Journal of Neurophysiology

Traynelis, S. F.; Dingledine, R.

doi: N/Apmid: 3343603

Abstract 1. The CA1 region of rat hippocampal slices bathed in 8.5 mM interstitial K+ (K+o) exhibited spontaneous 20- to 90-s electrographic seizures at regular intervals of 1–8 min. In these same slices CA3 neurons generated spontaneous interictal bursts that propagated throughout the pyramidal cell subfields. CA1 electrographic seizures contained components reminiscent of discharges recorded in vivo during tonic-clonic motor seizures. The tonic phase lasted 1–10 s, consisted of a sustained depolarization and firing of CA1 pyramidal cells, and was associated with a negative extracellular potential in the cell layer. The clonic phase lasted tens of seconds and was composed of paroxysmal bursts with afterdischarges in pyramidal cells. 2. Electrographic seizures in CA1 were focal in nature in that they did not invade the CA3 region. Moreover, in approximately 85% of all slices the frequency and amplitude of interictal bursts in CA3 did not change during a CA1 seizure. 3. Both the tonic phase and each clonic discharge of an electrographic seizure were triggered synaptically by a CA3 interictal burst. Microlesions of the Schaffer collateral input abolished CA1 seizures in high K+o, and electrical stimulation of these afferents, in a pattern designed to mimic interictal input, restored seizures. Likewise, similarly patterned electrical stimulation of these fibers in slices bathed in high K+o with the CA3 region removed reliably evoked electrographic seizures with period and duration similar to spontaneous seizures in whole slices. 4. Electrographic seizures but not CA3 interictal bursts could be reversibly abolished by lowering the temperature from 35–37 to 28–30 degrees C or by the competitive N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (5–10 microM). The inactive isomer, L-2-amino-5-phosphonovaleric acid (25 microM) did not eliminate seizures. 5. Neither the frequency nor intensity of interictal bursts recorded in the CA3 region changed in the minute preceding seizure initiation. Thus, although the presence of interictal input from the CA3 region is required for CA1 seizure generation, it appears that electrographic seizures do not result from a change in the quality or quantity of interictal input to the CA1 region. 6. During the 30- to 60-s period leading to a seizure the excitability of CA1 pyramidal cells appeared to increase gradually. Over the interseizure interval both CA1 pyramidal cells and glia gradually depolarized, the intensity of interictal bursts recorded in the CA1 region increased, and the extracellular DC potential recorded in the CA1 cell layer drifted negative.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Tsuchitani, C.

doi: N/Apmid: 3343600

Abstract 1. Preliminary to extending a point process model of lateral superior olive (LSO) unit activity to describe the units' binaural responses, the statistical properties of their discharges to binaural tone bursts were studied. The hypothesis that stimulation of the contralateral ear results in the simple reduction of the ipsilateral input was also examined. Single-unit activity was recorded extracellularly from the LSO of the anesthetized cat. The sustained discharges to characteristic frequency (CF) tone bursts presented simultaneously to the two ears were examined to determine whether the fine temporal (statistical) properties of these discharges differed from those of the discharges elicited by stimulating the ipsilateral ear alone. 2. The major effect of simultaneously stimulating the contralateral ear was the inhibition (i.e., the reduction in the mean discharge rate) of the sustained discharges to the ipsilateral control stimulus. The temporal pattern of discharges to the ipsilateral stimulus was also affected by stimulation of the contralateral ear. The discharges to binaural stimulation were more irregular in pattern: they often produced bimodal or multimodal interval histograms where unimodal interval histograms had been produced by the discharges to the ipsilateral control stimulus alone. The hazard function, an estimate of the unit recovery function, also often differed in form for the binaural and monaural discharges. 3. The binaural discharges could be distinguished from an ipsilaterally elicited discharge of comparable mean rate: there was a greater incidence of “short” interspike intervals in the binaural discharge. These short interspike intervals occurred most frequently in the discharges to the ipsilateral control stimulus alone and infrequently in the discharges to an ipsilateral stimulus that produced a mean rate similar to that of the binaural discharge. Thus the dead time estimates derived from the binaural discharges were more similar to the estimates derived from the ipsilateral control discharges than to those derived from the comparable-rate ipsilaterally elicited discharges. 4. Although the measures of the recovery properties of LSO unit discharges differed under monaural and binaural stimulus conditions, the serial dependence observed between successive interspike intervals in the binaurally elicited discharges was similar to that in the ipsilaterally elicited discharges. The conditional mean function, an estimate of the serial dependence or unit shifting function, did not differ greatly in form for the monaural and binaural discharges.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Puil, E.; Gimbarzevsky, B.; Spigelman, I.

