Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Piriform Cortex”

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 1,477 records · Page 82Linked to original sources
PubMed2001

Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata.

The infralimbic area (IL) and prelimbic area (PL) have been postulated as an autonomic motor region in the medial prefrontal cortex. The present study was conducted to reveal the projection sites of IL and PL of the monkey, Macaca fuscata, using biotinylated dextran amine as an anterograde tracer. IL and PL projected densely to the ventromedial caudate nucleus, the core and shell of the nucleus accumbens (Acb), parvicellular lateral basal and magnocellular accessory basal nuclei of the amygdala, lateral preoptic area, ventromedial hypothalamic nucleus, tubero-mammillary nucleus (TM), medial part of the magnocellular and dorsal part of the parvicellular (MDpc) dorsomedial thalamic nuclei, reunience and medial part of the medial pulvinar nucleus, and dorso-lateral part of the periaqueductal gray (PAGdl) in the mesencephalon. Moderately to weakly projected areas were the intermediate and lateral parts of the agranular insular cortex, orbital part of area 12, agranular and dysgranular part of the temporal pole cortex (TPa-g), auditory temporal cortex, lateral and medial (MS) septal nuclei, bed nucleus of the stria terminalis, diagonal band of Broca, substantia innominata, and medial preoptic area, dorsomedial, lateral, and posterior hypothalamic nuclei, magnocellular lateral basal and lateral amygdaloid nuclei, paratenial, paraventricular (PV), inter-antero-medial (IAM), reticular, central medial (CeM), parafascicular (PF) and limitans nuclei of the thalamus, lateral habenular nucleus, pedunculo-pontine nucleus, dorsal part of the lateral lemniscal nucleus, ventral tegmental area (VTA), dorsal raphe, superior central nucleus, medial and lateral parabrachial nuclei (PBl) and nucleus locus coeruleus (LC). A few scattered terminals were observed in the perifornical nucleus of the hypothalamus and substantia nigra pars compacta. PL and area 24 were characterized by projections to the entorhinal (Ent) and piriform (Pir) cortex as well as to the magnocellular part of the ventral anterior thalamic nucleus (VAmc). The morphology of the terminal arborization in each nuclei was different in appearance, perhaps reflecting the synaptic interaction between the nerve terminals and postsynaptic dendrites. PL projected uniquely to Ent, Pir and VAmc and IL projected uniquely to TPa-g, MS, IAM, CeM, MDpc, PF, PBl and LC. IL projected more strongly than PL to the shell of Acb, amygdaloid nuclei, PV, TM, VTA and PAGdl. The present results support the hypothesis that IL is a major cortical autonomic motor area and PL integrates limbic and autonomic inputs in the primate.

Animals↗
PubMed1993

The organization of projections from the mediodorsal nucleus of the thalamus to orbital and medial prefrontal cortex in macaque monkeys.

The organization of interconnections between the mediodorsal nucleus of the thalamus (MD) and the orbital and medial prefrontal cortex and the agranular insular cortex in the monkey was studied by retrograde and anterograde tracing techniques. In addition to the magnocellular and parvicellular divisions of MD, three other subdivisions can be recognized on the basis of myeloarchitecture, cytoarchitecture, and connections. The first two of these represent a parcellation of the magnocellular division into a lateral, fiber-rich MD pars fibrosa and a medial, poorly myelinated MD pars paramediana adjacent to the midline. The third is a small, poorly myelinated area located at the caudomedial and dorsal edges of MD; it is referred to as MD pars caudodorsalis. MD pars fibrosa is reciprocally interconnected primarily with areas 11, 12 and 13 in the central and lateral part of the orbital cortex. There is a general organization within this projection, with the rostrocaudal axis of the cortex represented from dorsal to ventral in the pars fibrosa, and the mediolateral cortical axis represented from medial to lateral. Cells that project to area 12 also extend laterally into the adjacent pars parvicellularis. MD pars paramediana is more heavily interconnected with the caudal and medial portions of the orbital region, particularly the agranular insular areas and the caudal parts of areas 13 and 14. Cells that project to two caudal areas, 13a and Iad, do not fit with the general organization, in that they are located in the dorsomedial parts of the pars fibrosa and pars paramediana, where they overlap with cells that project to area 14. The pars fibrosa and pars paramediana receive inputs from areas of the ventral forebrain such as the amygdala, piriform (olfactory) cortex, and entorhinal cortex, which project directly to the orbital and agranular insular cortex, as well as from the ventral pallidum. MD pars caudodorsalis is reciprocally interconnected with areas 14, 24, and 32 on the medial surface of the prefrontal cortex. In this part of the nucleus the dorsoventral axis of the medial prefrontal cortex is represented from caudal to rostral in the thalamus. The amygdala and other ventral forebrain structures do not send fibers into the pars caudodorsalis, even though some of these structures project directly to the medial prefrontal cortex. Ventral to MD, and separated from it by the internal medullary lamina, a small region was recognized that appears to be comparable to the anteroventral part of the submedial nucleus previously defined in the rat and cat.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

