Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “interneurons”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources

Myelinated and unmyelinated primary afferent axons form contacts with cholinergic interneurons in the spinal dorsal horn.

Cholinergic interneurons in laminae III/IV of the dorsal horn contain co-localised gamma-aminobutyric acid (GABA) and frequently form axoaxonic synapses with terminals of primary afferents. They are therefore probably last-order interneurons involved in presynaptic inhibition. The purpose of the present investigation was to determine if these cells receive direct input from primary afferents. Relationships between primary afferents and interneurons were investigated in adult rats. Myelinated primary afferents were labelled with the B-subunit of cholera toxin (CTb). Unmyelinated afferents were labelled with IB4 lectin and an antibody to identify calcitonin-gene-related peptide (CGRP). Cholinergic neurons were labelled with an antibody raised against choline acetyltransferase and examined with a confocal microscope. Cells were reconstructed with NeuroLucida for Confocal and afferent contacts plotted. Interneurons (N=30) received an average of 20.2+/-11.9 (SD) contacts from CTb-labelled primary afferents, which were preferentially distributed on proximal and intermediate dendrites. Interneurons with dendrites which extended into lamina II (N=20) received an average of 27.4+/-19.0 IB4 contacts (on intermediate and distal dendrites) and 9.2+/-6.8 CGRP contacts. It is concluded that cholinergic interneurons receive contacts from both myelinated and unmyelinated primary afferents and different classes of afferent target particular dendritic domains. Cholinergic interneurons are likely to be components of an inhibitory feedback pathway that is monosynaptically activated by primary afferents.

Acetylcholine↗

Coding of a sexually dimorphic song feature by auditory interneurons of grasshoppers: the role of leading inhibition.

The shape of stimulus onset is a distinct feature of many acoustic communication signals. In some grasshopper species the steepness of amplitude rise of the pulses which comprise the song subunits is sexually dimorphic and a major criterion of sex recognition. Here, we describe potential mechanisms by which auditory interneurons could transmit the information on onset steepness from the metathoracic ganglion to the brain of the grasshopper. Since no single interneuron unequivocally encoded onset steepness, it appears that this information has to reside in the relative spike counts or the relative spike timing of a small group of ascending auditory interneurons. The decisive component of this mechanism seems to be the steepness-dependent leading inhibition displayed by two interneurons (AN3, AN4). The inhibition increased with increasing onset steepness, thus delayed the excitatory response, and in one interneuron even strongly reduced the spike count. Other ascending interneurons, whose responses were little affected by onset steepness, could serve as reference neurons (AN6, AN12). Thus, our results suggest that a comparison of both, spike count and first-spike timing within a small set of ascending interneurons could yield the information on signal onset steepness, that is on the sex of the sender.

Action Potentials↗

Early involvement of small inhibitory cortical interneurons in Alzheimer's disease.

Work on acute models of cortical injury has revealed a population of small GABAergic interneurons that are induced to increase their low constitutive expression of neuronal nitric oxide (NO) synthase (nNOS). In some cases, this activation may play a role in NO-mediated degeneration of pyramidal neurons. In this report, we explore the anatomy of various classes of cortical nNOS (+) (nitrergic) neurons, with emphasis on small interneurons, in the medial temporal lobe of subjects with Alzheimer's disease (AD) from two well-characterized cohorts, the Baltimore Longitudinal Study on Aging (BLSA) and the Religious Order Study (ROS). We find that small calbindin (+) cortical interneurons are induced to high levels of NADPHd/nNOS reactivity early in AD and abound in areas with emerging neurofibrillary pathology, that is, in entorhinal cortex in the beginning of the limbic stage of Braak, in hippocampal CA1 in the mature limbic stage and in temporal neocortex in the late limbic stage. This pattern was robust and significant in the younger of the two AD cohorts studied (BLSA), but persisted as a trend in the older cohort (ROS). In optimally prepared material, we find a significant correlation between numbers of these interneurons and markers of neuronal cell death, for example, caspase-3 activation. Our results show that small cortical inhibitory interneurons represent an extensive signaling system that is induced to higher levels of NADPHd/nNOS expression early in the paralimbic-limbic-neocortical sequence of AD progression. We propose that nNOS/NO signaling initiated in these interneurons can serve as a marker of early cortical injury in AD. The specific role played by inhibitory interneurons and NO in the elaboration of specific neuropathologies associated with AD, that is, Abeta and neurofibrillary deposits and cell death deserves further exploration in experimental animal models.

