Electrical membrane properties of rat substantia nigra compacta neurons in an in vitro slice preparation

The electrical membrane properties of rat substantia nigra pars compacta (SNC) neurons were studied in an in vitro slice preparation. Some of the recorded neurons were intracellularly labeled with HRP and were found to have morphological characteristics resembling the presumed SNC dopaminergic neurons, as reported by others. The input resistance of SNC neurons at resting membrane potential ranged between 70 and 250 M omega. The membrane resistance showed strong anomalous rectification when the membrane was hyperpolarized by current injection. The anomalous rectification was decreased by the addition of tetraethylammonium bromide (TEA) to the bathing Ringer solution. Injection of depolarizing current or termination of hyperpolarizing current induced slow depolarizing potentials. Their amplitude was dependent on the membrane potential and the current intensity. In neurons treated with tetrodotoxin (TTX) and TEA, slow action potentials were triggered from the slow depolarizing potentials. Both the slow depolarizing potential and slow action potential were TTX resistant and abolished by superfusion of Ca2+-free medium. Long duration hyperpolarizations were observed following the injection of depolarizing current pulses. The hyperpolarization was abolished by the superfusion of Ca2+-free medium or decreased by addition of TEA to the Ringer solution indicating an involvement of a Ca2+-dependent K+-conductance in generation of the hyperpolarization. The long duration hyperpolarization was also observed following action potentials. The spike after hyperpolarization consisted of an initial short duration fast component and a long lasting component. The amplitude of both components seems to be reduced but not abolished by TEA (up to 10 mM). When hyperpolarizing current pulses were applied to neurons that were held either continuously depolarized or were superfused with Ca2+-free medium, the pattern of the membrane potential after the offset of current pulses consisted of an initial fast and a later slow ramp-shaped phase. The latter was associated with a membrane conductance increase and interpreted to be due to an early K+ current. This early K+ current was relatively resistant to TEA. Injections of strong depolarizing currents triggered action potentials with multiple inflections on their rising phase. The amplitudes of action potentials changed abruptly during current application. These data indicate that SNC neurons have multiple generation sites for action potential.     

Synaptic basis of orbital cortically induced rhythmical masticatory activity of trigeminal motoneurons in immobilized cats

Synaptic basis of the centrally induced masticatory rhythm was studied by intracellular recording from jaw closer and opener motoneurons during repetitive stimulation of the orbital gyrus (OG) of the encéphale isoléof immobilized cats, with the following results.

(1) Repetitive OG stimulation induced a rhythmical alternation of hyperpolarizing and depolarizing potentials in jaw closer motoneurons. Rhythmical efferent burst discharges induced in the digastric nerve by OG stimulation coincided with the hyperpolarizing phase. The hyperpolarizing potential was reversed to a depolarizing potential by intracellular Cl⁻ injection, while the depolarizing potential was not reversed to hyperpolarization, indicating that the hyperpolarizing and depolarizing potentials consisted at least mainly of IPSPs and EPSPs, respectively.

(2) Repetitive OG stimulation induced rhythmical depolarizing potentials superimposed by bursts in jaw opener motoneurons, corresponding in time with the rhythmical efferent bursts in the digastric nerve. Synaptic activation noise was increased coincidentally with the depolarizing potential, indicating that EPSPs were involved in the degeration of the depolarizing potential. No or little hyperpolarization if any was observed between successive depolarizing potentials.

(3) Repetitive OG stimulation induced efferent burst discharges in the digastric nerve with the masticatory rhythm unaccompanied by any spike potential in the supratrigeminal neurons responsible for peripherally evoked inhibition of jaw closer motoneurons, indicating that the peripheral inhibitory mechanisms do not play an essential role in the central generation of the masticatory rhythm by OG stimulation.

