Voltage-dependent membrane potential oscillations of rat striatal fast-spiking interneurons

We used whole-cell recordings to investigate subthreshold membrane potential oscillations and their relationship with intermittent firing in striatal fast-spiking interneurons. During current injections (100–500 pA, 1 s), these cells displayed a highly variable pattern of spike bursts (comprising 1–30 action potentials) interspersed with membrane potential oscillations. The oscillation threshold was  −42 ± 10 mV  , and coincided with that for action potentials. The oscillation frequency was voltage dependent and ranged between 20 and 100 Hz. Oscillations were unaffected by the calcium channel blockers cadmium and nickel and by blockers of ionotropic glutamate and GABA receptors. Conversely, the sodium channel blocker tetrodotoxin fully abolished the oscillations and the spike bursts. The first spike of a burst appeared to be triggered by an oscillation, since the timing and rate of rise of the membrane potential in the subthreshold voltage region was similar for the two events. Conversely, the second spike (and the subsequent ones) displayed much faster depolarisations in the subthreshold voltage range, indicating that they were generated by a different mechanism. Consistent with these notions, a small pulse of intracellular current delivered during the oscillation was effective in triggering a burst of action potentials that largely outlasted the pulse. We conclude that fast-spiking interneuron oscillations are generated by an intrinsic membrane mechanism that does not require fast synaptic transmission, and which depends on sodium conductance but not calcium conductance, and that such oscillations are responsible for triggering the intermittent spike bursts that are typical of these neurons.     

Spinal nerve injury enhances subthreshold membrane potential oscillations in DRG neurons: relation to neuropathic pain

Primary sensory neurons with myelinated axons were examined in vitro in excised whole lumbar dorsal root ganglia (DRGs) taken from adult rats up to 9 days after tight ligation and transection of the L(5) spinal nerve (Chung model of neuropathic pain). Properties of subthreshold membrane potential oscillations, and of repetitive spike discharge, were examined. About 5% of the DRG neurons sampled in control DRGs exhibited high-frequency, subthreshold sinusoidal oscillations in their membrane potential at rest (V(r)), and an additional 4.4% developed such oscillations on depolarization. Virtually all had noninflected action potentials (A(0) neurons). Amplitude and frequency of subthreshold oscillations were voltage sensitive. A(0) neurons with oscillations at V(r) appear to constitute a population distinct from A(0) neurons that oscillate only on depolarization. Axotomy triggered a significant increase in the proportion of neurons exhibiting subthreshold oscillations both at V(r) and on depolarization. This change occurred within a narrow time window 16-24 h postoperative. Axotomy also shifted the membrane potential at which oscillation amplitude was maximal to more negative (hyperpolarized) values, and lowered oscillation frequency at any given membrane potential. Most neurons that had oscillations at V(r), or that developed them on depolarization, began to fire repetitively when further depolarized. Spikes were triggered by the depolarizing phase of oscillatory sinusoids. Neurons that did not develop subthreshold oscillations never discharged repetitively and rarely fired more than a single spike or a short burst, on step depolarization. The most prominent spike waveform parameters distinguishing neurons capable of generating subthreshold oscillations, and hence repetitive firing, was their brief postspike afterhyperpolarization (AHP) and their low single-spike threshold. Neurons that oscillated at V(r) tended to have a more prolonged spike, with slower rise- and fall-time kinetics, and lower spike threshold, than cells that oscillated only on depolarization. The main effects of axotomy were to increase spike duration, slow rise- and fall-time kinetics, and reduce single-spike threshold. Tactile allodynia following spinal nerve injury is thought to result from central amplification ("central sensitization") of afferent signals entering the spinal cord from residual intact afferents. The central sensitization, in turn, is thought to be triggered and maintained in the Chung model by ectopic firing originating in the axotomized afferent neurons. Axotomy by spinal nerve injury enhances subthreshold membrane potential oscillations in DRG neurons, augments ectopic discharge, and hence precipitates neuropathic pain.     