Aged↗

Pyramidal cells in piriform cortex receive a convergence of inputs from monoamine activated GABAergic interneurons.

Previously, serotonin (5-HT) was shown to increase inhibitory post-synaptic potentials (IPSPs) in layer II pyramidal cells, and excite a subpopulation of interneurons located on the layer II/III border of piriform cortex in rat in vitro brain slices. In the present study, the effects of norepinephrine (NE) and dopamine (DA) on these two populations of neurons were examined in brain slices using intracellular and extracellular recordings. All three monoamines increased GABAergic IPSPs in many pyramidal cells; overall, 5-HT was most effective in eliciting IPSPs (58% of cells), followed by NE (45%), then DA (24%). Commonly, pyramidal cells responded with an increase in IPSPs to more than one of the monoamines. The increase in IPSPs was found to include an increase in the frequency of IPSPs present at baseline, as well as recruitment of additional IPSPs of different amplitudes. In interneurons the effects of the monoamines paralleled that which was found for the pyramidal cells. Thus, all three monoamines increased the firing rate of many interneurons; again 5-HT was most effective (56%), followed by NE (51%), then DA (42%). In about 10% of the interneurons the monoamines inhibited cell firing. Interneurons frequently had responses to more than one of the monoamines. The excitatory amino acid (EAA) antagonist, kynurenic acid (200-400 microM), spared most 5-HT and NE responses on interneurons, suggesting that these effects were directly mediated. We conclude that IPSPs elicited by monoamines in pyramidal cells result from a convergence of inputs from populations of layer II/III interneurons that are activated by one, two or all three of the monoamines.

Animals↗

Loss of calbindin-immunoreactivity in CA1 hippocampal stratum radiatum and stratum lacunosum-moleculare interneurons in the aged rat.

Alterations in hippocampal circuitry may underly age-related learning and memory impairment. We showed in a previous study that the GABAB-mediated slow inhibitory postsynaptic potential (IPSP) induced in CA1 pyramidal neurons by electrical stimulation of stratum radiatum, is depressed in the hippocampus of the aged rat. This could be due to alterations in GABAergic interneuron functions. We report in this study that the number of hippocampal calbindin-immunoreactive (CaBP-IR) GABAergic interneurons is decreased in the aged rat. The mean number of CaBP-IR interneurons per slice decreases by 50% in the aged rat. The most severe loss was observed in the stratum radiatum of CA1 (78%), with a less consistent loss of immunoreactivity in CA3 (35%). In contrast, the mean number of interneurons containing parvalbumin (PV), was not significantly decreased in the aged rat. Our results show a loss of CaBP immunoreactivity in a population of GABAergic interneurons, which might be related to an altered function of these interneurons and consequently of GABAergic synaptic transmission in the aged rat. In contrast, PV immunoreactivity in interneurons located close to the pyramidal layer does not decrease in the hippocampus of the aged rat.

Aging↗

Inhibition of an identified snail postsynaptic neuron evoked by stimulation of a peptidergic interneuron initiating bursting pacemaker activity in another neuron.

Beating neuron V8, whose activity is abolished upon interneuronal stimulation, has been found and identified in the CNS of the snail, Helix pomatia. It was found earlier that stimulation of the same interneuron initiates bursting pacemaker activity in another neuron. Under voltage clamp conditions interneuronal stimulation evoked a slow outward current in the V8 neuron with a latency of about 2 s. Intracellular injection of tetraethylammonium or Cs+ ions into the interneuron greatly increased the slow outward current amplitude. External application of CdCl2 (1 mM), LaCl3 (5 mM) or replacement of Ca2+ by Mg2+ ions reversibly abolished transmission between the interneuron and the V8 neuron. The neuronal membrane conductance increased by about three times on the maximum of the slow outward current development. Computer fitting showed that a decay of the slow outward current can be approximated by the sum of two exponentially decaying components with time constants of about 1 s and 16 s. Extrapolated reversal potential for a fast (1 s) component of the current was about -70 mV. A slow (16 s) component asymptotically decreased upon hyperpolarization and it was observed at even more negative potential than Ek. Theophylline (1 mM) and 3-isobutyl-1-methylxanthine (0.1 mM) reversibly increased the slow outward current amplitude, whereas imidazole (5 mM) and tolbutamide (5 mM) caused its reversible decrease. It is concluded that inhibitory monosynaptic transmission exists between the interneuron and the beating V8 neuron. Interneuronal simulation evokes an increase in the membrane potassium conductance and probably a decrease in stationary potential-dependent sodium conductance of the postsynaptic V8 neuron. The cellular cyclase system seems to be involved in the postsynaptic response.