doi: N/Apmid: 2449522

Abstract 1. The complex impedances and impedance magnitude functions were obtained from neurons in in vitro slices of trigeminal root ganglia using frequency-domain analyses of intracellularly recorded voltage responses to specified oscillatory input currents. A neuronal model derived from linearized Hodgkin-Huxley-like equations was used to fit the complex impedance data. This procedure yielded estimates for membrane electrical properties. 2. Membrane resonance was observed in the impedance magnitude functions of all investigated neurons at their initial resting membrane potentials and was similar to that reported previously for trigeminal root ganglion neurons in vivo. Tetrodotoxin (10(-6) M), a Na+-channel blocker, applied in the bathing medium for 20 min produced only minor changes, if any, in the resonance, although gross impairment of Na+-spike electrogenesis was apparent in most of the neurons. Brief applications (1-5 min) of a K+-channel blocker, tetraethylammonium (TEA; 10(-2) M), increased the impedance magnitude and abolished, in a reversible manner, the resonant behavior. In all cases, the resonant frequency was decreased by TEA administration prior to total blockade of resonance. 3. The TEA-induced blockade of resonance was associated with decreases in the estimates of the membrane conductances, without significant alterations of input capacitance. A particularly large decrease was observed in Gr, the time-invariant resting conductance that includes a lumped leak conductance component. The voltage- and time-dependent conductance, GL, and associated relaxation time constant, tau u, also declined progressively during administration of TEA. 4. Systematic variations in the membrane potentials of trigeminal root ganglion neurons were produced by intracellular injections of long-lasting step currents with superposition of the oscillatory current stimuli, in order to assess the effects of TEA on the relationship of the electrical properties to the membrane potential. Applications of TEA led to a depolarizing shift in the dependence of the membrane property estimates, suggesting voltage-dependence of the effects of TEA on presumed K+ channels in the membrane. 5. These data suggest a primary involvement of K+ conductance in the genesis of membrane resonance. This electrical behavior or its ionic mechanism is a major modulator of the subthreshold electrical responsiveness of trigeminal root ganglion neurons. Copyright © 1988 the American Physiological Society

Christian, E. P.; Dudek, F. E.

doi: N/Apmid: 2893830

Abstract 1. Evidence for local excitatory synaptic connections in CA1 of the rat hippocampus was obtained by recording excitatory postsynaptic potentials (EPSPs) intracellularly from pyramidal cells during local microapplications of glutamate. 2. Experiments were performed in hippocampal slices cut parallel to (transverse slice) or perpendicular to (longitudinal slice) alvear fibers. In normal solutions, glutamate microdrops (10–20 mM, 10–20 micron diam) applied in CA1 within 400 micron of recorded cells sometimes increased the frequency of inhibitory postsynaptic potentials for 5–10 s in both transverse and longitudinal slices. Increases in EPSP frequency were also occasionally observed, but only in transverse slices. Tetrodotoxin (1 microgram/ml) blocked glutamate-induced increases in PSP frequency, thus indicating that they were not caused by subthreshold effects on presynaptic terminals. Increases in PSP frequency were interpreted to result from glutamate activation of hippocampal neurons with inhibitory and excitatory connections to recorded neurons. 3. In both slice orientations, local excitatory circuits were studied in more isolated conditions by surgically separating CA1 from CA3 (transverse slices) and by blocking GABAergic inhibitory synapses with picrotoxin (5–10 microM). Microdrops were systematically applied at 200 and 400 micron on each side of the recording site. Significant glutamate-induced increases in EPSP frequency were observed in neurons from both slice orientations to microdrops in at least one of the locations. This provided evidence that excitatory synapses are present in both transverse and longitudinal slices. 4. Substantial increases in EPSP frequency only occurred in neurons from longitudinal slices when glutamate was microapplied 200 micron or less from the recording site. In transverse slices, however, large increases in EPSP frequency were observed to glutamate microapplications at 200 or 400 micron. These data suggest that CA1 local excitatory connections project for longer distances in the transverse than in the longitudinal plane of section. 5. Increases in EPSP frequency, averaged across cells, did not differ significantly in the four microapplication sites in either transverse or longitudinal slices. Thus local excitation in CA1 does not appear to be asymmetrically arranged in the way suggested for CA3. 6. The densities of local excitatory circuits in CA1 versus CA3 were studied by quantitatively comparing glutamate-induced increases in EPSP frequency.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Wilcox, K. S.; Gutnick, M. J.; Christoph, G. R.

