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At least 631 records · Page 35Linked to original sources
PubMed1994

The development of parvalbumin and calbindin-D28k immunoreactive interneurons in kitten visual cortical areas.

Calbindin-D and parvalbumin are calcium binding proteins which are found in non-overlapping subpopulations of GABA-ergic interneurons in mammalian neocortex. We studied the development of these calcium-binding proteins in interneurons of cat striate and extrastriate cortical areas which have differing patterns of connectivity and follow different developmental timetables. We examined primary visual areas 17 and 18, secondary visual area 19, medial lateral suprasylvian and lateral suprasylvian areas (MLS and LLS) and association areas 7 and the splenial visual area from the day of birth (P0) through P101. Parvalbumin-immunoreactive (ir) interneurons followed the inside-out pattern of maturation of cortical laminae. They were located only in infragranular layers at the earliest ages and were not observed in the overlying cortical plate. At 3 weeks of age, when cortical lamination is mature, parvalbumin stained cells were found in all cortical layers except layer I. The number of stained secondary and tertiary dendrites in the parvalbumin-ir interneuronal population decreased with age. This change was associated with a shift in the molecular weight of parvalbumin detected on Western blots. During the first postnatal week, the area 17/18 border contained more parvalbumin-ir neurons than other visual areas. The developmental pattern of calbindin staining differed considerably from the parvalbumin staining pattern. Very few calbindin-ir interneurons were seen in area 17 during the first 2 weeks of life. In lateral cortical areas, calbindin-ir neurons were located in cortical plate, infragranular layers of cortex and white matter/subplate. Calbindin-ir neurons increased in supragranular layers of secondary cortical areas by P7 and in area 17 by P20. In the mature cortex, the calbindin staining pattern was bilaminar, with a dense band of calbindin-ir cells in layer II and a second band in layers V-VI. There was no difference in the distribution of calbindin-ir neurons among visual areas at maturity.

Animals↗
PubMed1994

Delayed damage of striatal interneurons after cerebral ischemia in the gerbil.

Immunohistochemical changes of striatal interneurons in the gerbil were investigated 1 h-7 days after 10 min cerebral ischemia. Marked reduction of parvalbumin-immunoreactive interneurons was seen in the striatum from 24 h after ischemia. MAP2 (microtubule-associated protein 2) immunoreactivity markedly decreased in striatal neurons 5 h after ischemia but was unaffected in interneurons. Thereafter, a severe loss of MAP2 immunoreactivity in the interneurons was found 48 h and 7 days after ischemia. The results demonstrate that transient cerebral ischemia can cause a loss of parvalbumin and MAP2 immunoreactivity in interneurons in the dorsolateral striatum in a delayed fashion as compared with a rapid loss of striatal neurons.

Animals↗
PubMed1995

The activity of hippocampal interneurons and pyramidal cells during the response of the hippocampus to repeated auditory stimuli.

Interneurons and pyramidal cells were identified electrophysiologically in the hippocampus of anesthetized rats. Paired tones were presented 500 ms apart, and the resulting neuronal response was compared to differences in the amplitude of an auditory evoked potential (N40) elicited by each of the tones. Generally, the N40 elicited in response to the second tone is less than the response to the first. Pyramidal cells exhibited their most pronounced activation within 40 ms after the first tone. The post-stimulus discharge activation of interneurons was less than the pyramidal cells, but activation of different interneurons occurred at various times throughout the interval between the two tones. The presence or absence of suppression of N40 amplitude in the paired stimulus paradigm correlated with differences in the auditory response of both the interneurons and pyramidal cells. The activity of interneurons in relationship to gating of hippocampal auditory response is discussed.

Acoustic Stimulation↗
PubMed1996

Correlated morphological and neurochemical features identify different subsets of vasoactive intestinal polypeptide-immunoreactive interneurons in rat hippocampus.

Vasoactive intestinal polypeptide-immunoreactive interneurons have been classified according to their axonal and dendritic patterns and neurochemical features in the hippocampus of the rat. A correlation of these characteristics unravelled three distinct types of vasoactive intestinal polypeptide-containing cells. Interneurons forming a dense axonal plexus at the border of stratum oriens and alveus always contain the calcium binding protein, calretinin, but lack the neuropeptide cholecystokinin. The axon of another type of vasoactive intestinal polypeptide-positive interneuron surrounds pyramidal cell bodies in a basket-like manner, and co-localizes cholecystokinin but not calretinin. Vasoactive intestinal polypeptide-containing cells projecting to stratum radiatum form two subsets distinguished by dendritic morphology. Those with dendrites restricted to stratum lacunosum-molecular lack both calretinin and cholecystokinin, whereas the other subtype with dendrites spanning all layers contains calretinin in 40% of the cases and occasionally also cholecystokin. GABA was shown to be present, and the calcium binding proteins calbindin D-28k and parvalbumin absent from all three types of vasoactive intestinal polypeptide-positive interneurons. The specific dendritic and axonal arbours imply different input and output properties for the three interneuron types. The correlation of these features with the content of neurochemical markers strongly suggests that they are specialized for distinct inhibitory functions in the hippocampal network.