Electrophysiological effects of FLFQPQRF amide, an endogenous brain morphine modulating peptide, on cultured mouse spinal-cord neurons

Intracellular recordings were made from dissociated fetal mouse spinal cord neurones in primary culture. Micropressure application of FLFQPQRFamide (10(-5) M in the delivery pipette), an endogenous mammalian brain morphine modulating peptide, onto the surface of spinal cord neurones induced, in a dose dependent manner, a transitory hyperpolarization followed by a long lasting depolarization of the membrane potential (n = 37). In contrast, no response was observed when the peptide was applied on dorsal root ganglia neurones (n = 30). The depolarizing phase of this response was underlied by an increase of the input resistance. Extrapolated reversal potential for the depolarizing phase was close to -80 mV while it was close to -40 mV for the hyperpolarizing phase. Increasing extracellular K+ concentration raised the reversal potential value of depolarizing phases to more positive values. The amplitude of the depolarizing phase was reduced by application of tetraethylammonium (50 mM) while it was enhanced by application of 4-aminopyridine (3 mM). CaCl2 application (3 mM) reversibly blocked the hyperpolarization and decreased the subsequent depolarization. In presence of Ba2+ the extrapollated reversal potential of the hyperpolarizing phase was dramatically shifted to a more positive value. Finally FLFQPQRFamide induced response can be partially mimicked by FMRFamide application. Our observations indicate that FLFQPQRFamide can have multiple effects on membrane conductance of mammalian spinal cord neurones by acting on a single class of receptor. These effects of FLFQPQRFamide were found to be mainly excitatory.     

On the mechanism of action of GABA in pelvic vesical ganglia: Biphasic responses evoked by two opposing actions on membrane conductance

Intracellular recording techniques were used to study the response of cat vesical pelvic ganglion neurones loaded with permeable anions to the application of GABA in vitro. In 106/127 neurones GABA evoked a biphasic response, the initial phase of which was depolarizing and associated with a conductance increase; the latter phase was hyperpolarizing and associated with a conductance decrease. The GABA evoked hyperpolarization and conductance decrease were related and behaved as though generated by closure of ion channels open in the resting membrane. The hyperpolarization had a strong inhibitory action on both spontaneous activity, and excitation evoked by depolarizing current injection and pre-synaptic nerve stimulation. Ion substitution experiments suggest that the conductance decrease is primarily to chloride ions, although other ionic species may contribute. Short iontophoretic applications of GABA-evoked monophasic depolarizing excitatory responses, even during the hyperpolarizing response evoked by perfusion of GABA, suggesting no cross-desensitization between the mechanisms generating the initial and late phases of the biphasic response.     

Synaptic responses of neurons of the nucleus tractus solitarius in vitro

Postsynaptic responses of neurons in the nucleus tractus solitarius (NTS) have been studied in an in vitro slice preparation using extra- and intracellular recording. Single or paired pulse stimulations were delivered to afferent fibers within the tractus solitarius (TS) to activate orthodromic responses in these neurons. Most NTS neurons displayed an initial synaptic excitation followed by inhibition of spontaneous or evoked firing lasting up to 150-200 ms after stimulation. Excitatory postsynaptic potentials (EPSPs), recorded intracellularly, were increased in amplitude by membrane hyperpolarization. Large afterhyperpolarizations followed action potentials triggered by the EPSPs or evoked by intracellular current injections. Intracellular evidence for synaptic inhibition within the NTS included: (1) the presence, after Cl-injection, of flurries of spontaneous PSPs likely to be inverted inhibitory postsynaptic potentials; (2) reduction of the size of a test EPSP by a previous subthreshold TS conditioning volley; and (3) hyperpolarizing PSPs recorded in some neurons. Other NTS neurons exhibited prolonged excitatory responses to TS stimulation and could be local inhibitory interneurons. These results may help specify synaptic mechanisms in the NTS that could play an integrative role in the relay of visceral sensory inputs to higher order effectors.     

Inward rectification of resting and opiate-activated potassium currents in rat locus coeruleus neurons

