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C M Gall

Publications and source records attributed to C M Gall.

At least 37 records · Page 2Linked to original sources
PubMed1998

Experimentally induced lysosomal dysfunction disrupts processing of hypothalamic releasing factors.

Previous studies have shown that experimentally induced lysosomal dysfunction elicits various features of aging in the cortical telencephalon. The present study used cultured slices to test if: (1) it causes similar changes in the hypothalamus, and/or (2) modifies the processing of two releasing factors important to aging. A 2-day exposure to N-CBZ-L-phenylalanyl-L-alanine-diazomethylketone (ZPAD), a selective inhibitor of cathepsins B and L, triggered a pronounced increase in the numbers of lysosomes in the ventromedial and dorsomedial nuclei, and in lateral hypothalamus. Continued incubation with the inhibitor for 3-12 days resulted in the spread of endosomes-lysosomes into dendrites and, in the lateral hypothalamus, the formation of massive, lysosome-filled expansions of neuronal processes (meganeurites). These effects did not occur in the arcuate nucleus, making it the first region so far examined in which lysosomal proliferation is not initiated by hydrolase inhibitors. Despite this, a dense plexus of axons and terminals in the median eminence was partially depleted of growth hormone releasing hormone (GHRH) within 48 hours after addition of ZPAD. Moreover, the inhibitor caused axonal GHRH to become collected into large puncta, an effect highly suggestive of a partial failure in axonal transport. GHRH mRNA levels were not greatly affected by 6 days of ZPAD exposure, indicating that reduced expression did not play a major role in the peptide changes seen at 48 hours. Similar but less pronounced immunocytochemical changes were recorded for the somatostatin system in the arcuate and periventricular nucleus. It is concluded that lysosome dysfunction: (1) has different consequences for the arcuate nucleus than other brain regions, and (2) disrupts transport of hypothalamic releasing factors. The potential significance of the results to endocrine senescence is discussed.

Animals↗
PubMed1998

Endogenous protein kinase A inhibitor (PKIalpha) modulates synaptic activity.

Protein kinase A (PKA) has long been known to be involved in major regulatory mechanisms underlying synaptic plasticity and complex behaviors such as learning and memory. The endogenous PKA inhibitor, PKIalpha, has been extensively studied for its effects on PKA and PKA-mediated signal transduction. Clear functions for PKIalpha in vivo, however, remain to be established. Here we describe that several forms of synaptic stimulation in the rat hippocampus cause a dramatic decrease in the concentration of PKIalpha in dentate granule cells. Furthermore, chronic infusion of antisense oligonucleotides against PKIalpha into the rat brain results in a dramatic reduction of the excitability of these neurons and elimination of their ability to exhibit long-term potentiation (LTP) and long-term depression (LTD), suggesting a stimulus-dependent regulatory role for PKIalpha in PKA signal transduction.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Transcript-specific effects of adrenalectomy on seizure-induced BDNF expression in rat hippocampus.

Activity-induced brain-derived neurotrophic factor (BDNF) expression is negatively modulated by circulating adrenal steroids. The rat BDNF gene gives rise to four major transcript forms that each contain a unique 5' exon (I-IV) and a common 3' exon (V) that codes for BDNF protein. Exon-specific in situ hybridization was used to determine if adrenalectomy has differential effects on basal and activity-induced BDNF transcript expression in hippocampus. Adrenalectomy alone had only modest effects on BDNF mRNA levels with slight increases in exon III-containing mRNA with 7-10-day survival and in exon II-containing mRNA with 30-days survival. In the dentate gyrus granule cells, adrenalectomy markedly potentiated increases in exon I and II cRNA labeling, but not increases in exon III and IV cRNA labeling, elicited by one hippocampal afterdischarge. Similarly, for the granule cells and CA1 pyramidal cells, hilus lesion (HL)-induced recurrent limbic seizures elicited greater increases in exon I and II cRNA hybridization in adrenalectomized (ADX) as compared to adrenal-intact rats. In this paradigm, adrenalectomy modestly potentiated the increase in exon III-containing mRNA in CA1 but had no effect on exon IV-containing mRNA content. These results demonstrate that the negative effects of adrenal hormones on activity-induced BDNF expression are by far the greatest for transcripts containing exons I and II. Together with evidence for region-specific transcript expression, these results suggest that the effects of stress on adaptive changes in BDNF signalling will be greatest for neurons that predominantly express transcripts I and II.