Pacemaker frequency is increased by sodium nitroprusside in the guinea pig gastric antrum

The basis of rhythmic activity observed at the dorsal column nuclei (DCN) is still open to debate. This study has investigated the electrophysiological properties of isolated DCN neurones deprived of any synaptic influence, using the perforated-patch technique. About half of the DCN neurones (64/130) were spontaneously active. More than half of the spontaneous neurones (36/64) showed a low threshold membrane oscillation (LTO) with a mean frequency of 11.4 Hz (range: 4.3–22.1 Hz, n = 20; I = 0). Cells showing LTOs also invariably showed a rhythmic 1.2 Hz clustering activity (groups of 2–5 action potentials separated by silent LTO periods). Also, more than one-third of the silent neurones presented clustering activity, always accompanied by LTOs, when slightly depolarised. The frequency of LTOs was voltage dependent and could be abolished by TTX (0.5 μM) and riluzole (30 μM), suggesting the participation of a sodium current. LTOs were also abolished by TEA (15 mM), which transformed clustering into tonic activity. In voltage clamp, most DCN neurones (85 %) showed a TTX-/riluzole-sensitive persistent sodium current ( I _Na,p), which activated at about -60 mV and had a half-maximum activation at −49.8 mV. An M-like, non-inactivating outward current was present in 95 % of DCN neurones, and TEA (15 mM) inhibited this current by 73.7 %. The non-inactivating outward current was also inhibited by barium (1 mM) and linopirdine (10 μM), which suggests its M-like nature; both drugs failed to block the LTOs, but induced a reduction in their frequency by 56 and 20 %, respectively. These results demonstrate for the first time that DCN neurones have a complex and intrinsically driven clustering discharge pattern, accompanied by subthreshold membrane oscillations. Subthreshold oscillations rely on the interplay of a persistent sodium current and a non-inactivating TEA-sensitive outward current.     

Early development of intrinsic and synaptic properties of chicken nucleus laminaris neurons

Onset of auditory brainstem responses in chickens takes place at about embryonic day 11/12 (E11/12). We investigated early development of neuronal properties of chicken nucleus laminaris neurons, the third-order auditory neurons critically involved in sound localization. Whole-cell patch recordings were performed in brainstem slices obtained at E10, E11, E12, E14, E16, and E18. At E18 neurons acquired an adult-like firing pattern in response to prolonged depolarizing current injections, with a single spike at the onset of the current injection followed by a plateau of membrane potential. At earlier ages, however, multiple spikes and/or subthreshold membrane potential oscillations were generated. We observed a >threefold reduction in input resistance from E10 to E18, and progressive changes in excitability properties, such as elevated threshold currents for spike generation, increased spike rising and falling rates, accompanied by reduced spike width and enhanced ability to follow high frequency inputs. Consistent with development of firing properties, the amplitude of voltage-gated potassium channel (Kv) currents increased by approximately threefold from E10 to E18, with a dramatic increase ( approximately ninefold) in the low threshold component. Excitatory postsynaptic potentials (EPSPs) were first recorded at E10, prior to and independent of the cochlear afferent inputs from the auditory nerve to the cochlear nucleus. EPSPs became markedly briefer in duration during the period studied. We conclude that the basic features of the key neuronal properties of NL neurons are well constructed during early development from E10 to E18.     

