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PubMed2001

Rapid signaling at inhibitory synapses in a dentate gyrus interneuron network.

Mutual synaptic interactions between GABAergic interneurons are thought to be of critical importance for the generation of network oscillations and for temporal encoding of information in the hippocampus. However, the functional properties of synaptic transmission between hippocampal interneurons are largely unknown. We have made paired recordings from basket cells (BCs) in the dentate gyrus of rat hippocampal slices, followed by correlated light and electron microscopical analysis. Unitary GABA(A) receptor-mediated IPSCs at BC-BC synapses recorded at the soma showed a fast rise and decay, with a mean decay time constant of 2.5 +/- 0.2 msec (32 degrees C). Synaptic transmission at BC-BC synapses showed paired-pulse depression (PPD) (32 +/- 5% for 10 msec interpulse intervals) and multiple-pulse depression during repetitive stimulation. Detailed passive cable model simulations based on somatodendritic morphology and localization of synaptic contacts further indicated that the conductance change at the postsynaptic site was even faster, decaying with a mean time constant of 1.8 +/- 0.6 msec. Sequential triple recordings revealed that the decay time course of IPSCs at BC-BC synapses was approximately twofold faster than that at BC-granule cell synapses, whereas the extent of PPD was comparable. To examine the consequences of the fast postsynaptic conductance change for the generation of oscillatory activity, we developed a computational model of an interneuron network. The model showed robust oscillations at frequencies >60 Hz if the excitatory drive was sufficiently large. Thus the fast conductance change at interneuron-interneuron synapses may promote the generation of high-frequency oscillations observed in the dentate gyrus in vivo.

Action Potentials↗
PubMed2001

Multiple types of control by identified interneurons in a sensory-activated rhythmic motor pattern.

Modulatory interneurons that can drive central pattern generators (CPGs) are considered as good candidates for decision-making roles in rhythmic behaviors. Although the mechanisms by which such neurons activate their target CPGs are known in detail in many systems, their role in the sensory activation of CPG-driven behaviors is poorly understood. In the feeding system of the mollusc Lymnaea, one of the best-studied rhythmical networks, intracellular stimulation of either of two types of neuron, the cerebral ventral 1a (CV1a) and the slow oscillator (SO) cells, leads to robust CPG-driven fictive feeding patterns, suggesting that they might make an important contribution to natural food-activated behavior. In this paper we investigated this contribution using a lip-CNS preparation in which feeding was elicited with a natural chemostimulant rather than intracellular stimulation. We found that despite their CPG-driving capabilities, neither CV1a nor SO were involved in the initial activation of sucrose-evoked fictive feeding, whereas a CPG interneuron, N1M, was active first in almost all preparations. Instead, the two interneurons play important and distinct roles in determining the characteristics of the rhythmic motor output; CV1a by modulating motoneuron burst duration and SO by setting the frequency of the ongoing rhythm. This is an example of a distributed system in which (1) interneurons that drive similar motor patterns when activated artificially contribute differently to the shaping of the motor output when it is evoked by the relevant sensory input, and (2) a CPG rather than a modulatory interneuron type plays the most critical role in initiation of sensory-evoked rhythmic activity.

Action Potentials↗
PubMed2001

Prefrontal microcircuits: membrane properties and excitatory input of local, medium, and wide arbor interneurons.

