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PubMed1996

Sense and antisense transcripts of the developmentally regulated murine hsp70.2 gene are expressed in distinct and only partially overlapping areas in the adult brain.

We have examined the spatial pattern of expression of a member of the hsp70 gene family, hsp70.2, in the mouse central nervous system. Surprisingly, RNA blot analysis and in situ hybridization revealed abundant expression of an 'antisense' hsp70.2 transcript in several areas of adult mouse brain. Two different transcripts recognized by sense and antisense riboprobes for the hsp70.2 gene were expressed in distinct and only partially overlapping neuronal populations. RNA blot analysis revealed low levels of the 2.7 kb transcript of hsp70.2 in several areas of the brain, with highest signal in the hippocampus. Abundant expression of a slightly larger (approximately 2.8 kb) 'antisense' transcript was detected in several brain regions, notably in the brainstem, cerebellum, mesencephalic tectum, thalamus, cortex, and hippocampus. In situ hybridization revealed that the sense and antisense transcripts were both predominantly neuronal and localized to the same cell types in the granular layer of the cerebellum, trapezoid nucleus of the superior olivary complex, locus coeruleus and hippocampus. The hsp70.2 antisense transcripts were particularly abundant in the frontal cortex, dentate gyrus, subthalamic nucleus, zona incerta, superior and inferior colliculi, central gray, brainstem, and cerebellar Purkinje cells. Our findings have revealed a distinct cellular and spatial localization of both sense and antisense transcripts, demonstrating a new level of complexity in the function of the heat shock genes.

Animals↗

PubMed1995

Developmental expression of the neural adhesion molecule F3 in the rat brain.

We cloned a cDNA encoding rat F3 and analyzed the nucleotide sequences. The results have shown that rat F3 is comprised of 1021 amino acid residues. It shared 99% and 76% identities with mouse and chicken homologs, respectively, at the amino acid sequence level. During postnatal development of the rat brain, cells expressing F3 mRNA appeared in the cortex, hippocampus, superior and inferior colliculi, anterior olfactory nucleus, olfactory bulb and cerebellum, whereas little was observed at postnatal day 1 (P1). Extraordinarily high expression of F3 mRNA was observed in the cerebral cortical neurons of layer 5 at P7. The number of cells with high expression of F3 mRNA expanded to the entire region of the cerebral cortex at P14. The whole cerebrum displayed expression at P90 in which the cortex still showed the highest expression level, although the overall signals were weak in comparison with those at P14. In the hippocampal formation, F3-expressing granule cells of the dentate gyrus were restricted to the outer aspect, then expanded to the inner aspect during development. Finally the granule cells in the entire region of the dentate gyrus transcribed F3 mRNA. We discuss the significance of the expression pattern of F3 mRNA during development.

Amino Acid Sequence↗

PubMed1985

Autoradiographic mapping of somatostatin receptors in the rat central nervous system and pituitary.

Somatostatin receptor-binding sites have been visualized by autoradiography in the rat central nervous system and the pituitary using the [Tyr3] derivative of the stable octapeptide somatostatin analogue SMS 201-995, code named 204-090 (sequence in text), which has been shown to label specifically high-affinity somatostatin receptors in brain homogenates. Receptors are particularly concentrated in the deeper layers of the cerebral cortex and large areas of the limbic system are rich in somatostatin receptors, in particular the hippocampus (CA1, CA2, dentate gyrus), most amygdaloid nuclei, the medial habenula and the septum. Parts of the olfactory, visual and auditory, as well as visceral and somatic sensory systems are heavily labelled, in particular the anterior olfactory nucleus and tubercle, the superior and inferior colliculi, the nucleus of the solitary tract, the substantia gelatinosa of the spinal cord and the spinal trigeminal nucleus. It is of interest that the central grey and locus coeruleus are also substantially labelled with [125I]204-090. Striatum has moderate amounts of somatostatin receptors, distributed in a patchy and heterogeneous way. Cerebellum and substantia nigra are virtually devoid of somatostatin receptors. The described receptors are likely to represent the molecular target for a variety of pharmacological actions of somatostatin in the central nervous system and they emphasize the role played by somatostatin as a neuropeptide in this organ.

