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PubMed1985

Oscillations of the spontaneous slow-wave sleep rhythm in lateral geniculate nucleus relay neurons of behaving cats.

Intracellular recordings of 31 lateral geniculate nucleus relay neurons were performed in darkness in behaving cats in order to analyse electrical postsynaptic events which appeared during slow-wave sleep. A specific pattern characterized slow-wave sleep: a rapid depolarizing potential arising from baseline initiated a slow depolarization lasting for 40-60 ms which in turn most often elicited delayed fast spikes. This pattern recurred at a frequency of 6-12/s. The slow depolarizations were voltage dependent, usually not separated by any obvious phasic hyperpolarization and showed refractoriness. Other rapid depolarizing potentials occurring during the time course or at the end of a slow depolarization could have generated spike(s) but were followed by a rapid decay. Slow depolarizations were not observed during arousal or paradoxical sleep when the neurons tonically depolarized and displayed either rapid depolarizing potentials with a fast decay or repetitive firing and long high frequency bursts. In five of the studied neurons, decreases in frequency of the spontaneous rapid depolarizing potentials occurred during slow-wave sleep for 3-30 s oscillatory periods without any change in the behavioural state. During these periods all of the few remaining rapid depolarizing potentials arose from a flat baseline, had a higher amplitude and initiated a slow depolarization which always elicited a spike or burst of spikes after a brief delay. The slow-wave sleep rhythm decreased to 1-5/s. Simultaneously the baseline membrane potential hyperpolarized by a few millivolts and reached a level for reversal of inhibitory postsynaptic potentials. Imposed hyperpolarization of the membrane during wakefulness did not reveal any slow depolarization. But strong synaptic excitatory inputs and direct excitation (a break of the current pulse) from a hyperpolarized membrane did evoke the slow depolarization and eventually the fast spike(s) in both control and oscillatory neurons. A rhythm similar to that of slow-wave sleep was elicited during wakefulness by optic tract stimulation and was enhanced by membrane hyperpolarization. But under these conditions the rhythm was initiated by a phasic hyperpolarization and was composed of an alternating hyperpolarization-depolarization. Spontaneously and synaptically evoked rapid depolarizing potentials arising from baseline had a similar rising slope. The spontaneous ones initiated a slow depolarization leading to fast spike(s) during slow-wave sleep and could directly generate fast spike(s) during wakefulness.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1996

Responses of the superficial entorhinal cortex in vitro in slices from naive and chronically epileptic rats.

1. The main purposes of this study are to characterize the intracellular and extracellular responses of cells in superficial layers of entorhinal cortex (EC) in chronically epileptic animals, determine whether their altered physiology is dependent on being connected to hippocampus, and investigate whether there is evidence of augmented excitation and inhibitory interneuron disconnection. 2. Functional connectivity was maintained between the hippocampal area and the EC in vitro in a combined rat hippocampal-parahippocampal slice preparation by slicing with a vibratome at a 30-deg angle to the base of the brain. Three groups of animals were studied: naive animals, animals that had experienced a previous episode of (nonconvulsive) self-sustaining limbic system status epilepticus (SSLSE) induced by electrical stimulation resulting in a chronically epileptic state, and animals in an electrode control group. In chronically epileptic rats and the electrode control group, studies were done on tissue contralateral to the side of electrode implantation. 3. Extracellular and intracellular recordings were made from the superficial layers of EC. Neurons in the superficial layers of the EC were activated by stimulation of the deep layers within the EC or the angular bundle adjacent to the EC, which contains axons from EC neurons. Responses could be elicited by antidromic and synaptic mechanisms by stimulation at either site. In addition, a monosynaptic protocol was used that involved direct activation of interneurons with a stimulating electrode placed near the recording electrode in the presence of the ionotropic glutamate blockers D(-)-2-amino-5-phosphonovaleric acid (APV) and 6,7-dinitroquinoxaline-2-3-dione (DNQX). 4. Responses were collected over a range of stimulus intensities, from very low to high intensities, to construct input/output function (I/O) curves. Amplitudes and durations were measured at the lowest stimulus intensity that elicited a maximum responses. 5. Extracellular field potential responses from electrode controls did not differ from naives qualitatively with respect to morphology of field potential responses or quantitatively with respect to response duration and amplitude. Field potential responses in tissue from post-SSLSE rats differed markedly in morphology from naive and electrode controls, being more complex, significantly longer in duration, and decreased in amplitude. These epileptiform responses were shortened markedly by blockade of N-methyl-D-aspartate (NMDA) receptors with APV, but this manipulation did not convert responses to a normal morphology. These responses were abolished by blockade of non-NMDA mediated ionotropic glutamate receptors with DNQX. 6. During intracellular recordings of neurons in slices from both control and epileptic animals, neurons were quiescent under resting conditions in the absence of electrical stimulation. 7. Intracellular responses in electrode controls were identical to naive, and together were considered "controls." In control tissue, evoked intracellular responses were similar to those previously described and most commonly consisted of an excitatory postsynaptic potential (EPSP) that was blocked partially by the NMDA-receptor antagonist APV, followed by hyperpolarizing potentials, which were identified electrophysiologically and pharmacologically as gamma-aminobuturic acid-A (GABAA)- and GABAB-receptor-mediated inhibitory postsynaptic potentials (IPSPs). EPSPs were blocked completely by DNQX. 8. In chronically epileptic tissue, evoked intracellular responses differed markedly from responses in control animals, exhibiting all-or-none prolonged paroxysmal depolarizing events with multiple superimposed action potentials in response to a single shock. These depolarizing events were reduced in duration and amplitude, but not abolished, in APV. IPSPs were not seen or markedly reduced at all stimulus intensities. These intracellular responses never resembled control responses. Intracellur responss correlated precisely in morphology and duration with extracellular field potentials. (ABSTRACT TRUNCATED)