Animals↗
PubMed1996

Plateau properties in mammalian spinal interneurons during transmitter-induced locomotor activity.

We examined the organization of spinal networks controlling locomotion in the isolated spinal cord of the neonatal rat, and in this study we provide the first demonstration of plateau and bursting mechanisms in mammalian interneurons that show locomotor-related activity. Using tight-seal whole-cell recordings, we characterized the activity of interneurons from spinal regions previously suggested to be involved in locomotor rhythm generation. Most (63%) interneurons showed rhythmic, oscillating membrane potentials in phase with rhythmic ventral root activity induced by the glutamate receptor agonist, N-methyl-D-aspartate and 5-hydroxytryptamine or activation of muscarinic acetylcholine receptors. We focused our attention on these cells because they appeared most likely to be participating in locomotor networks. The rhythmic oscillations of most of these interneurons (88%) appeared to be driven mainly by excitatory and inhibitory synaptic inputs. A smaller number of interneurons, however, also displayed intrinsic plateau properties or bursting capabilities which amplified their response to excitatory input, and which were correlated with the presence of negative slope regions in the steady-state I-V curve, and with the ability to burst in the absence of synaptic drive. Although the bursting properties of these neurons may contribute to the generation of the locomotor rhythm, as suggested previously in studies of lower vertebrates, we suggest that a prime role of intrinsic plateau properties in mammalian locomotor networks is to facilitate or shape and time the propagation of information in the network.

Action Potentials↗
PubMed1992

Dopamine inhibits transmission between the interneuron initiating pacemaker activity in a bursting neuron and the bursting neuron on the snail Helix pomatia.

1. The effect of external application of dopamine on connection between a peptidergic interneuron initiating bursting pacemaker activity in non-active burster RPa1 and the bursting neuron itself of the snail Helix pomatia has been investigated under clamp conditions. 2. External application of dopamine in a dose-dependent manner (Kd 15 microM) produces a reversible inhibition of slow inward current (SIC) in the RPa1 neuron evoked by stimulation of peptidergic interneuron. At the same time, an increase of duration and amplitude of interneuronal action potential was observed. 3. Stimulation of the anal nerve evokes in RPa1 neuron postsynaptic current consisting of at least three components: two fast ones with reversal potentials -50 and -70 mV and a long-lasting one with no reversal potential between -50 and -95 mV. 4. It is concluded that inhibition of SIC by dopamine is due to the processes occurring in the postsynaptic RPa1 neuron. 5. Based on the hypothesis that bursting activity of RPa1 neuron results from the activation of presynaptic unidentified peptidergic interneuron(s) with persistent activity and on data presented it is suggested that inhibition of bursting activity evoked by application of dopamine or anal nerve stimulation is a consequence of decreased efficiency of synaptic transmission between the interneuron initiating bursting activity and the burster.

Action Potentials↗
PubMed1995

The neuronal network for locomotion in the lamprey spinal cord: evidence for the involvement of commissural interneurons.

The spinal cord of the lamprey, a primitive vertebrate, has been used as a model system for investigating the cellular basis of rhythmic locomotor activity. Three classes of interneurons have been characterized that are active during locomotor activity in the isolated spinal cord (ie fictive swimming). The identified synaptic interactions of these neurons form a network which has been proposed to underlie locomotor rhythmogenesis. Modeling studies confirmed that the network can produce oscillatory activity with phase relations among the neurons similar to those found in the spinal cord. Within the network, inhibitory commissural interneurons form reciprocal inhibitory connections and play a key role in rhythmogenesis. Several experiments have been done to test whether these cells participate in the generation of rhythmic activity in the spinal cord. First, midline lesions that sever the axons of commissural interneurons eliminate rhythmic ventral root bursting. Second, photo-ablation of commissural interneurons on one side of the spinal cord alters the symmetry of ventral root bursts, alters the cycle period, and can eliminate rhythmic bursting. Taken together, these experiments support the model that commissural interneurons are involved in rhythmogenesis in the lamprey spinal cord.