To elucidate cortical mechanisms involved in higher cortical functions such as working memory, we have examined feedforward excitation transmitted by identified pyramidal cells to interneurons with predominantly horizontal axonal arbors, using dual somatic recordings in prefrontal cortical slices. Interneurons with local (narrow) axonal arbors, especially chandelier interneurons, exhibited extremely narrow action potentials and high evoked firing rates, whereas neurons identified with wide arbor axons generated wider spikes and lower evoked firing rates with considerable spike adaptation, resembling that of pyramidal cells. Full reconstruction of differentially labeled neuronal pairs revealed that local arbor cells generally received a single but functionally reliable putative synaptic input from the identified pyramidal neuron member of the pair. In contrast, more synapses (two to five) were necessary to depolarize medium and wide arbor neurons reliably. The number of putative synapses and the amplitude of the postsynaptic response were remarkably highly correlated within each class of local, medium, and wide arbor interneurons (r = 0.88, 0.95, and 0.99, respectively). Similarly strong correlations within these subgroups were also present between the number of putative synapses and variance in the EPSP amplitudes, supporting the validity of our morphological analysis. We conclude that interneurons varying in the span of their axonal arbors and hence in the potential regulation of different numbers of cortical modules differ also in their excitatory synaptic input and physiological properties. These findings provide insight into the circuit basis of lateral inhibition and functional interactions within and between cortical columns in the cerebral cortex.

Action Potentials↗
PubMed2002

Facilitation of monosynaptic and complex PSPs in type I interneurons of conditioned Hermissenda.

Synaptic plasticity and intrinsic changes in neuronal excitability are two mechanisms for Pavlovian conditioning. Pavlovian conditioning of Hermissenda produces synaptic facilitation of monosynaptic medial B-medial A IPSPs and intrinsic changes in excitability of type A and B cells in isolated and intact sensory neurons of the conditioned stimulus (CS) pathway. Recently two types of interneurons that receive either excitatory or inhibitory monosynaptic or polysynaptic input from photoreceptors have been identified. On the basis of morphological and electrophysiological criteria, the interneurons have been classified as type I(e), I(i) (direct), and type II(e), II(i) (indirect). We have now examined synaptic facilitation of monosynaptic PSPs in type I(e) and I(i) interneurons after conditioning and pseudorandom control procedures. Here we report that CS-elicited spike activity is increased in type I(e) interneurons and decreased in type I(i) interneurons of conditioned animals relative to their respective baseline activity and pseudorandom control groups. Classical conditioning resulted in synaptic facilitation of type I(e) and I(i) monosynaptic PSPs elicited by lateral B spikes and enhancement of the amplitude of complex PSPs elicited by the CS. These results provide additional sites of plasticity in the neural circuit involved with the expression of learned behavior produced by Pavlovian conditioning of Hermissenda.

Action Potentials↗
PubMed2003

Four-dimensional migratory coordinates of GABAergic interneurons in the developing mouse cortex.

We have used time-lapse multiphoton microscopy to map the migration and settling pattern of GABAergic interneurons that originate in the ganglionic eminence of the ventral forebrain and incorporate into the neocortex of the cerebral hemispheres. Imaging of the surface of the cerebral hemispheres in both explant cultures and brains of living mouse embryos revealed that GABAergic interneurons migrating within the marginal zone originate from three different sources and migrate via distinct and independent streams. After reaching their areal destination, interneurons descend into the underlying cortex to assume positions with isochronically generated, radially derived neurons. The dynamics and pattern of cell migration in the marginal zone (see movies, available at www.jneurosci.org) suggest that the three populations of interneurons respond selectively to distinct local cues for directing their migration to the appropriate areas and layers of the neocortex. This approach opens a new avenue for study of normal and abnormal neuronal migration in their native environment and indicate that interneurons have specific programs for their areal and laminar deployment.

Animals↗
PubMed1992

Regeneration of an interneuronal network in Helisoma: re-establishment of synaptic contacts.

We have identified a network of three interneurons located in the central ring ganglia of Helisoma. Two of these interneurons, designated Left Pedal Dorsal 1 (LPeD1) and Right Pedal Dorsal 1 (RPeD1), are the largest neurons of the pedal ganglia and appear to contain dopamine and serotonin, respectively. A third interneuron, identified as Visceral Dorsal 4 (VD4), is a small FMRFamide immunoreactive cell located on the dorsal surface of the visceral ganglion. Monosynaptic chemical connections exist between all these interneurons. For instance, a reciprocal inhibitory connection exists between LPeD1 and RPeD1, whereas VD4 has inhibitory effects on both LPeD1 and RPeD1. Furthermore, LPeD1, but not RPeD1, has an excitatory connection with VD4. We demonstrate that following axotomy these interneurons not only regenerate their axons but re-establish their appropriate synaptic connections.