Expression of neurotrophin-3 in the mouse forebrain: insights from a targeted LacZ reporter.

To obtain insights into the expression of neurotrophin-3 (NT-3) in the mouse, we have utilized mice in which the Escherichia coli lacZ gene is integrated into the neurotrophin-3 locus (NT-3(lacZneo), Fariñas et al. [1994] Nature 369:658-661). In this mouse strain, beta-galactosidase production is under control of the NT-3 promoter in its normal chromosomal environment, and histochemical measurement of beta-galactosidase provides a simple, sensitive method to determine which cells express NT-3. Our data correlate well with previous in situ mRNA and immunocytochemical studies reporting the localization of NT-3. For example, in adult NT-3(lacZneo)/+ mice, beta-galactosidase is expressed in high amounts in limbic areas of the cortex (cingulate, retrosplenial, piriform, and entorhinal), in the visual cortex, in the hippocampal formation (dentate granule cells, CA2 cells, fasciola cinereum, induseum griseum, tenia tecta, presubiculum, and parasubiculum), and in the septum (septohippocampal nucleus and lateral dorsal septum). In contrast with other studies, our results suggest more extensive expression of NT-3 in adult and aged mouse brains with cortical expression apparent at 4.5 months. To further define the cell populations expressing NT-3 in adult mice, we have combined immunocytochemistry with histochemical staining and found that beta-galactosidase is coexpressed with a neuronal marker (NeuN) and with parvalbumin and neuropeptides, markers for GABAergic interneurons. Our studies of embryonic beta-galactosidase expression in NT-3(lacZneo)/+ mice suggest sites of NT-3 expression not previously described, including embryonic piriform cortical cells and dentate granule cell precursors.

Animals↗
PubMed1996

Neurogranin in the development of the rat telencephalon.

We have used a novel antibody to map the distribution of the protein kinase C substrate protein RC3/neurogranin during the development of the rat telencephalon. Neurogranin appearance in the rat brain is biphasic: it shows an early stage of anatomically restricted, low-intensity expression, and a juvenile stage of anatomically widespread, high-intensity expression. Most of the structures that express neurogranin during development conserve it in the adult stage. Neurogranin expression starts on embryonic day 18 in two different sites-the amygdalar primordium and in the piriform cortex-and is confined to these structures until the first postnatal day (P1). On P1, neurogranin expression increases dramatically in intensity, and appears in the olfactory cortex, isocortex, subiculum and hippocampus. In the striatum, expression starts on P1 and extends to the caudoputamen and parts of the globus pallidus and septum. Particularly complex patterns of labelling can be seen in the amygdala and cerebral cortex. Cortical layers showing early expression are the presumptive layers 4 and 5 in the somatosensory cortex, and layers 2 and 5 in the anterior cingulate and agranular insular cortices. Immunoreactivity is found mostly in cell bodies during the early and juvenile stages, but by the end of the first postnatal week it starts being more apparent in the neuropil. This phenomenon probably reflects the intracellular translocation of neurogranin to distal parts of the dendrites and dendritic spines. This process culminates by the end of the second postnatal week, when the adult pattern is reached. According to the timing and anatomy of its distribution, expression of neurogranin seems to be independently regulated in each telencephalic region by specific signalling mechanisms. It is proposed, on this basis, that neurogranin could be implicated in neuronal differentiation and synaptogenesis during telencephalic development.