Adrenal Cortex Hormones↗
PubMed1998

Lysosomal dysfunction reduces brain-derived neurotrophic factor expression.

Brain-derived neurotrophic factor (BDNF) expression in hippocampus and cortex is considerably reduced in Alzheimer's disease. The present study tested if lysosomal disturbances, a concomitant of brain aging, impair basal and/or induced expression of BDNF. Cultured hippocampal slices were incubated with N- CBZ-L-phenylalanyl-L-alanine-diazomethylketone (ZPAD), an inhibitor of cathepsins B and L, for 6 days and processed for in situ hybridization using radiolabeled cRNA probes against BDNF mRNA. Multiple densitometric readings were collected from each of the three principal hippocampal subdivisions. Within-slice averages were substantially lower in the ZPAD-treated group compared to controls. Treatment with the inhibitor did not change average neuron diameter or packing density. Intense stimulation of glutamate receptors with kainate for 30 min (followed by a 90-min recovery period) caused a nearly threefold increase in BDNF mRNA concentrations in the dentate gyrus while having only marginal effects in the other subdivisions. Slice averages of ZPAD-exposed cultures treated with kainate were lower than those of controls exposed to the excitotoxin; however, on a percentage basis, the kainate-induced increase in the dentate gyrus was comparable for the two groups (175 +/- 31 vs 179 +/- 39%). Kainate for 1 h (with a 5-h recovery) affected BDNF mRNA in a manner similar to that found with shorter infusions, i.e., induction in stratum granulosum but not elsewhere, lower overall slice averages with ZPAD treatment, and no evidence that ZPAD blocked the percentage increase in the dentate gyrus. These results provide evidence that lysosomal dysfunction occurring during brain aging could disrupt ongoing BDNF production without substantially impairing the neurotrophin response to intense physiological activity. The first observation suggests a plausible aging sequence leading to pathology while the second may be of interest with regard to possible therapeutics.

Aging↗
PubMed1998

Localization and seizure-regulation of integrin beta 1 mRNA in adult rat brain.

Recent findings indicate that RGD-binding integrin receptors play a critical role in the maintenance of long-term potentiation but the identity and location of the integrin proteins involved are not known. The integrin beta1 is of particular interest in regard to synaptic plasticity because it is a component of many of the RGD-binding integrins and beta1-immunoreactivity has been localized within synaptic density fractions. The present study used in situ hybridization to evaluate the distribution of beta1 mRNA in adult rat brain and to determine if expression is altered by seizures. In untreated rats, beta1 mRNA is present at high levels in the ventricular epithelium and discrete neuronal groups including the magnocellular hypothalamic and efferent cranial nerve nuclei and the cerebellar Purkinje cells. Hybridization was less dense in the substantia nigra and hippocampal stratum pyramidale and low but present throughout the gray matter. Limbic seizures increased beta1 cRNA labeling of both neurons (e.g., hippocampal stratum pyramidale) and astroglial cells from 8 h through 48 h after seizure onset. These results indicate that in adult rat brain, beta1 mRNA is expressed by both neurons and glia; neuronal expression is highest in hypothalamic and peripherally projecting neurons capable of substantial morphological plasticity. Seizure effects demonstrate that beta1 is positively regulated by activity, and suggest that activity-dependent expression may play a role in synaptic plasticity in the adult brain.

Animals↗
PubMed1998

Deafferentation-induced increases in hippocampal insulin-like growth factor-1 messenger RNA expression are severely attenuated in middle aged and aged rats.

Deafferentation of the adult rat dentate gyrus induces reactive axonal growth by surviving afferent systems. In middle aged and aged rats, axonal sprouting is delayed and reduced relative to young adults. The cause for this age-related decline is not known, but it may reflect a decrement in trophic signals which initiate sprouting. Insulin-like growth factor-1 may play a role in sprouting because it (i) promotes axonal growth, (ii) is expressed at elevated levels by microglia just prior to sprouting onset, and (iii) is expressed with better spatiotemporal correspondence to hippocampal sprouting than other trophic factors examined. The present study used in situ hybridization to evaluate the influence of age on deafferentation-induced insulin-like growth factor-1 messenger RNA expression in the dentate gyrus. Messenger RNA levels were markedly elevated 4 days after an entorhinal cortex lesion at 3 months of age. Comparable lesions at 12 months did not significantly increase labeling whereas lesions at 18-26 months caused only a modest increase at 8 days postlesion. These data demonstrate that deafferentation induces more modest and delayed increases in insulin-like growth factor-1 expression in middle aged and aged rats than in young adults. The loss of reactive insulin-like growth factor-1 expression at ages exhibiting an attenuated sprouting response supports (i) an association between insulin-like growth factor-1 and sprouting and (ii) the possibility that impairments in the expression of this factor contributes to reduced axonal plasticity with age.