Animals↗

PubMed1990

Demonstration of extensive brainstem projections to medial and lateral thalamus and hypothalamus in the rat.

We use the method of retrograde transport of colloidal gold with silver intensification to map locations of brainstem neurons projecting to various nuclei of the medial and lateral thalamus (Menetrey, Histochemistry 83, 391-395, 1985; Seeley and Field, Brain Res. 449, 177-191, 1988). In rats injections of less than 1.0 microliters of a gold-wheatgerm agglutinin-horseradish peroxidase complex were restricted to the centrum medianum, centralis lateralis, medialis dorsalis, zona incerta, ventrobasal thalamic complex, or medial or lateral hypothalamus. Injections in the centralis lateralis, with some involvement of centrum medianum and medial medialis dorsalis, labeled numerous neurons throughout the rostrocaudal extent of the midbrain periaqueductal gray, and adjacent reticular formation, dorsal raphe nucleus and substantia nigra. These labeled neurons were distributed bilaterally, but with a preponderance ipsilaterally. Numerous neurons in the deep layers of the ipsilateral superior colliculus and in the anterior pretectal nucleus were also labeled. Many neurons in the pontomedullary raphe nuclei (including nucleus raphe magnus), locus coeruleus and dorsolateral parabrachial nuclei, and in the pontomedullary reticular formation, were labeled bilaterally. Fewer were seen bilaterally in the lateral reticular nucleus and nucleus of the solitary tract, with relatively few in the dorsal aspect of the trigeminal nucleus caudalis. Injections restricted largely to the centrum medianum labeled fewer cells in the brainstem, but with similar distributions. An injection restricted to the centralis lateralis also resulted in a similar distribution of labeled neurons in midbrain and nucleus raphe magnus but did not label neurons at more caudal medullary levels. An injection restricted to zona incerta labeled numerous neurons in a distribution similar to that following medial thalamic injections, except that many more were observed in the contralateral sensory trigeminal nucleus and in the dorsal column nuclei. Injections of the ventrobasal thalamic nucleus labeled many neurons in the trigeminal and dorsal column nuclei, but many fewer neurons in the midbrain, periaqueductal gray and reticular formation compared with medial thalamic injections. Labeled neurons were also seen in the superior and inferior colliculi, due presumably to involvement by the injection of the lateral posterior and magnocellular medial geniculate nuclei, respectively. Injections in the lateral hypothalamus labeled numerous neurons in a distribution similar to that seen following medial thalamic injections.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1991

Autoradiographic localization of subtypes of angiotensin II antagonist binding in the rat brain.

The non-peptide angiotensin II receptor compounds DuP 753 and WL 19 were utilized to detect subtypes of [125I]Sar1-Ile8-angiotensin II binding to angiotensin II receptors in the rat brain. In rat forebrain homogenates, DuP 753 and WL 19 produced a partial displacement of [125I]Sar1-Ile8-angiotensin II binding with DuP 753 displacing approximately 65% of the binding and WL 19 displacing approximately 35% of the binding. Using the techniques of quantitative receptor autoradiography, a distinct regional distribution of the subtypes of angiotensin II antagonist bind was detected. The angiotensin II-1 binding site (the receptor subtype preferentially displaced by DuP 753) appeared to predominate in the dipsogenic, cardiovascular and endocrine areas, including the subfornical organ, paraventricular and periventricular nuclei of the hypothalamus, anterior pituitary, dorsal motor nucleus of the vagus, nucleus of the solitary tract and the area postrema. Additional areas that contained predominantly the angiotensin II-1 receptor subtype were the ventral hippocampus, substantia gelatinosa of the trigeminal nucleus, nucleus of the lateral olfactory tract, piriform cortex and median preoptic nucleus. The angiotensin II-2 binding site (displaced by WL 19) was the predominant subtype in the thalamus, inferior olive, lateral septum, subthalamic nucleus, locus coeruleus, medial geniculate and medial amygdala. Several areas of the brain appeared to contain both receptor subtypes, including the superior and inferior colliculi, and the olfactory bulb. The angiotensin II-1 binding site was concentrated in areas of the brain involved in mediating angiotensin II effects on drinking, endocrine status and blood pressure. Localization of angiotensin II-2 sites in the thalamus and areas of the brain which process sensory information suggests a novel modulatory role for angiotensin II at this receptor subtype. These results indicate that DuP 753 and WL 19 are highly selective for angiotensin II binding site subtypes in the brain and that, in general these subtypes are compartmentalized in distinct brain regions. The non-peptide compounds used in these studies should provide excellent tools to discern the functional role of angiotensin II receptor subtypes in the brain.