Intracellular recordings were made from rat locus coeruleus neurons in vitro, and membrane currents were measured at potentials from -50 to -130 mV. In the absence of any applied agonists, the slope conductance of the cells increased 3-fold when the cell was hyperpolarized from -60 to -120 mV. This conductance increase was complete within 5 msec of the onset of a hyperpolarizing command and was subsequently independent of time for several seconds. The conductance increase was blocked by cesium chloride (1-2 mM), rubidium chloride (1-2 mM), or barium chloride (1-100 microM). The membrane potential range over which the conductance increased was centered at the potassium equilibrium potential (EK; extracellular potassium concentration, 2.5-10.5 mM): the current/voltage (I/V) relation of the cell could be well described by supposing that there were 2 potassium conductances, one voltage independent (G1) and the other (inward rectifier, Gir) activated according to the expression Gir = Gir,max/(1 + exp[(V - EK)/k]), where k ranged from 15 mV in 2.5 mM potassium to 6 mV in 10.5 mM potassium. The additional membrane potassium conductance that developed when agonists at mu-opioid and alpha 2-adrenoceptors were applied also became larger with membrane hyperpolarization, and this voltage dependence was also reduced or blocked by rubidium, cesium, and barium; in the presence of these agonists the current also reached its final value within 5 msec. However, the conductance increased by the agonists (Gag) was not well expressed by simply increasing the values of G1 and Gir,max. It was best described by a potassium conductance that increased according to Gag,max/(1 + exp[(V - Vm)/k]), where Vm (the potential at which the conductance was half-maximum) was close to the resting potential of the cell.(ABSTRACT TRUNCATED AT 400 WORDS)     

gamma-Aminobutyric acid (GABA) causes consistent depolarization of neurons in the guinea pig supraoptic nucleus due to an absence of GABAB recognition sites

The action of gamma-aminobutyric acid (GABA) in the supraoptic nucleus was investigated using guinea pig brain slices. GABA produced a membrane depolarization accompanied by a decrease in the input resistance. The action of GABA was concentration-dependent throughout a wide range of concentrations (10(-7)-10(-3) M). In none of the cells examined, a membrane hyperpolarization was observed. The reversal potential for the depolarization induced by GABA was about 25 mV positive to the resting membrane potential. The amplitude of the GABA-induced depolarization was increased to 1.5 X the control by reducing the external Cl- from 134.2 mM to 10.2 mM. The action of GABA was readily antagonized by relatively low concentrations of bicuculline (10(-5) M). The action of GABA in the hippocampus or in the anterior hypothalamus was markedly different from that in the supraoptic nucleus, i.e. GABA produced both depolarizing and hyperpolarizing responses in the hippocampus and consistently a hyperpolarization in the anterior hypothalamus. The depolarizing but not the hyperpolarizing response in the hippocampus was selectively blocked by picrotoxin (2 X 10(-5) M) or by bicuculline (10(-5) M). The depolarizing component was dependent on the external Cl- concentration and had a reversal potential similar to that of the depolarization induced by GABA in the supraoptic nucleus. The hyperpolarizing component was resistant to bicuculline and had a reversal potential about 30 mV negative to the resting membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)     

Local stimulation induced GABAergic response in rat striatal slice preparations: Intracellular recordings on QX-314 injected neurons

Gamma-aminobutyric acid (GABA)ergic responses evoked by electrical stimulation in the neostriatal slice preparation were studied in neurons injected intracellularly with Na-conductance blocker QX-314. Local stimulation elicited depolarizing postsynaptic potentials (DPSPs) in the QX-314-injected neurons when the membrane potential was morenegative than −60 mV. When DPSPs were minimized by depolirizing current injection in the QX-314-injected neuron, hyperpolarization was clearly observed following local stimulation. The maximum duration of the hyperpolarizing response to strong local stimulation was about 130 ms. The hyperpolarizing response was blocked by the addition of bicuculine or picrotoxin to the Ringer solution. Intracellular Cl^- injections produced changes in the pattern of the local stimulations-induced responses; the initial depolarizing response was followed by a relatively large amplitude long duration depolarization. The polarity of the long duration of depolarizing response could not be reversed by depolarizing currents which were normally sufficient to reverse the polarity of DPSPs in the neurons without Cl^- injection. The application of pentobarbital enhanced the amplitude and the duration of the hyperpolarizing responses. The revealed potential of the pentobarbital-enhanced response was estimated to be −60 mV. On the basis of their reversal potential, sensitivity to injected Cl^-, sensitivity to GABA blockers picrotoxin and bicuculine, and the effect of pentobarbital, these hyperpolarizing responses are shown to be GABAergic Cl^- mediated inhibitory postsynaptic potentials (IPSPs).     