Afferent Pathways↗
PubMed1998

Attenuation of the seizure-induced expression of BDNF mRNA in adult rat brain by an inhibitor of calcium/calmodulin-dependent protein kinases.

We have examined the potential involvement of calcium/calmodulin-dependent protein kinases in the regulation of brain-derived neurotrophic factor mRNA in vivo following kainic acid (kainate)-induced seizure activity by in situ hybridization. KN-62, a specific inhibitor of calcium/calmodulin-dependent protein kinase type II and IV, blocked the characteristic induction of brain-derived neurotrophic factor mRNA seen following seizure activity. This blockade was specific to calcium/calmodulin-dependent protein kinase type II and IV as inhibitors of both protein kinase C and cAMP-dependent protein kinase had no effect. Inhibition of brain-derived neurotrophic factor mRNA increases varied between brain regions; an almost complete inhibition was seen throughout cortical regions, whereas only partial inhibitory effects were noted within hippocampus. A similar inhibition of increased c-fos mRNA was observed throughout cortical, hippocampal and diencephalic regions. The two predominant brain-derived neurotrophic factor transcripts induced by kainate, containing exons I or III, were differentially affected by KN-62. The cortical induction of exon I was blocked by KN-62, whereas exon III was not, providing additional evidence for the differential regulation of individual brain-derived neurotrophic factor transcripts and demonstrating that inhibition of brain-derived neurotrophic factor induction was not due to general blockade of seizure activity throughout the neocortex. These data implicate calcium/calmodulin-dependent protein kinase type II or IV in the regulation of brain-derived neurotrophic factor mRNA in vivo and suggest regionally specific mechanisms occur throughout the brain.

Animals↗
PubMed1998

Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic deficits and reduces dendritic branching and spine density of neocortical pyramidal neurons.

The role of basal forebrain-derived cholinergic afferents in the development of neocortex was studied in postnatal rats. Newborn rat pups received intraventricular injections of 192 IgG-saporin. Following survival periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological consequences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic axons are reduced throughout the cortical layers; this reduction is more marked in medial than in lateral cortical areas. The thickness of neocortex is reduced by approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal cells reveals a reduction in cell body size and also a reduction in numbers of branches of apical dendrites. Spine densities on apical dendrites are reduced by approximately 20-25% in 192 IgG-saporin-treated cases; no change was detected in number of spines on basal dendrites. These results indicate a developmental or maintenance role for cholinergic afferents to cerebral cortical neurons.

Acetylcholinesterase↗
PubMed1998

Lipomatous differentiation in ependymomas: a report of three cases and comparison with similar changes reported in other central nervous system neoplasms of neuroectodermal origin.

Three cases of surgically removed ependymomas with lipomatous transformation of tumor cells are reported. Patients' ages were 13, 16, and 48 years at the time of operation. One patient's tumor was located in the third ventricle; the other two occupied paraventricular hemispheric white matter. Histologically all three cases fulfilled the criteria of ependymomas. In case 1, electron microscopy also confirmed this diagnosis, and preoperative radiologic studies (scans) suggested large amounts of lipids to be present in the tumor. Histologically, in all three cases many tumor cells contained fat droplets coalescing into a single large droplet, resulting in an appearance indistinguishable from adipocytes by conventional stains, but maintaining immunohistological positivity for glial fibrillary acidic protein and neuron-specific enolase in the cytoplasmic rims of the affected cells, attesting to their glial nature as opposed to being true adipocytes in a mixed glial/mesenchymal hamartoma. The alterations were also different from the "xanthomatous" changes seen in some gliomas. Lipomatous transformation of neuroectodermal tumor cells has been previously observed in neurocytomas, medulloblastomas, cerebellar and spinal cord astrocytomas, and primitive neuroectodermal tumors. Our three cases represent the first reported ependymomas with such changes. In medulloblastomas of adults, lipomatous changes have been found to signal relatively benign biologic behavior. So far, all three of our patients are doing well, but only more extended follow-up will show whether such benign behavior applies to lipomatous ependymomas as well.