doi: N/Apmid: 3343602

Abstract 1. The electroresponsive characteristics of neurons in the lateral habenula were studied with intracellular recordings in a brain slice preparation of guinea pig diencephalon maintained in vitro. One hundred and two neurons met the criteria for recording stability, and of these, 18 were analyzed in detail. For these 18 neurons, the mean resting membrane potential was -61.9 mV, the mean input resistance was 124 M omega, and the mean spike amplitude of fast action potentials was 60.3 mV. 2. Lateral habenula neurons were found to have distinct patterns of activity dependent on membrane potential. At membrane potentials more positive than -65 mV, depolarization elicited trains of sodium-dependent fast action potentials. At membrane potentials more negative than -65 mV, slight depolarization elicited a tetrodotoxin-insensitive wave of depolarization, called a low-threshold spike (LTS), from which a burst of fast action potentials were triggered. The principal conductance underlying the LTS is a low-threshold calcium conductance, which is inactivated at membrane potential more positive than -65 mV and deinactivated when the membrane is hyperpolarized to potentials more negative than -65 V. 3. Upon termination of injected hyperpolarizing current, many neurons displayed oscillation in membrane potential at a frequency of 3–10 Hz, thereby generating repetitive bursts of fast spikes. 4. The pattern of neuronal activity in lateral habenula neurons was highly sensitive to slight alterations in membrane potential. The ability of these neurons to fire action potentials in two modes, tonically and in bursts, and the propensity of these neurons to dramatically alter their output in response to transient hyperpolarizing input, indicate that transmission through this relay in the dorsal diencephalic conduction system may be greatly augmented by relatively small hyperpolarizing influences on the individual neurons. Copyright © 1988 the American Physiological Society

Berkley, K. J.; Robbins, A.; Sato, Y.