Active and Passive Membrane Properties of Spinal Cord Neurons that Are Rhythmically Active during Swimming in Xenopus Embryos

Cellular properties have been examined in ventrally located Xenopus spinal cord neurons that are rhythmically active during fictive swimming and presumed to be motoneurons. Resting potentials and input resistances of such neurons are - 75 +/- 2 mV (mean +/- standard error) and 118 +/- 17 M ohm respectively. Most cells fire a single impulse, 0.5 to 2.0 ms in duration and 48.5 +/- 1.8 mV in amplitude, in response to a depolarizing current step. A minority fire several spikes of diminishing amplitude to more strongly depolarizing current. Cells held above spike, threshold fire on rebound from brief hyperpolarizing pulses. Spikes are blocked by 0.1 to 1.0 microM tetrodotoxin (TTX) and are therefore Na+-dependent. Current/voltage (I/V) plots to injected current are approximately linear near the resting potential but become non-linear at more depolarized levels. Cells recorded in TTX with CsCI-filled microelectrodes show a linearized I/V plot at depolarized membrane potentials suggesting the normal presence of a voltage-dependent K+ conductance activated at relatively depolarized levels. Most cells recorded in this way but without TTX fire long trains of spikes of near constant amplitude, pointing to a role of the K+ conductance in limiting firing in normal cells. Spike blockage with TTX reveals, in some cells, a transient depolarizing Cd2+-sensitive and therefore presumably Ca2+-dependent potential that increases in amplitude with depolarization. Cells in TTX, Cd2+, and strychnine, and recorded with CsCI-filled microelectrodes to block active conductances respond to hyperpolarizing current steps with a two component exponential response. The cell time constant (tau0) obtained from the longer of these by exponential peeling is relatively long (mean 15.7 ms). These findings contribute to an increased understanding of the cellular properties involved in spinal rhythm generation in this simple vertebrate.     

Angiotensin evokes in polyploid rat glioma cells hyperpolarization-depolarization responses and cross-desensitization with bradykinin

Angiotensins I, II and III induced a hyperpolarizing response of up to 1 min duration followed by a depolarizing response of up to 4 min when applied by pressure pulses or iontophoresis to polyploid rat glioma cells C6-4-2. The hyperpolarization (depolarization) was associated with a 50% decrease (no measurable change) in membrane resistance. The reversal potential (ca. −90 mV) of the hyperpolarization most likely points to an increased K⁺ conductance. Cells desensitized to angiotensins on application of high doses of either angiotensins or bradykinin.     

Low magnesium epileptogenesis in the rat hippocampal slice: electrophysiological and pharmacological features

Extra- and intracellular recording techniques were used to study the epileptiform activity generated by rat hippocampal slices perfused with Mg2(+)-free artificial cerebrospinal fluid (ACSF). This procedure induced in both CA1 and CA3 subfields the appearance of synchronous, spontaneously occurring epileptiform discharges which consisted of extracellularly recorded 100-800 ms long, positive shifts with superimposed negative going population spikes. Simultaneous, extracellular recordings from CA1 and CA3 subfields revealed that the epileptiform discharges in CA3 preceded those occurring in CA1 by 5-25 ms. Surgical separation of the two areas led to the disappearance of spontaneous events in the CA1 but not in the CA3 subfield. In this type of experiment CA1 pyramidal cells still generated epileptiform discharges following orthodromic stimuli. The intracellular counterpart of both spontaneous and stimulus-induced epileptiform discharges in CA1 and CA3 pyramidal cells was a large amplitude depolarization with high frequency discharge of action potentials which closely resembled the paroxysmal depolarizing shift recorded in the experimental epileptogenic focus. A hyperpolarizing potential triggered by alvear stimuli was recorded in CA1 cells perfused with Mg2(+)-free ACSF. This hyperpolarization was blocked by bicuculline methiodide (BMI) indicating that it represented a GABAergic inhibitory postsynaptic potential (IPSP). BMI also caused a prolongation of both spontaneous and stimulus-induced Mg(+)-free epileptiform discharges. Perfusion of the slices with the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphono-valerate (APV) reduced and eventually abolished the Mg(+)-free epileptiform discharges. These effects were more pronounced in the CA1 than in the CA3 subfield. APV also reduced the amplitude and the duration of the alveus-induced IPSP. These data demonstrate that Mg(+)-free epileptiform activity is present in the hippocampal slice at a time when inhibitory GABAergic potentials are operant as well as that in the CA1 subfield this type of epileptiform activity is dependent upon NMDA-activated conductances. Our experiments also indicate that NMDA receptors might be involved in the neuronal circuit responsible for the hyperpolarizing IPSP generated by CA1 pyramidal neurons.     