Animals↗

PubMed1986

Synaptic actions of cutaneous A delta and C fibers on primate hindlimb alpha-motoneurons.

Postsynaptic potentials evoked in hindlimb alpha-motoneurons by stimulation of a cutaneous nerve (sural) with finely graded stimulus strengths were analyzed in the primate, monitoring the spinal cord potentials and afferent nerve volleys in the sural nerve. It was observed that activities in A alpha beta, A delta and C fibers of the cutaneous nerve elicited characteristic excitatory and/or inhibitory postsynaptic potentials (EPSPs and/or IPSPs) with different latencies and durations in extensor and flexor motoneurons. Volleys in A delta fibers of the cutaneous nerve produced EPSPs in 57% of flexor and 31% of extensor motoneurons tested, whereas IPSPs were produced by A delta volleys in 41% of flexor and 62% of extensor motoneurons. EPSPs with longer latencies and longer durations were evoked by cutaneous C fiber volleys in 55% of flexor and 34% of extensor motoneurons, whereas IPSPs due to C volleys were recorded in 9% of flexor and 14% of extensor motoneurons. A alpha beta and A delta volleys caused motoneurons to fire in several instances, and some motoneurons discharged repetitively during the depolarizations evoked by activities in C fibers of the nerve. Central latency for transmission in interneuronal chains in the spinal cord was estimated from the onset of the cord potential (N3 wave) to the onset of the postsynaptic potential evoked by A delta volleys. Ranges of central latencies of the EPSPs and IPSPs evoked by A delta volleys were 2.0-7.0 ms and 3.5-8.5 ms, respectively. It is postulated that there may be at least two interneurons interposed in the excitatory reflex pathway from A delta afferent fibers to motoneurons and the A delta inhibitory pathway may involve longer interneuronal chains. In a few motoneurons, however, sural volleys with strengths sufficient to activate A delta fibers produced EPSPs with a central latency of about 1 ms, suggesting activation of a disynaptic segmental pathway with one interposed interneuron. Stimulation of the sural nerve with strengths sufficient to activate cutaneous C fibers produced slow negative cord dorsum potentials with long latencies. It is proposed that primate motoneurons, which show characteristic postsynaptic potentials evoked by cutaneous A delta and C fiber volleys, may provide a suitable model for analyzing the role of high threshold cutaneous afferent fibers not only in the flexor withdrawal reflex but also in motor control functions.

Afferent Pathways↗

PubMed1997

Recurrent inhibitory interneurons of the Rabbit's lateral posterior-pulvinar complex.