Regulation of granule cell excitability by a low-threshold calcium spike in turtle olfactory bulb

Granule cells excitability in the turtle olfactory bulb was analyzed using whole cell recordings in current- and voltage-clamp mode. Low-threshold spikes (LTSs) were evoked at potentials that are subthreshold for Na spikes in normal medium. The LTSs were evoked from rest, but hyperpolarization of the cell usually increased their amplitude so that they more easily boosted Na spike initiation. The LTS persisted in the presence of TTX but was antagonized by blockers of T-type calcium channels. The voltage dependence, kinetics, and inactivation properties of the LTS were characteristic of a low-threshold calcium spike. The threshold of the LTS was slightly above the resting potential but well below the Na spike threshold, and the LTS was often evoked in isolation in normal medium. Tetraethylammonium (TEA) and 4-aminopyridine (4-AP) had only minimal effects on the LTS but revealed the presence of a high-threshold Ca2+ spike (HTS), which was antagonized by Cd2+. The LTS displayed paired-pulse attenuation, with a timescale for recovery from inactivation of about 2 s at resting membrane potential. The LTS strongly boosted Na spike initiation; with repetitive stimulation, the long recovery of the LTS governed Na spike initiation. Thus the olfactory granule cells possess an LTS, with intrinsic kinetics that contribute to sub- and suprathreshold responses on a timescale of seconds. This adds a new mechanism to the early processing of olfactory input.     

Phasic stimuli evoke precisely timed spikes in intermittently discharging mitral cells

Mitral cells, the principal cells of the olfactory bulb, respond to sensory stimulation with precisely timed patterns of action potentials. By contrast, the same neurons generate intermittent spike clusters with variable timing in response to simple step depolarizations. We made whole cell recordings from mitral cells in rat olfactory bulb slices to examine the mechanisms by which normal sensory stimuli could generate precisely timed spike clusters. We found that individual mitral cells fired clusters of action potentials at 20-40 Hz, interspersed with periods of subthreshold membrane potential oscillations in response to depolarizing current steps. TTX (1 microM) blocked a sustained depolarizing current and fast subthreshold oscillations in mitral cells. Phasic stimuli that mimic trains of slow excitatory postsynaptic potentials (EPSPs) that occur during sniffing evoked precisely timed spike clusters in repeated trials. The amplitude of the first simulated EPSP in a train gated the generation of spikes on subsequent EPSPs. 4-aminopyridine (4-AP)-sensitive K(+) channels are critical to the generation of spike clusters and reproducible spike timing in response to phasic stimuli. Based on these results, we propose that spike clustering is a process that depends on the interaction between a 4-AP-sensitive K(+) current and a subthreshold TTX-sensitive Na(+) current; interactions between these currents may allow mitral cells to respond selectively to stimuli in the theta frequency range. These intrinsic properties of mitral cells may be important for precisely timing spikes evoked by phasic stimuli that occur in response to odor presentation in vivo.     

Modification of membrane excitability of neurons in the rat's dorsal cortex of the inferior colliculus by preceding hyperpolarization

The inferior colliculus (IC) is among the largest nuclei in the central auditory system and is considered to be a major integration center in the auditory pathway. To understand how IC contributes to auditory processing, we investigated the effects of preceding hyperpolarization on membrane excitability and firing behavior of neurons located in the dorsal cortex of the inferior colliculus (ICD). We made whole-cell patch clamp recordings from ICD neurons (n=96) in rat brain slices. We classified ICD neurons into three types, i.e. sustained-regular, sustained-adapting and buildup, according to their responses to depolarizing current injection. Nearly 91% of the neurons had sustained firing throughout the period of current injection, showing either regular or adapting pattern. About 9% of the neurons exhibited a buildup pattern, in which sustained firing started after a long delay. Rebound depolarization and spikes after hyperpolarization were seen in 51.7% of the sustained neurons, but were not seen in buildup neurons. When depolarizing current was preceded by a hyperpolarizing current, various forms of the modification on membrane excitability were observed. For non-rebound neurons, the membrane excitability was either suppressed or unchanged after pre-hyperpolarization. The first spike latency lengthened in neurons whose firing changed to a buildup pattern, shortened in those whose firing changed to a pauser pattern, and remained unchanged in those whose discharge pattern remained sustained. For rebound neurons, the firing rate decreased in neurons whose firing pattern was changed to onset or pauser, increased in neurons whose firing was changed to adapting, or remained unchanged in neurons whose firing became irregular. The first spike latency was shortened in all the rebound cells. The results suggest that intrinsic membrane properties can play an important role in integration of excitatory and inhibitory inputs and thereby in determination of the output of ICD neurons.     