doi: N/Apmid: 2449520

Abstract 1. In the present three-part study electrophysiological techniques were used to characterize responses of afferent fibers in the rat hypogastric nerve to mechanical or chemical stimulation of the uterus, and anatomical techniques were used to identify the spinal segments through which uterine afferent fibers enter the spinal cord. 2. In an in vivo barbiturate-anesthetized preparation, hypogastric afferent fibers responded in a time-locked manner to mechanical stimulation confined to restricted regions of the uterus and adjacent ligament. Receptive fields were most often located on the uterine body, particularly over the cervix. The few located on the uterine horn were usually near regions irritated during preparative surgery. Effective mechanical stimuli (pressure, stretching, squeezing, probing, rarely contractions) were typically greater than 5 g and simultaneously accompanied by transient ischemia around the probe or contracted area. Distension, unless extreme, was not an effective stimulus. Retrospective analysis of the data indicated that fibers may be more sensitive to uterine stimulation when rats are in vaginal estrus/proestrus than in diestrus/metestrus. 3. In an in vitro preparation, hypogastric afferent fibers responded in a dose-dependent fashion to injections into the uterine artery of the algesic chemicals bradykinin, 5-hydroxytryptamine, and KCl. They also responded to high doses of CO2 (in saline) and NaCN, but rarely to lower doses. Nearly all fibers responded to more than one chemical with response characteristics unique to each chemical (e.g., latency, duration, peak rate). 4. Injections of horseradish peroxidase into the uterine body and small portions of the adjacent horns in rats in vaginal estrus consistently labeled a small number of cells in the L1-S1 dorsal root ganglia, with peaks at L2 and L6. Virtually no cells were labeled in rats whose estrous cycle had been disrupted (by inadvertently keeping them in constant light conditions for several weeks). 5. These results indicate that uterine afferent fibers travel to the central nervous system through both the hypogastric (e.g., L1-L4 ganglia) and pelvic (e.g., L5-S1 ganglia) nerves in the rat, and that hypogastric fibers are capable of conveying fairly precise information about temporal and spatial aspects of uterine mechanical and chemical stimulation. The results also encourage future research into the possibility that the responses of these fibers vary as a function of estrous stage or other aspects of the condition of the uterus (e.g., its irritation).(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Komatsu, Y.; Fujii, K.; Maeda, J.; Sakaguchi, H.; Toyama, K.

doi: N/Apmid: N/A

Abstract Y. Komatsu, K. Fujii, J. Maeda, H. Sakaguchi, and K. Toyama, “Long-Term Potentiation of Synaptic Transmission in Kitten Visual Cortex.” Page 140: the fifth and sixth lines of the left-hand column should be deleted. Copyright © 1988 the American Physiological Society

Christian, E. P.; Dudek, F. E.

doi: N/Apmid: 2893832

Abstract 1. Local neuronal circuits in CA3 of hippocampal slices were studied by recording excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) intracellularly during glutamate microapplication in CA3. Control experiments validated this approach by providing evidence that glutamate microdrops stimulated neurons but not axons-of-passage or axon terminals in CA3. 2. Glutamate microdrops (10-20 mM, 10-20 microns diam) increased the firing frequency of extracellularly recorded dentate granule cells for 5–10 s when applied to their somata but not when applied to their mossy fiber axons and terminals in the hilus and in CA3. 3. Glutamate microapplications to granule cell somata, but not to mossy fiber axons, also increased the frequency of intracellularly recorded EPSPs in CA3 pyramidal cells for 5-10 s. This provided a second line of evidence that glutamate did not cause firing in mossy fiber axons synapsing in CA3. 4. In slices where the CA3 region was surgically separated from the dentate gyrus and CA2, glutamate microdrops placed in the CA3 stratum pyramidale within 400 microns of intracellularly recorded pyramidal cells increased the frequency of EPSPs and IPSPs. Tetrodotoxin (1 microgram/ml) blocked these increases in PSP frequency, indicating that they did not result from glutamate-induced depolarization and associated transmitter release from presynaptic terminals. Increases in PSP frequency were interpreted to reflect glutamate activations of CA3 neurons with local synaptic connections to recorded cells. 5. Low concentrations of picrotoxin (PTX, 5-10 microM) blocked glutamate-induced increases in IPSP frequency and often revealed increases in EPSP frequency where they were not previously observed. This suggests that recurrent inhibitory circuits normally mask or block transmission through recurrent excitatory pathways in CA3. 6. In five experiments following PTX treatment (7.5–10 microM), large and prolonged (up to 2 min) increases in EPSP frequency were observed in CA3 pyramidal cells to glutamate microapplications in CA3. Rhythmic epileptiform bursts eventually occurred in two of these cases, suggesting that the protracted increases in EPSP frequency represent a form of reverberating excitation during a transition from normal to epileptic states. 7. Sixteen CA3 pyramidal cells were recorded in PTX (5-10 microM) during glutamate microapplications at 200 and 400 microns on each side of the recording site. The most consistent glutamate-induced increases in EPSP frequency occurred to microapplications 200 microns from recording sites on the hilar side.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Suzuki, D. A.; Keller, E. L.