We recorded from 118 neurons in the visual sector of the thalamic reticular nucleus (TRN) in anesthetized rabbits. Cells were identified by their location and characteristic burst responses to stimulation of the primary visual cortex (Cx) and optic chiasm (OX) and were classified into two groups. Type I cells had relatively short latencies from both OX and Cx stimulation, and the latency from OX was always longer than from Cx. In contrast, type II cells had much longer latencies after OX and Cx stimulation, and the latency from OX was always shorter than from Cx. Type I cells were located in the dorsal part of TRN, whereas type II cells were located in the ventral part of TRN. The physiological properties and location of type I TRN cells indicate that they are recurrent inhibitory interneurons of the dorsal lateral geniculate nucleus (LGN). Type II TRN cells most likely function as recurrent inhibitory interneurons for the lateral posterior nucleus-pulvinar complex (LP) because they could be activated antidromically by LP stimulation and orthodromically activated via axonal collaterals of LP cells. Type II TRN cells exhibited a prolonged depression after Cx or OX stimulation. Intracellular recordings showed that a prolonged inhibitory postsynaptic potential was evoked by Cx or OX stimulation. Therefore, these recurrent interneurons of LP, type II cells form mutual inhibitory connections just like those recurrent interneurons of LGN, type I cells. Our data suggest that the geniculocortical and extrageniculate visual pathways have similar recurrent inhibitory circuits.

Animals↗

PubMed1999

Tonic inhibition alternates in paired neurons that set direction of fish escape reaction.

Crossed antagonism between activities in neurons subserving alternating movements such as swimming or walking has been described in a number of systems. The role of reciprocal inhibition has been implicated in these activities, but involvement of rhythmic ongoing fluctuations of membrane potential, called synaptic "noise," has not been examined. In the Mauthner (M) cells, which control the direction of escape, this activity is inhibitory. We report that in the zebrafish (Danio rerio), inhibitory synaptic noise exhibits prolonged bursts of rhythmic, inhibitory postsynaptic potentials, which attenuate the M cell's sensibility to excitatory sensory drives. Furthermore, paired intracellular recordings have shown that inhibitory synaptic noise alternates between two distinct states, noisy and quiet, which are out of phase in the two cells. Firing of either M cell resets this pattern by reducing the inhibition in the contralateral one. This suggests that an avoidance reflex in one direction may favor initiation, by the opposite M cell, of a subsequent escape toward a more appropriate location.

Action Potentials↗

PubMed1989

Diazepam potentiates postsynaptic inhibition in bulbar respiratory neurons of cats.

The purpose of this study was to assess the effect of benzodiazepine on inhibitory postsynaptic potentials (IPSPs) of medullary respiratory neurons in decerebrate, paralyzed cats. Diazepam (0.05 and 0.1 mg/kg i.v.) reversibly increased the IPSP waves occurring during the inactive phase of the respiratory cycle in all inspiratory and postinspiratory neurons examined. Input resistances of these neurons were reduced at that phase. The reversal potential for the IPSP wave was unaltered. Intracellular injection of chloride ions reversed the IPSP to depolarization, and diazepam produced a purely depolarizing effect. The drug effects observed during the active phase of each neuron include a decrease in the firing rate and a shortening of the burst activity. The firing threshold and shape of these spikes, however, remained unaltered. These results suggest that diazepam depresses the bulbar respiratory neuronal activities specifically by potentiating the periodic postsynaptic inhibition.

Animals↗

PubMed2003

Medullary reticulospinal tract mediating a generalized motor inhibition in cats: III. Functional organization of spinal interneurons in the lower lumbar segments.

The previous report of intracellular recording of hindlimb motoneurons in decerebrate cats [ 511] has suggested that the following mechanisms are involved in a generalized motor inhibition induced by stimulating the medullary reticular formation. First, the motor inhibition, which was prominent in the late latency (30-80 ms), can be ascribed to the inhibitory effects in parallel to motoneurons and to interneuronal transmission in reflex pathways. Second, both a group of interneurons receiving inhibition from flexor reflex afferents and a group of Ib interneurons mediate the late inhibitory effects upon the motoneurons. To substantiate the above mechanisms of motor inhibition we examined the medullary stimulus effects upon intracellular (n=55) and extracellular (n=136) activity of spinal interneurons recorded from the lower lumbar segments (L6-L7). Single pulses or stimulus trains (1-3) pulses, with a duration of 0.2 ms and intensity of 20-50 microA) applied to the medullary nucleus reticularis gigantocellularis evoked a mixture of excitatory and inhibitory effects with early (<20 ms) and late (>30 ms) latencies. The medullary stimulation excited 55 interneurons (28.8%) with a late latency. Thirty-nine of the cells, which included 10 Ib interneurons, were inhibited by volleys in flexor reflex afferents (FRAs). These cells were mainly located in lamina VII of Rexed. On the other hand, the late inhibitory effects were observed in 67 interneurons (35.1%), which included cells mediating reciprocal Ia inhibition, non-reciprocal group I (Ib) inhibition, recurrent inhibition and flexion reflexes. Intracellular recording revealed that the late inhibitory effects were due to inhibitory postsynaptic potentials with a peak latency of about 50 ms and a duration of 50-60 ms. The inhibitory effects were attenuated by volleys in FRAs. Neither excitatory nor inhibitory effects with a late latency were observed in 69 (36.1%) cells which were located in the intermediate region and dorsal horn. These results suggest the presence of a functional organization of the spinal cord with respect to the production of the generalized motor inhibition. Lamina VII interneurons that receive inhibition from volleys in FRAs possibly mediate the postsynaptic inhibition from the medullary reticular formation in parallel to motoneurons and to interneurons in reflex pathways.