Contributions of Kv7-mediated potassium current to sub- and suprathreshold responses of rat layer II/III neocortical pyramidal neurons

After block of Kv1- and Kv2-mediated K(+) currents in acutely dissociated neocortical pyramidal neurons from layers II/III of rat somatosensory and motor cortex, the remaining current is slowly activating and persistent. We used whole cell voltage clamp to show that the Kv7 blockers linopirdine and XE-991 blocked a current with similar kinetics to the current remaining after combined block of Kv1 and Kv2 channels. This current was sensitive to low doses of linopirdine and activated more slowly and at more negative potentials than Kv1- or Kv2-mediated current. The Kv7-mediated current decreased in amplitude with time in whole cell recordings, but in most cells the current was stable for several minutes. Current in response to a traditional M-current protocol was blocked by muscarine, linopirdine, and XE-991. Whole cell slice recordings revealed that the Q?? for channel deactivation was ～2.5. Sharp electrode current-clamp recordings from adult pyramidal cells demonstrated that block of Kv7-mediated current with XE-991 reduced rheobase, shortened the latency to firing to near rheobase current, induced more regular firing at low current intensity, and increased the rate of firing to a given current injection. XE-991 did not affect single action potentials or spike frequency adaptation. Application of XE-991 also eliminated subthreshold voltage oscillations and increased gain for low-frequency inputs (<10 Hz) without affecting gain for higher frequency inputs. These data suggest important roles for Kv7 channels in subthreshold regulation of excitability, generation of theta-frequency subthreshold oscillations, regulation of interspike intervals, and biasing selectivity toward higher frequency inputs.     

Properties and role of I(h) in the pacing of subthreshold oscillations in entorhinal cortex layer II neurons

Various subsets of brain neurons express a hyperpolarization-activated inward current (I(h)) that has been shown to be instrumental in pacing oscillatory activity at both a single-cell and a network level. A characteristic feature of the stellate cells (SCs) of entorhinal cortex (EC) layer II, those neurons giving rise to the main component of the perforant path input to the hippocampal formation, is their ability to generate persistent, Na(+)-dependent rhythmic subthreshold membrane potential oscillations, which are thought to be instrumental in implementing theta rhythmicity in the entorhinal-hippocampal network. The SCs also display a robust time-dependent inward rectification in the hyperpolarizing direction that may contribute to the generation of these oscillations. We performed whole cell recordings of SCs in in vitro slices to investigate the specific biophysical and pharmacological properties of the current underlying this inward rectification and to clarify its potential role in the genesis of the subthreshold oscillations. In voltage-clamp conditions, hyperpolarizing voltage steps evoked a slow, noninactivating inward current, which also deactivated slowly on depolarization. This current was identified as I(h) because it was resistant to extracellular Ba(2+), sensitive to Cs(+), completely and selectively abolished by ZD7288, and carried by both Na(+) and K(+) ions. I(h) in the SCs had an activation threshold and reversal potential at approximately -45 and -20 mV, respectively. Its half-activation voltage was -77 mV. Importantly, bath perfusion with ZD7288, but not Ba(2+), gradually and completely abolished the subthreshold oscillations, thus directly implicating I(h) in their generation. Using experimentally derived biophysical parameters for I(h) and the low-threshold persistent Na(+) current (I(NaP)) present in the SCs, a simplified model of these neurons was constructed and their subthreshold electroresponsiveness simulated. This indicated that the interplay between I(NaP) and I(h) can sustain persistent subthreshold oscillations in SCs. I(NaP) and I(h) operate in a "push-pull" fashion where the delay in the activation/deactivation of I(h) gives rise to the oscillatory process.     