Aging↗
PubMed2006

Depressive behavior in mice due to immune stimulation is accompanied by reduced neural activity in brain regions involved in positively motivated behavior.

BACKGROUND: Immune stimulation inhibits positively motivated behavior and induces depressive illness. To help clarify the mechanism of these effects, neural activity in response to a positive stimulus was examined in brain regions associated with positively motivated activity defined on the basis of prior behavioral studies of central alpha1-adrenoceptor action. METHODS: Mice pretreated with either lipopolysaccharide or, for comparison, reserpine were exposed to a motivating stimulus (fresh cage) and subsequently assayed for fos expression and mitogen-activated protein kinase (MAPK) phosphorylation, two measures associated with alpha1-adrenoceptor-dependent neural activity, in several positive-activity-related (motor, piriform, cingulate cortex, nucleus accumbens, locus coeruleus) and stress-related brain regions (paraventricular hypothalamus, bed nucleus stria terminalis). RESULTS: Both lipopolysaccharide and reserpine pretreatment abolished fresh cage-induced fos expression and MAPK activation in the positive activity-related brain regions but enhanced these measures in the stress-related areas. CONCLUSIONS: The results support the hypothesis that immune activation reduces alpha1-adrenoceptor-related signaling and neural activity in brain regions associated with positive activity while it increases these functions in stress-associated areas. It is suggested that neural activities of these two types of brain regions are mutually antagonistic and that a reciprocal shift toward the stress regions is a factor in the loss of positively motivated behaviors in sickness behavior and depressive illness.

Adjuvants, Immunologic↗
PubMed2000

Immunohistochemical localisation of the 5-HT2C receptor protein in the rat CNS.

5-HT2C receptor mRNA has a widespread distribution in the human and rat CNS but the absence of a specific high affinity ligand has made autoradiographic localisation of the receptor difficult. By raising polyclonal antibodies against the rat 5-HT2C receptor protein this study reports the immunohistochemical distribution of this receptor in the rat CNS. A sephadex purified 5-HT2C antiserum visualised a single immunopositive band (54 kDa) in Western blots of membranes prepared from several rat brain regions and caused intense membrane immunofluorescence in HEK 293 cells transfected with h5-HT2C cDNA, which were both attenuated by incubation with the antigenic peptide sequence (200-300 microM). 5-HT2C-like immunoreactivity was located on neurones throughout the CNS. The most abundant 5-HT2C-like immunoreactive cell bodies were in the anterior olfactory nucleus, medial and intercalated amygdaloid nuclei, hippocampus layers CA1 to CA3, laterodorsal and lateral geniculate thalamic nuclei, caudate-putamen and several areas of the cortex (including piriform and frontal), consistent with this receptor being located postsynaptic to serotonergic neurones. Immunopositive neurones were also found in the dorsal raphé, suggesting that 5-HT2C receptors may be on some serotonergic neurones. The overall distribution of 5-HT2C-like immunoreactivity complements previous findings with conventional radioligands and agrees well with reported levels of 5-HT2C receptor mRNA.

Amino Acid Sequence↗
PubMedDate not supplied

Olfactory tests as possible probes for detecting and monitoring Alzheimer's disease.

One of the characteristics of Alzheimer's disease is the early loss of neurons in pathways involved in processing olfactory information. Olfactory function was assessed in subjects with Alzheimer's disease using a conventional Smell Identification Test and a simple three odor match-to-sample problem. The patients exhibited a diminished capacity to identify common odors but were severely impaired in their ability to use novel odors in a match-to-sample task. Subjects with Parkinson's disease had a severe deficit for identifying common odors with the majority scoring as anosmic. Multiple sclerosis was not accompanied by detectable changes in olfactory functioning. The results of the Alzheimer's group are similar to recent animal studies that have shown lesions of the piriform-entorhinal cortex produce a variety of memory deficits that are particularly acute in tasks involving novel odors.

