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Effects of unilateral cochlea ablation on the distribution of calretinin mRNA and immunoreactivity in the guinea pig ventral cochlear nucleus.

The predominantly neuronal, calcium-binding protein calretinin is highly expressed in the guinea pig auditory system. Within the ventral cochlear nucleus (VCN), calretinin-positive auditory nerve fibers terminate on many calretinin-containing bushy, octopus, and multipolar cells. The abundance of calretinin in the cochlear nucleus provides an ideal system for examining the effects of altered neuronal input on the expression of this calcium-binding protein. The present experiments examined the effects of unilateral cochlea ablation on calretinin immunoreactivity and mRNA levels in the VCN. Calretinin mRNA was labeled by in situ hybridization histochemistry using a radioactive oligonucleotide probe and was quantified by optical density measures on autoradiograms. Survival times of 1, 7, and 56 days postlesion were examined. The results revealed a consistent increase in calretinin mRNA in the rostral portion of the ipsilateral anterior VCN 1 day postlesion but no effect on calretinin mRNA in this region at 7 and 56 days postlesion. The intensity of immunohistochemical label was also increased at 1 and 7 days after surgery. In contrast, calretinin mRNA was not affected 1 day postlesion in the ipsilateral posterior VCN but was decreased at both 7 and 56 days postlesion. The decrease in calretinin mRNA in the posterior VCN at longer survival times was accompanied by decreased immunolabeling of fibers projecting from VCN cells to the superior olivary complex. These results suggest that calretinin gene expression is regulated in part by auditory nerve activity in some cochlear neurons but that additional factors related to the unique cellular milieu also control calretinin expression.

Analysis of Variance↗

Human orbitofrontal cortex: cytoarchitecture and quantitative immunohistochemical parcellation.

The primate orbitofrontal cortex is a component of the paralimbic cortical "belt" and consists of several distinct areas. It is involved in high order association functions that include the integration of emotion, behavior, and various sensory processes. To define the cyto- and chemo-architectonic organization of the human orbitofrontal cortex, we have used antibodies to the nonphosphorylated neurofilament triplet protein and to the calcium-binding proteins parvalbumin and calretinin. Immunohistochemistry revealed labeling patterns corresponding to the cytoarchitecture defined by Nissl preparations. Neurofilament protein-immunoreactive pyramidal neurons were located only in layers V-VI in the agranular posterior orbitofrontal cortex, whereas they were distributed in both layers III and V-VI in the anteromedial and anterolateral granular regions. The intermediate dysgranular portion of the orbitofrontal cortex represented a transition zone with a progressive decrease in layer III labeled pyramidal cell numbers posteriorly. The distribution of parvalbumin- and calretinin-immunoreactive interneurons was more homogeneous, although the posteromedial region and the cortex of the inferior rostral sulcus had slightly lower parvalbumin-positive neuron counts than the other orbitofrontal areas. Parvalbumin immunoreactivity in the neuropil exhibited a high degree of regional specialization in that it was consistently less intense in the cortex of the intermediate and posterior part of the gyrus rectus, whereas the other orbitofrontal areas had a very dense neuropil staining in layers III to V. Also, there was a dense plexus of parvalbumin-immunoreactive fibers restricted to layer I in the posterolateral orbitofrontal cortex, and patches of neuropil staining in layer III of the inferior rostral sulcus. These region-specific neuropil staining patterns may correspond to the distribution of parvalbumin-immunoreactive thalamocortical projections to distinct domains of the orbitofrontal cortex. This regional parcellation of the human orbitofrontal cortex as defined by specific neuronal markers, may represent an anatomical substrate for the localization of the various functions attributed to this poorly understood cortical region.

Aged↗

Calretinin immunoreactive structures in the human hippocampal formation.