Intrinsic theta-frequency membrane potential oscillations in hippocampal CA1 interneurons of stratum lacunosum-moleculare

The ionic conductances underlying membrane potential oscillations of hippocampal CA1 interneurons located near the border between stratum lacunosum-moleculare and stratum radiatum (LM) were investigated using whole cell current-clamp recordings in rat hippocampal slices. At 22 degrees C, when LM cells were depolarized near spike threshold by current injection, 91% of cells displayed 2-5 Hz oscillations in membrane potential, which caused rhythmic firing. At 32 degrees C, mean oscillation frequency increased to 7.1 Hz. Oscillations were voltage dependent and were eliminated by hyperpolarizing cells 6-10 mV below spike threshold. Blockade of ionotropic glutamate and GABA synaptic transmission did not affect oscillations, indicating that they were not synaptically driven. Oscillations were eliminated by tetrodotoxin, suggesting that Na+ currents generate the depolarizing phase of oscillations. Oscillations were not affected by blocking Ca2+ currents with Cd2+ or Ca2+-free ACSF or by blocking the hyperpolarization-activated current (Ih) with Cs+. Both Ba2+ and a low concentration of 4-aminopyridine (4-AP) reduced oscillations but TEA did not. Theta-frequency oscillations were much less common in interneurons located in stratum oriens. Intrinsic membrane potential oscillations in LM cells of the CA1 region thus involve an interplay between inward Na+ currents and outward K+ currents sensitive to Ba2+ and 4-AP. These oscillations may participate in rhythmic inhibition and synchronization of pyramidal neurons during theta activity in vivo.     

Consequences of 4-aminopyridine applications to trigeminal root ganglion neurons

1. The effects of 4-aminopyridine (4-AP) on the electrical properties of 30 trigeminal root ganglion (TRG) neurons were determined from the membrane voltage responses to step and sinusoidal current injections using intracellular microelectrode techniques in in vitro slice preparations (guinea pigs). 2. Comparisons of results from 4-AP applications (0.05-5 mM) with those from tetraethylammonium (TEA) applications (0.1-10 mM) revealed very different actions of these agents. Both agents produced an increase in input resistance and a decrease in threshold for spike generation. Applications of 4-AP increased subthreshold oscillations of the membrane potential and enhanced the repetitive spike firing evoked by intracellular injections of current pulses. However, TEA applications blocked the potential oscillations and did not exaggerate repetitive spike discharges. Spontaneous spike activity or bursts were observed in four neurons that received 4-AP applications. 3. Membrane properties were determined in 20 of the 30 neurons by fitting impedance data in the frequency domain with a four-parameter membrane model by the use of computer-intensive techniques. In the majority of neurons, the time-invariant and time-dependent membrane conductances decreased during 4-AP application. The time constant for the time-dependent conductance also decreased, suggesting that the closing of K+-channels was facilitated in the membrane. 4. Applications of 4-AP in a dose range of 50 microM-5 mM produced rapid (approximately tens of seconds) responses of the neurons, resulting in a dose-dependent increase of the impedance magnitude functions and in a leftward shift of the resonant "humps" to lower frequencies. This shift indicates that the TRG neuronal membrane is capable of producing large voltage responses to current inputs at low frequencies. Recovery from the effects of 4-AP was slow (usually greater than 30 min). 5. Applications of 4-AP at high doses (greater than or equal to 1 mM) and at various imposed membrane potentials in four neurons resulted in poorly reversible unspecific changes in certain membrane parameters (increased input capacitance and conductance) and an insensitivity of the input conductance to the imposed membrane potential. These effects could be interpreted as membrane breakdown. 6. The tendencies of TRG neurons to fire repetitively and in bursts of spikes during 4-AP application result from the increased oscillatory behavior of their membrane potentials and changes in membrane resonance induced by presumed blockade of K+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)     

Spike-Dependent Intrinsic Plasticity Increases Firing Probability in Rat Striatal Neurons In Vivo