Aged↗
PubMed1997

Mouse model of GM2 activator deficiency manifests cerebellar pathology and motor impairment.

The GM2 activator deficiency (also known as the AB variant), Tay-Sachs disease, and Sandhoff disease are the major forms of the GM2 gangliosidoses, disorders caused by defective degradation of GM2 ganglioside. Tay-Sachs and Sandhoff diseases are caused by mutations in the genes (HEXA and HEXB) encoding the subunits of beta-hexosaminidase A. The GM2 activator deficiency is caused by mutations in the GM2A gene encoding the GM2 activator protein. For degradation of GM2 ganglioside by beta-hexosamindase A, the GM2 activator protein must participate by forming a soluble complex with the ganglioside. In each of the disorders, GM2 ganglioside and related lipids accumulate to pathologic levels in neuronal lysosomes, resulting in clinically similar disorders with an onset in the first year of life, progressive neurodegeneration, and death by early childhood. We previously have described mouse models of Tay-Sachs (Hexa -/-) and Sandhoff (Hexb -/-) diseases with vastly different clinical phenotypes. The Hexa -/- mice were asymptomatic whereas the Hexb -/- mice were severely affected. Through gene disruption in embryonic stem cells we now have established a mouse model of the GM2 activator deficiency that manifests an intermediate phenotype. The Gm2a -/- mice demonstrated neuronal storage but only in restricted regions of the brain (piriform, entorhinal cortex, amygdala, and hypothalamic nuclei) reminiscent of the asymptomatic Tay-Sachs model mice. However, unlike the Tay-Sachs mice, the Gm2a -/- mice displayed significant storage in the cerebellum and defects in balance and coordination. The abnormal ganglioside storage in the Gm2a -/- mice consisted of GM2 with a low amount of GA2. The results demonstrate that the activator protein is required for GM2 degradation and also may indicate a role for the GM2 activator in GA2 degradation.

Animals↗
PubMed2005

Dynamics of learning-induced spine redistribution along dendrites of pyramidal neurons in rats.

We have previously shown that olfactory-discrimination (OD) learning is accompanied by enhanced spine density along proximal apical dendrites of layer II pyramidal neurons in the piriform (olfactory) cortex. Here we studied the temporal dynamics of learning-induced modifications in dendritic spine density throughout the dendritic trees of these neurons. We observed a transient increase in proximal apical spine density after OD learning, suggesting a strengthening of intrinsic excitatory inputs interconnecting neurons within the olfactory cortex. By contrast, the afferent pathway receiving direct input from the olfactory bulb shows spine pruning, suggesting that the connectivity is weakened. The changes in spine density can be attributed to a net change in number of spines, as the morphometric parameters of the dendrites are unaffected by learning. We suggest that spine density changes may represent a mechanism of selective synaptic reorganization required for olfactory learning consolidation.

Animals↗
PubMed2005

Cortical metabotropic glutamate receptors contribute to habituation of a simple odor-evoked behavior.

Defining the circuits that are involved in production and cessation of specific behaviors is an ultimate goal of neuroscience. Short-term behavioral habituation is the response decrement observed in many behaviors that occurs during repeated presentation of non-reinforced stimuli. Within a number of invertebrate models of short-term behavioral habituation, depression of a defined synapse has been implicated as the mechanism. However, the synaptic mechanisms of short-term behavioral habituation have not been identified within mammals. We have shown previously that a presynaptic metabotropic glutamate receptor (mGluR)-dependent depression of synapses formed by olfactory bulb afferents to the piriform (olfactory) cortex significantly contributes to adaptation of cortical odor responses. Here we show that blockade of mGluRs within the olfactory cortex of awake, behaving rats diminishes habituation of a simple odor-induced behavior, strongly implicating a central mechanism for sensory gating in olfaction.

Animals↗
PubMed1993

Developmental differences in neural damage following trimethyl-tin as demonstrated with GFAP immunohistochemistry.