Angiotensin II↗

PubMed1992

Distribution of cells expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide precursor messenger RNA in the rat brain.

The distribution of cells expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide precursor messenger RNA was investigated in the rat brain and pituitary by in situ hybridization using a synthetic 35S-labeled oligonucleotide probe. Detection of labeled neurons by light-microscopic radioautography revealed a selective repartition of the messenger RNA-expressing cells. Several major vasoactive intestinal peptide/peptide histidine isoleucine-amide messenger RNA-containing cell groups were demonstrated including layers II-VI of the cerebral cortex, the suprachiasmatic nucleus and various thalamic structures such as the ventrolateral, posterior, lateral reticular, paracentralis and gelatinosus nuclei. Positive cells, to a lesser extent, were also found in the limbic system, medial preoptic area, superior and inferior colliculi as well as in the central gray matter. They were totally absent in the pituitary and the pineal gland of normal rats. The results of the present study provide a detailed mapping of neurons expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide messenger RNA in the adult rat brain. The predominance of vasoactive intestinal peptide/peptide histidine isoleucine-amide messenger RNA-containing neurons in the cerebral cortex, suprachiasmatic nucleus and thalamus suggest that vasoactive intestinal peptide is mainly involved in the control of cortical informations, circadian rhythms and sensory perception in agreement with several physiological data.

Animals↗

PubMed1993

Spinal and hindbrain structures involved in visceroception and visceronociception as revealed by the expression of Fos, Jun and Krox-24 proteins.

We have used the evoked expression of the immediate early gene-encoded proteins (Krox-24, c-Fos, Fos B, Jun D, Jun B, c-Jun) to monitor visceral processing in both the spinal cord and hindbrain structures of rats undergoing either mechanical colorectal or chemical intraperitoneal stimulation. Experiments were conducted under controlled volatile anaesthesia to suppress affective reactions that visceral stimulations may induce. The results refer to the effects of anaesthesia alone, and of both innocuous and noxious stimulations. Non-nociceptive and nociceptive stimulation but not anaesthesia were effective in evoking c-Fos, c-Jun, Jun B and Krox-24 expressions in the spinal cord. Intraperitoneal injections labelled cells mostly at the thoracolumbar junction levels, while colorectal distension labelled cells mostly at the lumbrosacral junction levels. Labelling was widely distributed throughout the gray matter including superficial layers, deep dorsal horn, lamina X and sacral parasympathetic columns. Krox-24- and, to a lesser degree, c-Jun-labelled cells were quite numerous in the superficial layers of the dorsal horn; Jun B, and especially c-Fos, were very effective in demonstrating inputs to all parts of the spinal cord. Both anaesthesia and noxious visceral stimulation were effective in evoking c-Fos, Krox-24 and Jun B expressions in discrete hindbrain subregions. The structures which are primarily labelled under anaesthesia are the rostral ventrolateral medulla, the external medial and lateral nuclei of the parabrachial area, the medial and dorsal subnuclei of the nucleus of the solitary tract, the area postrema, the central gray including pars alpha and nucleus O, the nucleus beta of the inferior olive, the locus coeruleus, and the inferior colliculi and adjacent parts of central gray. The structures which are primarily labelled following noxious visceral stimulation are the caudal intermediate reticular nucleus as part of the caudalmost ventrolateral medulla and the superior lateral nucleus of the rostrolateral parabrachial area. Labelling in the caudal intermediate reticular nucleus was maximal for colorectal distension. Labelling in the superior lateral nucleus was specific to peritoneal inflammation. The Edinger-Westphal nucleus is a structure in which noxious-evoked labelling was superposed onto the anaesthesia-evoked labelling. Nociception-evoked overexpression in this nucleus was maximal for intraperitoneal inflammation. The present work demonstrates that the central effects induced by either anaesthesia or visceroception including pain can be effectively monitored through the induction of an array of immediate early genes.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia, Inhalation↗

PubMed1994

Nitric oxide synthase immunoreactivity in rat pontine medullary neurons.