Action Potentials↗

Membrane properties of interneurons in stratum oriens-alveus of the CA1 region of rat hippocampus in vitro.

The membrane properties of interneurons situated near the border of stratum oriens and the alveus of the CA1 region were examined with intracellular recording and staining in rat hippocampal slices in vitro. Cellular staining with Lucifer Yellow indicated that the somata of these interneurons were multipolar and their dendrites projected horizontally along the alveus and vertically toward stratum lacunosum-moleculare. Intrinsic properties (input resistance, action potential amplitude, time constant) and spike after-potentials were typical of non-pyramidal cells. Action potential duration, however, was of relatively medium duration (1.15 ms) and slow afterhyperpolarizations followed depolarization-induced trains of action potentials. Spontaneous activity of interneurons was prominent and of either of two types: single action potentials or high frequency bursts of action potentials. Interneurons displayed marked, voltage- and time-dependent inward rectification and anodal break excitation. Analysis of the slope of the charging function of hyperpolarizing transients, suggested that these interneurons were electrically compact (dendrite to soma conductance ratio, p approximately 2.7; and electrotonic length constant, L approximately 1.1). Characteristically, interneurons sustained high frequency repetitive firing during long depolarizing pulses. The slope of the frequency-current relation was 442 Hz/nA for the first interspike interval and 117 Hz/nA for later intervals (no. 60), suggesting the presence of spike frequency adaptation. Physiologically, these interneurons resembled more closely basket cells of stratum pyramidale than stellate cells of stratum lacunosum-moleculare.

Action Potentials↗

Cell type-specific changes in spontaneous and minimally evoked excitatory synaptic activity in hippocampal CA1 interneurons of kainate-treated rats.

The epileptiform activity in the kainic acid (KA) model of epilepsy arises from complex changes in excitation and inhibition. To assess the involvement of excitatory drive onto inhibitory interneurons in this epileptiform activity, we examined changes in spontaneous and minimally evoked excitatory post-synaptic currents (sEPSCs and eEPSCs) in CA1 interneurons in stratum oriens/alveus (O/A) and stratum radiatum (RAD) in rat hippocampal slices after KA treatment. The frequency and amplitude of sEPSCs and the amplitude of eEPSCs were unchanged in O/A interneurons, but the EPSC kinetics were significantly slower. These changes appear to be due to altered kinetics and voltage-dependent properties of the NMDA component of EPSCs in O/A interneurons. In contrast, sEPSCs and eEPSCs in RAD interneurons did not change after KA treatment. The distinct changes in excitatory synaptic activity in interneurons differentially involved in feedback (O/A) versus feedforward (RAD) inhibition suggest a cell type-specific reorganization of excitatory synapses after KA treatment. These modifications in excitatory input to interneurons could contribute to the maintenance of inhibition of CA1 pyramidal cells after KA treatment, or may also create network conditions favourable to epileptiform activity.

Animals↗

Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1.

Most cortical interneurons arise from the subcortical telencephalon, but the molecules that control their migration remain largely unidentified. Here, we show that different isoforms of Neuregulin-1 are expressed in the developing cortex and in the route that migrating interneurons follow toward the cortex, whereas a population of the migrating interneurons express ErbB4, a receptor for Neuregulin-1. The different isoforms of Neuregulin-1 act as short- and long-range attractants for migrating interneurons, and perturbing ErbB4 function in vitro decreases the number of interneurons that tangentially migrate to the cortex. In vivo, loss of Neuregulin-1/ErbB4 signaling causes an alteration in the tangential migration of cortical interneurons and a reduction in the number of GABAergic interneurons in the postnatal cortex. These observations provide evidence that Neuregulin-1 and its ErbB4 receptor directly control neuronal migration in the nervous system.

