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PubMed1992

Anatomical and physiological study of interneurons in an oligosynaptic cutaneous reflex pathway in the cat hindlimb.

Morphological and physiological studies were undertaken in the cat lumbosacral spinal cord in order to examine individual last-order excitatory interneurons in the disynaptic pathway between low threshold superficial peroneal (SP) afferents and flexor digitorum longus (FDL) motoneurons. Last-order interneurons projecting to the FDL motor nucleus were visualized with activity-dependent trans-synaptic transport of lectin-conjugated horseradish peroxidase (WGA-HRP). The location of lumbar interneurons that responded at short latencies (less than 3 ms) to electrical stimulation of the SP nerve was further defined using extracellular recording. The projection of individual interneurons to motoneurons in the L6 segment was defined by spike-triggered averaging of population ventral root potentials (VRPs) using the sucrose gap technique. Measurements of the central latencies from the arrival of the SP afferent volley to interneuron firing, and from interneuron spike to the onset of the VRP EPSPs, confirm the existence of a low threshold, disynaptic SP pathway that excited motoneurons. These data provide useful latency constraints for the interpretation of the synaptic length of cutaneous reflex pathways in the cat hindlimb.

Afferent Pathways↗
PubMed1982

Rhythmic activity of spinal interneurons in harmaline-treated cats. A model for olivo-cerebellar influence at the spinal level.

After harmaline administration, rhythmic discharges at 8-12 c/s were obtained by intracellular recording from interneurons in the lumbo-sacral cord of decerebrate paralyzed cats. Unitary extracellular recordings were also made from cerebellar Purkinje cells, showing a rhythmic complex spike activity. Simultaneous recordings of cerebellar and spinal interneurons reveal a precise time relation between rhythmic activities recorded at these two levels. Following each rhythmic cerebellar signal one can note an interruption of interneuron activity. It is also noted that sustained high frequency tonic firing of interneurons coincides with cessation of cerebellar rhythmic activity. These facts are related to the impingement of a disfacilitatory supraspinal influence on spinal interneurons. A model of the mechanisms of signal transfer along the olivo-cerebello-bulbo-spinal system is proposed, according to which tremorogenic supraspinal influences might act on motoneurons by disfacilitating excitatory or inhibitory interneurons.

Action Potentials↗
PubMed1990

Different neuronal types in transneuronally WGA-HRP-labeled premotor interneurons of the rat spinal cord.

Interneurons presynaptic to motoneurons were labeled by retrograde transneuronal transport of WGA-HRP. The tracer was injected either into the quadriceps muscles or into the posterior biceps muscles, thus labeling interneurons presynaptic to the quadriceps motoneurons (QINs) or interneurons presynaptic to posterior biceps motoneurons (PBINs). Statistical cluster analysis of area, perimeter, equivalent diameter and form factor of the labeled interneurons permitted the identification of 4 different types of premotor interneurons in the lumbar enlargement of the rat. Type I are small elongated interneurons which prevail in PBINs. Type II are medium-sized ellipsoidal cells prevailing in the QINs. Type 3 are small ellipsoidal neurons, slightly more frequent in PBINs. Type 4 is the smallest group and it is composed of large multipolar neurons. A different distribution of the 4 morphological neuronal types was found between the population of the QINs and the PBINs and in the laminae of ventral horn for each group.

Afferent Pathways↗
PubMed1993

Hippocampal interneuron activity in unanesthetized rats: relationship to the sleep-wake cycle.

Evoked population spikes and interneuronal discharges were recorded throughout the sleep-wake cycle in hippocampal regions CA1 and dentate gyrus (DG) of ten chronically implanted rats. During quiet wakefulness (QW) and slow-wave-sleep (SWS) (non-theta rhythm states), the primary shock of paired stimuli evoked in CA1 both high amplitude population spikes and multiple interneuron discharges when compared to active wakefulness (AW) and rapid-eye-movement (REM) sleep (theta rhythm states). A second shock was delivered to CA1 afferents 60 ms after the first shock. This second shock evoked a small population spikes during non-theta states, whereas it evoked higher amplitude population spikes in theta states. The second shock also evoked unit interneuron discharges in non-theta states but not in theta states. In the dentate gyrus, identical primary afferent stimulation evoked similar interneuron activity and uniform amplitude population spikes throughout the sleep-wake cycle. In contrast, the secondary shocks evoked a striking potentiation of the field population spike during sleep, SWS and REM sleep compared to AW and OW. Evoked DG interneuron spikes following the second population spike were greater in number during SWS compared to the other stages. Our findings suggest that hippocampal field potentials and interneuron activity recorded in vivo are regionally regulated, have unique state-dependent expression and are strongly influenced by inhibitory feed-forward mechanisms.