Properties of excitatory junction potentials and currents in smooth muscle cells of the mouse vas deferens

Intracellular recordings made from superficial smooth muscle cells of the mouse vas deferens confirmed the presence of two populations of cells, distinguishable by their membrane potential and measured input resistance. In this study, we have concentrated on cells with high input resistance (50-500 M omega) and membrane potentials of -45 to -65 mV. These cells fired action potentials when depolarized by intracellular current injection and appeared to be electrically isolated from adjacent cells. Stimulation of the intramural nerves evoked excitatory junction potentials (e.j.p.s.), which fluctuated in amplitude, with the largest firing action potentials. The e.j.p. amplitude was increased by hyperpolarizing and decreased by depolarizing the cell membrane. Under voltage-clamp, nerve stimulation evoked excitatory junction currents (e.j.c.s.) which reached a peak in 5 ms, and declined exponentially with a time-constant of 28 ms. The e.j.c. amplitude was linearly related to membrane potential with a reversal potential near -10 mV.     

Low-threshold calcium spikes in hypothalamic neurons recorded near the paraventricular nucleus in vitro

From guinea-pig hypothalamic slices, intracellular studies demonstrate the existence of neurons responding to depolarizing current pulses by bursts of fast spikes riding on slow depolarizing potentials, when activated at the resting potential or from hyperpolarized levels (44 cells). Slow depolarizing potentials have a mean amplitude of 17.6 mV and a mean duration of 65.2 msec. They are also produced at the termination of hyperpolarizing current pulses. The ionic basis for these slow potentials have been investigated. Fast spikes constituting the burst discharge are blocked by TTX but the slow component is unaffected, being blocked by Co++ and enhanced by Ba++. Taken together, these results show that the slow depolarizing potentials are generated by a low-threshold Ca++ conductance which is de-inactivated by membrane hyperpolarization. When the neurons are spontaneously active, they exhibit bursts arising from slow depolarizing potentials reminiscent of those evoked by direct stimulation. They also show longer episodes of repetitive firing. Twelve neurons were intracellularly stained and were found in the periphery of the paraventricular nucleus (PVN), in close proximity to the groups of neurophysin-positive neuroendocrine neurons present in the lateral part of this nucleus. Injected neurons have the morphology of reticular cells, judging by their few multipolar, rectilinear and sparsely branched dendrites. Some of their processes are directed towards PVN. Because of their intrinsic electrophysiological properties and their possible relationships with PVN, the population of cells described in the present study may play a role in functions relating to the PVN.     

Contrasting properties of K+ conductances induced by baclofen and gamma-aminobutyric acid in slices of the guinea pig hippocampus

Properties of membrane K+ conductances induced by baclofen and gamma-aminobutyric acid (GABA) in the hippocampus were investigated by using guinea-pig brain slices. Baclofen hyperpolarized the membrane and decreased the input resistance of pyramidal cells through the activation of a membrane K+ conductance. GABA caused a biphasic response in pyramidal cells, consisting of hyperpolarizing and depolarizing components. Combined application of picrotoxin and bicuculline eliminated the major part of the depolarizing component of the biphasic response and produced a relatively pure hyperpolarizing response which was also mediated by an increase in K+ conductance. The K+ conductance change induced by baclofen showed prominent inward rectification. However, the K+ conductance induced by GABA did not show an obvious rectifying property. The K+ conductance activated by baclofen was strongly antagonized by a low concentration (5 x 10(-6) M) of 4-aminopyridine (4-AP). In contrast, the K+ conductance activated by GABA was insensitive to 4-AP even at a high concentration of 10(-3) M. The slow inhibitory postsynaptic potential (slow i.p.s.p.) evoked by stimulation of the mossy fibres was totally suppressed by a low concentration of baclofen (5 x 10(-6) M). Whereas GABA (10(-3) M) decreased the amplitude of the slow i.p.s.p., the reduction of the amplitude was proportional to the decrease in the amplitude of the electrotonic potentials produced by constant inward current injections. These results suggest that the hyperpolarizations induced by GABA and baclofen may be generated by K+ conductances of different kinetic and pharmacologic properties.     