The calcium-binding protein calretinin is present in an intrinsic GABAergic and an extrinsic non-GABAergic system in the rat and monkey hippocampal formation. Important species differences have been noted in hippocampal cell types immunostained for calretinin and the termination pattern of calretinin containing hypothalamic afferents in the hippocampus. In the present study, calretinin-containing neurons were visualized using immunocytochemistry in the human hippocampal formation of individuals which showed no significant neuropathological alterations. Calretinin-immunoreactivity was present exclusively in non-granule cells of the dentate gyrus and in non-pyramidal cells of Ammon's horn. Calretinin-positive neurons were found most frequently in the hilus of the fascia dentata and in strata radiatum and lacunosum-moleculare of CA1, whereas neurons in CA2 and CA3 were rarely immunostained. The majority of calretinin-immunoreactive neurons were small, bipolar or fusiform neurons. The dendritic trees of the calretinin-positive neurons were, for the most part, parallel to the dendrites of the principal cells. In the hilus, however, we observed cells with dendrites restricted to the hilar area. These dendrites were parallel to the granule cell layer. In the stratum lacunosum-moleculare, neurons with dendrites oriented parallel to the hippocampal fissure were frequently detected. In general, dendrites were smooth or sparsely spiny, displaying small conventional spines. The axons usually emerged from the proximal dendrite and could be followed over long distances. Axons were thin, had small varicosities and displayed only few collaterals which branched relatively far away from the cell body. Distinct bands of darkly stained calretinin-positive fibers occupied the innermost portion of the dentate molecular layer and the pyramidal cell layer of CA2. This distribution of calretinin-immunoreactive structures in the human hippocampus is similar to that observed in other primates but differs from that described in lower mammals, i.e., the rat. Our findings suggest that primates may share a common hippocampal calretinin-containing system, presumably both the intrinsic GABAergic and the extrinsic hypothalamic non-GABAergic components.

Aged↗

Development of calretinin immunoreactivity in the neocortex of the rat.

The prenatal and postnatal development of calretinin (CR)-containing elements in the neocortex of the rat was analyzed using immunohistochemistry. CR immunoreactivity in the cortical anlage appeared early at embryonic day 14 (E14), with CR-positive neurons located in the primitive plexiform layer and in the emerging subplate and marginal zones. At later prenatal and early postnatal stages, these two layers showed the highest CR immunostaining in the cortex, and large numbers of cell bodies and fibers were immunostained. From postnatal day 3 (P3) onwards, CR immunostaining disappeared progressively from the subplate-layer VIb and the marginal zone-layer I, so that very few cells remained stained in these layers in the adult. In the cortical plate and prospective layers VIa to II-III, CR-positive neurons were seen at prenatal stages, their numbers increasing markedly during the first postnatal week. Most neurons showed undifferentiated nonpyramidal shapes, and matured during the second and third postnatal weeks, when the adult pattern of CR immunostaining was achieved. In addition, some pyramidal-like neurons in the infragranular layers and in layer II-III transiently expressed CR during the postnatal period, most notably between P3 and P12. Colocalization experiments performed at P0-P3 with antibodies against the neurotransmitter gamma-aminobutyric acid (GABA) showed that most nonpyramidal CR-positive neurons in the derivates of the cortical plate were also GABAergic during development. In contrast, large numbers of CR-containing neurons in the subplate and marginal zone were GABA-negative. The present results show that in addition to recording the early development of a subset of nonpyramidal neurons, CR is transiently expressed in certain GABA-negative populations of the subplate and marginal zone, and most likely in pyramidal neurons.

Animals↗

The rod pathway of the macaque monkey retina: identification of AII-amacrine cells with antibodies against calretinin.