Activity Cycles↗
PubMed1995

Single axon fast inhibitory postsynaptic potentials elicited by a sparsely spiny interneuron in rat neocortex.

Many of the different morphological types of interneurons in mammalian neocortex are presumed to be inhibitory, but to date, conclusive functional data have been lacking. Using paired intracellular recordings in slices of adult rat somatosensory cortex, we present a sparsely spiny, burst firing interneuron that elicits in a simultaneously recorded pyramid a fast inhibitory postsynaptic potential, reversing at -78 mV. Neither inhibitory postsynaptic potential time course, nor paired pulse depression (inter-spike interval 15-120 ms), was affected by addition of the GABAB antagonist/partial agonist 2-OH-Saclofen (250 microM), but increasing extracellular [Ca2+] enhanced inhibitory postsynaptic potential amplitude at low firing rates and increased paired pulse depression at higher rates. Light microscopic examination of the biocytin-filled neurons revealed the presynaptic cell to be a sparsely spiny interneuron and the postsynaptic to be a small pyramidal neuron, both in layer II. Ultrastructural examination of 16 terminals of the presynaptic interneuron revealed that they formed symmetric contacts with unlabelled neurons, four with neuronal somata, 10 with dendritic shafts and two with spine shafts. This, therefore, is the first report of the properties of a single axon inhibitory postsynaptic potential in neocortex resulting from action potentials in an electro-physiologically and morphologically identified interneuron. We propose that at least some of the sparsely spiny, burst firing interneurons inhibit pyramidal neurons via GABAA receptors.

Animals↗
PubMed1995

Electrophysiological and pharmacological properties of interneurons in the cat dorsal lateral geniculate nucleus.

We investigated the electrophysiological and pharmacological properties of morphologically identified and putative interneurons within laminae A and A1 of the cat dorsal lateral geniculate nucleus maintained in vitro. These intralaminar interneurons possess unique electrophysiological characteristics, including (1) action potentials of a short duration (average width at half amplitude of 0.34 ms). (2) the ability to generate high-frequency trains of action potentials exceeding 500 Hz, without strong spike frequency adaptation, and (3) a low-threshold regenerative response with variable magnitude of expression, ranging from a subthreshold depolarization towards the generation of one to several action potentials in different cells. The low-threshold regenerative depolarization following a hyperpolarizing current pulse was increased in size by application of 4-aminopyridine, was reduced by nickel, and was not influenced by extracellular cesium. These findings indicate that this event is mediated by an underlying Ca(2+)-dependent mechanism, such as a low-threshold Ca(2+) current, that is regulated by the activation of opposing transient K+ currents. Every interneuron tested responded to glutamate, kainate, quisqualate, or N-methyl-D-aspartate with depolarization and action potential discharge. In contrast, we did not observe a postsynaptic response to activation of the metabotropic receptors with 1S,3R-(+/-)-1-amino-cyclopentane-1,3-dicarboxylate. Application of gamma-amino-butyric acid (GABA) strongly inhibited spike firing through a biphasic hyperpolarization and increase in membrane conductance, a response that reversed close to the presumed chloride equilibrium potential and was imitated by the GABAA receptor agonist muscimol. The GABAB receptor agonist baclofen evoked only a weak membrane hyperpolarization from rest and suppression of spontaneous spike activity. Application of acetylcholine, or the muscarinic agonist acetyl-beta-methylcholine, inhibited spontaneous action potential activity through hyperpolarization of the membrane potential, presumably resulting from an increase in membrane potassium conductance. In contrast, application of serotonin only slightly facilitated tonic activity in a subpopulation of interneurons, histamine induced a small slow depolarization apparently through activation of presynaptic excitatory pathways, and noradrenaline and adenosine had no detectable effect on the spontaneous firing or resting potential of interneurons. We suggest that intralaminar interneurons may function in a relatively linear manner to transform retinal and cortical inputs into a local field of inhibition in the dorsal lateral geniculate and that the excitability of these neurons is largely controlled by retinal, cortical, GABAergic, and cholinergic (brainstem) afferents.

Action Potentials↗
PubMed2005

Evidence for a perisomatic innervation of parvalbumin-containing interneurons by individual pyramidal cells in the basolateral amygdala.