Animals↗

The temporal and spatial origins of cortical interneurons predict their physiological subtype.

Interneurons of the cerebral cortex represent a heterogeneous population of cells with important roles in network function. At present, little is known about how these neurons are specified in the developing telencephalon. To explore whether this diversity is established in the early progenitor populations, we conducted in utero fate-mapping of the mouse medial and caudal ganglionic eminences (MGE and CGE, respectively), from which most cortical interneurons arise. Mature interneuron subtypes were assessed by electrophysiological and immunological analysis, as well as by morphological reconstruction. At E13.5, the MGE gives rise to fast-spiking (FS) interneurons, whereas the CGE generates predominantly regular-spiking interneurons (RSNP). Later at E15.5, the CGE produces RSNP classes distinct from those generated from the E13.5 CGE. Thus, we provide evidence that the spatial and temporal origin of interneuron precursors in the developing telencephalic eminences predicts the intrinsic physiological properties of mature interneurons.

Action Potentials↗

Changes in interneuronal phenotypes regulated by estradiol in the adult rat hippocampus: a potential role for neuropeptide Y.

Ovarian hormones regulate pyramidal cell synapse formation and excitability and interneuronal GABAergic tone in the CA1 region of the adult female rat hippocampus. The role of 17beta-estradiol in these effects is complex and appears to involve a subset of hippocampal interneurons, which express different calcium-binding protein and neuropeptide phenotypes and nuclear estrogen receptor alpha. We found that, in the hippocampus, nuclear estrogen receptor alpha-immunoreactive interneurons co-express neuropeptide Y, calbindin-D28k and calretinin but do not parvalbumin or cholecystokinin. Moreover, a proportion of neuropeptide Y-immunoreactive interneurons co-expresses calbindin-D28k and calretinin. This pattern is similar in the presence or absence of 17beta-estradiol treatment in ovariectomized rats. We then used immunohistochemistry and in situ hybridization to determine whether 17beta-estradiol treatment regulates expression of CA1 interneuronal phenotypic markers via nuclear estrogen receptor alpha activation. We found that 17beta-estradiol treatment of ovariectomized rats increased neuropeptide Y mRNA levels (25%) and the neuropeptide Y mRNA-associated grain density per cell (11%), as well as the number of neuropeptide Y-immunoreactive cells (11%), predominantly in the pyramidal cell layer (stratum pyramidale). Treatment with CI628, a selective estrogen response modulator that acts as an antagonist for nuclear estrogen receptor, blocked 17beta-estradiol-induced increase of neuropeptide Y mRNA levels. 17beta-Estradiol treatment did not alter the number of parvalbumin, calretinin, and cholecystokinin immunoreactive cells, nor mRNA levels for parvalbumin and cholecystokinin. Therefore, the present study has identified neuropeptide Y expression as the main interneuronal phenotype that co-expresses nuclear estrogen receptor alpha and shown that neuropeptide Y is responsive to 17beta-estradiol in CA1 pyramidal cell layer. We suggest that 17beta-estradiol may regulate neuropeptide Y expression mediated by nuclear estrogen receptor alpha-dependent activation in a subset of hippocampal interneurons, and we speculate that subsequent neuropeptide Y release may indirectly contribute to regulate glutamate-dependent neuronal activity in the adult rat hippocampus.

Animals↗

Complex effects of CNQX on CA1 interneurons of the developing rat hippocampus.

We have investigated the effect of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), on spontaneous GABA(A) receptor-mediated transmission in the hippocampal CA1 subfield. On average, simultaneous recordings from CA1 str. radiatum interneurons and pyramidal cells showed that CNQX application doubled the frequency of bicuculline sensitive spontaneous inhibitory postsynaptic currents (sIPSCs) without apparently changing their amplitude. However, despite the increase in sIPSC frequency, current-clamp recording showed that CNQX application was sufficient in most cases to depolarize interneurons to firing threshold. In contrast, CNQX application could not induce firing in pyramidal cells. In the presence of tetrado-toxin (TTX), CNQX increased interneuron membrane conductance, and depolarized interneurons from resting potentials. The axons of the studied interneurons ramify widely in the CA1 region and suggest that the cells of our sample are mostly involved with control of dendritic excitability. Our results indicate that CNQX-induced increase of sIPSC frequency is not limited to excitatory cells, but also impacts GABAergic interneurons. However, despite the increase of sIPSC frequency, CNQX-induced depolarization is sufficient to selectively generate firing in interneurons and thus modify the network properties mediated by GABA(A) receptors in the hippocampus.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Response properties of spinal interneurons in awake, behaving primates.

