berger, Albert J., Stéphane Dieudonné, and Philippe Ascher. Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J. Neurophysiol. 80: 3336–3340, 1998. At central synapses occupation of glycine binding sites of N-methyl-d-aspartate receptors (NMDA-Rs) is a necessary prerequisite for the excitatory neurotransmitter glutamate to activate these receptors. There is conflicting evidence as to whether glycine binding sites normally are saturated. If they are not, then alterations in local glycine concentration could modulate excitatory synaptic transmission. By using an in vitro brain stem slice preparation we investigated whether the glycine site is saturated for synaptically activated NMDA-Rs in neonatal rat hypoglossal motoneurons. We found that the NMDA-R–mediated component of spontaneous miniature excitatory postsynaptic currents could be potentiated by exogenously applied glycine as well as by d-serine. The effects of glycine were observed only at concentrations (100 μM or more) two orders of magnitude above the apparent dissociation constant of glycine from NMDA receptors. In contrast, d-serine, a nontransported NMDA-R glycine site agonist, was effective in the low micromolar range, i.e., at concentrations similar to those found to be effective on isolated cells or on outside-out patches. We conclude that at these synapses the glycine concentration around synaptic NMDA-Rs is set below the concentration required to saturate their glycine site and is likely to be stabilized by a powerful glycine transport mechanism.
Slow Covariations in Neuronal Resting Potentials Can Lead to Artefactually Fast Cross-Correlations in Their Spike Trains
Authors: Brody Carlos D.
Published: December 2017

Brody, Carlos D. Slow covariations in neuronal resting potentials can lead to artefactually fast cross-correlations in their spike trains. J. Neurophysiol. 80: 3345–3351, 1998. A model of two lateral geniculate nucleus (LGN) cells, which interact only through slow (tens of seconds) covariations in their resting membrane potentials, is used here to investigate the effect of such covariations on cross-correlograms taken during stimulus-driven conditions. Despite the slow timescale of the interactions, the model generates cross-correlograms with peak widths in the range of 25–200 ms. These bear a striking resemblance to those reported in studies of LGN cells by Sillito et al., which were taken at the time as evidence of a fast spike timing synchronization interaction; the model highlights the possibility that those correlogram peaks may have been caused by a mechanism other than spike synchronization. Slow resting potential covariations are suggested instead as the dominant generating mechanism. How can a slow interaction generate covariogram peaks with a width 100–1,000 times thinner than its timescale? Broad peaks caused by slow interactions are modulated by the cells' poststimulus time histograms (PSTHs). When the PSTHs have thin peaks (e.g., tens of milliseconds), the cross-correlogram peaks generated by slow interactions will also be thin; such peaks are easily misinterpretable as being caused by fast interactions. Although this point is explored here in the context of LGN recordings, it is a general point and applies elsewhere. When cross-correlogram peak widths are of the same order of magnitude as PSTH peak widths, experiments designed to reveal short-timescale interactions must be interpreted with the issue of possible contributions from slower interactions in mind.
ATP P2× Receptors and Sensory Synaptic Transmission Between Primary Afferent Fibers and Spinal Dorsal Horn Neurons in Rats
Authors: Li Ping , Calejesan Amelita A. , Zhuo Min
Published: December 2017

Li, Ping, Amelita A. Calean, and Min Zhuo. ATP P2× receptors and sensory synaptic transmission between primary afferent fibers and spinal dorsal horn neurons in rats. J. Neurophysiol. 80: 3356–3360, 1998. Glutamate is a major fast transmitter between primary afferent fibers and dorsal horn neurons in the spinal cord. Recent evidence indicates that ATP acts as another fast transmitter at the rat cervical spinal cord and is proposed to serve as a transmitter for nociception and pain. Sensory synaptic transmission between dorsal root afferent fibers and neurons in the superficial dorsal horn of the lumbar spinal cord were examined by whole cell patch-clamp recording techniques. Experiments were designed to test if ATP could serve as a transmitter at the lumbar spinal cord. Monosynaptic excitatory postsynaptic currents (EPSCs) were completely abolished after the blockade of both glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate and N-methyl-d-aspartate receptors. No residual current was detected, indicating that glutamate but not ATP is a fast transmitter at the dorsal horn of the lumbar spinal cord. Pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), a selective P2× receptor antagonist, produced an inhibitory modulatory effect on fast EPSCs and altered responses to paired-pulse stimulation, suggesting the involvement of a presynaptic mechanism. Intrathecal administration of PPADS did not produce any antinociceptive effect in two different types of behavioral nociceptive tests. The present results suggest that ATP P2×2 receptors modulate excitatory synaptic transmission in the superficial dorsal horn of the lumbar spinal cord by a presynaptic mechanism, and such a mechanism does not play an important role in behavioral responses to noxious heating. The involvement of other P2× subtype receptors, which is are less sensitive to PPADS, in acute nociceptive modulation and persistent pain remains to be investigated.
New Mechanism That Accounts for Position Sensitivity of Saccades Evoked in Response to Stimulation of Superior Colliculus
Authors: Moschovakis A. K. , Dalezios Y. , Petit J. , Grantyn A. A.
Published: December 2017