The basolateral amygdala (ABL) contains pyramidal projection neurons (PNs) and several discrete subpopulations of nonpyramidal interneurons. Interneurons containing the calcium-binding protein parvalbumin (PV) constitute about half of all ABL interneurons, and provide a robust innervation of the perisomatic domain of PNs. Although it is known that PNs reciprocate this projection by innervating PV interneurons, little is known about the details of these connections. In the present study, we investigated the innervation of PV interneurons by individual PNs in rat amygdalar slices. PNs in the basolateral nucleus, identified in vitro by their distinctive electrophysiological characteristics in whole cell patch-clamp recordings, were filled with biocytin by diffusion from the patch electrode. PV interneurons and biocytin-labeled PNs were visualized with a two-color immunoperoxidase procedure using nickel-enhanced DAB (black) for biocytin and non-enhanced DAB (brown) for PV. In slices with well-stained PN axons and PV neurons, light microscopy revealed numerous synapse-like contacts between these structures. The main PV+ targets of PN axons were the somata and proximal dendrites of PV neurons, although there were also contacts with more distal PV dendrites. In many cases, the PN axons ran along PV somata and/or proximal dendrites, forming multiple contacts. However, the great majority the PN axon terminals did not contact PV neurons. These observations suggest that there are robust reciprocal perisomatic PN-to-PV connections that may be important for the precise timing of rhythmic activity in the basolateral amygdala.

Amygdala↗
PubMed2004

The GABAergic septohippocampal pathway in control and reeler mice: target specificity and termination onto Reelin-expressing interneurons.

The septohippocampal pathway contains two separate components: the cholinergic and the GABAergic. Whereas cholinergic fibers terminate on many hippocampal cell types, GABAergic septohippocampal fibers selectively contact the cell bodies of hippocampal interneurons. We examined whether the GABAergic septohippocampal system was altered in reeler mice. First, we found that both components of the septohippocampal pathway in mice present a distribution and target-cell specificity similar to that described in rats. We also show that GABAergic septohippocampal axons terminate on subpopulations of interneurons expressing reelin, which may implicate this extracellular matrix protein in the targeting of septohippocampal axons. We thus examined the septohippocampal pathway in reeler mice defective in Reelin. In contrast to wild-type animals, reeler mice displayed an ectopic location of both cholinergic and GABAergic fibers, which accumulate close to the hippocampal fissure. Despite their altered distribution, GABAergic septal axons maintain their target-cell selectivity innervating exclusively the perisomatic region of hippocampal interneurons. Thus, as in wild type, GABAergic septal fibers formed complex baskets around the cell body of GAD-positive hippocampal neurons in reeler mice. In addition, we found that reeler hippocampi have an altered distribution of hippocampal interneurons expressing PARV or CALB, many of which are located close to the hippocampal fissure. We thus conclude that although reeler mice have an altered distribution of hippocampal interneurons, GABAergic septohippocampal axons nevertheless terminate on their specific target interneurons. Thus, whereas target layer termination of septal fibers is severely impaired in reeler mice, our data indicate that the cell-specific targeting of GABAergic septohippocampal axons is governed by Reelin-independent signals.

Animals↗
PubMed2006

A novel subpopulation of 5-HT type 3A receptor subunit immunoreactive interneurons in the rat basolateral amygdala.

The amygdalar basolateral nuclear complex (BLC) has very high levels of the 5-HT type 3 receptor (5-HT(3)R). Previous studies have reported that 5-HT(3)R protein in the BLC is expressed in interneurons and that 5-HT(3)R mRNA is coexpressed with GABA and certain neuropeptides or calcium-binding proteins in these cells. However, there have been no detailed descriptions of the distribution of 5-HT(3)R+ neurons in the rat amygdala, and no quantitative studies of overlap of neurons expressing 5-HT(3)R protein with distinct interneuronal subpopulations in the BLC. The present investigation employed dual-labeling immunohistochemistry using antibodies to the 5-HT-3A receptor subunit (5-HT(3A)R) and specific interneuronal markers to address these questions. These studies revealed that there was a moderate density of nonpyramidal 5-HT(3A)R+ neurons in the BLC at all levels of the amygdala. In addition, immunostained cells were also seen in anterior portions of the cortical and medial nuclei. Although virtually all 5-HT(3A)R+ neurons in the BLC were GABA+, very few expressed neuropeptide or calcium-binding protein markers for individual subpopulations. The main interneuronal marker expressed by 5-HT(3A)R+ neurons was cholecystokinin (CCK), but only 8-16% of 5-HT(3)R+ neurons in the BLC, depending on the nucleus, were CCK+. Most of these CCK+/5-HT(3A)R+ double-labeled neurons appeared to belong to the subpopulation of large type L CCK+ interneurons. Very few 5-HT(3A)R+ neurons expressed calretinin, vasoactive intestinal peptide, or parvalbumin, and none expressed somatostatin or calbindin. Thus, the great majority of neurons expressing 5-HT(3A)R protein appear to constitute a previously unrecognized subpopulation of GABAergic interneurons in the BLC.