AII-amacrine cells were characterized from Golgi-stained sections and wholemounts of the macaque monkey retina. Similar to other mammalian retinae, they are narrow-field, bistratified amacrine cells with lobular appendages in the outer half of the inner plexiform layer (IPL) and a bushy, smoother dendritic tree in the inner half. AII cells of the monkey retina were stained immunocytochemically with antibodies against the calcium-binding protein calretinin. Their retinal mosaic was elaborated, and their density distribution across the retina was measured. Convergence within the rod pathway was calculated. Electron microscopy of calretinin-immunolabelled sections was used to study the synaptic connections of the AII cells. They receive a major input from rod bipolar cells, and their output is largely onto cone bipolar cells. Thus, the rod pathway of the primate retina follows the general mammalian scheme as it is known from the cat, the rabbit, and the rat retina. The spatial sampling properties of macaque AII-amacrine cells are discussed and related to human scotopic visual acuity.

Animals↗

Developmental changes in calretinin expression in GABAergic and nonGABAergic neurons in monkey striate cortex.

The development of the calcium-binding protein calretinin (CaR) and its co-localization with GABA was studied in the striate cortex of Macaca monkeys from fetal day (Fd) 45 to adult. At Fd45, early neurons resembling Cajal-Retzius cells are stained in the marginal zone (MZ). At Fd55 the MZ is filled with CaR+ Cajal-Retzius cells and their processes, and scattered CaR+ cells are also found in deep cortical plate (CP), intermediate zone (IZ), and subventricular zone (SVZ). At Fd66, a band of CaR+ fibers appears in the IZ, corresponding to the location of the geniculocortical axons. This fiber band labels heavily until Fd130 but then ceases to be immunoreactive by postnatal (P) 16 weeks. At Fd85-101, the number of CaR+ cells in the CP, SVZ, and ventricular zone (VZ) reaches its highest cell density. After Fd130, CaR+ cells are concentrated in layer II and upper layer III, and this distribution changes little into adulthood. After mid-gestation, there is a progressive loss of CaR+ cell bodies and processes in the MZ, and these are rare in the adult cortex. Just before birth, a weakly stained CaR+ cell band appears in layer IVA at the border between layer IVA and IVB, but this band disappears immediately after birth. Another CaR+ cell band appears transiently in upper layer V just below the border with layers IV at P6 months. These results suggest that CaR is expressed early in fetal development in the cell populations that are immunoreactive for CaR in the adult. However, developmental events related to cortical maturation during late prenatal and early postnatal stages result in transient expression of CaR in neurons that are not immunoreactive for CaR in the adult. CaR-immunoreactivity is colocalized with GABA in almost all CaR+ cells with the exception of Cajal-Retzius cells in the MZ and some large cells observed at Fd70-101 in the VZ. The band of CaR+ fibers in the IZ is GABA-. At Fd90, almost all (> 96%) CaR+ cells are GABA+ in the CP and the first developed layers V/VI. This percentage declines later, so that on average 80% of CaR+ cells are GABA+ in adult cortex. At Fd135, 53% of GABA+ neurons located in layers II/III are CaR+; this percentage declines to 37% in the adult. These double-label patterns suggest that early in fetal development the majority of GABA+ cells stain for CaR and that expression of CaR may be related to the migration of these neurons into the cortical plate. Once they attain their final position in the cortex many GABA+ cells loose CaR-immunoreactivity, so that in postnatal life only a minority of GABA+ neurons contain this calcium-binding protein.

Animals↗

Fine-needle aspiration biopsy and intraoperative cytologic smear findings in a case of benign mesothelial-cell inclusions involving a lymph node: case report and review of the literature.

Although first described over a decade ago, the rare entity of mesothelial lymph node inclusions (nonneoplastic mesothelial cells involving lymph node sinuses) is not well-known among pathologists. Unlike most lymph node inclusions such as Müllerian inclusions or nevus cells, which usually occur in the capsule of the lymph node, mesothelial cells involve the lymph node sinus, mimicking metastatic carcinoma or metastatic mesothelioma. The spectrum of histologic findings ranges from a few mesothelial cells, perhaps only detectable by immunohistochemical stains, to a massive distention of the lymph node sinus with abundant mesothelial cells. Mesothelial-cell inclusions in lymph nodes are usually found in mediastinal lymph nodes of patients with pleural and/or pericardial effusions. It is hypothesized that the effusion, due to whatever cause, allows for mesothelial-cell migration into the submesothelial lymphatics and regional lymph nodes. To our knowledge, cytologic findings on aspiration biopsy and intraoperative smear preparations of a lymph node with mesothelial-cell inclusions have never been described. Familiarity with this entity is important in preventing misdiagnosis of malignancy.