Afferent Pathways↗

PubMed1998

Serotonin reduces polysynaptic inhibition via 5-HT1A receptors in the superficial entorhinal cortex.

The superficial cells of the entorhinal cortex (EC), main input to the hippocampus, receive a serotonergic input from the raphe nuclei and express 5-hydroxytryptamine creatine sulfate complex (5-HT) receptors at high density. With the use of intracellular recordings, we investigated the effects of serotonin on synaptic inhibition of layer II and III neurons of the EC. Serotonin reduced both polysynaptic fast and slow inhibitory postsynaptic potentials (IPSPs) in projection neurons of the superficial EC. Polysynaptic fast and slow IPSPs were depressed by serotonin in a dose-dependent manner (0.1-100 microM). Serotonin in a concentration of 1 microM reduced the amplitudes of polysynaptic fast and slow IPSPs by approximately 40 and 50%, respectively. To identify the subtype of the 5-HT-receptor mediating the effects on polysynaptic IPSPs, we applied various 5-HT-receptor agonists and antagonists. Although the serotonin agonists for the 5-HT1B,2C,3 receptors were ineffective, the effects were mimicked by the 5-HT1A-receptor agonists (8-OH-DPAT, 5-CT) and prevented by the 5-HT1A-receptor antagonist NAN-190. To look at the direct effects of 5-HT on inhibitory interneurons, we elicited monosynaptic IPSPs in the absence of excitatory synaptic transmission. In contrast to the polysynaptic IPSPs, monosynaptic IPSPs were not significantly affected by serotonin. Recordings from putative inhibitory interneurons revealed that their excitatory postsynaptic potentials (EPSPs) were reversibly reduced by serotonin. We conclude that serotonin suppresses polysynaptic inhibition in projection neurons of layers II and III of the EC by depression of EPSPs on inhibitory interneurons via 5-HT1A receptors.

2-Amino-5-phosphonovalerate↗

PubMed1997

Synaptic effects of identified interneurons innervating both interneurons and pyramidal cells in the rat hippocampus.

GABAergic interneurons sculpt the activity of principal cells and are themselves governed by GABAergic inputs. To determine directly some of the sources and mechanisms of this GABAergic innervation, we have used dual intracellular recordings with biocytin-filled microelectrodes and investigated synaptic interactions between pairs of interneurons in area CA1 of the adult rat hippocampus. Of four synaptically-coupled interneuron-to-interneuron cell pairs, three presynaptic cells were identified as basket cells, preferentially innervating somata and proximal dendrites of pyramidal cells, but one differing from the other two in the laminar distribution of its dendritic and axonal fields. The fourth presynaptic interneuron was located at the border between strata lacunosum moleculare and radiatum, with axon ramifying within stratum radiatum. Action potentials evoked in all four presynaptic interneurons were found to elicit fast hyperpolarizing inhibitory postsynaptic potentials (mean amplitude 0.35 +/- 0.10 mV at a membrane potential of -59 +/- 2.8 mV) in other simultaneously recorded interneurons (n=4). In addition, three of the presynaptic interneurons were also shown to produce similar postsynaptic responses in subsequently recorded pyramidal cells (n=4). Electron microscopic evaluation revealed one of the presynaptic basket cells to form 12 synaptic junctions with the perisomatic domain (seven somatic synapses and five synapses onto proximal dendritic shafts) of the postsynaptic interneuron in addition to innervating the same compartments of randomly-selected local pyramidal cells (50% somatic and 50% proximal dendritic synapses, n=12). In addition, light microscopic analysis also indicated autaptic self-innervation in basket (12 of 12) and bistratified cells (six of six). Electron microscopic investigation of one basket cell confirmed six autaptic junctions made by five of its boutons. Together, these data demonstrate that several distinct types of interneuron have divergent output to both principal cells and local interneurons of the same (basket cells) or different type. The fast synaptic effects, probably mediated by GABA in both postsynaptic interneurons and principal cells are similar. These additional sources of GABA identified here in the input to GABAergic cells could contribute to the differential temporal patterning of distinct GABAergic synaptic networks.