Amygdala↗
PubMed2001

Spinal interneurons play a minor role in generating ongoing renal sympathetic nerve activity in spinally intact rats.

The purpose of the present study was to determine whether spinal interneurons play a role in the regulation of sympathetic activity in spinally intact rats. In acutely spinally transected rats, we have described a population of spinal interneurons that, by virtue of correlations between their ongoing firing rates and the magnitude of ongoing renal sympathetic nerve activity (RSNA), are candidates for generators of sympathetic activity. Further evidence for a sympathetic role for these neurons comes from our observation that cervical spinal stimulation that reduces RSNA also reduces their discharge rates. In chloralose-anesthetized, spinally intact and spinally transected rats, we recorded ongoing RSNA and the ongoing activities of T(10) dorsal horn and intermediate zone interneurons, and we determined the incidence of sympathetically related neurons in these rats by cross-correlating their activities with RSNA. The incidence of correlated neurons was much smaller in spinally intact than in spinally transected rats. We stimulated the dorsolateral, C(2-3) spinal cord before and after acute C(1) spinal transection. Dorsolateral cervical stimulation in spinally transected rats reduced both RSNA and the activities of most T(10) interneurons, but stimulation in spinally intact rats increased RSNA while still reducing the activities of most T(10) interneurons. Both the low incidence of sympathetically correlated spinal neurons in intact rats and the dissociation between the effects of cervical stimulation on RSNA and the discharge rates of spinal interneurons argue against these neurons playing a major role in regulating sympathetic activity in intact rats.

Action Potentials↗
PubMed2001

Alpha7-nicotinic receptor expression and the anatomical organization of hippocampal interneurons.

C3H and DBA/2 mice differ in their hippocampal inhibitory function, as measured by the inhibitory gating of pyramidal neuron response to repeated auditory stimulation. This functional difference appears to be related to differences in expression of the alpha7 nicotinic cholinergic receptor, which may be generally expressed by interneurons. This study examines the relationship between genetic variation in alpha7 receptor subunit expression and GABAergic interneuron distribution in various regions and layers of the hippocampus in the two mouse strains. Subpopulations of hippocampal interneurons in both mouse strains were found to bind [(125)I]alpha-bungarotoxin. However, the distribution of the [(125)I]alpha-bungarotoxin-positive hippocampal interneurons was significantly different between C3H and DBA/2 mice. In region CA1, and to a lesser extent in region CA3, DBA/2 mice had increased numbers of [(125)I]alpha-bungarotoxin-positive neurons in stratum lacunosum-moleculare and decreased numbers in stratum oriens. Similar differences in GABAergic neuron distribution were observed in region CA1 in the two strains. C3H/DBA/2 F1 animals were backcrossed to the C3H parental strain for six generations, with selection for either the DBA/2 or C3H allelic variant of the alpha7 receptor gene. The distribution of [(125)I]alpha-bungarotoxin labeling closely resembled the DBA/2 parental phenotype in animals retaining the DBA/2 allele of the alpha7 gene. These data suggest that the alpha7 receptor gene locus may influence the anatomical organization of at least a subset of hippocampal interneurons by an as yet unidentified mechanism. This difference in interneuron anatomy may also contribute to functional differences in inhibitory sensory gating between the two strains.

Alleles↗
PubMed1997

Short-latency interneurons in the dorsal nucleus of the little skate, Raja erinacea.