Nitric oxide synthase immunoreactivity was detected in neurons and fibers of the rat pontine medulla. In the medulla, nitric oxide synthase-positive neurons and processes were observed in the gracile nucleus, spinal trigeminal nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus, nucleus ambiguus, medial longitudinal fasciculus, reticular nuclei and lateral to the pyramidal tract. In the pons, intensely labeled neurons were observed in the pedunculopontine tegmental nucleus, paralemniscal nucleus, ventral tegmental nucleus, laterodorsal tegmental nucleus, and lateral and medial parabrachial nuclei. Labeled neurons and fibers were seen in the interpeduncular nuclei, dorsal and median raphe nuclei, central gray and dorsal central gray, and superior and inferior colliculi. Double-labeling techniques showed that a small population (< 5%) of nitric oxide synthase-positive neurons in the medulla also contained immunoreactivity to the aminergic neuron marker tyrosine hydroxylase. The majority of nitric oxide synthase-immunoreactive neurons in the dorsal and median raphe nuclei were 5-hydroxytryptamine-positive, whereas very few 5-hydroxytryptamine-positive cells in the caudal raphe nuclei were nitric oxide synthase-positive. Virtually all nitric oxide synthase-positive neurons in the pedunculopontine and laterodorsal tegmental nuclei were also choline acetyltransferase-positive, whereas nitric oxide synthase immunoreactivity was either low or not detected in choline acetyltransferase-positive neurons in the medulla. The results indicate a rostrocaudal gradient in the intensity of nitric oxide synthase immunoreactivity, i.e. it is highest in neurons of the tegmentum nuclei and neurons in the medulla are less intensely labeled. The majority of cholinergic and serotonergic neurons in the pons are nitric oxide synthase-positive, whereas the immunoreactivity was either too low to be detected or absent in the large majority of serotonergic, aminergic and cholinergic neurons in the medulla.

Amino Acid Oxidoreductases↗

PubMed1996

Rapid distribution of intraventricularly administered sucrose into cerebrospinal fluid cisterns via subarachnoid velae in rat.

The intracranial distribution of [14C]sucrose, an extracellular marker infused for 30 s into one lateral ventricle, was determined by autoradiography of frozen-dried brain sections. Within 3.5 min [14C]sucrose appeared in: (i) the third ventricle, including optic, infundibular and mammillary recesses; (ii) the aqueduct of Sylvius; (iii) the velum interpositum, a part of the subarachnoid space that runs along the roof of the third ventricle and contains many blood vessels; (iv) the mesencephalic and fourth ventricles; and (v) the superior medullary velum, a highly vascular extension of the subarachnoid space that terminates at the walls of the mesencephalic and fourth ventricles. Within 5 min, radioactivity was present in the interpeduncular, ambient and quadrigeminal cisterns, which encircle the midbrain. By 10 min, approximately 11% of the radioactivity had passed into the subarachnoid space via a previously undescribed flow pathway that included the velum interpositum and superior medullary velum. At many places along the ventricular system, [14C]sucrose appeared to move from cerebrospinal fluid into the adjacent tissue by simple diffusion, as reported previously (Blasberg R. G. et al. (1974) J. Pharmac. exp. Ther. 195, 73-83; Levin V. A. et al. (1970) Am. J. Physiol. 219, 1528-1533; Patlak C. and Fenstermacher J.D. (1975) Am. J. Physiol. 229, 877-884; Rosenberg G. A. and Kyner W.T. (1980) Brain Res. 193, 56-66; Rosenberg G. A. et al. (1986) Am. J. Physiol 251, F485-F489). Little sucrose was, however, taken up by: (i) circumventricular organs such as the subfornical organ; (ii) medullary and cerebellar tissue next to the lateral recesses; and (iii) the superior and inferior colliculi and cerebral peduncles. For the latter two groups of structures, entry from cerebrospinal fluid was apparently blocked by a thick, multilayered glia limitans. Although [14C]sucrose was virtually absent from the rest of the subarachnoid system after 1 h, it remained in the perivascular spaces and/or walls of pial arteries and arterioles for more than 3 h. Certain transport proteins, protease inhibitors, growth factors and other neurobiologically active materials are present in cerebrospinal fluid, and their distribution to the brain and its blood vessels may be important. The present work shows, in the rat, that the flow of cerebrospinal fluid and the disposition of its constituents is fairly complex and differs among regions. Flow was rapid throughout the ventricular system and into various subarachnoid velae and cisterns, but was surprisingly slow and slight over the cerebral and cerebellar cortices. The cerebrospinal fluid-to-tissue flux of material was relatively free at many interfaces, but was greatly restricted at others, the latter indicating that the old concept of a "cerebrospinal fluid-brain barrier" may hold at such places. Finally, radiolabeled sucrose was retained longer within the walls and perivascular spaces of pial arteries and arterioles than in other subarachnoid tissues; one function of the cerebrospinal fluid system or "third circulation" may thus be delivering factors and agents to these pial blood vessels.