Animals↗

PubMed1961

Electrophysiology of the insect dorsal ocellus. III. Responses to flickering light of the dragonfly ocellus.

The ERG of the dragonfly ocellus has been analyzed into four components, two of which originate in the photoreceptor cells, two in the ocellar nerve fibers (Ruck, 1961 a). Component 1 is a sensory generator potential, component 2 a response of the receptor axons. Component 3 is an inhibitory postsynaptic potential, component 4, a discharge of afferent nerve impulses in ocellar nerve fibers. Responses to flickering light are examined in terms of this analytic scheme. It has been found that the generator potential can respond to higher rates of flicker-up to 220/sec.-than can the receptor axon responses, the postsynaptic potential, or the ocellar nerve impulses. The maximum flicker fusion frequency as measured by fusion of the ERG is that of the sensory generator potential itself.

Animals↗

PubMed1973

Pentobarbital: selective depression of excitatory postsynaptic potentials.

The effects of pentobarbital (Nembutal) on synaptic transmission and postsynaptic potentials were studied by the use of several invertebrate preparations. Pentobarbital selectively and reversibly depressed both excitatory postsynaptic potentials and sodium-dependent postsynaptic responses to putative excitatory transmitters without affecting either inhibitory postsynaptic potentials or chloride- and potassium-dependent postsynaptic responses to putative transmitters. A selective depression of postsynaptic excitatory events was also observed with other central nervous system depressants (ethanol, chloroform, chloralose, diphenylhydantoin, and urethane). The results suggest that central and peripheral depression observed during general anesthesia is due to a selective depression of excitatory synaptic events.

Acetylcholine↗

PubMed2004

Encoding the timing of inhibitory inputs.

Many neuronal systems represent information by the timing of individual spikes, and it is generally assumed that spike timing predominantly encodes excitatory inputs. We show here that the timing of inhibition can also be explicitly encoded in spike times using time-dependent and voltage-dependent properties of a rapidly inactivating potassium channel (I(KIF)). In vitro recordings in rat dorsal cochlear nucleus show that the effects of inhibition on spike timing can long outlast the duration of the inhibitory potential and that this depends only on the membrane voltage change during the inhibitory postsynaptic potential. Modeling results show that small neuronal populations with a heterogeneous distribution of I(KIF) voltage dependence can robustly encode intervals of >100 ms between inhibition and excitation. Thus neuronal systems can detect and represent the precise timing of inhibition, suggesting the importance of inhibition in information encoding.

Action Potentials↗

PubMed2002

Local circuit properties underlying cortical reorganization.

Peripheral denervation has been shown to cause reorganization of the deafferented somatotopic region in primary somatosensory cortex (S1). However, the basic mechanisms that underlie reorganization are not well understood. In the experiments described in this paper, a novel in vivo/in vitro preparation of adult rat S1 was used to determine changes in local circuit properties associated with the denervation-induced plasticity of the cortical representation in rat S1. In the present studies, deafferentation of rat S1 was induced by cutting the radial and median nerves in the forelimb of adult rats, resulting in a rapid shift of the location of the forepaw/lower jaw border; the amount of the shift increased over the times assayed, through 28 days after denervation. The locations of both borders (i.e., original and reorganized) were marked with vital dyes, and slices from the marked region were used for whole-cell recording. Responses were evoked using electrical stimulation of supragranular S1 and recorded in supragranular neurons close to either the original or reorganized border. For each neuron, postsynaptic potentials (PSPs) were evoked by stimulation of fibers that crossed the border site (CB stim) and by equivalent stimulation that did not cross (NCB stim). Monosynaptic inhibitory postsynaptic potentials (IPSPs) were also examined after blocking excitatory transmission with 15 microM CNQX plus 100 microM DL-APV. The amplitudes of PSPs and IPSPs were compared between CB and NCB stimulation to quantify effects of the border sites on excitation and inhibition. Previous results using this preparation in the normal (i.e., without induced plasticity) rat S1 demonstrated that at a normal border both PSPs and IPSPs were smaller when evoked with CB stimulation than with NCB stimulation. For most durations of denervation, a similar bias (i.e., smaller responses with CB stimulation) for PSPs and IPSPs was observed at the site of the novel reorganized border, while no such bias was observed at the suppressed original border site. Thus changes in local circuit properties (excitation and inhibition) can reflect larger-scale changes in cortical organization. However, specific dissociations between these local circuit properties and the presence of the novel border at certain durations of denervation were also observed, suggesting that there are several intracortical processes contributing to cortical reorganization over time and that excitation and inhibition may contribute differentially to them.