This paper reviews studies on spinal interneurons in awake, behaving monkeys inspired by the work of Prof Patrick D. Wall. Early studies documented the sensory responses of spinal interneurons in unanesthetized monkeys to natural cutaneous and proprioceptive stimulation. More recently, cervical interneurons were documented in monkeys performing an active step-tracking task. During alternating wrist movements, most task-related interneurons showed bidirectional activity, firing during both flexion and extension (in surprising contrast to the unidirectional activity of muscles and corticomotoneuronal cells). Premotor interneurons were identified by post-spike effects in spike-triggered averages of forelimb muscle activity. The cells' post-spike effects were generally congruent with their activity in their preferred direction, although many fired during components of movement when their output effects would seem inappropriate. In an instructed delay period task many interneurons showed preparatory delay period activity, much like cortical neurons. Other studies tested the excitability of corticospinal axons to electrical stimulation and demonstrated both post-spike and task-related modulations in excitability. Together, these studies suggest that many behavioral functions of spinal interneurons remain to be revealed by recording their activity in awake, behaving animals.

Animals↗

Medullary reticulospinal tract mediating the generalized motor inhibition in cats: parallel inhibitory mechanisms acting on motoneurons and on interneuronal transmission in reflex pathways.

The present study was designed to elucidate the spinal interneuronal mechanisms of motor inhibition evoked by stimulating the medullary reticular formation. Two questions were addressed. First, whether there is a parallel motor inhibition to motoneurons and to interneurons in reflex pathways. Second, whether the inhibition is mediated by interneurons interposed in known reflex pathways. We recorded the intracellular activity of hindlimb motoneurons in decerebrate cats and examined the effects of medullary stimulation on these neurons and on interneuronal transmission in reflex pathways to them. Stimuli (three pulses at 10-60microA and 1-10ms intervals) delivered to the nucleus reticularis gigantocellularis evoked inhibitory postsynaptic potentials in alpha-motoneurons (n=147) and gamma-motoneurons (n=5) with both early and late latencies. The early inhibitory postsynaptic potentials were observed in 66.4% of the motoneurons and had a latency of 4.0-5.5ms with a segmental delay of more than 1.4ms. The late inhibitory postsynaptic potentials were observed in 98.0% of the motoneurons and had a latency of 30-35ms, with a peak latency of 50-60ms. Both types of inhibitory postsynaptic potentials were evoked through fibers descending in the ventrolateral quadrant. The inhibitory postsynaptic potentials were not influenced by recurrent inhibitory pathways, but both types were greatly attenuated by volleys in flexor reflex afferents. Conditioning medullary stimulation, which was subthreshold to evoke inhibitory postsynaptic potentials in the motoneurons, neither evoked primary afferent depolarization of dorsal roots nor reduced the input resistance of the motoneurons. However, the conditioning stimulation often facilitated non-reciprocal group I inhibitory pathways (Ib inhibitory pathways) to the motoneurons in early (<20ms) and late (30-80ms) periods. In contrast, it attenuated test postsynaptic potentials evoked through reciprocal Ia inhibitory pathways, and excitatory and inhibitory pathways from flexor reflex afferent and recurrent inhibitory pathways. The inhibitory effects were observed in both early and late periods. The present results provide new information about a parallel inhibitory process from the medullary reticular formation that produces a generalized motor inhibition by acting on alpha- and gamma-motoneurons, and on interneurons in reflex pathways. Interneurons receiving inhibition from flexor reflex afferents and a group of Ib interneurons may mediate the inhibitory effects upon motoneurons.

Animals↗

Properties of interneurones in the intermediolateral cell column of the rat spinal cord: role of the potassium channel subunit Kv3.1.