Long-Evans rat pups received intraperitoneal (i.p.) injections of trimethyl-tin (TMT) 6 mg/kg hydroxide or saline on postnatal day (PND) 10 or PND 18 and were sacrificed for immunohistochemical staining for glial fibrillary acidic protein (GFAP) on PND 12, 18, 20, or 25. After dosing with TMT on PND 10 there was a transient increase in GFAP immunoreactivity (IR) in the amygdala, piriform, and entorhinal cortex 2 days post-dosing (PND 12) and a persistent increase in GFAP IR in the hippocampus and cingulate cortex up to two weeks post-dosing. Following dosing with TMT on PND 18 there was a delayed (PND 25) increase in GFAP IR in the amygdala, hippocampus, cingulate, piriform, and entorhinal cortex. In addition, increases in GFAP IR were observed in the neocortex 7 days post-dosing, which was not observed following earlier postnatal dosing. The regions in which gliosis and loss of Nissl-staining were consistent for the different time points of TMT treatment were the amygdala, hippocampus, cingulate, piriform, and entorhinal cortex. The present findings indicate the GFAP immunohistochemistry can be used to reveal regional effects of developmental neurotoxicant exposure during early stages of development.

Animals↗
PubMed1986

Circadian rhythms in neurotransmitter receptors in discrete rat brain regions.

Circadian rhythms were measured in alpha 1-, alpha 2- and beta-adrenergic, acetylcholine muscarinic (ACh), and benzodiazepine (BDZ) receptor binding in small regions of rat brain. Rhythms in alpha 1-receptor binding were measured in olfactory bulb, frontal, cingulate, piriform, parietal, temporal and occipital cortex, hypothalamus, hippocampus, pons-medulla, caudate-putamen and thalamus-septum. No rhythm was found in cerebellum. Rhythms in alpha 2-receptor binding were measured in frontal, parietal and temporal cortex, and pons-medulla. No rhythm was found in cingulate, piriform or occipital cortex, or hypothalamus. Rhythms in binding to beta-receptors were measured in olfactory bulb, piriform, insular, parietal and temporal cortex, hypothalamus and cerebellum. No rhythms were found in frontal, entorhinal, cingulate, or occipital cortex, hippocampus, caudate-putamen, or pons-medulla. Rhythms in ACh receptor binding were measured in olfactory bulb, parietal cortex and caudate-putamen. No rhythms were found in frontal or occipital cortex, nucleus accumbens, hippocampus, thalamus-septum, pons-medulla or cerebellum. Rhythms in BDZ receptor binding were measured in olfactory bulb, olfactory and occipital cortex, olfactory tubercle, nucleus accumbens, amygdala, caudate-putamen, hippocampus and cerebellum. No rhythms were found in parietal cortex, pons-medulla or thalamus-septum. The 24-hr mean binding to receptors varied between 3- and 10-fold, the highest in cortex and the lowest, usually, in cerebellum. The piriform cortex was particularly high in alpha 1- and alpha 2-adrenergic receptors; the nucleus accumbens and caudate, in ACh receptors; and the amygdala, in BDZ receptors. Most adrenergic and ACh receptor rhythms peaked in subjective night (the period when lights were off under L:D conditions), whereas most BDZ receptor rhythms peaked in subjective day (the time lights were on in L:D). Perhaps in the rat, a nocturnal animal, the adrenergic and ACh receptors mediate activity and the functions that accompany it, and the BDZ receptors mediate rest, and with it, sleep.

Animals↗
PubMed1995

Down-regulation of AMPA receptor subunit GluR2 in amygdaloid kindling.

Alterations in glutamatergic transmission are postulated to be important in kindling and epilepsy. The levels of alpha-amino-3-hydroxy- 5-methylisoxazole-4-propionic acid (AMPA) receptor subunits (GluR1, 2, and 4) were compared in amygdala-kindled and sham-operated animals using subunit-specific antibodies and quantitative western blotting. Four limbic regions were examined: limbic forebrain, piriform cortex/amygdala, hippocampus, and entorhinal cortex. When subunit levels were examined 24 h after the last stage 5 seizure, levels of GluR2 were found to be selectively reduced in limbic forebrain (30%) and piriform cortex/amygdala (25%), with no changes in other regions examined. In addition, no changes in the other subunits were observed in any region. The decrease in GluR2 that was observed in kindled animals at 24 h was no longer present at 1 week and 1 month after the last stage 5 seizure. Because the GluR2 subunit uniquely determines the calcium permeability of these receptors and because the piriform cortex has been implicated as a source of excitatory drive for limbic seizures, reduced GluR2 expression may be important in increasing neuronal excitability in kindling-induced epilepsy, or may reflect a compensatory mechanism resulting from kindling.