Animals↗
PubMed1992

GABAergic septal and serotonergic median raphe afferents preferentially innervate inhibitory interneurons in the hippocampus and dentate gyrus.

Postsynaptic targets of the GABAergic septohippocampal and the serotonergic raphe-hippocampal pathways were studied using anterograde tracing with Phaseolus vulgaris leucoagglutinin combined with pre- and postembedding immunocytochemistry in the rat. Two types of afferents were labeled in the hippocampus and dentate gyrus from the medial septum-diagonal band of Broca complex, one with large diameter varicosities and another with smaller terminals. The former type was shown to be immunoreactive for gamma-aminobutyric acid (GABA), and to innervate predominantly GABA-immunoreactive interneurons. Subsequently, these target interneurons were demonstrated to include all subpopulations of GABAergic cells which could be visualized by antisera against parvalbumin, calbindin D28k, calretinin, cholecystokinin, somatostatin, neuropeptide Y and vasoactive intestinal polypeptide. These types of interneurons have different afferent and efferent connections, and thus participate in different inhibitory processes in the hippocampal formation. The other subcortical pathway, the serotonergic projection from the median raphe nucleus, was also shown to establish synapses predominantly with GABAergic interneurons both in the hippocampus and in the dentate gyrus. In contrast to the septohippocampal projection, this pathway did not innervate all types of GABAergic neurons. They selected a particular subpopulation, i.e. those which contain calbindin D28k, and ignored those which contained parvalbumin or the other neurochemical markers. This suggests a strong functional specialization among local inhibitory circuits, as well as among the subcortical afferents originating in the septum and raphe. These findings suggest that a mechanism by which numerically small afferent pathways may have a profound global effect on the electrical activity of the hippocampal formation is the selective innervation of local interneurons. These GABAergic inhibitory cells, in turn, control the activity of large populations of principal cells. The level of GABAergic inhibition determines the degree of population synchrony and influences N-methyl-D-aspartate receptor-mediated epileptiform burst-firing. Thus, the specific subcortical modulation of hippocampal inhibitory circuits may also have fundamental implications for epileptogenesis.

Afferent Pathways↗
PubMed2003

Major differences in inhibitory synaptic transmission onto two neocortical interneuron subclasses.

Locally projecting GABAergic interneurons are the major providers of inhibition in the neocortex and play a crucial role in several brain functions. Neocortical interneurons are connected via electrical and chemical synapses that may be crucial in modulating complex network oscillations. We investigated the properties of spontaneous and evoked IPSCs in two morphologically and physiologically identified interneuron subtypes, the fast-spiking (FS) and low threshold-spiking (LTS) cells in layer V of rodent sensorimotor cortex. We found that IPSCs recorded in FS cells were several orders of magnitude more frequent, larger in amplitude, and had faster kinetics than IPSCs recorded in LTS cells. GABA(A) receptor alpha- and beta-subunit selective modulators, zolpidem and loreclezole, had different effects on IPSCs in FS and LTS interneurons, suggesting differential expression of GABA(A) receptor subunit subtypes. These pharmacological data indicated that the alpha1 subunit subtype is poorly expressed by LTS cells but makes a large contribution to GABA(A) receptors on FS cells. This was confirmed by experiments performed in genetically modified mice in which the alpha1 subunit had been made insensitive to benzodiazepine-like agonists. These results suggest that differences in IPSC waveform are likely attributable to distinctive expression of GABA(A) receptor subunits in FS and LTS cells. The particular properties of GABAergic input on different interneuronal subtypes might have important consequences for generation and pacing of cortical rhythms underlying several brain functions. Moreover, selective pharmacological manipulation of distinct inhibitory circuits might allow regulation of pyramidal cell activities under specific physiological and pathophysiological conditions.