The elasmobranch electrosensory system is the most thoroughly understood of the non-teleost electrosensory systems and is useful for studying central nervous system mechanisms for the separation of behaviorally relevant signals from self-generated noise. In the little skate, Raja erinacea, the electrosensory primary afferents are responsive to electrical potentials created during the animal's own ventilation, while second-order neurons in the dorsal nucleus of the medulla suppress responses to ventilatory potentials (self-generated noise) but retain their extreme sensitivity to electric signals in the environment. The selective suppression of ventilatory noise in second-order cells is due in part to the fact that ventilatory potentials stimulate all receptors equally and simultaneously. The neuronal circuitry mediating rejection of such 'common mode' signals in the dorsal nucleus likely includes inhibitory interneurons. This study describes physiological and anatomical characteristics of a group of dorsal nucleus interneurons that are distinguished from previously described interneurons by their shorter orthodromic activation latencies and higher spontaneous firing rates. The interneurons show sustained responses to an external dipole stimulus and respond well during simultaneous activation of all afferents by a 'common mode' stimulus. Intracellular labeling indicates that the short-latency interneurons are located in the central and peripheral zones of the dorsal nucleus and the extent of their labeled processes is limited to the projection area of afferents from a single ampullary cluster. These features are consistent with a hypothesized role for these interneurons in inhibiting second-order cells, including inhibition which contributes to common mode rejection.

Afferent Pathways↗
PubMed2000

Interneuronal survival and calbindin-D28k expression following motoneuron degeneration.

Degeneration of both motoneurons and interneurons has been previously observed in amyotrophic lateral sclerosis. It is unclear whether interneuronal loss is due to an intrinsic neuronal defect or if it occurs secondary to loss of their target motoneurons. We have examined the target dependence of interneurons, their survival and alterations in the expression of the calcium binding protein, calbindin-D28k (CB), in the ventral horn of the rat lumbar cord after extensive motoneuron degeneration was induced by unilateral rhizotomy of spinal nerves L2-L6 at postnatal day 3 (P3). Counts of Nissl-stained cells at P21 revealed no significant interneuronal death despite loss of 80% of their target motoneurons. At P6, some motoneurons transiently expressed CB on the operated side compared to the control side. Since most of these cells are destined to die, this transiently increased CB expression may represent an abortive attempt by the axotomised motoneurons to buffer the neurotoxic consequences of high intracellular calcium. In contrast, there was a time-dependent decrease in CB expression in ventral horn interneurons, with only 35% of putative Renshaw cells expressing CB by P21. These results indicate that neonatal interneurons are capable of surviving the loss of their motoneuron targets, but alter their phenotype as indicated by functional alterations in calcium-binding proteins.

Amyotrophic Lateral Sclerosis↗
PubMed2002

Relative picrotoxin insensitivity distinguishes ionotropic GABA receptor-mediated IPSCs in hippocampal interneurons.

Inhibitory GABAergic signalling in the hippocampus plays an important role in synchronizing principal cells and regulating the excitability of this seizure-prone structure. Distinct mechanisms modulate release from GABAergic terminals in the hippocampus, depending on whether the postsynaptic partner is an interneuron or a principal cell. Here, we report that postsynaptic ionotropic GABA receptors in principal cells and interneurons also show a striking pharmacological difference. The broad-spectrum antagonist picrotoxin (PTX) was less potent at blocking IPSCs evoked in stratum radiatum interneurons than in pyramidal neurons in the CA1 region. GABA-evoked currents in membrane patches from interneurons showed a smaller mean unitary conductance than in patches from pyramidal neurons. Because retinal GABA(C) receptors show decreased picrotoxin sensitivity and conductance, we examined the effect of the GABA(C) receptor agonist cis-aminocrotonic acid (CACA). Although this agent evoked picrotoxin-resistant currents in interneurons, these were enhanced by the GABA(A) allosteric modulator pentobarbital. Moreover, both picrotoxin-resistant IPSCs and CACA-evoked currents were blocked by the GABA(A) receptor-selective antagonist bicuculline. The presence of relatively picrotoxin-resistant GABA(A) receptors in interneurons provides a potential target for agents to modulate the activity of sub-populations of hippocampal neurons.

Animals↗
PubMed1999

Glutamatergic synapses onto hippocampal interneurons: precision timing without lasting plasticity.

In the hippocampal formation GABAergic inhibitory interneurons have a major role in the synchronization of neuronal activity and are involved in the generation of large-scale network oscillations. Thus, interneurons function as a 'clock' that dictates when principal cells fire during suprathreshold excitatory drive. Interneurons receive strong excitatory innervation from glutamatergic neurons and it has been much debated whether these synapses show mechanisms of long-term plasticity similar to those found at principal-cell synapses. Recent findings support the lack of conventional forms of LTP and LTD in most interneurons, partly owing to the distinct anatomical and neurochemical features of interneuronal excitatory synapses. The uncommon properties of excitatory synapses on interneurons might be required for their functioning as accurate and reliable neuronal oscillators.