Amygdala↗
PubMed2002

NMDA receptor-dependent long-term synaptic depression in the entorhinal cortex in vitro.

The entorhinal cortex receives a large projection from the piriform (primary olfactory) cortex and, in turn, provides the hippocampal formation with most of its cortical sensory input. Synaptic plasticity in this pathway may therefore affect the processing of olfactory information and memory encoding. We have recently found that long-term synaptic depression (LTD) can be induced in this pathway in vivo by repetitive paired-pulse stimulation but not by low-frequency (1 Hz) stimulation with single pulses. Here, we have used field potential recordings to investigate the stimulation parameters and transmitter receptors required for the induction of LTD in the rat entorhinal cortex in vitro. The effectiveness of low-frequency stimulation (900 pulses at 1 or 5 Hz) and repeated delivery of pairs of stimulation pulses (30-ms interpulse interval) was assessed. Only repeated paired-pulse stimulation resulted in lasting LTD, and a low-intensity paired-pulse stimulation protocol that induces LTD in vivo was only effective in the presence of the GABA(A) receptor antagonist bicuculline (50 microM). LTD could also be induced in normal ACSF, however, by increasing the number of pulse-pairs delivered and by increasing the stimulation intensity during LTD induction. The induction of LTD was blocked by constant bath application of the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist d-2-amino-5-phosphonovalerate (50 microM), indicating that LTD is dependent on NMDA receptor activation. However, LTD was not blocked by the group I/II mGluR antagonist (RS)-alpha-ethyl-4-carboxyphenylglycine (500 microM) or by bicuculline (50 microM). The induction of LTD in the entorhinal cortex in vitro is therefore dependent on intense stimulation that recruits activation of NMDA receptors, but does not require concurrent activation of mGluRs or inhibitory synaptic inputs.

2-Amino-5-phosphonovalerate↗
PubMed2004

Nutritional iron deprivation attenuates kainate-induced neurotoxicity in rats: implications for involvement of iron in neurodegeneration.

There is evidence suggesting that oxidative stress contributes to kainate neurotoxicity. Since iron promotes oxidative stress, the present study explores how change in nutritional iron content modulates kainate-induced neurotoxicity. Rats received an iron-deficient diet (ID) from 22 days of age for 4 weeks. One control group received the same diet supplemented with iron and another control group received standard rodent diet. Cellular damage after subcutaneous kainate (10 mg/kg) was assessed by silver impregnation and gliosis by staining microglia. ID reduced cellular damage in piriform and entorhinal cortex, in thalamus, and in hippocampal layers CA1-3. ID also attenuated gliosis, except in the hippocampal CA1 layer. Given involvement of zinc in hippocampal neurotransmission and in oxidative stress, we tested for a possible interaction of nutritional iron with nutritional zinc. Rats were made iron-deficient and then assigned to supplementation with iron, zinc, or iron + zinc. Controls were continued on ID diet. After 2 weeks, rats were treated with kainate. Iron supplementation abolished the protective effect of ID in piriform and entorhinal cortex. In hippocampal CA1 and dorsal thalamus, neither iron nor zinc supplementation alone abolished the protective effect of ID against cellular damage. Iron + zinc supplementation abolished ID protection in dorsal thalamus, but not in reuniens nucleus. Kainate-induced gliosis in CA1 remained unaffected by nutritional treatments. Thus, in piriform and entorhinal cortex, nutritional iron has a major impact on cellular damage and gliosis. In hippocampal CA1, gliosis may associate with synaptic plasticity not modulated by nutritional iron, while cellular damage is sensitive to nutritional iron and zinc.