Action Potentials↗
PubMed1992

The role of premotor interneurons in phase-dependent modulation of a cutaneous reflex during swimming in Xenopus laevis embryos.

Phase-dependent reflex modulation during fictive "swimming" in Xenopus laevis embryos has been examined with intracellular recordings from rhythmically active spinal neurons. (1) At rest, cutaneous trunk or tail skin stimulation evokes EPSPs in motoneurons and premotor excitatory and inhibitory interneurons of the opposite motor system. During swimming, these EPSPs can only be evoked during the depolarized phase of activity and can then produce extra action potentials that lead to phase-dependent reflexes in ventral roots. On the stimulated side, IPSPs are evoked in rhythmic neurons that can block centrally generated action potentials if the stimulus coincides with the inhibited phase of the swimming cycle. This inhibition suppresses ventral root discharge in a phase-dependent manner. (2) The presence of premotor interneurons in the crossed reflex pathway suggests two parallel routes for cutaneous excitation to reach the motoneurons, one direct and the other indirect through excitatory premotor interneurons. During swimming, the crossed excitation through both routes is gated by the rhythm-generating circuit to allow summation in motoneurons only during the depolarized phase of the swim cycle. (3) Following phase-dependent reflexes, the frequency of swimming is raised for several cycles, a phenomenon that requires sensory activation of premotor rhythm-generating interneurons. The results provide evidence on the role of identified premotor spinal interneurons in phase-dependent reflex modulation.

Animals↗
PubMed1989

[Effect of dopamine on the background and evoked activity of interneurons from isolated spinal cord segments of newborn rats].

The effects of dopamine on the background and dorsal root stimulation-evoked activity of spinal interneurons and on the field potentials in the dorsal horn were studied in the isolated superfused spinal cord of 11-18 days old rats. It was established that application of dopamine in concentration 1.10(-6)-1.10(-3) mol/l caused exciting and depressing effects on the background and evoked activity of spinal cord cells. The postsynaptic wave of field potentials was depressed by dopamine. In some interneurons the effects of dopamine disappeared in the solution with 0.01 mmol/l Ca2+ and 1.5-2 mmol/l Mn2+ (trans-synaptic effects). In other cells exciting or inhibiting effects of dopamine were preserved in the medium blocking synaptic transmission, that evidenced for direct depolarization and hyperpolarization of the interneuron membrane. The effects of dopamine were reversible and dose-dependent. These results suggest that dopamine may have influence on the transmission of excitation in the spinal cord on the interneurons level. It is supposed to be possible that different types of interneurons responses are the result of the existence of two types of dopamine receptors in the spinal cord.

Animals↗
PubMed1986

Modulation of embryonic chick motoneuron glutamate sensitivity by interneurons and agonists.

Embryonic chick motoneurons grown in culture together with other spinal cord cells are more sensitive to L-glutamate than are sorted motoneurons grown in isolation. After 6 d in vitro, the difference in peak sensitivity reached 6-fold. Comparable increases in aspartate and kainate currents were observed, indicating that both G1 and G2 amino acid receptors were affected. Elimination of proliferating non-neuronal cells from mixed spinal cord cell cultures by addition of cytosine arabinoside (ara C) did not prevent the increase in motoneuron chemosensitivity, so the induction is probably due to the presence of interneurons. In contrast to their effect on glutamate response, interneurons did not affect the sensitivity of motoneurons to the inhibitory neurotransmitters GABA and glycine. Glutamate receptors expressed by sorted and unsorted motoneurons are identical in terms of their ED50, reversal potential, mean channel open time, and conductance, implying that the increased sensitivity of motoneurons in mixed cultures is due to an increase in the number of open channels. In addition to an increase in the number of channels, the distribution of glutamate sensitivity over the surface of individual motoneurons was altered in interneuron-containing cultures. The sensitivity of isolated motoneurons was greatest at the soma and decreased with distance along major processes, but the sites of highest sensitivity on motoneurons in mixed cultures occurred along their processes. Sharp peaks identified by focal iontophoresis of glutamate were separated by areas of lower sensitivity. The inductive effect of interneurons cannot be due to glutamate, the most likely excitatory interneuron-motoneuron transmitter in 6 d chick cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Characteristics of interneurons in the ocellar system of the honeybee.