Biopsy, Fine-Needle↗

Comparison of immunomarkers for the identification of adrenocortical cells in cytology specimens.

We studied the immunoreactivity of three antibodies--A103, calretinin, and inhibin alpha in destained Papanicolaou (Pap) smears and cell-blocks of 40 fine-needle aspiration biopsy cases of adrenocortical lesions (35 cases of hyperplasia/adenoma and 5 cases of carcinoma). Five cases of carcinoma (4) and melanoma (1) metastases to the adrenal gland and five cases of renal-cell carcinoma were also included for comparison. In benign adrenocortical lesions, A103 staining was noted in 82% of the destained Pap smears and in 92% of cell-blocks. In malignant adrenocortical lesions, A103 staining was noted in 50% of the destained Pap smears and in 80% of cell-blocks. In comparison, calretinin staining was noted in 6% and 50% of destained smears and in 78% and 60% of the cell-blocks of benign and malignant adrenocortical lesions. Inhibin alpha was not positive in any of the smears and showed the lowest level of positivity in the cell-block sections, namely in 11% of the benign lesions and 25% of the malignant lesions. The sensitivity of A103 was 90% on cell-blocks and 74% on smears, that of calretinin 75% on cell-blocks and 11% on smears, and that of inhibin alpha, 13% on cell-blocks alone. The specificity of A103 was lower than the other two makers, 90% vs. 100% because of positivity in metastatic melanoma in the adrenal gland. Our data show A103 to be the immunomarker with the highest sensitivity for identifying cells of adrenocortical origin in destained Pap's smears and cell-block sections with, however, a lower specificity when compared with calretinin and inhibin alpha. Calretinin is comparable in sensitivity with A103 on cell-block sections alone and not on smears. The results of this study suggest that if metastatic melanoma in adrenal gland is not a consideration then A103 is the marker of choice for identifying cells of adrenocortical origin in the limited material available for diagnostic purposes in cytology specimens.

Adrenal Cortex↗

Formation of supernumerary muscle spindles at the expense of Golgi tendon organs in ER81-deficient mice.

ER81, a member of the ETS family of transcription factors, is essential for the formation of connections between sensory and motor neurons in the spinal cord. Mice lacking Er81 genes exhibit reduced monosynaptic sensory-motoneuron connectivity in response to muscle nerve stimulation. Proximal muscle nerve stimulation elicits fewer monosynaptic potentials than stimulation of distal nerves in hindlimbs, a deficit that is paralleled by a paucity of muscle spindles in proximal muscles (Arber et al., 2000). We examined whether a presence of spindles innervated by afferents in distal muscles correlated with the increased preservation of monosynaptic sensory-motor potentials in distal muscle nerves. Not only were spindles and Ia afferents present, but also they were supernumerary in distal muscles such as the soleus, medial gastrocnemius, and extensor hallucis longus. Concomitantly, a deficiency of Golgi tendon organs (GTOs) and Ib afferents was observed in distal muscles, as if supernumerary spindles formed at the expense of tendon organs in the absence of Er81. Thus, ER81 may be involved in mechanisms that regulate acquisition of the Ia and Ib phenotypes by subsets of proprioceptive muscle afferents. Segmental differences in muscle spindle and GTO dependence on ER81 suggest that more than one ETS transcription factor may participate in the regulation of limb proprioceptive system assembly in the mouse.

Alleles↗

NeuroD induces the expression of visinin and calretinin by proliferating cells derived from toxin-damaged chicken retina.