Development of rabbit hippocampus: physiology

The postnatal development of the CA1 region of rabbit hippocampus was studied using intracellular techniques in the in vitro slice preparation. Recordings from immature hippocampal neurons revealed spiking activity and functional synaptic contacts, even in the newborn animal. Resting potentials and time constants in such cells were similar to those of mature cells; input resistance was higher and action potential duration longer in the immature rabbits. These cell properties reach adult values by 2-3 weeks. Presumed calcium spikes, as well as sodium spikes, were elicited in animals as young as 1 day, so that it was not possible to determine whether calcium or sodium spikes occur earlier. Synaptic potentials recorded in immature CA1 neurons were long duration depolarizing events associated with a large conductance increase. The postsynaptic potentials (PSPs) were shown to be predominantly excitatory in nature, and could be potentiated by repetitive stimulation at slow rates and low intensities. Such stimulation in many cases could trigger seizure-like activity. Inhibitory PSPs in CA1 neurons were rare in animals less than 1-2 weeks old. Increased occurrence of hyperpolarizing inhibitory PSPs was correlated in time with the appearance of interneuron cell types in physiological recordings. These data reinforce the indication from morphological studies that inhibition is late in developing in rabbit hippocampus.     

Neuroactive steroids induce GABAA receptor‐mediated depolarizing postsynaptic potentials in hippocampal CA1 pyramidal cells of the rat

Intracellular recordings were performed in area CA1 pyramidal cells of rat hippocampal slices to determine the effects of certain steroids on inhibitory postsynaptic potentials/currents (IPSP/Cs) mediated by GABA_A receptors. Following application of the steroids 5α-pregnan-3α,21-diol-20-one (5α-THDOC), alphaxalone and 5β-pregnan-3α-ol-20-one (pregnanolone) hyperpolarizing PSPs developed into biphasic responses consisting of an early hyperpolarizing and a late depolarizing PSP sequence. Steroid-induced depolarizing PSPs could be elicited in the presence of antagonists to non-NMDA, NMDA, and GABA_B receptors, indicating that these receptor types do not contribute significantly to the initiation of these responses. Depolarizing PSPs were completely blocked by both GABA_A receptor antagonists bicuculline and t-butylbicyclophosphorothionat (TBPS) providing evidence for their mediation by GABA_A receptors. The reversal potential of steroid-induced late inward PSCs, measured in single-electrode voltage clamp, was ?29.9 ± 5.3 mV, whereas the early outward current, which corresponded to the early hyperpolarizing component of PSPs, reversed at ?68.2 ± 1.5 mV. Depolarizing PSPs and late inward PSCs were sensitive to reduction of extracellular [HCO₃^–] and block of carbonic anhydrase by application of acetazolamide. The results suggest that certain neuroactive steroids can induce GABA_A receptor-mediated depolarizing PSPs, which are dependent on HCO₃^–.     

Metabolic and ionic dependence of neuronal responses evoked by serotonin in the rat sensory ganglia

The membrane potential and conductance alterations of rat dorsal root ganglion neurons evoked by serotonin applied in bath or from a micropipette under pressure have been studied by intracellular technique. Serotonin application evoked depolarization with a decrease in membrane conductance and hyperpolarization with an increase in its conductance. A part of depolarization responses mediated by 5-HT2 receptor activation were independent of intracellular AMP concentration and associated with blockade of M-current channels. The other part of depolarizing and all hyperpolarizing responses mediated by 5-HT1A receptor activation were depressed by pertussis toxin and considerably modulated by intracellular AMP alterations. These responses were shown to be associated with disturbances in the function of AMP-dependent potassium ionic channels.     