doi: N/Apmid: 3343598

Abstract 1. The observation of smooth-pursuit eye and retinal image velocity signals in lobules VI and VII of the vermis has given rise to the hypothesis that a neural correlate of a target velocity signal exists in this region of the cerebellum (29). However, activity signaling head velocity is also required to regenerate a target velocity signal. Vermal Purkinje cell activity was, therefore, recorded during the performance of paradigms designed to dissociate head movement-related responses. 2. The activity of 107 Purkinje cells was found to be related to horizontal head velocity. Of these, 52% increased their discharge rate for ipsilaterally directed passive head movement (type I), and 48% were excited by contralateral head movements (type II). 3. In five Purkinje cells in which sufficient data were obtained, cell discharge rate increased monotonically with head velocity over the range of 5–40 deg/s. The sensitivity to head velocity at 0.4 Hz +/- 25 deg/s averaged approximately 0.5 spikes.s-1/deg.s-1 in a larger sample of cells (n = 39). The sensitivities to head velocity, at this same frequency and velocity, of type I and type II Purkinje cells were comparable at 0.44 and 0.51 spikes.s-1/deg.s-1, respectively. 4. The Purkinje cell responses led head velocity by an average of 12 degrees at 0.4 Hz +/- 25 deg/s of passive head rotation. The phase shifts associated with type I and II responses were similar with phase leads of 13 and 9 degrees with respect to head velocity, respectively. 5. A linear interaction of smooth-pursuit eye and head velocity signals was observed during the performance of a variety of antiphase and inphase eye and head movement paradigms. The results support the conclusion that some Purkinje cells in lobules VI and VII of the cerebellar vermis encode a gaze velocity signal. Contributions of the head velocity signal to the regeneration of target velocity are considered in a companion paper (32). Copyright © 1988 the American Physiological Society

Glantz, R. M.; Nudelman, H. B.

doi: N/Apmid: 3343605

Abstract 1. Crayfish exhibit steady-state compensatory eyestalk rotations in response to rotations of the organism or the visual surround. For stimuli in the vertical planes (pitch or roll) the visual reflexes are mediated by identified visual interneurons sustaining fibers (SFs), which synapse on identified oculomotor neurons (Mns) (18). 2. The optimal visual stimulus is broad-field intense illumination (simulated skylight) distributed over the dorsal half of the cornea. These stimuli are also optimal for eliciting a regular pacing discharge in SFs with dorsal receptive fields (17). Since a unique discharge pattern is associated with the reflex stimulus, we proposed that the pacing discharge interval encodes the stimulus condition and is optimal for driving the motoneuron discharge. 3. The cross-correlation of SF and Mn impulse trains exhibit large peaks (or troughs) at short latencies associated with strong excitatory (or inhibitory) interactions and “secondary effects” at longer delays associated with the periodicity of the Mn impulse train. The secondary peaks and troughs indicate delayed periods of elevated or depressed Mn excitability synchronized to the reference train (SF) events. From the structure of the cross-correlograms and the motoneuron autocorrelograms we predicted that the spike-to-spike synaptic throughput should be differentially sensitive to the various classes of SF interspike intervals. 4. The hypotheses were tested with logical-correlation functions that directly measure the relative synaptic efficacy of several classes of SF intervals during a continuous train at constant mean rate. The results indicate that the SF-to-Mn excitatory synapse is maximally driven by SF impulses separated by approximately 85 ms. These events are about 2.5 times as effective as the impulses associated with short intervals (less than 20 ms) and 1.4 times as effective as the spikes of long intervals (250 ms). The optimal interval in the various preparations is highly to correlated to the period of the Mn discharge and the SF modal interspike interval. Inhibitory synapses are also differentially sensitive to the SF interspike intervals, but they exhibit summation rather than depression in response to short interspike intervals. 5. These results are generally consistent with previously formulated relationships (39), which govern the synaptic modulation of pacemakers and may apply to any synaptic interaction in which the postsynaptic neuron exhibits a regular discharge. 6. Combinations of long and short intervals with the same mean rate as the optimal interval are not as effective in driving the SF-to-Mn synapse.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society