Animals↗
PubMed2004

The corticostriatal input to giant aspiny interneurons in the rat: a candidate pathway for synchronising the response to reward-related cues.

Tonically active neurons (TANs) in the mammalian striatum show a pause in their ongoing firing activity in response to an auditory cue that is paired with a reward. This response to reward-related cues develops through learning and becomes expressed synchronously by TANs located throughout the striatum. The pause response is abolished by inactivating the thalamic inputs to the striatum but a short-latency excitatory response to reward-related cues remains, which may originate in the cortex. We investigated the cortical inputs to striatal neurons to determine the electrophysiological properties of their cortical projections. We made in vivo intracellular recordings from 14 giant aspiny interneurons (which correspond to the TANs) and from a control group of spiny projection neurons (n=18) in urethane-anaesthetised rats. All giant aspiny interneurons were tonically active (firing rate: 3.0+/-1.5 Hz) and displayed small-amplitude subthreshold fluctuations in membrane potential. These fluctuations in membrane potential were correlated with the cortical electroencephalogram (EEG). Test stimulation of the contralateral cortex induced postsynaptic potentials (PSPs) in giant aspiny interneurons. These PSPs were significantly shorter in latency (5.1+/-1.6 ms) than those measured in spiny projection neurons (9.3+/-2.8 ms; p<0.01), whereas the latencies of ipsilaterally evoked PSPs did not differ. Taken together, these observations suggest that giant aspiny interneurons are under the significant influence of spontaneous excitatory inputs and receive specialised input from either faster conducting or less branching cortical fibres than spiny projection neurons. These inputs may be involved in the synchronised convergence of reward-related cues from spatially distinct cortical areas onto giant aspiny interneurons.

Action Potentials↗
PubMed2006

Abnormal laminar position and dendrite development of interneurons in the reeler forebrain.

The majority of cortical and hippocampal interneurons originate in the subcortical telencephalon and migrate tangentially into pallial regions before settling in various cortical layers. The molecular cues that regulate final positioning of specific interneurons in cortical structures have not yet been identified. The positioning of radially migrating principal neurons of the cortex and hippocampus depends upon Reelin, an extracellular protein expressed near the pial surface during embryonic development that is absent in reeler mutant mice. To determine whether the layer specification of interneurons, like that of principal neurons, requires Reelin, we crossed reeler with transgenic mice that contain Green Fluorescent Protein (GFP)-expressing Inhibitory Neurons (GINs). These neurons express basal forebrain markers Dlx1/2 in normal and reeler mice. In normal mice, GINs express Reelin and are localized to specific layers of the cortex and hippocampus. In reeler mutant mice, we show that GINs migrate normally into the pallium, but fail to acquire proper layer position. Double labeling experiments indicate that the neurochemical profile of these interneurons is not generally altered in reeler mice. However, the extension of their cellular processes is abnormal. Quantitative analysis of GINs in the cortex revealed that they are hypertrophic, bearing longer neuritic branches than normal. Thus, the lack of Reelin signaling results in abnormal positioning and altered morphology of forebrain interneurons.

Animals↗
PubMed2006

Acetylcholine receptor binding and cholinergic interneuron density are unaltered in a genetic animal model of primary paroxysmal dystonia.

The underlying pathophysiological mechanisms of hereditary types of paroxysmal dyskinesias are still unknown, but basal ganglia dysfunctions seem to play a critical role. In fact, numerous pharmacological, neurochemical, immunohistochemical and electrophysiological investigations in the dt(sz) hamsters, a unique rodent model of age-dependent primary paroxysmal dystonia, revealed alterations within the basal ganglia, particularly of the GABAergic and dopaminergic neurotransmitter systems. A deficit in several types of striatal GABAergic interneurons in dt(sz) mutant hamsters seems to play a crucial pathophysiological role, but deficits in other types of striatal interneurons cannot be excluded by previous studies. In view of ameliorating effects of anti-cholinergic drugs in dystonic patients, we therefore investigated the density of striatal cholinergic interneurons in the present study. These interneurons were marked specifically by the enzyme choline acetyltransferase and counted by using a stereological counting method in a blinded fashion. Additionally, acetylcholine receptor binding was determined in mutant and nondystonic control hamsters by autoradiographic analyses with the nonselective muscarinic ligand [(3)H]-quinuclidinyl benzilate (QNB) in 11 brain (sub)regions. There were no significant differences in the density of striatal cholinergic interneurons between dt(sz) mutant hamsters (789 +/- 39 interneurons/mm(3)) and nondystonic controls (807 +/- 36 interneurons/mm(3)). [(3)H]QNB binding was also comparable between mutant and control hamsters. These results point to an unaltered striatal cholinergic neurotransmitter system in dt(sz) hamsters under basal conditions.