Animals↗

PubMed2003

Reduced inhibition and sensitivity to neurosteroids in hippocampus of mice lacking the GABA(A) receptor delta subunit.

The delta subunit of the gamma-aminobutyric acid (A) receptor (GABA(A)R) is expressed postnatally mostly in the cerebellum, thalamus, and dentate gyrus. Previous studies in mice with a targeted disruption of the delta subunit revealed a considerable attenuation of behavioral responses to neuroactive steroids but not to other neuromodulatory drugs. Here we show that delta subunit loss leads to a concomitant reduction in hippocampal alpha4 subunit levels. These changes were accompanied by faster decay of evoked inhibitory postsynaptic potentials (IPSPs) in dentate granule neurons of -/- mutants (decay tau = 25 ms) compared with +/+ controls (tau = 50 ms). Furthermore, the GABA(A)R-mediated miniature inhibitory postsynaptic currents (mIPSCs) also decayed faster in delta-mutants (tau = 6.3 ms) than controls (tau = 7.2 ms) and had decreased frequency (controls, 10.5 Hz; mutants, 6.6 Hz). Prolongation of mIPSCs by the neuroactive steroid anesthetic, alphaxalone (1-10 microM), was smaller in delta-mutants (at 10 microM, 65% increase) compared with +/+ littermates (308% increase). In competition binding experiments, alphaxalone (0.03-1 microM) modulation of [35S]t-butylbicyclophosphorothionate binding was reduced in delta-mutant brain homogenates, indicating that the decreased alphaxalone effects on mIPSCs were due to changes in the GABA(A)R protein. Faster decay of evoked IPSPs and mIPSCs in delta-mutants suggests presence of the delta subunit at both synaptic and extrasynaptic GABA(A)Rs. Decreased synaptic and extrasynaptic inhibition likely contributes to the pro-epileptic phenotype of delta-mutants. Reduced neurosteroid sensitivity might also contribute to seizure susceptibility. While the simplest explanation is that delta subunit-containing GABA(A)Rs represent the actual target of neurosteroids, it is possible that the behavioral and physiological sensitivity to neuroactive steroids is indirectly altered in the delta -/- mice.

Anesthetics↗

PubMed1986

Presynaptic inhibition produced by an identified presynaptic inhibitory neuron. I. Physiological mechanisms.

We have examined the synaptic conductance mechanisms underlying presynaptic inhibition in Aplysia californica in a circuit in which all the neural elements are identified cells (Fig. 1). L10 makes connections to identified follower cells (RB and left upper quadrant cells, L2-L6). These connections are presynaptically inhibited by stimulating cells of the L32 cluster (4). L32 cells produce a slow inhibitory synaptic potential on L10. This inhibitory synaptic potential is associated with an apparent increased membrane conductance in L10. Both the inhibitory postsynaptic potential (IPSP) and the conductance increase are voltage dependent; the IPSP could not be reversed by hyperpolarizing the membrane potentials to - 120 mV. The hyperpolarization of L10 induced by L32 reduces the transmitter output of L10 and thereby contributes to presynaptic inhibition. However, this hyperpolarization accounts for about 30% of the effect because presynaptic inhibition can still be observed even when the hyperpolarization of L10 by L32 is prevented by voltage clamping. When L10 is voltage clamped, stimulation of L32 produces a slow outward synaptic current associated with an apparent increased conductance. Both the synaptic current and conductance change measured under clamp are voltage dependent, and the outward current could not be reversed. This synaptic current is not mediated by an increase in C1- conductance. It is sensitive to external K+ concentration, especially at hyperpolarized membrane potentials. With L10 under voltage clamp, stimulation of L32 also reduces a slow inward current in L10. This current has time and voltage characteristics similar to those of the Ca2+ current. Presynaptic inhibition is still produced by L32 when L10 is voltage clamped, and transmitter release is elicited by depolarizing voltage-clamp pulses. This component of presynaptic inhibition, which accounts for approximately 70% of the inhibition, appears to be due to a decrease in the Ca2+ current in the presynaptic neuron.