The collision of pre- and postynaptic activity is known to provide a trigger for controlling the gain of synaptic transmission between neurons. Here, using in vivo intracellular recordings of rat striatal output neurons, we analyse the effect of a single action potential, generated by ongoing synaptic activity, on subsequent excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the cerebral cortex. This pairing induced a short-term increase in the probability that cortically evoked EPSPs caused striatal cells to fire. This enhanced EPSP-spike coupling was associated with a decrease in the voltage firing threshold with no apparent change in the synaptic strength itself. Antidromic action potentials in striatal cells were also able to induce the facilitation while subthreshold EPSPs were ineffective, indicating that the postsynaptic spike was necessary and sufficient for the induction of the plasticity. A prior spontaneous action potential also enhanced the probability with which directly applied current pulses elicited firing, suggesting that the facilitation originated from changes in the intrinsic electrical properties of the postsynaptic cell. Using whole-cell recordings in cortico-striatal slices, we found that the increase in membrane excitability as well as in EPSP-spike coupling was abolished by low concentration of 4-aminopyridine. This suggests that the intrinsic plasticity results from a time-dependent modulation of a striatal voltage-dependent potassium current available close to the firing threshold. Action potentials thus provide a postsynaptic signal, not only for associative synaptic plasticity but also for activity-dependent intrinsic plasticity, which directly controls the efficacy of coupling between pre- and postsynaptic neurons.     

Physiological studies on neurons in the dorsal cochlear nucleus of cat

Results reported here support the conclusion that an individual neuron in the dorsal cochlear nucleus (DCN) can exhibit pauser, buildup, and chopper patterns in response to tone pips. Fusiform cells have been previously identified as the principal cell exhibiting these patterns. Fusiform cells can also exhibit an onset response followed by suppression of spontaneous activity at their characteristic frequency (CF). Off CF only suppression is seen. These neurons are characterized by a restricted excitatory region near threshold. All these cells can exhibit nonmonotonic rate curves, narrow excitatory regions, and inhibitory sidebands. Nonmonotonicity occurred in 34% of pausers, 52% of buildup, 89% of onsets with a graded response, and 50% overall in the DCN cells. Chopper units occur as often as the other types combined in the DCN. Only 14% show nonmonotonic rate curves. Those with high-spontaneous activity also show inhibitory sidebands. Cells with a predominant buildup pattern occur most frequently in the fusiform cell layer, whereas pausers occur throughout the DCN below the molecular layer. Intracellular potentials often reflect the average response pattern. Sharply delimited response areas indicate that these cells may be useful for performing a spectral analysis. These cells show almost no phase locking suggesting that temporal encoding is an unlikely function. It is suggested that the effects of anesthetic on the function of the DCN is not as marked as previously indicated.     

Subthreshold inward membrane currents in guinea-pig frontal cortex neurons

Current-clamp and single-electrode voltage-clamp recordings were used to study the inward currents activated in the subthreshold membrane potential range of cortical pyramidal neurons. The experiments were done on slices from guinea-pig frontal cortex and all recordings were obtained at a distance of 600-900 microm from the pial surface. In current-clamp recordings and from membrane potentials hyperpolarized to about -70 mV, the depolarization leading to spike firing was partially blocked by 1 microM tetrodotoxin, but not by calcium-free extracellular solution. The calcium-free solution only affected this depolarization when the membrane potential was held at a level more negative than -75 mV. Under voltage-clamp, an inward current was recorded between the resting membrane potential and the level of spike firing. This current was activated at about -60 mV and part of it was blocked by 1 microM tetrodotoxin; the remaining current was blocked by calcium-free extracellular solution. In five neurons both components were recorded and isolated in the same cell. The tetrodotoxin-sensitive component activated at close to -60 mV, was similar to the persistent sodium current (I(Na-p)). The Ca2+-sensitive component activated at close to -60 or -65 mV, was less voltage-dependent than I(Na-p). This component was similar to the low threshold calcium current (I(T)). These results suggest that the subthreshold depolarization which led to spike firing was dependent on I(Na-p) and I(T), I(Na-p) being the most important factor up to resting membrane potentials of -70 or -75 mV. A physiological role of this finding is revealed by the action of dopamine, which (at 10 microM) prevented the firing of action potentials from -60 mV, but not from -80 mV due to the inhibition of I(Na-p) and the lack of effect on I(T).     