Acetylcholine↗
PubMed2004

Turning the heterogeneous into homogeneous: studies on selectively isolated GABAergic interneuron subsets.

The amazing morphological and electrophysiological diversity of cortical GABAergic interneurons subserves the broad diversity of processes these cells modulate in neuronal networks. Until recently, interneuron development and functions have been extensively studied in heterogeneous in vitro and in vivo systems containing both excitatory and inhibitory components. However, mechanisms of interneuron specification during development, key signaling mechanisms controlling the establishment of particular inhibitory neuron subsets, and the spatial and temporal regulation of their integration in neuronal microcircuits remain poorly understood. Selective isolation of particular interneuron subsets may significantly extend our knowledge on the scenario of neurochemical and electrophysiological specification of developing interneurons, identification of signaling cues directing their axon growth, and principles of their anterograde and retrograde synaptic communication with other cell types. Here, we show that selective isolation of perisomatic inhibitory cells containing either parvalbumin or cholecystokinin reveals major differences in the temporal dynamics of their functional differentiation, and their dependence on target-derived signals like brain-derived neurotrophic factor and endocannabinoids. In addition, we discuss therapeutic prospects of modulating increased excitatory output in the hippocampus and subthalamic nucleus by re-adjusting the inhibitory control of principal cells.

Animals↗
PubMed2006

Choline acetyltransferase immunoreactive cortical interneurons do not occur in all rodents: a study of the phylogenetic occurrence of this neural characteristic.

The present study was designed to provide results aimed at testing whether the interneurons with choline acetyltransferase immunoreactivity (ChAT), probably representing GABA interneurons, found in the cerebral cortex of the rat represent a common feature of the order Rodentia. Initially we verified the presence of ChAT immunoreactive bipolar cell bodies, axons and terminal-like fibres in pigmented (Long-Evans) and non-pigmented (Sprague-Dawley) strains of Rattus norvegicus, confirming that the ChAT polyclonal antibodies (AB144P and AB143, Chemicon; VChAT, Sigma) with the immunohistochemical techniques used provided the same staining as previously described for this species. We then examined pigmented (AKR3) and non-pigmented (C3H) strains of Mus musculus, wild caught striped mice (Rhabdomys pumilio), bushveld gerbil (Tatera brantsii), greater canerat (Thryonomys swinderianus) and common molerat (Cryptomys hottentotus). The AB144P antibody revealed cortical interneurons in both strains of M. musculus and in R. pumilio, but not in the other species. In all species/strains cortical ChAT immunoreactive axons and terminal-like fibres were localized with the AB144P antibody. In the non-Rattus species/strains there was no evidence for localization of ChAT immunoreactivity in any cortical cell bodies using the AB143 and vesicular acetylcholine transporter (VChAT) antibodies despite extensive localization in axons and terminal-like fibres. It is concluded that bipolar cortical GABA interneurons in certain rodent species may develop ChAT immunoreactivity but not VChAT immunoreactivity making the cholinergic relevance of ChAT in the GABA interneurons uncertain and may exclude these neurons from being part of the traditionally defined cholinergic system.

Acetylcholine↗
PubMed2006

Netrin1 exerts a chemorepulsive effect on migrating cerebellar interneurons in a Dcc-independent way.

Few studies have addressed the issue of how GABAergic interneurons in the cerebellar cortex migrate or what guidance cues steer them. Recent data show that their development starts at the cerebellar germinal epithelium on top of the fourth ventricle. These interneurons continue to proliferate in the postnatal cerebellar white matter and later migrate to their final position in the cerebellar cortex. Here we report the chemorepulsive action of Netrin1 on postnatal cerebellar interneurons in vitro and also show the expression pattern of Netrin1 and its receptors Dcc and Unc5. Our expression results further suggest that Netrin1 is involved in the migration of GABAergic interneurons in vivo. Moreover, our data point to Bergmann glial fibers as possible tracks for these cells en route to the molecular layer. Finally, experiments using blocking antibodies allow us to conclude that Dcc, although expressed by postnatal cerebellar interneurons, is not involved in the repulsive response triggered by Netrin1 in these cells.