Animals↗

PubMed1984

Analysis of the frequency following response in the cat.

The generators of the frequency following response (FFR) were characterized for three frequency ranges by studying changes in FFR response after lesioning the nuclei within the central brainstem auditory pathway. Responses to low frequency (200-500 Hz) stimulation demonstrated changes in the complexity of the FFR waveform in both time and frequency domains following lesions in the brainstem auditory pathway. The results indicate that the complexity of the low frequency FFR is due to activity from multiple sites within the auditory pathway. The intermediate frequency (700-1500 Hz) responses showed unpredictable amplitude changes following similar lesions and no conclusion could be drawn about the generators of the FFR in this frequency range. The responses to high frequency (3-8 Hz) stimulation showed no reduction in amplitude following serial lesioning. These results, combined with other experimental evidence presented, indicate that the high frequency FFR response originates from the cochlear microphonic. Different electrode configurations were used to evaluate the low frequency FFR. In contrast to multiple generator sources recorded with the standard vertex-mastoid electrode configuration, we were able to record a response contributed primarily by the inferior colliculi with a less peripherally sensitive electrode configuration (vertex-linked-pinnae) at low intensity stimulation. The fact that auditory brainstem nuclei contribute to the FFR in varying amounts depending on the electrode configuration may explain some of the conflicting characterizations of this response in the literature. Despite this difficulty, the FFR neural generators were identified and characterized in the low frequency range using our most sensitive electrode configuration (vertex-mastoid) and in the high frequency range where the single generator is the cochlear microphonic.

Animals↗

PubMed1995

Immunohistochemical localization of the cloned mu opioid receptor in the rat CNS.

Three opioid receptor types have recently been cloned that correspond to the pharmacologically defined mu, delta and kappa 1 receptors. In situ hybridization studies suggest that the opioid receptor mRNAs that encode these receptors have distinct distributions in the central nervous system that correlate well with their known functions. In the present study polyclonal antibodies were generated to the C terminal 63 amino acids of the cloned mu receptor (335-398) to examine the distribution of the mu receptor-like protein with immunohistochemical techniques. mu receptor-like immunoreactivity is widely distributed in the rat central nervous system with immunoreactive fibers and/or perikarya in such regions as the neocortex, the striatal patches and subcallosal streak, nucleus accumbens, lateral and medial septum, endopiriform nucleus, globus pallidus and ventral pallidum, amygdala, hippocampus, presubiculum, thalamic and hypothalamic nuclei, superior and inferior colliculi, central grey, substantia nigra, ventral tegmental area, interpeduncular nucleus, medial terminal nucleus of the accessory optic tract, raphe nuclei, nucleus of the solitary tract, spinal trigeminal nucleus, dorsal motor nucleus of vagus, the spinal cord and dorsal root ganglia. In addition, two major neuronal pathways, the fasciculus retroflexus and the stria terminalis, exhibit densely stained axonal fibers. While this distribution is in excellent agreement with the known mu receptor binding localization, a few regions, such as neocortex and cingulate cortex, basolateral amygdala, medial geniculate nucleus and the medial preoptic area fail to show a good correspondence. Several explanations are provided to interpret these results, and the anatomical and functional implications of these findings are discussed.