Electrophysiological characteristics of immunochemically identified rat oxytocin and vasopressin neurones in vitro.

1. Intracellular recordings were made from supraoptic neurones in vitro from hypothalamic explants prepared from adult male rats. Neurones were injected with biotinylated markers, and of thirty-nine labelled neurones, nineteen were identified immunocytochemically as containing oxytocin-neurophysin and twenty as containing vasopressin-neurophysin. 2. Vasopressin and oxytocin neurones did not differ in their resting membrane potential, input resistance, membrane time constant, action potential height from threshold, action potential width at half-amplitude, and spike hyperpolarizing after-potential amplitude. Both cell types exhibited spike broadening during brief, evoked spike trains (6-8 spikes), but the degree of broadening was slightly greater for vasopressin neurones. When hyperpolarized below -75 mV, all but one neurone exhibited a transient outward rectification to depolarizing pulses, which delayed the occurrence of the first spike. 3. Both cell types exhibited a long after-hyperpolarizing potential (AHP) following brief spike trains evoked either with a square wave pulse or using 5 ms pulses in a train. There were no significant differences between cell types in the size of the AHP evoked with nine spikes, or in the time constant of its decay. The maximal AHP evoked by a 180 ms pulse was elicited by an average of twelve to thirteen spikes, and neither the size of this maximal AHP nor its time constant of decay were different for the two cell types. 4. In most oxytocin and vasopressin neurones the AHP, and concomitantly spike frequency adaptation, were markedly reduced by the bee venom apamin and by d-tubocurarine, known blockers of a Ca(2+)-mediated K+ conductance. However, a minority of neurones, of both cell types, were relatively resistant to both agents. 5. In untreated neurones, 55% of vasopressin neurones and 32% of oxytocin neurones exhibited a depolarizing after-potential (DAP) after individual spikes or, more commonly, after brief trains of spikes evoked with current pulses. For each neurone with a DAP, bursts of spikes could be evoked if the membrane potential was sufficiently depolarized such that the DAP reached spike threshold. In four out of five vasopressin neurones a DAP became evident only after pharmacological blockade of the AHP, whereas in six oxytocin neurones tested no such masking was found. 6. The firing patterns of neurones were examined at rest and after varying the membrane potential with continuous current injection. No identifying pattern was strictly associated with either cell type, and a substantial number of neurones were silent at rest.(ABSTRACT TRUNCATED AT 400 WORDS)     

Subthreshold rectification in neostriatal spiny projection neurons

Intracellular recordings from slice preparations were used to assess the subthreshold electrophysiological behavior of rat neostriatal projection neurons. Both current steps and ramp currents were used to estimate the current-voltage relationship (I–V plot). Inward rectification in the subthreshold range was a characteristic of most neurons. The amount of rectification varied greatly, and it was complex: membrane voltage trajectories in response to ramps were made up by almost piecewise changes in the rate of voltage rise, suggesting that multiple conductances contribute to the subthreshold range. Inward current blockers such as tetrodotoxin (TTX) or Cd²⁺ decreased inward rectification, whereas outward current blockers such as tetraethylammonium (TEA) or 4-aminopyridine (4-AP) increased inward rectification. However, most inward rectification was due to TEA- and Cs⁺-sensitive conductances and not to TTX- or Cd²⁺-sensitive conductances. Cs⁺-sensitive conductances predominated at more negative membrane potentials, whereas 4-AP-sensitive conductances predominated at just ±10 mV below the firing threshold. In spite of a very slow activation, there was evidence for transient outward currents modulating the response, i.e., 4-AP-sensitivity, and voltage-sensitivity for firing frequency and threshold. TEA-sensitive conductances also contributed toward fixing the firing threshold. These results imply the contribution of various ion conductances on the shaping of the characteristic physiological firing recorded in vivo. Modulation of these responses by transmitters or peptides may help to understand neural processing in the neostriatum.     