Animals↗
PubMed2002

Differential effects of novel wasp toxin on rat hippocampal interneurons.

We studied the effects of a wasp toxin beta-pompilidotoxin (beta-PMTX) on rat hippocampal CA1 interneurons by the current-clamp technique. The firing patterns of pyramidal neurons and pyramidale interneurons were not affected by beta-PMTX, but in oriens and radiatum interneurons, beta-PMTX converted the action potentials to prolonged depolarizing potentials by slowing the inactivation of Na(+) channels. In lacunosum moleculare interneurons, beta-PMTX induced initial bursting spikes followed by block of succeeding spikes. Comparison of beta-PMTX with a sea anemone toxin, ATX II, revealed that ATX II altered the firing properties of pyramidal neurons and pyramidale interneurons that were unchanged by beta-PMTX. Our results suggest that beta-PMTX modulates Na(+) currents in CA1 interneurons differently in various CA1 neurons and the toxin is useful to classify Na(+) channel subtypes.

Action Potentials↗
PubMed2001

Regulation of the activity of hippocampal stratum oriens interneurons by alpha7 nicotinic acetylcholine receptors.

GABAergic interneurons have been shown to be a major target of cholinergic inputs to the hippocampus. Because these interneurons project to pyramidal neurons as well as other interneurons, activation of the cholinergic system is likely to produce a complex modulation of local inhibitory activity. To better understand the role of post-synaptic alpha7 nicotinic acetylcholine receptors in the hippocampus, we have characterized the effects of nicotinic agents on local interneurons of the rat CA1 stratum oriens in terms of activation, desensitization, and region of axonal termination. Fast application of acetylcholine onto stratum oriens interneurons during whole-cell recordings from hippocampal slices activated the majority of cells tested, and these responses were mediated almost entirely by alpha7 nicotinic acetylcholine receptors. Anatomical reconstructions showed no clear relationship between the acetylcholine responsivity of interneurons and the regions to which their axons project. Currents mediated by alpha7 receptors declined markedly during repetitive activation in the theta rhythm range (4-12 Hz) when activated by either pressure application or synaptic release of acetylcholine. However, the decay of alpha7 receptor-mediated currents was unaffected by treatment with the cholinesterase inhibitor neostigmine (10 nM-10 microM), suggesting that hydrolysis of acetylcholine is not a rate-limiting step in the termination of these responses. From these findings we suggest that nicotinic receptor activity in this region has an extensive and complex impact on local inhibitory circuits that is mediated by activation of several classes of intrinsic GABAergic cells. In addition, desensitization of the alpha7 nicotinic acetylcholine receptor is likely to contribute to the decay of individual responses to pressure application of agonist, and may also act in a cumulative fashion to impair the ability of these receptors to support repetitive activity during trains of activation. If applicable to alpha7 receptor responses in vivo, we suggest it may be difficult to enhance these responses for therapeutic purposes with cholinesterase inhibitors.

Acetylcholine↗
PubMed2003

Light microscopic study of GluR1 and calbindin expression in interneurons of neocortical microgyral malformations.

Rat neocortex that has been injured on the first or second postnatal day (P0-1) develops an epileptogenic, aberrantly layered malformation called a microgyrus. To investigate the effects of this developmental plasticity on inhibitory interneurons, we studied a sub-population of GABAergic cells that co-express the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit and the calcium-binding protein, calbindin (CB). Both malformed and control cortex of adult (P40-60) animals contained numerous interneurons double-stained for CB and GluR1. Immunoreactivity (IR) for CB was up-regulated in perikarya of interneurons within supragranular layers of control cortex between P12 and P40. However, in malformed adult (P40) cortex, CB-IR levels were significantly lower than in adult controls, and fell midway between levels in immature and adult control animals. Between P12 and P40, GluR1-IR was down-regulated in perikarya of interneurons in control cortex. Somatic GluR1-IR levels in malformed adult (P40) cortex were not different from adult controls. These neurons formed a dense plexus of highly GluR1-positive spiny dendrites within layer II. The dendritic plexus in the malformation was more intensely GluR1-immunoreactive than that in layer II of control cortex. This was due to apparent changes in thickness and length of dendrites, rather than to significant changes in the number of interneuronal perikarya in the microgyral cortex. Results indicate that the population of GluR1/CB-containing interneurons is spared in malformed microgyral cortex, but that these cells sustain lasting decreases in their somatic expression of calbindin and alterations of dendritic structure. Potential functional implications of these findings are discussed.

Age Factors↗