Amino Acid Sequence↗

PubMed2005

Neural segregation of Fos-protein distribution in the brain following freezing and escape behaviors induced by injections of either glutamate or NMDA into the dorsal periaqueductal gray of rats.

Freezing and escape responses induced by gradual increases in the intensity of the electrical current applied to dorsal regions of the periaqueductal gray (dPAG) cause a distinct pattern of Fos distribution in the brain. From these studies, it has been suggested that a pathway involving the dPAG itself, dorsomedial hypothalamus and the cuneiform nucleus (CnF) would mediate responses to immediate danger and another one involving the amygdala and ventrolateral periaqueductal gray (vlPAG) would mediate cue-elicited responses. As electrical stimulation activates body cells and fibers of passage the need of studies with chemical stimulation of only post-synaptic fibers of the dPAG is obvious. To examine further this issue we measured Fos protein expression in brain areas activated by stimulation of the dPAG with glutamate (5 nmol/0.2 microL) and N-methyl-D-aspartate (NMDA) at doses that provoke either freezing (4 nmol/0.2 microL) or escape (7 nmol/0.2 microL) responses, respectively. The results showed that glutamate-induced freezing caused a selective increase in Fos expression in the superior and inferior colliculi as well as in the laterodorsal nucleus of the thalamus. On the other hand, NMDA-induced escape led to widespread increases in Fos labeling in almost all structures studied. Differently from glutamate, NMDA at doses provoking freezing caused significant increase of Fos labeling in the dPAG and CnF. Therefore, the present data support the notion that freezing behavior induced by activation of either non-NMDA or NMDA receptors in the dorsolateral periaqueductal gray (dlPAG) is neurally segregated: glutamate activates only structures that are mainly involved in the sensorial processing and NMDA-induced freezing structures involved in the motor output of defensive behavior. Therefore, the freezing elicited by the activation of non-NMDA receptors seem to be related to the acquisition of aversive information, whereas that resulting from the activation of NMDA receptors could serve as a preparatory response for flight.

Amygdala↗

PubMed2005

Differential transcription of Barhl1 homeobox gene in restricted functional domains of the central nervous system suggests a role in brain patterning.

The mouse Barhl1 homeogene, member of the BarH subfamily, play a crucial role in the cerebellum development and its human ortholog BARHL1 has been proposed as a positional and functional candidate gene for the Joubert syndrome, a form of cerebellar ataxia. The Barhl1 expression has been demonstrated to be induced by the transcription factor Math1 involved in BMP responses. We isolated the mouse Barhl1 by screening of a cDNA library with the Xenopus Xvent-2, member of the BarH subfamily, which acts in the BMP4 pathway during embryonic patterning and neural plate differentiation. We studied the detailed Barhl1 expression pattern and showed its transcription in spatio-temporally and functionally restricted domains of the developing central nervous system (CNS). Using our new optical microscopy technology, we compare the transcript steady state level and cell density in the Barhl1-expressing regions. We found that Barhl1 was transcribed in superior and inferior colliculi in the dorsal mesencephalon at a relatively low transcriptional level. In the diencephalon, Barhl1 was found higher expressed first within the basal plate and later in the mammillary region. In the cerebellum, Barhl1 showed the highest transcriptional level restricted to the anterior and posterior rhombic lips giving rise to the external and internal cerebellar granular cells and to the deep nuclei. In the spinal cord, Barhl1 showed similar expression level than in the cerebellum and is delimited to a subset of dorsal interneurons. Therefore, our results indicated that Barhl1 homeodomain gene is exclusively transcribed in restricted CNS domain at differential transcription levels which suggest a highly regulated transcriptional mechanism. In addition, these regional and cellular specificities indicated that Barhl1 may be involved in the differentiation of the specific subsets of neuronal progenitors.

Amino Acid Sequence↗

PubMed2004

Comparative fos immunoreactivity in the brain after forebrain, brainstem, or combined seizures induced by electroshock, pentylenetetrazol, focally induced and audiogenic seizures in rats.