Abdomen↗

PubMed1997

Synaptic and synaptically activated intrinsic conductances underlie inhibitory potentials in cat lateral amygdaloid projection neurons in vivo.

The companion paper demonstrated that the responses of lateral amygdaloid (LAT) projection neurons to the stimulation of major input and output structures are dominated by monophasic hyperpolarizing potentials of large amplitude. To characterize the mechanisms underlying these inhibitory potentials, intracellular recordings of cortically evoked responses were obtained from morphologically and/or physiologically identified LAT projection neurons in barbiturate anesthetized cats. The reversal potential of the cortically evoked hyperpolarization was measured at its peak, and 115 ms later (tail), an interval corresponding to the peak latency of the gamma-aminobuturic acid-B (GABAB) response previously recorded in vitro. When recorded with K-acetate (KAc) pipettes, these reversal potentials were -86.9 +/- 1.6 mV (peak; mean +/- SE) and -90.7 +/- 1.7 mV (tail), suggesting that both Cl- and K+ conductances contribute throughout the cortically evoked hyperpolarization. The small, but consistent, difference between the two reversal potentials suggested that an additional slowly activating K(+)-mediated component contributed to the inhibitory postsynaptic potential (IPSP) tail. To determine whether Cl- conductances contributed to the evoked hyperpolarization, recordings were performed with KCl; the peak (-57.8 +/- 2.2 mV) and tail (-61.3 +/- 2.1 mV) reversal potentials were approximately 15-20 mV more depolarized than those recorded with KAc pipettes. However, the difference between the peak and tail reversals remained. In an attempt to block the Cl- conductance, recordings were obtained with pipettes filled with KAc or KCl and 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), a Cl- pump blocker that also was reported to block GABAA responses. With KAc and DIDS, the initial depolarization was prolonged and the amplitude of the hyperpolarization decreased relative to that seen with KAc alone. However, with KCl and DIDS, the reversal potential was shifted to an even greater extent than with KCl pipettes with the evoked response consisting entirely of a large depolarization, which produced a spike burst. These results suggest that LAT neurons have a Cl- pump that is blocked by DIDS, but that their Cl- channels are not blocked by DIDS. To assess the contribution of K+ conductances to cortically evoked hyperpolarizing potentials, recordings were obtained with Cs-acetate pipettes. Under these conditions, the response reversed at more depolarized potentials (peak, -71.9 +/- 1.0 mV; tail, -72.0 +/- 0.9 mV) compared with KAc recordings, with no difference between the peak and tail reversal potentials. These cells also had depolarized resting potentials (-66.2 +/- 1.8 mV) compared with those of cells recorded with KAc pipettes (-73.6 +/- 1.8 mV); however, this difference was too small to attribute the shift in reversals to a redistribution of Cl- ions across the membrane. The action potentials generated by LAT neurons under Cs+ had a shoulder that prolonged their falling phase. The increased duration of the spikes was presumably due to a dendritic Ca2+ conductance because LAT amygdaloid neurons are known to possess such conductances and Cs+ blocks the delayed rectifier and some Ca(2+)-dependent K+ currents. The dramatic reduction of this shoulder by spontaneous and evoked IPSPs suggests that the activation of dendritic conductances by back-propagating somatic action potentials is regulated tightly by synaptic events. Intracellular injection of the Ca2+ chelating agent, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (100 mM) caused a depolarization of the peak (-75.3 +/- 1.3 mV) and tail (-77.7 +/- 1.7 mV) reversal potentials during a time course of 15-45 min. Concurrently, the amplitude of the excitatory postsynaptic potential increased whereas that of the hyperpolarization decreased, suggesting that a Ca(2+)-dependent K+ conductance contributes significantly to the evoked hyperpolarization. (ABSTRACT TRUNCATED)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1998

Local circuit abnormalities in chronically epileptic rats after intrahippocampal tetanus toxin injection in infancy.