Intracellular recording and staining has revealed new aspects of the anatomy and physiology of ocellar interneurons in the honeybee (Apis mellifera). Homologous large first-order interneurons (L-neurons) from different individuals vary in structure as well as in their response to light. Even the response patterns of one type of L-neuron may present a continuum from graded responses to spiking responses. The response depends on the state of the L-neuron and cannot be correlated with particular morphological types. Graded responses are unimodal and can be elicited exclusively by stationary illumination of the ocelli, whereas spiking L-neurons can also respond to stimuli of other sensory modalities. Recordings from the same type of multimodal spiking L-neuron in different individuals demonstrate considerable variation in responses to different modalities. The existence of two response patterns in the same cell that can encode different information may be of general importance with respect to the processing of information in the brain. There appears to be a variety of different pathways enabling interaction of ocellar and compound eye signals either by direct contact between ocellar and optic lobe neurons or by convergence of the two pathways to a common descending or local interneuron. Two examples are discussed: an ocellar small first-order interneuron (S-neuron) that project directly to the optic lobes and a local interneuron that is situated in the posterior midbrain close to situated in the posterior midbrain close to ocellar terminals and optic lobe outputs and that responds to stimulation of both visual systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Slow oscillations of membrane potential in interneurons that control heartbeat in the medicinal leech.

In the preceding paper (Arbas and Calabrese, 1987), we identified several properties that contribute to the activity of neurons (HN cells) that control heartbeat in the medicinal leech. Premotor HN (7) interneurons, which do not generate the heartbeat rhythm, exhibit Na+-dependent fast action potentials, Ca2+-mediated plateau potentials in the absence of Na+, and hyperpolarization-activated "restorative" changes in membrane potential that depolarize the membrane potential on hyperpolarization due to injected currents or synaptic inhibition. HN interneurons of ganglia 3 and 4 (i.e., timing oscillator interneurons) exhibit all of the properties described for HN (7) interneurons and have the additional characteristic that they are connected in oscillatory circuits. Reciprocal oscillations in membrane potential occurred in the bilateral HN interneurons (3) and (4) in the presence of elevated Ca2+ that were independent of Na+ -mediated action potentials. Their ability to oscillate in this way is based on 3 parameters: (1) production of a regenerative plateau potential by one of the pair of HN neurons in either ganglion, (2) inhibition of the contralateral HN neuron by the HN neuron in plateau, and (3) a phase transition mediated by escape from inhibition by the hyperpolarized HN neuron. The conductances responsible for restorative membrane potential shifts activated by hyperpolarization during synaptic inhibition may mediate the escape from inhibition that times the phase transition of the 2 HN neurons.

Action Potentials↗
PubMed1995

NMDA receptor subunit mRNA expression by projection neurons and interneurons in rat striatum.

N-Methyl-D-aspartate (NMDA) receptors are enriched in the neostriatum and are thought to mediate several actions of glutamate including neuronal excitability, long-term synaptic plasticity, and excitotoxic injury. NMDA receptors are assembled from several subunits (NMDAR1, NMDAR2A-D) encoded by five genes; alternative splicing gives rise to eight isoforms of subunit NMDAR1. We studied the expression of NMDA receptor subunits in neurochemically identified striatal neurons of adult rats by in situ hybridization histochemistry using a double-labeling technique. Enkephalin-positive projection neurons, somatostatin-positive interneurons, and cholinergic interneurons each have distinct NMDA receptor subunit phenotypes. Both populations of striatal interneurons examined express lower levels of NMDAR1 and NMDAR2B subunit mRNA than enkephalin-positive neurons. The three striatal cell populations differ also in the presence of markers for alternatively spliced regions of NMDAR1, suggesting that interneurons preferentially express NMDAR1 splice forms lacking one (cholinergic neurons) or both (somatostatin-positive neurons) alternatively spliced carboxy-terminal regions. In addition, somatostatin- and cholinergic-, but not enkephalin-positive neurons express NMDAR2D mRNA. Thus, these striatal cell populations express different NMDAR-subunit mRNA phenotypes and therefore are likely to display NMDA channels with distinct pharmacological and physiological properties. Differences in NMDA receptor expression may contribute to the relative resistance of striatal interneurons to the neurotoxic effect of NMDA receptor agonists.