To help discern sites of focal activation during seizures of different phenotype, the numbers of Fos immunoreactive (FI) neurons in specific brain regions were analyzed following "brainstem-evoked," "forebrain-evoked" and forebrain/brainstem combination seizures induced by a variety of methods. First, pentylenetetrazol (PTZ, 50 mg/kg) induced forebrain-type seizures in some rats, or forebrain seizures that progressed to tonic/clonic brainstem-type seizures in other rats. Second, minimal electroshock induced forebrain seizures whereas maximal electroshock (MES) induced tonic brainstem-type seizures in rats. Third, forebrain seizures were induced in genetically epilepsy-prone rats (GEPRs) by microinfusion of bicuculline into the area tempestas (AT), while brainstem seizures in GEPRs were induced by audiogenic stimulation. A final set was included in which AT bicuculline-induced forebrain seizures in GEPRs were transiently interrupted by audiogenic seizures (AGS) in the same animals. These animals exhibited a sequence combination of forebrain clonic seizure, brainstem tonic seizure and back to forebrain clonic seizures. Irrespective of the methods of induction, clonic forebrain- and tonic/clonic brainstem-type seizures were associated with considerable Fos immunoreactivity in several forebrain structures. Tonic/clonic brainstem seizures, irrespective of the methods of induction, were also associated with FI in consistent brainstem regions. Thus, based on Fos numerical densities (FND, numbers of Fos-stained profiles), forebrain structures appear to be highly activated during both forebrain and brainstem seizures; however, facial and forelimb clonus characteristic of forebrain seizures are not observable during a brainstem seizure. This observation suggests that forebrain-seizure behaviors may be behaviorally masked during the more severe tonic brainstem seizures induced either by MES, PTZ or AGS in GEPRs. This suggestion was corroborated using the sequential seizure paradigm. Similar to findings using MES and PTZ, forebrain regions activated by AT bicuculline were similar to those activated by AGS in the GEPR. However, in the combination seizure group, those areas that showed increased FND in the forebrain showed even greater FND in the combination trial. Likewise, those areas of the brainstem showing FI in the AGS model, showed an even greater effect in the combination paradigm. Finally, the medial amygdala, ventral hypothalamus and cortices of the inferior colliculi showed markedly increased FND that appeared dependent upon activation of both forebrain and brainstem seizure activity in the same animal. These findings suggest these latter areas may be transitional areas between forebrain and brainstem seizure interactions. Collectively, these data illustrate a generally consistent pattern of forebrain Fos staining associated with forebrain-type seizures and a consistent pattern of brainstem Fos staining associated with brainstem-type seizures. Additionally, these data are consistent with a notion that separate seizure circuitries in the forebrain and brainstem mutually interact to facilitate one another, possibly through involvement of specific "transition mediating" nuclei.

Animals↗

PubMed2006

Multisensory processing via early cortical stages: Connections of the primary auditory cortical field with other sensory systems.

It is still a popular view that primary sensory cortices are unimodal, but recent physiological studies have shown that under certain behavioral conditions primary sensory cortices can also be activated by multiple other modalities. Here, we investigate the anatomical substrate, which may underlie multisensory processes at the level of the primary auditory cortex (field AI), and which may, in turn, enable AI to influence other sensory systems. We approached this issue by means of the axonal transport of the sensitive bidirectional neuronal tracer fluorescein-labeled dextran which was injected into AI of Mongolian gerbils (Meriones unguiculatus). Of the total number of retrogradely labeled cell bodies (i.e. cells of origin of direct projections to AI) found in non-auditory sensory and multisensory brain areas, approximately 40% were in cortical areas and 60% in subcortical structures. Of the cell bodies in the cortical areas about 82% were located in multisensory cortex, viz., the dorsoposterior and ventroposterior, posterior parietal cortex, the claustrum, and the endopiriform nucleus, 10% were located in the primary somatosensory cortex (hindlimb and trunk region), and 8% in secondary visual cortex. The cortical regions with retrogradely labeled cells also contained anterogradely labeled axons and their terminations, i.e. they are also target areas of direct projections from AI. In addition, the primary olfactory cortex was identified as a target area of projections from AI. The laminar pattern of corticocortical connections suggests that AI receives primarily cortical feedback-type inputs and projects in a feedforward manner to its target areas. Of the labeled cell bodies in the subcortical structures, approximately 90% were located in multisensory thalamic, 4% in visual thalamic, and 6% in multisensory lower brainstem structures. At subcortical levels, we observed a similar correspondence of retrogradely labeled cells and anterogradely labeled axons and terminals in visual (posterior limitans thalamic nucleus) and multisensory thalamic nuclei (dorsal and medial division of the medial geniculate body, suprageniculate nucleus, posterior thalamic cell group, zona incerta), and in the multisensory nucleus of the brachium of the inferior colliculus. Retrograde, but not anterograde, labeling was found in the multisensory pontine reticular formation, particularly in the reticulotegmental nucleus of the pons. Conversely, anterograde, but no retrograde, labeling was found in the visual laterodorsal and lateroposterior thalamic nuclei, in the multisensory peripeduncular, posterior intralaminar, and reticular thalamic nuclei, as well as in the multisensory superior and pericentral inferior colliculi (including cuneiform and sagulum nucleus), pontine nuclei, and periaqueductal gray. Our study supports the notion that AI is not merely involved in the analysis of auditory stimulus properties but also in processing of other sensory and multisensory information. Since AI is directly connected to other primary sensory cortices (viz. the somatosensory and olfactory ones) multisensory information is probably also processed in these cortices. This suggests more generally, that primary sensory cortices may not be unimodal.