Animals↗
PubMed1997

Neuropathology of bovine herpesvirus type 5 (BHV-5) meningo-encephalitis in a rabbit seizure model.

The suitability of a rabbit seizure model for studying the neuropathogenesis of bovine herpesvirus type 5 (BHV-5) encephalitis was evaluated. Intranasal administration of BHV-5 (strain TX89) together with intramuscular administration of dexamethasone produced seizures in 70% of rabbits tested and meningo-encephalitis in 100%. Infectious BHV-5 was consistently isolated from the following sites: olfactory bulb; anterior cortex, containing the frontal cortex, olfactory tract and anterior portion of the olfactory cortex; posterior cortex, containing the temporal, parietal, piriform, entorhinal and occipital cortices; amygdala; hippocampus. Less frequently, BHV-5 was isolated from the midbrain and diencephalon, the pons and medulla, the cerebellum, and the trigeminal ganglia. Rabbits similarly infected with the Cooper strain of bovine herpesvirus type 1 showed no neurological signs or meningo-encephalitis, and virus was not recovered from the brain. The brains of BHV-5-infected rabbits showed neuronal degeneration, leptomeningitis, gliosis and perivascular cuffing, predominantly in the olfactory cortex (piriform and entorhinal cortices), amygdala and hippocampus. Mild lymphocytic meningitis was seen in the olfactory bulb and focal lymphocytic infiltration was sometimes present in the medulla and cerebellum. BHV-5, specific antigens and nucleic acids were detected in the olfactory cortex, amygdala and hippocampus by immunohistochemical methods and in-situ hybridization. The results suggested that, after intranasal BHV-5 inoculation, the virus spread to the central nervous system via the olfactory and trigeminal pathways. The olfactory pathway was more susceptible than the trigeminal pathway to neuropathogenic effects.

Animals↗
PubMed1993

JUN, FOS, KROX, and CREB transcription factor proteins in the rat cortex: basal expression and induction by spreading depression and epileptic seizures.

The expression of the nuclear c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB transcription factors was investigated in the cortex of adult rats by immunocytochemistry. The expression patterns were studied in untreated rats and up to 24 hours following topical application of 1 M KCl to the cortical surface (KCl) or i.v. injection of bicuculline (BIC). Topical KCl induced cortical spreading depression and systemic injection of bicuculline evoked generalized tonic-clonic seizures. In untreated rats, JUN B, c-FOS, and FOS B were expressed in a small number of neurons in the piriform, perirhinal, entorhinal, and insular cortex and in layers II, III, and VI of all neocortical areas. In contrast, c-JUN, JUN D, and KROX-24 were expressed in all cortical layers but with different intensities of immunoreactivity (IR): c-JUN-IR was generally weak and predominantly present in layers II, III, and VI. JUN D-IR was equally strong in all layers. KROX-24 showed a prominent expression in layers II, IV, and VI. The CREB protein exhibited a slight preponderance in layer II and piriform cortex. Following KCl or BIC, a strong induction was seen for c-FOS, JUN B, and KROX-24, whereas c-JUN, JUN D, and FOS B showed only a moderate increase compared to basal levels. Changes of CREB-IR could not be detected. The localization of induced JUN, FOS, and KROX proteins reflected the pattern of labelling in untreated animals but demonstrated a higher intensity of labelling and an increased number of immunoreactive nuclei. The intensity and persistence of IR as well as the number of labelled cells following BIC exceeded those following KCl. Following BIC, increased levels of FOS B and JUN D were still present after 24 hours. Counterstaining with cresyl-violet and GFAP, a marker for astrocytes, revealed that JUN, FOS, and KROX proteins were expressed in neurons but not in glial cell populations. The present data demonstrate that CREB, JUN, FOS, and KROX transcription factors exhibit a layer-specific expression in the cerebral cortex with only slight area-specific differences both in untreated rats and following stimulation with KCl and BIC. The expression of transcription factor proteins indicate complex molecular genetic changes in cortical neurons due to pathophysiological events such as seizure activity and spreading depression.

Activating Transcription Factor 1↗