Animals↗
PubMed1993

Physiological, morphological, and histochemical characterization of three classes of interneurons in rat neostriatum.

Interneurons in lateral part of neostriatum were studied in isolated slices from juvenile rats (16-20 d postnatal) by whole-cell, current-clamp recording at 33-34 degrees C, followed by intracellular staining with biocytin and double immunocytochemical or histochemical staining for parvalbumin, ChAT, and NADPH diaphorase. Medium-sized spiny neurons (MS cells) had distal dendrites with many spines and were likely projection cells, while interneurons had dendrites with fewer spines. The neostriatal interneurons could be further divided into three classes by physiological, chemical, and morphological criteria. The first class of interneurons (fast-spiking cells, FS cells) fired very short-duration action potentials with short-duration afterhyperpolarizations at constant spike frequency during depolarizing current pulses. FS cells had more negative resting potentials and lower input resistances than the other two classes. At depolarized potentials, FS cells fired repetitive spikes in response to synaptic excitation. FS cells were immunoreactive for parvalbumin. As all parvalbumin-immunoreactive cells in the neostriatum were also immunoreactive for GABA, FS cells were considered to be GABAergic. FS cells were further divided into two morphological types: FS cells with local dendritic fields and FS cells with extended dendritic fields. The axons of both types of FS cells had their densest collateralization within or near their dendritic fields. The other two classes of interneuron, PLTS cells (persistent and low-threshold spike cells) and LA cells (long-lasting afterhyperpolarization cells), were distinguished from FS cells by longer-duration action potentials and larger input resistances, had less negative resting potentials, and had longer-lasting afterhyperpolarizations. Afterhyperpolarizations of PLTS cells had a shorter time to peak than those of LA cells. PLTS cells fired both Na(+)-dependent, persistent depolarization spikes and Ca(2+)-dependent, low-threshold spikes in addition to fast spikes. Low-threshold spikes in PLTS cells were induced only from hyperpolarized potentials. Both persistent depolarizations and low-threshold spikes could also be evoked by synaptic activation. PLTS cells were histochemically identified as NADPH diaphorase-positive cells. As all NADPH diaphorase-positive cells in the same tissue were immunoreactive for nitric oxide (NO) synthase, PLTS cells were considered to release NO. PLTS cells had the largest axonal fields. Some PLTS cells appeared to have two axonal origins from the somata and dendrites. LA cells were mostly large aspiny cells with Ca(2+)-dependent long-lasting afterhyperpolarizations and strong time-dependent hyperpolarizing rectification. As this slowly occurring anomalous rectification was blocked by 2 mM cesium, this potential was considered to be due to activation of Ih.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Oxidoreductases↗
PubMed1995

Cartesian representation of stimulus direction: parallel processing by two sets of giant interneurons in the cockroach.

The cockroach Periplaneta americana responds to wind puffs by turning away, both on the ground and when flying. While on the ground, the ventral giant interneurons (ventrals) encode the wind direction and specify turn direction, whereas while flying the dorsal giant interneurons (dorsals) appear to do so. We report here on responses of these cells to controlled wind stimuli of different directions. Using improved methods of wind stimulation and of positioning the animal revealed important principles of organization not previously observed. All six cells of largest axonal diameter on each side respond preferentially to ipsilateral winds. One of these cells, previously thought to respond non-directionally (giant interneuron 2), was found to have a restricted directional response (Fig. 3). The organization of directional coding among the ventral giant interneurons is nearly identical to that among the dorsals (Fig. 2). Each group contains, on each side, one cell that responds primarily to wind from the ipsilateral front, another primarily in the ipsilateral rear, and a third responding more broadly to ipsilateral front and rear. These results are discussed in terms of the mechanisms of directional localization by the assembly of giant interneurons.