Afferent Pathways↗

PubMed2001

Constitutive expression of c-myb mRNA in the adult rat brain.

In this study, we demonstrated the c-myb mRNA expression in the adult rat brain using an in situ hybridization technique. We found c-myb mRNA signals in the various regions of the forebrain and midbrain including the cerebral cortex, thalamus, hippocampus, hypothalamus, superior and inferior colliculi and central gray. In the cerebellum, a diffuse signal was found in the granular layer while some positive cells were detected in the molecular layer as well. In addition, a number of cells showed intense signals in many nuclei of the medulla oblongata. The constitutive expression of c-myb mRNA in the different kinds of neural cells suggests that this gene might be involved in the normal function of these neurons.

Animals↗

PubMed1998

Precise distribution of neuronal nitric oxide synthase mRNA in the rat brain revealed by non-radioisotopic in situ hybridization.

Regional distribution of neurons expressing neuronal nitric oxide synthase mRNA in the rat brain was examined by non-radioisotopic in situ hybridization, using digoxigenin-labeled complementary RNA probes. Clustering of intensely positive neurons was observed in discrete areas including the main and accessory olfactory bulbs, the islands of Calleja, the amygdala, the paraventricular nucleus of the thalamus, several hypothalamic nuclei, the lateral geniculate nucleus, the magnocellular nucleus of the posterior commissure, the superior and inferior colliculi, the laterodorsal and pedunculopontine tegmental nuclei, the nucleus of the trapezoid body, the nucleus of the solitary tract and the cerebellum. Strongly-stained isolated neurons were scattered mainly in the cerebral cortex, the basal ganglia and the brain stem, especially the medulla reticular formation. In the hippocampus, an almost uniform distribution of moderately stained neurons was observed in the granular cell layer of the dentate gyrus and in the pyramidal cell layer of the Ammon's horn, while more intensely stained isolated neurons were scattered over the entire hippocampal region. These observations can serve as a good basis for studies on function and gene regulation of neuronal nitric oxide synthase.

Animals↗

PubMedDate not supplied

Auditory 40-Hz responses in the guinea pig.

Auditory evoked potentials in response to tone bursts repeated at a rate of 40 per second (auditory 40-Hz responses) were studied in the guinea pig. The potentials, consisting of a sequence of 40-Hz waves with a periodicity of about 25 msec, were distributed widely over the skull, and the largest potentials were recorded from the vertex (midline) and the temporal area contralateral to the stimulated ear. Administration of pentobarbital did not affect the midline response but reduced the amplitude of the contralateral response. Investigations of the effects of acute lesions demonstrated that the auditory 40-Hz responses from the contralateral temporal area were eliminated by aspiration of the contralateral cerebral cortex, whereas the responses from the midline continued to appear after bilateral aspiration of the cerebral cortex. The response from the midline was maintained after bilateral aspiration of the inferior colliculi, and the basic 40-Hz rhythm was still observed after decerebration. These data suggest different generation areas for the midline and contralateral 40-Hz responses in the guinea pig.

Acoustic Stimulation↗