Sympathetic preganglionic neurones located in the intermediolateral cell column (IML) are subject to inputs descending from higher brain regions, as well as strong influences from local interneurones. Since interneurones in the IML have been rarely studied directly we examined their electrophysiological and anatomical properties. Whole cell patch clamp recordings were made from neurones in the IML of 250 microM slices of the thoracic spinal cord of the rat at room temperature. Action potential durations of interneurones (4.2+/-0.1 ms) were strikingly shorter than those of sympathetic preganglionic neurones (9.4+/-0.2 ms) due to a more rapid repolarisation phase. Low concentrations of tetraethylammonium chloride (TEA) (0.5 mM) or 4-aminopyridine (4-AP) (30 microM) affected interneurones but not sympathetic preganglionic neurones by prolonging the action potential repolarisation as well as decreasing both the afterhypolarisation amplitude and firing frequency. Following recordings, neurones sensitive to TEA and 4-AP were confirmed histologically as interneurones with axons that ramified extensively in the spinal cord, including the IML and other autonomic regions. In contrast, all cells that were insensitive to TEA and 4-AP were confirmed as sympathetic preganglionic neurones. Both electrophysiological and morphological data are therefore consistent with the presence of the voltage-gated potassium channel subunit Kv3.1 in interneurones, but not sympathetic preganglionic neurones. Testing this proposal immunohistochemically revealed that Kv3.1b was localised in low numbers of neurones within the IML but in higher numbers of neurones on the periphery of the IML. Kv3.1b-expressing neurones were not sympathetic preganglionic neurones since they were not retrogradely labelled following intraperitoneal injections of Fluorogold. Since Kv3.2 plays a similar role to Kv3.1 we also tested for the presence of Kv3.2 using immunohistochemistry, but failed to detect it in neuronal somata in the spinal cord. These studies provide electrophysiological and morphological data on interneurones in the IML and indicate that the channels containing the Kv3.1 subunit are important in setting the firing pattern of these neurones.

4-Aminopyridine↗

Cholecystokinin-immunopositive basket and Schaffer collateral-associated interneurones target different domains of pyramidal cells in the CA1 area of the rat hippocampus.

Two types of GABAergic interneurone are known to express cholecystokinin-related peptides in the isocortex: basket cells, which preferentially innervate the somata and proximal dendrites of pyramidal cells; and double bouquet cells, which innervate distal dendrites and dendritic spines. In the hippocampus, cholecystokinin immunoreactivity has only been reported in basket cells. However, at least eight distinct GABAergic interneurone types terminate in the dendritic domain of CA1 pyramidal cells, some of them with as yet undetermined neurochemical characteristics. In order to establish whether more than one population of cholecystokinin-expressing interneurone exist in the hippocampus, we have performed whole-cell current clamp recordings from interneurones located in the stratum radiatum of the hippocampal CA1 region of developing rats. Recorded neurones were filled with biocytin to reveal their axonal targets, and were tested for the presence of pro-cholecystokinin immunoreactivity. The results show that two populations of cholecystokinin-immunoreactive interneurones exist in the CA1 area (n=15 positive cells). Cholecystokinin-positive basket cells (53%) preferentially innervate stratum pyramidale and adjacent strata oriens and radiatum. A second population of cholecystokinin-positive cells, previously described as Schaffer collateral-associated interneurones [Vida et al. (1998) J. Physiol. 506, 755-773], have axons that ramify almost exclusively in strata radiatum and oriens, overlapping with the Schaffer collateral/commissural pathway originating from CA3 pyramidal cells. Two of seven of the Schaffer collateral-associated cells were also immunopositive for calbindin. Soma position and orientation in stratum radiatum, the number and orientation of dendrites, and the passive and active membrane properties of the two cell populations are only slightly different. In addition, in stratum radiatum and its border with lacunosum of perfusion-fixed hippocampi, 31.6+/-3.8% (adult) or 26.8+/-2.9% (postnatal day 17-20) of cholecystokinin-positive cells were also immunoreactive for calbindin. Therefore, at least two populations of pro-cholecystokinin-immunopositive interneurones, basket and Schaffer collateral-associated cells, exist in the CA1 area of the hippocampus, and are probably homologous to cholecystokinin-immunopositive basket and double bouquet cells in the isocortex. It is not known if the GABAergic terminals of double bouquet cells are co-aligned with specific glutamatergic inputs. However, in the hippocampal CA1 area, it is clear that the terminals of Schaffer collateral-associated cells are co-stratified with the glutamatergic input from the CA3 area, with as yet unknown functional consequences. The division of the postsynaptic neuronal surface by two classes of GABAergic cell expressing cholecystokinin in both the hippocampus and isocortex provides further evidence for the uniform synaptic organisation of the cerebral cortex.