Müller glia have been shown to be a potential source of neural regeneration in the avian retina. In response to acute damage Müller glia de-differentiate, proliferate, express transcription factors found in embryonic retinal progenitors, and some of the progeny differentiate into neurons and glia (Fischer and Reh [2001a] Nat. Neurosci. 4:247-252). However, most of the cells produced by proliferating Müller cells appear to remain undifferentiated. The purpose of this study was to test whether the neurogenic gene NeuroD can promote the differentiation of proliferating cells derived from the postnatal chick retina. We used recombinant avian retroviruses to transfect green fluorescent protein (GFP) or NeuroD. The majority of cells transfected with GFP remained undifferentiated, with a few cells differentiating into calretinin-immunoreactive neurons. Many cells transfected with the NeuroD-virus expressed calretinin, neurofilament, or visinin, while most cells remained undifferentiated. The number of calretinin-expressing cells that were generated was increased approximately 20-fold with forced expression of NeuroD. In addition, we found that cells transfected with NeuroD never expressed glutamine synthetase, a marker of mature Müller glia, suggesting that NeuroD suppresses glial differentiation. We conclude that NeuroD stimulates cells from the toxin-damaged chicken retina to acquire some neuronal phenotypes. We propose that most of these cells were derived from Müller glia.

Animals↗

Isolation and characterization of the laure olfactory behavioral mutant in the zebrafish, Danio rerio.

To initiate a genetic analysis of olfactory development and function in the zebrafish, Danio rerio, we developed a behavioral genetic screen for mutations affecting the olfactory sensory system. First, we characterized olfactory responses of wild-type zebrafish to various odors. We found that 3-day-old juvenile zebrafish reacted to the amino acid L-cysteine with an aversive behavioral response. We isolated one mutant, laure (lre), which showed no aversive behavioral response to L-cysteine at 3 days of development, and carried out a preliminary characterization of this mutant's defects. We found that lre mutant fish were also defective in their response to L-serine and L-alanine, but not to taurocholic acid, as young adults. In addition, lre mutant fish had significantly fewer primary olfactory sensory neurons than normal, and the axons of these neurons did not form the characteristic axon termination pattern in the developing olfactory bulb. Nevertheless, the olfactory epithelium of lre mutant fish showed normal or near normal electrophysiological responses to several odorants. Our data suggest that the behavioral defects observed in the lre mutant result from the disruption of the developing olfactory sensory neurons and their axonal connections within the olfactory bulb. The isolation of the lre mutant shows that our behavior-based screen represents a viable approach for carrying out a genetic dissection of olfactory behaviors in this vertebrate model system.

Animals↗

ETS transcription factor ER81 is required for the Pacinian corpuscle development.

ER81, a member of the ETS family of transcription factors, is involved in processes of specification of neuronal identity, control of sensory-motor connectivity, and differentiation of muscle spindles. Spindles either degenerate or are abnormal in mutant mice lacking ER81. We examined whether ER81 is required for the development of another class of mechanoreceptors, the Pacinian corpuscle. ER81 was expressed by the inner core cells of the corpuscles, as reflected by expression of the lacZ reporter gene in Er81(+/lacZ) mutants, thereby suggesting a role for ER81 in the corpuscle development. No Pacinian corpuscles or their afferent nerve fibers were present in the crus of Er81 null mice at birth. Legs of mutant embryos examined at E16.5 were also devoid of the corpuscles, but not of their afferents. Thus, Pacinian corpuscles do not form, and their afferents do not survive, in the absence of ER81. A deficiency of dorsal root ganglia neurons expressing calretinin, a marker for neurons subserving Pacinian corpuscles, correlated with the absence of corpuscles and their afferents in Er81 null mice. These observations indicate a requirement for ER81 in the assembly of Pacinian corpuscles and the survival of the sensory neurons that innervate them.