Sensory stimulus evokes inhibition rather than excitation in cerebellar Purkinje cells in vivo in mice

Cerebellar Purkinje cells (PC) response precisely to tactile stimulus via granule cells, however, the interaction between sensory evoked synaptic input and the resulting pattern of output spikes in cerebellar cortex is unclear. In this study, we used electrophysiological recording and pharmacological methods to investigate the cerebellar PC in response to natural stimulus on ipsilateral whisker pad in urethane-anesthetized mice. We found that air-puff stimulus on ipsilateral whisker pad evoked neither complex spikes nor simple spike firing, but indeed evoked a strong GABA(A) receptor-mediated inhibition in PCs in cerebellar cortex folium Crus II. Field potential recordings from both molecular layer and PC layer showed that air-puff stimulus evoked a sequence of parallel fiber volley followed by a GABA(A) receptor-mediated inhibition, which completely blocked by AMPA receptor antagonist, NBQX. Cell-attached recordings showed that air-puff stimulus evoked a pause of simple spike firing, GABA(A) receptor antagonist abolished the pause, revealed the tactile stimulus-evoked spike firing in PCs. These results indicated that natural stimulus of whisker pad neither evoked complex spikes, nor fired simple spikes, but induced inhibition in PCs, suggesting that the interneuron network are rapid activated and involved in controlling the spread of sensory information processing in mouse cerebellar cortex folium Crus II.     

Synaptic inputs to granule cells of the dorsal cochlear nucleus

The mammalian dorsal cochlear nucleus (DCN) integrates auditory nerve input with nonauditory signals via a cerebellar-like granule cell circuit. Although granule cells carry nonauditory information to the DCN, almost nothing is known about their physiology. Here we describe electrophysiological features of synaptic inputs to granule cells in the DCN by in vitro patch-clamp recordings from P12 to P22 rats. Granule cells ranged from 6 to 8 microm in cell body diameter and had high-input resistance. Excitatory postsynaptic currents consisted of both AMPA receptor-mediated and N-methyl-D-aspartate receptor-mediated currents. Synaptically evoked excitatory postsynaptic currents ranged from -25 to -140 pA with fast decay time constants. Synaptic stimulation evoked both short- and long-latency synaptic responses that summated to spike threshold, indicating the presence of a polysynaptic excitatory pathway in the granule cell circuit. Synaptically evoked inhibitory postsynaptic currents in Cl(-)-loaded cells ranged from -30 to -1,021 pA and were mediated by glycine and, to a lesser extent, GABA(A) receptors. Unlike cerebellar granule cells, DCN granule cells lacked tonic inhibition by GABA. The glycinergic synaptic conductance was mediated by heteromeric glycine receptors and was far stronger than the glutamatergic conductance, suggesting that glycinergic neurons may act to gate nonauditory signals in the DCN.     

Medial vestibular nucleus in the guinea-pig

Summary Intracellular recordings were obtained from medial vestibular nuclei neurones (MVNn) in guinea-pig brainstem slices. Two main distinct neuronal classes were encountered. Type A MVNn (32.3%) were characterized by a broad action potential followed by a deep single afterhyperpolarization, a transient A-like rectification, and a single range of firing in response to current injection. Type B MVNn (47.1%), in contrast, were distinguished by the presence of a thin action potential followed first by a fast and then by a delayed and slower afterhyperpolarization. In addition, they displayed a secondary range of firing in their response to current injection. A majority of B MVNn also had either subthreshold plateau potentials or low threshold spike bursts or a combination thereof. A third, non-homogeneous class of cells, could not be fitted into either one of the two main classes (20.6%, type C MVNn).