Action Potentials↗

Medial septal and median raphe innervation of vasoactive intestinal polypeptide-containing interneurons in the hippocampus.

Vasoactive intestinal polypeptide-immunoreactive interneurons are known to form three anatomically and neurochemically well-characterized neuron populations in the hippocampus. Two of these establish synaptic contacts selectively with other GABAergic cells (interneuron-selective cells), whereas the third type innervates pyramidal cell bodies and proximal dendrites like a conventional basket cell. Our aim was to examine which of the vasoactive intestinal polypeptide-containing interneuron populations are among the targets of GABAergic septohippocampal and serotonergic raphe-hippocampal pathways. Anterograde tracing with Phaseolus vulgaris leucoagglutinin combined with double immunocytochemistry for vasoactive intestinal polypeptide was used at the light and electron microscopic levels. Our results show that both interneuron-selective cells and vasoactive intestinal polypeptide-containing basket cells receive synaptic input from the medial septum and median raphe nucleus. The GABAergic component of the septohippocampal pathway establishes multiple contacts on both cell types. In the case of the raphe-hippocampal projection, single or double contacts were more frequent on vasoactive intestinal polypeptide-positive interneuron selective cells (76%), whereas multiple contacts predominated on basket cells (83%). The extrinsic GABAergic innervation of interneuron-selective cells in the hippocampus indicates a complex interaction among GABAergic systems, which might ensure the timing and rhythmic synchronization of inhibitory processes in the hippocampus. On the other hand, our results suggest that the serotonergic effect on perisomatic inhibition is exerted via vasoactive intestinal polypeptide-containing basket cells that are functionally distinct from their parvalbumin-positive relatives, which appear to escape control of serotonergic as well as local interneuron-selective cells.

Afferent Pathways↗

Properties of a hyperpolarization-activated cation current in interneurons in the rat lateral geniculate nucleus.

A hyperpolarization-activated cation conductance contributes to the membrane properties of a variety of cell types. In the thalamus, a prominent hyperpolarization-activated cation conductance exists in thalamocortical cells, and this current is implicated in the neuromodulation of complex firing behaviors. In contrast, the GABAergic cells in the reticular nucleus in the thalamus appear to lack this conductance. The presence and role of this cation conductance in the other type of thalamic GABAergic cells, local interneurons, is still unclear. To resolve this issue, we studied 54 physiologically and morphologically identified local interneurons in the rat dorsal lateral geniculate nucleus using an in vitro whole-cell patch recording technique. We found that hyperpolarizing current injections induced depolarizing voltage sags in these geniculate interneurons. The I-V relationship revealed an inward rectification. Voltage-clamp study indicated that a slow, hyperpolarization-activated cation conductance was responsible for the inward rectification. We then confirmed that this slow conductance had properties of the hyperpolarization-activated cation conductance described in other cell types. The slow conductance was insensitive to 10 mM tetraethylammonium and 0.5 mM 4-aminopyridine, but was largely blocked by 1-1.5 mM Cs+. It was permeable to both K+ and Na+ ions and had a reversal potential of -44 mV. The voltage dependence of the hyperpolarization-activated cation conductance in interneurons was also studied: the activation threshold was about -55 mV, half-activation potential was about -80 mV and maximal conductance was about 1 nS. The activation and deactivation time constants of the conductance ranged from 100 to 1000 ms, depending on membrane potential. The depolarizing voltage sags and I-V relationship were further simulated in a model interneuron, using the parameters of the hyperpolarization-activated cation conductance obtained from the voltage-clamp study. The time-course and voltage dependence of the depolarizing voltage sags and I-V relationship in the model cell were very similar to those found in geniculate interneurons in current clamp. Taken together, the results of the present study suggest that thalamic local interneurons possess a prominent hyperpolarization-activated cation conductance, which may play important roles in determining basic membrane properties and in modulating firing patterns.

Animals↗