Adolescent↗
PubMed1998

Anterograde transport of neurotrophin proteins in the CNS--a reassessment of the neurotrophic hypothesis.

The basic tenets of the neurotrophic hypothesis are that i) limiting quantities of a given factor are produced in specific target tissues; ii) responsive neurons projecting to these targets compete for the limiting amounts of the factor; iii) the factor is bound within the target by selective receptors on afferent terminals, internalized, and retrogradely transported to the neuronal cell body where it provides signals affecting neuronal survival and differentiation. Although originally formulated on the basis of evidence for NGF's actions on peripheral sensory and sympathetic neurons, the neurotrophic hypothesis appeared to be upheld for CNS neuronal systems as well, where NGF was found to function primarily as a target-derived trophic factor for basal forebrain cholinergic neurons. With the discovery of additional neurotrophins sharing considerable structural homology with NGF, the question arose of whether the neurotrophic hypothesis held true for all members of this protein family. Recent investigations into the localization and function of neurotrophins other than NGF, particularly BDNF and NT-3, have provided evidence indicating that these molecules may not act in a manner consistent with the neurotrophic hypothesis, as originally postulated. Numerous studies in the peripheral and central nervous systems have now demonstrated that BDNF (and NT-3) may be preferentially trafficked anterogradely along axonal processes and stored within pre-synaptic terminals. Other studies have suggested that these factors may be released in an activity-dependent, rather than constitutive, manner and can act in autocrine or paracrine fashions to subserve an assortment of biological functions including anterograde effects on cell survival and differentiation, as well as more novel roles in synaptic transmission. These recent findings strongly suggest that, while the various neurotrophin proteins may be grouped into a single family based upon their structural homology, they should be considered as a heterogeneous group of trophic factors based upon function and mode of action.

Animals↗
PubMed1997

Astroglial ciliary neurotrophic factor mRNA expression is increased in fields of axonal sprouting in deafferented hippocampus.

Evidence that ciliary neurotrophic factor promotes axonal sprouting and regeneration in the periphery raises the possibility that this factor is involved in reactive axonal growth in the brain. In situ hybridization was used in the present study to determine whether ciliary neurotrophic factor mRNA expression is increased in association with axonal sprouting in deafferented adult rat hippocampus. In untreated rats, ciliary neurotrophic factor cRNA labeling density was high in the olfactory nerve, pia mater, and aspects of the ventricular ependyma and was relatively low within areas of white matter (fimbria, internal capsule) and select neuronal fields (hippocampal cell layers, habenula). After an entorhinal cortex lesion, hybridization was markedly increased in fields of anterograde degeneration, including most prominently the ipsilateral dentate gyrus outer molecular layer and hippocampal stratum lacunosum moleculare. Labeling in these fields was increased by 3 days postlesion, was maximal at 5 days, and returned to normal levels by 14 days. Double labeling demonstrated that, in both control and experimental tissue, ciliary neurotrophic factor mRNA was colocalized with glial fibrillary acidic protein immunoreactivity in astroglia, but it was not colocalized with markers for oligodendrocytes or microglia. These results demonstrate that astroglial ciliary neurotrophic factor expression is increased in fields of axonal and terminal degeneration and that increased expression is coincident with 1) increased insulin-like growth factor-1 and basic fibroblast growth factor expression and 2) the onset of reactive axonal growth. The synchronous expression of these glial factors in fields of deafferentation suggests the possibility of additive or synergistic interactions in the coordination of central axonal growth.

Afferent Pathways↗
PubMed1997

Stoichiometries of AMPA receptor subunit mRNAs in rat brain fall into discrete categories.