Age Factors↗
PubMed2003

Cytochrome oxidase activity in the monkey globus pallidus and subthalamic nucleus after ablation of striatal interneurons expressing substance P receptors.

To understand functional roles of striatal interneurons in primate basal ganglia circuitry, we ablated interneurons expressing substance P (SP) receptors (SPR) in the putamen with SP-saporin, a SPR selective neurotoxin. The effect of SP-saporin injection into the putamen was evaluated by examining the loss of cholinergic interneurons and NADPHd-positive (nicotinamide adenine dinucleotide phosphate diaphorase positive) interneurons. We then analyzed regional metabolic changes using cytochrome oxidase (CO) histochemistry. CO activity in some regions of the internal and external segments of the globus pallidus (GP) in the lesioned hemisphere was lower than that in the contralateral or surrounding GP regions. CO activity in the subthalamic nucleus, however, showed no significant change. The present findings suggest that striatopallidal projection neurons exert enhanced inhibitory influence on the GP without modulatory control by the striatal SPR-expressing interneurons.

Animals↗
PubMed2005

Developmental mechanisms underlying the generation of cortical interneuron diversity.

GABAergic interneurons are critical components of cortical circuits. However, understanding their function has become extremely challenging because they constitute one of the most diverse groups of cells in the central nervous system. Indeed, cortical GABAergic interneurons are heterogeneous in so many different ways--morphology, molecular profiling, electrical properties--that even attempts to discern what parameters should be used to identify cortical interneuron subtypes have failed to generate broad consensus among experts in the field. The extent to which cortical interneuron diversity emerges during development is largely unknown, but it is likely that insights on how this process takes place may help us understand their role as integrative and synchronizing elements in cortical function. Here, we review recent data on how the large variety of distinct classes of cortical interneurons may arise during development.

Animals↗
PubMed2005

A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function.

The amygdala is under inhibitory control from the cortex through the activation of local GABAergic interneurons. This inhibition is greatly diminished during heightened emotional states due to dopamine release. However, dopamine excites most amygdala interneurons, suggesting that this dopaminergic gate may be mediated by an unknown subpopulation of interneurons. We hypothesized that this gate is mediated by paracapsular intercalated cells, a subset of interneurons that are innervated by both cortical and mesolimbic dopaminergic afferents. Using transgenic mice that express GFP in GABAergic interneurons, we show that paracapsular cells form a network surrounding the basolateral complex of the amygdala. We found that they provide feedforward inhibition into the basolateral and the central amygdala. Dopamine hyperpolarized paracapsular cells through D1 receptors and substantially suppressed their excitability, resulting in a disinhibition of the basolateral and central nuclei. Suppression of the paracapsular system by dopamine provides a compelling neural mechanism for the increased affective behavior observed during stress or other hyperdopaminergic states.

Action Potentials↗
PubMed2005

Origin and classification of neocortical interneurons.

Neocortical interneurons are very diverse in morphological, physiological, molecular, and developmental characteristics. Recent work is discovering strong correlations between these phenotypic features, confirming the intuition of Cajal and Lorente that distinct classes of interneurons exist, each presumably mediating a different circuit function. A paper by Butt et al. in this issue of Neuron describes correlations between the developmental origin of interneurons and their anatomical, electrophysiological, and molecular properties. An effort to standardize the nomenclature of interneurons is underway. Because different interneuron subtypes have different ontogenic origin, they could be classified based on their developmental specification by transcription factors.

Animals↗
PubMed2006

The zinc finger transcription factor Sp8 regulates the generation and diversity of olfactory bulb interneurons.

The molecular mechanisms that regulate the production and diversity of olfactory bulb interneurons remain poorly understood. With the exception of the GABAergic/dopaminergic subtype in the glomerular layer, no information exists concerning the generation of the other subtypes. Here we show that the recently identified zinc finger transcription factor Sp8 is expressed in neurogenic regions, which give rise to olfactory bulb interneurons at embryonic and postnatal time points and remains expressed in the calretinin-expressing and GABAergic/nondopaminergic interneurons of the glomerular layer. Conditional inactivation of Sp8 in the embryonic ventral telencephalon reveals a requirement for the normal generation of these interneuron subtypes. Sp8 conditional mutants exhibit an increase in cell death within the lateral ganglionic eminence and rostral migratory stream. Moreover, mutant neuroblasts/interneurons are misspecified and display abnormal migration patterns in the olfactory bulb, indicating that Sp8 contributes to olfactory bulb interneuron diversity by regulating the survival, migration, and molecular specification of neuroblasts/interneurons.

Animals↗