Cerebellar macroneurons in microexplant cell culture. Postsynaptic amino acid pharmacology

Cerebellar neurons derived from 17- to 19-day-old fetal rats have been grown in a monolayer in microexplant cell culture, and intracellular recording coupled with iontophoresis of amino acid neurotransmitters has been employed to characterize their amino acid chemosensitivity. Although these cultures contain at least 3 different neuronal cell types, intracellular recordings were obtained from large neurons (diameter greater than 15 microns) with 1-5 dendritic shafts and fine dendritic arborizations and which could, on morphological grounds, be identified as Purkinje cells. All neurons with resting membrane potentials greater than 25 mV and with action potentials evoked by intracellular stimulation, responded to iontophoretically applied glutamate and GABA. There was essentially no chemosensitivity to glycine, beta-alanine or taurine. Aspartate application evoked only small responses at high iontophoretic currents. GABA reversibly increased membrane conductance and produced hyperpolarization at resting membrane potential with reversal potentials between -50 and -40 mV (5-10 mV more negative than resting membrane potential). Glutamate reversibly increased membrane conductance and produced depolarizing responses with extrapolated reversal potentials between 0 and -10 mV. Aspartate augmented glutamate responses at low iontophoretic currents which did not directly alter membrane potential or conductance. Thus Purkinje cells grown in the absence of parallel fiber and climbing fiber input develop autonomous neuropharmacologic specificity similar to that of Purkinje cells in vivo.     

Actions of serotonin recorded intracellularly in rat dorsal lateral septal neurons

The actions of serotonin (5HT) on passive and active membrane properties of neurons in the rat dorsal lateral septal nucleus (LSN) were studied by using intracellular recordings in transverse, septal slices. Superfusion with 10 microM 5HT induced a hyperpolarization of the membrane in almost all neurons tested in the dorsolateral part of the LSN. The hyperpolarization was accompanied by a decrease in membrane resistance. These effects of 5HT persisted in a low-Ca2+/high-Mg2+-containing medium or medium with tetrodotoxin, indicating a post-synaptic site of action for 5HT. The reversal potential for the hyperpolarizing effect was ca. -95 mV. If the extracellular K+-concentration was raised, the reversal potential became less negative. These data suggest that 5HT hyperpolarizes LSN neurons by increasing a K+-conductance. Spontaneous, synaptically evoked action potentials and action potentials induced in LSN neurons by a depolarizing current step typically display a fast Na+-spike with a subsequent K+-afterhyperpolarization, followed by a much slower Ca2+-dependent afterdepolarization. The amplitude of the K+-afterhyperpolarization was decreased by 5HT, while at the same time the afterdepolarization became more pronounced. The Ca2+-spike of LSN neurons was not affected by 5HT. Synaptic responses that were evoked in LSN neurons by stimulation of the dorsal part of the LSN consisted of a fast EPSP or spike, followed by a Cl(-)-dependent fast IPSP and a K+-dependent late IPSP. Of these synaptic responses, 5HT suppressed particularly the late IPSP. The present data indicate that 5HT affects the conductance for active and passive K+-channels in LSN neurons.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unidentified neuroglia potentials during propagated seizures in neocortex

Cortical surface and intracellular recording of silent cells (neuroglia) was carried out in the pericruciate cortex of cats during propagated seizures produced by repetitive stimulation of the surface of the opposite homotopic neocortex. The membrane characteristics of these cells were similar to neuroglial cells studied in leech, amphibian, and rat optic nerves, tissue culture, and mammalian cerebral cortex. By varying the parameters of transcallosal stimulation, it was possible to obtain either minor or major propagated seizures. All cells with resting membrane potentials (RMP) greater than 30 mv recorded during minor propagated seizures exhibited a depolarizing response (5–14 mv) during the seizure episode followed by a postictal hyperpolarizing response (1–9 mv) and a slow return to the original resting level. The peak amplitude of the depolarizing response was proportional to the cell's RMP and the amplitude of the seizure waves in the EEG. During major propagated seizures, an augmentation of the depolarizing response to 16–30 mv and the hyperpolarizing response to 10–15 mv was noted. A membrane conductance change during these events was not observed. During major propagated seizures, an increase in [K⁺]_o over the resting [K⁺]_o was calculated to be 10 meq/liter. However, the level of [K⁺]_o reached in the extracellular clefts was probably much higher than this calculated value for reasons which are discussed. A model for seizure propagation is presented. The postictal hyperpolarization most likely represents the effect of a K⁺-sensitive electrogenic pump in the glial membrane.