In situ hybridization was used to estimate the relative concentrations of mRNAs encoding different subunits (GluR1-4) of alpha-amino 3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors in rat brain and to test the hypothesis that within-region expression profiles reflect a limited number of recurring patterns. Fractional subunit mRNA concentrations were calculated for 33 brain regions, and cluster analysis methods were applied to test for statistically meaningful groupings in the data. Four relatively homogeneous classes were identified and designated as AMPA receptor (AR) categories, numbered according to dominant subunit mRNAs. The AR-1 class (47% GluR1 mRNA) was expressed by structures near the mesodiencephalic border, including basal ganglia-related areas. The AR-2 class (57% GluR2 mRNA) was expressed in cortex and tectum. The AR-1,2 class (31% GluR1, 45% GluR2) was found in the largest number of regions, including such dissimilar cell fields as hippocampus and substantia nigra pars compacta. The AR-2,3 grouping (33% GluR2, 31% GluR3) was associated with the sensory relay and reticular thalamic nuclei. It is suggested that AR-1,2 and AR-2, the most closely related categories in clustering space, are largely telencephalic receptors with the former predominant in the subcortex and the latter in the cortex. The AR-2,3 class is associated with ascending sensory stations, whereas AR-1 appears to include several smaller categories expressed by specialized systems. If the balance of subunit mRNAs is reflected at the protein level, then the present data suggest that forebrain AMPA-type glutamate receptors can be classified into a limited number of recurring types.

Animals↗
PubMed1997

Prenatal ontogeny of the epidermal growth factor receptor and its ligand, transforming growth factor alpha, in the rat brain.

Transforming growth factor alpha (TGF alpha) interacts with the epidermal growth factor receptor (EGF-R) to produce its biological effects. TGF alpha induces the proliferation and differentiation of central nervous system (CNS) astrocytes and pluripotent stem cells, as well as the survival and differentiation of postmitotic CNS neurons. Both TGF alpha and EGF-R have been localized to the postnatal CNS. As the majority of CNS neuronal proliferation and migration occurs antenatally, we have examined the ontogeny of TGF alpha and EGF-R in the embryonic rat brain by in situ hybridization. EGF-R mRNA was expressed in the brain as early as embryonic day 11 (E11; the earliest age examined). It was initially detected in the midbrain, with subsequent expression first in multiple germinal zones, followed by expression in numerous cells throughout the brain. In many brain areas, EGF-R mRNA appeared in germinal centers during the later stages of neurogenesis and the early stages of gliogenesis. In the midbrain, the distribution of EGF-R mRNA overlapped extensively with that of tyrosine hydroxylase mRNA, suggesting that fetal dopaminergic neurons express EGF-R. Immunocytochemistry was used to demonstrate the presence of EGF-R-immunoreactive protein in brain areas that expressed EGF-R mRNA on E15 and E20. The expression of TGF alpha in many brain structures preceded that of EGF-R mRNA. TGF alpha mRNA was distributed throughout many non-germinal centers of the brain on E12 and later. Some brain areas, such as the external granule cell layer of the cerebellum, expressed EGF-R, but not TGF alpha mRNA. Northern blot analysis demonstrated that mRNA species for both TGF alpha and EGF-R were similar in embryos and adults. These data indicate that TGF alpha and EGF-R are positioned to have a role in the genesis, differentiation, migration, or survival of numerous cell populations in the embryonic brain.

Animals↗
PubMed1997

Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: evidence for anterograde axonal transport.

A sensitive immunohistochemical technique was used, along with highly specific affinity-purified antibodies to brain-derived neurotrophic factor (BDNF), to generate a detailed mapping of BDNF immunoreactivity (BDNF-ir) throughout the adult rat CNS. A parallel analysis of sites of BDNF synthesis was performed with in situ hybridization techniques using a cRNA probe to the exon encoding mature rat BDNF protein. These combined data revealed (1) groups of cell bodies containing diffuse BDNF-ir throughout the CNS that were strongly correlated with fields of cells containing BDNF mRNA; (2) varying degrees of BDNF-ir outside of cell bodies, in what appeared to be fibers and/or terminals; and (3) many regions containing extremely heavy BDNF-immunoreactive fiber/terminal labeling that lacked BDNF mRNA (e.g., medial habenula, central nucleus of the amygdala, bed nucleus of stria terminalis, lateral septum, and spinal cord). The latter observation suggested that in these regions BDNF was derived from anterograde axonal transport by afferent systems. In the two cases in which this hypothesis was tested by the elimination of select afferents, BDNF immunostaining was completely eliminated. These data, along with the observation that BDNF-ir was rarely found within dendrites or fibers en passage, suggest that BDNF protein produced in adult CNS neurons is polarized primarily along axonal processes and is preferentially stored in terminals within the innervation target.