Animals↗

Type II glucocorticoid receptor immunoreactivity in the mossy cells of the rat and the mouse hippocampus.

Hippocampal principal neurons, granule and pyramidal cells, are known to express type II glucocorticoid receptors (GR) and it is believed that glucocorticoids (GC) mediate at least some of their effects through GR. Under conditions of severe stress and trauma, these principal cells are vulnerable to damage and this mechanism may be exacerbated by GR. The mossy cell, an excitatory dentate gyrus neuron, is also damaged following trauma, with over 50% reported loss in rats after kainate-induced seizures. However, it has not been determined if GC play any role in protecting or exacerbating damage to this important hippocampal cell type. In the present study, we have undertaken an evaluation of the presence of GR in mossy cells of the rat and mouse utilizing an immunocytochemical double-labeling technique. To identify mossy cells in the rat, we utilized an antibody to the glutamate receptor subunit 2/3 (GluR2/3). In addition to GluR2/3 antibodies, in the mouse, an antibody to the calcium-binding protein, calretinin (CR), to identify mossy cells was also employed. Our results show that GR immunoreactivity (IR) was colocalized with GluR2/3-IR in approximately 90% of the rat and the mouse mossy cells. In addition, GR-IR was identified in the CR-IR mossy cells in the mouse hippocampus, whereas the CR-IR interneurons of rat and mouse were negative for GR-IR. The presence of GR on mossy cells may indicate the ability of GC to mediate cellular activity of these cells.

Animals↗

Comparison of commissural sprouting in the mouse and rat fascia dentata after entorhinal cortex lesion.

Reactive axonal sprouting occurs in the fascia dentata after entorhinal cortex lesion. This sprouting process has been described extensively in the rat, and plasticity-associated molecules have been identified that might be involved in its regulation. To demonstrate causal relationships between these candidate molecules and the axonal reorganization process, it is reasonable to analyze knockout and transgenic animals after entorhinal cortex lesion, and because gene knockouts are primarily generated in mice, it is necessary to characterize the sprouting response after entorhinal cortex lesion in this species. In the present study, Phaseolus vulgaris-leucoagglutinin (PHAL) tracing was used to analyze the commissural projection to the inner molecular layer in mice with longstanding entorhinal lesions. Because the commissural projection to the fascia dentata is neurochemically heterogeneous, PHAL tracing was combined with immunocytochemistry for calretinin, a marker for commissural/associational mossy cell axons. Using both techniques singly as well as in combination (double-immunofluorescence) at the light or electron microscopic level, it could be shown that in response to entorhinal lesion mossy cell axons leave the main commissural fiber plexus, invade the denervated middle molecular layer, and form asymmetric synapses within the denervated zone. Thus, the commissural sprouting response in mice has a considerable translaminar component. This is in contrast to the layer-specific commissural sprouting observed in rats, in which the overwhelming majority of mossy cell axons remain within their home territory. These data demonstrate an important species difference in the commissural/associational sprouting response between rats and mice that needs to be taken into account in future studies.

Animals↗

Co-expression of calretinin and gamma-aminobutyric acid in neurons of the entorhinal cortex of the common marmoset monkey.

The gamma-aminobutyric acid (GABA)-containing interneuron population in the entorhinal cortex has been shown to consist of several subpopulations. In addition to GABA, these neurons contain another neurochemical substance, such as a neuropeptide or a calcium binding protein. In the present study, we examined the co-localization of calretinin and GABA in the entorhinal cortex of the common marmoset Callithrix jacchus, a New World monkey. Although the function of calretinin remains unclear, there are indications that it might have a protective role against cell death in a number of neuropathological diseases. Furthermore, it might have a regulatory role in the neurotransmission of GABAergic neurons. In contrast to the rat brain, sparse data exist regarding the degree of co-expression of these two markers in the monkey brain. Using immunofluorescence and confocal laser scanning microscopy, we found that an average of 56% of the calretinin-positive neurons in the monkey entorhinal cortex contained GABA, whereas about 27% of the GABA-positive neurons co-expressed calretinin. Interestingly, these numbers were higher in the superficial layers of the entorhinal cortex in comparison with the deep layers. However, no differences were found in co-localization percentages between the different entorhinal subfields. In general, the degree of co-localization was higher in comparison to findings in the rat entorhinal cortex. The higher amount of co-localization observed in the present study might reflect species differences between the primate and the non-primate brain.