Moschovakis, A. K., Y. Dalezios, J. Petit, and A. A. Grantyn. New mechanism that accounts for position sensitivity of saccades evoked in response to stimulation of superior colliculus. J. Neurophysiol. 80: 3373–3379, 1998. Electrical stimulation of the feline superior colliculus (SC) is known to evoke saccades whose size depends on the site stimulated (the “characteristic vector” of evoked saccades) and the initial position of the eyes. Similar stimuli were recently shown to produce slow drifts that are presumably caused by relatively direct projections of the SC onto extraocular motoneurons. Both slow and fast evoked eye movements are similarly affected by the initial position of the eyes, despite their dissimilar metrics, kinematics, and anatomic substrates. We tested the hypothesis that the position sensitivity of evoked saccades is due to the superposition of largely position-invariant saccades and position-dependent slow drifts. We show that such a mechanism can account for the fact that the position sensitivity of evoked saccades increases together with the size of their characteristic vector. Consistent with it, the position sensitivity of saccades drops considerably when the contribution of slow drifts is minimal as, for example, when there is no overlap between evoked saccades and short-duration trains of high-frequency stimuli.
NMDA-Induced Intrinsic Voltage Oscillations Depend on L-Type Calcium Channels in Spinal Motoneurons of Adult Turtles
Authors: Guertin P. A. , Hounsgaard J.
Published: December 2017

Guertin, P. A. and J. Hounsgaard. NMDA-induced intrinsic voltage oscillations depend on L-type calcium channels in spinal motoneurons of adult turtles. J. Neurophysiol. 80: 3380–3382, 1998. In a slice preparation from adult turtles, bath-applied N-methyl-d-aspartate (NMDA) induced rhythmic activity in spinal motoneurons. The underlying intrinsic oscillation in membrane potential was revealed in the presence of tetrodotoxin (TTX). NMDA-induced rhythmicity, in the presence or absence of TTX, was abolished or reduced by NMDA receptor antagonists and by three different classes of antagonists for L-type calcium channels. It is suggested that both NMDA receptor channels and L-type calcium channels contribute to NMDA-induced intrinsic oscillations in mature spinal motoneurons.
Brain-Derived Neurotrophic Factor (BDNF) Modulates Inhibitory, But Not Excitatory, Transmission in the CA1 Region of the Hippocampus
Authors: Frerking M. , Malenka R. C. , Nicoll R. A.
Published: December 2017

Frerking, M., R. C. Malenka, and R. A. Nicoll. Brain-derived neurotrophic factor (BDNF) modulates inhibitory, but not excitatory, transmission in the CA1 region of the hippocampus. J. Neurophysiol. 80: 3383–3386, 1998. Brain-derived neurotrophic factor (BDNF) has been reported to have rapid effects on synaptic transmission in the hippocampus. We report here that bath application of BDNF causes a small but significant decrease in stimulus-evoked inhibitory postsynaptic currents (IPSCs) on CA1 pyramidal cells, which is prevented by the tyrosine kinase inhibitor lavendustin A. BDNF causes a decrease in the 1/CV2 of the IPSC, and also reduces paired-pulse depression of the IPSC, suggesting a presynaptic site of action. In contrast, BDNF did not have a detectable effect on field excitatory postsynaptic potentials measured in stratum radiatum. We conclude that BDNF has a selective depressant action on inhibitory transmission in the hippocampus, due at least in part to a presynaptic mechanism.
Intraneuronal [Ca2+] Changes Induced by 2-Deoxy-d-Glucose in Rat Hippocampal Slices
Authors: Tekkök S. , Medina I. , Krnjević K.
Published: December 2017

Tekkök, S., I. Medina, and K. Krnjević. Intraneuronal [Ca2+] changes induced by 2-deoxy-d-glucose in rat hippocampal slices. J. Neurophysiol. 81: 174–183, 1999. Temporary replacement of glucose by 2-deoxyglucose (2-DG; but not sucrose) is followed by long-term potentiation of CA1 synaptic transmission (2-DG LTP), which is Ca2+-dependent and is prevented by dantrolene or N-methyl-d-aspartate (NMDA) antagonists. To clarify the mechanism of action of 2-DG, we monitored [Ca2+]iwhile replacing glucose with 2-DG or sucrose. In slices (from Wistar rats) kept submerged at 30°C, pyramidal neurons were loaded with [Ca2+]-sensitive fluo-3 or Fura Red. The fluorescence was measured with a confocal microscope. Bath applications of 10 mM 2-DG (replacing glucose for 15 ± 0.38 min, means ± SE) led to a rapid but reversible rise in fluo-3 fluorescence (or drop of Fura Red fluorescence); the peak increase of fluo-3 fluorescence (Δ F/ F0), measured near the end of 2-DG applications, was by 245 ± 50% ( n = 32). Isosmolar sucrose (for 15–40 min) had a smaller but significant effect (Δ F/ F0= 94 ± 14%, n = 10). The 2-DG–induced Δ F/ F0was greatly reduced (to 35 ± 15%, n = 16) by d,l-aminophosphono-valerate (50–100 μM) and abolished by 10 μM dantrolene (−4.0 ± 2.9%, n = 11). A substantial, although smaller effect, of 2-DG persisted in Ca2+-free 1 mM ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid (EGTA) medium. Two adenosine antagonists, which do not prevent 2-DG LTP, were also tested; 2-DG–induced Δ F/ F0(fluo-3) was not affected by the A1antagonist 8-cyclopentyl-3,7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX 50 nM; 287 ± 38%; n = 20), but it was abolished by the A1/A2antagonist 8-SPT; 25 ± 29%, n = 19). These observations suggest that 2-DG releases glutamate and adenosine and that the rise in [Ca2+] may be triggered by a synergistic action of glutamate (acting via NMDA receptors) and adenosine (acting via A2breceptors) resulting in Ca2+release from a dantrolene-sensitive store. The discrepant effects of sucrose and 8-SPT on Δ F/ F0, on the one hand, and 2-DG LTP, on the other, support other evidence that increases in postsynaptic [Ca2+]iare not essential for 2-DG LTP.