Animals↗
PubMed1997

Induction of brain derived neurotrophic factor mRNA by seizures in neonatal and juvenile rat brain.

Seizures have been shown to regulate neurotrophin expression in adult mammalian brain. However, there has been some controversy as to whether seizures affect neurotrophin expression in very immature brain. In the present study, we have examined the effects of seizures induced by pilocarpine following lithium pretreatment or by kainic acid on the expression of brain derived neurotrophic factor (BDNF) mRNA in developing rat brain by in situ hybridization. In adult brain, lithium/pilocarpine treatment resulted in dramatic elevations of hybridization to BDNF cRNA in neocortical and limbic brain structures. In developing brain, lithium/pilocarpine induced elevations of BDNF mRNA in the hippocampus, piriform and entorhinal cortex as early as postnatal day 7 (P7). By P12, the pattern of enhanced expression was similar to that of the adult. Maximal elevations of hybridization were present 2 to 4 h following pilocarpine injection. Electrophysiological recording demonstrated that lithium/pilocarpine treatment resulted in electrographic seizures. Pretreatment with diazepam blocked the seizures as well as the elevation of BDNF mRNA. Kainic acid induced elevations of BDNF mRNA in the CA3 subfield of the hippocampal pyramidal cell layer, but not in other brain areas in pups as young as P7. These data indicate that seizures during the neonatal and early juvenile period of brain development induce elevated BDNF mRNA expression, and that different methods of seizure induction yield different patterns of elevations in hybridization. Furthermore, BDNF may be capable of playing a role in the development of seizure susceptibility in the immature brain.

Animals↗
PubMed1997

Comparison of the effects of an ampakine with those of methamphetamine on aggregate neuronal activity in cortex versus striatum.

The present study used in situ hybridization to c-fos mRNA to compare the effects of an 'ampakine' (a positive modulator of AMPA type glutamate receptors) with those of methamphetamine on the balance of aggregate neuronal activity in the cortex versus striatum. Methamphetamine (n = 11) induced a marked increase in c-fos mRNA in the dorsomedial quadrant of the striatum and a 21% smaller, but still reliable, increase in the ventrolateral quadrant. The drug also elevated c-fos mRNA levels in the ventral and medial segments of the orbitofrontal cortex but had no detectable effects in motor and somatosensory neocortices. The ampakine (n = 11) caused a near inverse pattern of changes; i.e. a sizable increase in somatosensory labeling and a significant decrease in striatal labeling with statistically insignificant effects in motor and orbitofrontal cortex. Within-rat cortical and striatal values were correlated in both the vehicle (n = 11) and ampakine groups, and appropriate comparisons established that the ampakine caused 27-55% increases in the ratio of cortical to striatal labeling. These results are in accord with the idea that facilitation of glutamatergic transmission has 'network level' effects that are opposite in nature to those resulting from enhanced dopaminergic transmission. The potential relevance of ampakines alone or in conjunction with dopamine antagonists for the treatment of schizophrenia is discussed.

Animals↗
PubMed1997

In situ hybridization for c-fos mRNA reveals the involvement of the superior colliculus in the propagation of seizure activity in genetically epilepsy-prone rats.

Previous work showed that bilateral lesions made between the inferior and superior colliculi reduced the severity of audiogenic seizures in genetically epilepsy-prone rats (GEPR-9s), and indicated that the connections between these two structures are vital for the propagation of seizure activity. To determine the involvement of the superior colliculus (SC) in seizure propagation, GEPR-9s were given four audiogenic seizures within 1 h by ringing a loud bell, and their brains were processed 30 min later for in situ hybridization for c-fos mRNA. Brain sections from such rats showed dense labeling in both the dorsal cortex and external nucleus of the inferior colliculus. Labeling continued rostrally into the intermediate and deep layers of the SC and the periaqueductal gray region. In addition, other brain regions such as the amygdala, piriform cortex and dorsal endopiriform nucleus showed dense labeling for c-fos mRNA. Comparable increases were not observed in the brains of Sprague-Dawley (SD) rats receiving auditory stimulation or in unstimulated GEPR-9s and SD rats, thereby indicating that increases in stimulated GEPR-9s are seizure-specific. This study provides further evidence that the SC is involved in the propagation of seizure activity in GEPR-9s, and also demonstrates the activation of other brain regions by audiogenic seizures.

Acoustic Stimulation↗