Animals↗
PubMed1996

Developmental expression and functional characterization of the potassium-channel subunit Kv3.1b in parvalbumin-containing interneurons of the rat hippocampus.

The expression of the voltage-gated K(+)-channel subunit Kv3.1b in the developing hippocampus was determined by immunoblot and immunohistochemical techniques. Kv3.1b protein was detected first at postnatal day (P) 8. The Kv3.1b-immunopositive cell number per tissue section reached a maximum at P14 and was maintained through P40. In contrast, the Kv3.1b protein content of isolated membrane vesicles in immunoblots progressively increased through P40, suggesting an increase in Kv3.1b content per cell throughout this time period. Kv3.1b protein was expressed selectively in the somata, proximal dendrites, and axons of cells lying within or near the pyramidal cell layer, consistent with their being GABAergic inhibitory interneurons. Kv3.1b was present in approximately 80% of parvalbumin-positive interneurons. The developmental onset of Kv3.1b and parvalbumin immunoreactivity was identical. In contrast, Kv3.1b was mostly absent from the subset of somatostatin-positive inhibitory interneurons. Electrophysiological recordings were made from stratum pyramidale interneurons in which morphology and Kv3.1b-positive immunoreactivity were confirmed post hoc. Outward currents had voltage-dependent and biophysical properties resembling those of channels formed by Kv3.1b. The current blocked by low concentrations of 4-aminopyridine (4-AP) showed marked inactivation, suggesting that Kv3.1b may coassemble with other members of the Kv3 subfamily. In current-clamp recordings, concentrations of 4-AP that blocked the current through Kv3.1b channels allowed us tentatively to assign a role to Kv3.1b-containing channels in action-potential repolarization. These data demonstrate that Kv3.1b is regulated developmentally in a specific subpopulation of hippocampal interneurons and that channels containing this subunit may be a major determinant in imparting "fast-spiking" characteristics to these and other cells throughout the central nervous system containing the Kv3.1b subunit.

Action Potentials↗
PubMed1996

Muscarinic (m2/m4) receptors reduce N- and P-type Ca2+ currents in rat neostriatal cholinergic interneurons through a fast, membrane-delimited, G-protein pathway.

The signaling pathways mediating the muscarinic modulation of Ca2+ currents in neostriatal cholinergic interneurons were studied by combined patch-clamp recording and single-cell reverse transcription-PCR. Cholinergic interneurons were identified by the presence of choline acetyltransferase mRNA. These neurons expressed Q-, N-, L-, P-, and R-type Ca2+ currents and the mRNA for the alpha1 subunits believed to form the channels underlying these currents (classes A, B, C, D, and E). Of the interneurons tested, nearly all expressed M2-class (m2, m4) receptor mRNAs, whereas m1 receptor mRNA was found in only a subset (approximately 30%) of the sample. The muscarinic agonist oxotremorine methiodide produced a dose-dependent reduction of N- and P-type Ba2+ currents through Ca2+ channels that was antagonized by atropine. N-ethylmaleimide eliminated the modulation, as did preincubation with pertussis toxin. The onset and offset of the modulation were rapid and dose-dependent. The modulation was also attenuated by strong depolarizing prepulses and was not observed in cell-attached membrane patches. Taken together, our results suggest that activation of M2-class muscarinic receptors in cholinergic interneurons reduces N- and P-type Ca2+ currents through a membrane-delimited pathway using a Gi/o-class G-protein. This signaling pathway provides a cellular mechanism for hetero- and homosynaptic control of interneuronal activity and acetylcholine release in the striatum.

Animals↗