Animals↗

Mu opioid receptors are in discrete hippocampal interneuron subpopulations.

In the rat hippocampal formation, application of mu opioid receptor (MOR) agonists disinhibits principal cells, promoting excitation-dependent processes such as epileptogenesis and long-term potentiation. However, the precise location of MORs in particular inhibitory circuits, has not been determined, and the roles of MORs in endogenous functioning are unclear. To address these issues, the distribution of MOR-like immunoreactivity (-li) was examined in several populations of inhibitory hippocampal neurons in the CA1 region using light and electron microscopy. We found that MOR-li was present in many parvalbumin-containing basket cells, but absent from cholecystokinin-labeled basket cells. MOR-li was also commonly in interneurons containing somatostatin-li or neuropeptide Y-li that resembled the "oriens-lacunosum-moleculare" (O-LM) interneurons innervating pyramidal cell distal dendrites. Finally, MOR-li was in some vasoactive intestinal peptide- or calretinin-containing profiles resembling interneurons that primarily innervate other interneurons. These findings indicate that MOR-containing neurons form a neurochemically and functionally heterogeneous subset of hippocampal GABAergic neurons. MORs are most frequently on interneurons that are specialized to inhibit pyramidal cells, and are on a limited number of interneurons that target other interneurons. Moreover, the distribution of MORs to different neuronal types in several laminae, some relatively far from endogenous opioids, suggests normal functional roles that are different from the actions seen with exogenous agonists such as morphine.

Animals↗

Long-term effects of amygdala GABA receptor blockade on specific subpopulations of hippocampal interneurons.

Growing evidence indicates that the amygdala modulates hippocampal functions. To test the hypothesis that this modulation may involve long-lasting effects on interneuronal networks in the hippocampus, changes in the expression of neurochemical markers specific for different interneuronal subpopulations were assessed in adult rats 96 h following acute infusion of low doses of the GABAA receptor antagonist picrotoxin into the amygdala. The numerical density (Nd) of somata showing immunoreactivity (IR) for parvalbumin (PVB) was decreased in dentate gyrus (DG) and the CA4-2 region, while that of calretinin (CR)-IR was decreased in DG and CA2. The Nd of calbindin D28k (CB)-IR somata was decreased in CA3-2. The densities of axon terminals arising from PVB-IR and cholecystokinin (CCK)-IR basket neurons were also altered, with those of CCK-IR terminals increased across all sectors, while PVB-IR terminals were decreased only in the CA region. Increases in CCK-IR terminals were paralleled by increases of terminals with IR for the 65-kD isoform of glutamate decarboxylase (GAD65). Mixed-effects statistical models, adapted specifically for these analyses, indicated that perturbations of amygdalar inputs to the hippocampus significantly alter the drive that hippocampal PVB-, CR-, and CB-IR neurons within the dentate gyrus/CA4 region exercise on CCK-IR terminals within the same region as well as in CA3-1. These results suggest that amygdalar modulation of specific neuronal subpopulations may induce lasting and far-reaching changes in the hippocampus during normal functioning, as well as in diseases involving a disruption of amygdalar activity. In particular, changes in specific interneuronal markers within selective hippocampal sectors detected in the present results are strikingly similar to those reported in this region in schizophrenia. These similarities suggest that, in this disease, a disruption of GABAergic transmission within the amygdala may play a significant role in the induction of abnormalities in the hippocampus.

Algorithms↗