In vitro slice experiments were undertaken in adult rats to investigate the physiological origins of a chronic epileptic condition that was initiated in infancy. A unilateral injection of a minute quantity of tetanus toxin into hippocampus on postnatal day 10 produced a severe convulsive syndrome characterized by brief but repeated seizures that lasted for 5-7 days. Hippocampal slices were then taken from these rats in adulthood because at this time previous studies have shown the occurrence of electrographic and behavioral seizures. Dramatic alterations in local circuit functioning were observed. In normal artificial cerebrospinal fluid (ACSF), spontaneous epileptiform network bursts were recorded in a majority (73%) of experimental rats. Network bursts occurred in area CA3 of both the injected and contralateral hippocampus. These consisted of intracellular depolarization shifts that were coincident with extracellularly recorded network bursts. Often they occurred at frequencies of 0.05-0.1 Hz and although variable in amplitude and duration, had all-or-none-like qualities. These events appeared to arise largely from local circuits in the CA3C subfield. Network bursts were rarely recorded in area CA1 and were never observed in the dentate gyrus. However in 31% of rats, a novel, higher frequency (2-8 Hz) field potential was recorded in area CA1. This was coincident with rhythmic, intracellularly recorded, inhibitory postsynaptic potentials (IPSPs). These summated IPSPs blocked action potential firing and reversed polarity near -75 mV. To understand the origins of network bursting in area CA3C, comparisons were made of the fundamental neurophysiological properties of pyramidal cells in epileptic and control rats. Of the passive and active membrane properties examined, all appeared normal. Unusually prolonged bursts of action potentials were observed in a small subset of pyramidal cells. However on average the duration of intrinsic bursts were unaltered in the CA3 neurons analyzed from experimental rats. To explore the role that alterations in CA3 recurrent excitatory network excitability may play in epileptiform discharges, picrotoxin was bath applied. On blockade of gamma-aminobutyric acid (GABAA) receptors, slices from experimental rats underwent prolonged electrographic seizures that were up to 10 s in duration. In contrast, slices from control rats produced only brief 100-ms network bursts. These results suggest that a change in excitability within CA3C recurrent excitatory networks likely contributes to seizures in chronically epileptic rats. However, at the same time, this hyperexcitability is controlled to an important degree by functional GABAA-mediated synaptic inhibition.

Action Potentials↗

PubMed1991

Physiology and pharmacology of epileptiform activity induced by 4-aminopyridine in rat hippocampal slices.

1. Conventional intracellular and extracellular recording techniques were used to investigate the physiology and pharmacology of epileptiform bursts induced by 4-aminopyridine (4-AP, 50 microM) in the CA3 area of rat hippocampal slices maintained in vitro. 2. 4-AP-induced epileptiform bursts, consisting of a 25-to 80-ms depolarizing shift of the neuronal membrane associated with three to six fast action potentials, occurred at the frequency of 0.61 +/- 0.29 (SD)/s. The bursts were generated synchronously by CA3 neurons and were triggered by giant excitatory postsynaptic potentials (EPSPs). A second type of spontaneous activity consisting of a slow depolarization also occurred but at a lower rate (0.04 +/- 0.2/s). 3. The effects of 4-AP on EPSPs and inhibitory postsynaptic potentials (IPSPs) evoked by mossy fiber stimulation were studied on neurons impaled with a mixture of K acetate and 2(triethyl-amino)-N-(2,6-dimethylphenyl) acetamide (QX-314)-filled microelectrodes. After the addition of 4-AP, the EPSP became potentiated and was followed by the appearance of a giant EPSP. This giant EPSP completely obscured the early IPSP recorded under control conditions and inverted at -32 +/- 3.9 mV (n = 4), suggesting that both inhibitory and excitatory conductances were involved in its generation. IPSPs evoked by Schaffer collateral stimulation increased in amplitude and duration after 4-AP application. 4. The spontaneous field bursts and the stimulus-induced giant EPSP induced by 4-AP were not affected by N-methyl-D-aspartate (NMDA) receptor antagonists 3-3 (2-carboxy piperazine-4-yl) propyl-1-phosphonate (CPP) and DL-2-amino-5-phosphonovalerate (APV) but were blocked by quisqualate/kainate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX). CNQX also abolished the presence of small spontaneously occurring EPSPs, thereby disclosing the presence of bicuculline-sensitive (BMI, 20 microM) IPSPs. 5. Small, nonsynchronous EPSPs played an important role in the generation of 4-AP-induced epileptiform activity. 1) After the addition of 4-AP, small EPSPs appeared randomly on the baseline and then became clustered to produce a depolarizing envelope of irregular shape that progressively formed an epileptiform burst, 2) These small EPSPs were more numerous in the 100 ms period that preceded burst onset. 3) The frequency of occurrence of small EPSPs was positively correlated with the frequency of occurrence of synchronous bursts. 4) Small EPSPs and bursts were similarly decreased after the addition of different concentrations of CNQX (IC50 in both cases of approximately 1.2 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