Biomedical subjects

C M Gall

Publications and source records attributed to C M Gall.

At least 55 records · Page 3Linked to original sources

PubMed1996

Differential effects of protein synthesis inhibition on the activity-dependent expression of BDNF transcripts: evidence for immediate-early gene responses from specific promoters.

In the adult rat forebrain, brain-derived neurotrophic factor (BDNF) expression is very rapidly induced by neuronal activity, suggesting that this might occur without intervening protein synthesis. The rat BDNF gene has four differentially regulated promoter regions; each gives rise to an mRNA containing a unique 5' exon (I-IV) and a common 3' exon (V) that codes for mature BDNF protein. The present study used exon-specific in situ hybridization and both in vivo and in vitro preparations to determine whether activity induces BDNF as an "immediate-early gene" (IEG) from specific promoter regions and to compare the regulation of BDNF and nerve growth factor (NGF). In cultured hippocampal slices, kainic acid markedly increased pan-BDNF (exon V) and NGF mRNA content; cycloheximide attenuated the effect of kainic acid on both. In vivo stimulation of a paroxysmal afterdischarge increased both pan-BDNF and NGF mRNA levels in the dentate gyrus granule cells; pretreatment with anisomycin modestly attenuated the paroxysmal afterdischarge-induced increase of both transcripts. To determine whether partial drug effects on BDNF expression reflect the differential regulation of transcript species, levels of mRNAs containing exons I-IV were evaluated. A single afterdischarge increased exon I-IV-containing mRNA levels; anisomycin significantly attenuated the increase in exon I- and II-containing mRNAs but had no effect on the increase in exon III- and IV-containing mRNAs. These data show that for mature forebrain neurons, activity induces the expression of BDNF exon III- and IV-containing transcripts as IEG responses.

Animals↗

PubMed1996

NMDA-receptor modulation of lateral inhibition and c-fos expression in olfactory bulb.

Olfactory bulb primary output neurons, mitral/tufted cells, are glutamatergic and excite inhibitory interneurons, granule cells, by activation of both alpha-amino-3-hydroxy-5-methyl-ioxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors. The data presented here demonstrate that the NMDA antagonists MK-801 and CGP39551, but not ketamine, significantly enhanced expression of c-fos mRNA by mitral cells as measured by in situ hybridization. All three antagonists significantly reduced mitral/tufted cell excitation of granule cells as measured with extracellular field potentials following antidromic stimulation of the lateral olfactory tract (LOT). In turn, the NMDA antagonists significantly reduced granule cell mediated feedback inhibition of mitral/tufted cells, as measured with field potential recordings of paired-pulse LOT stimulation, suppression of mitral/tufted cell single-unit spontaneous activity following LOT stimulation, and intracellularly recorded IPSP amplitude in mitral/tufted cells following LOT stimulation. While there was not a perfect correlation between the effects of the NMDA antagonists on c-fos mRNA expression and on inhibition, the results suggest that disinhibition of mitral/tufted cells accounts for the observed enhancement in c-fos mRNA expression induced by NMDA receptor antagonists.

2-Amino-5-phosphonovalerate↗

PubMed1996

Acidic fibroblast growth factor mRNA is expressed by basal forebrain and striatal cholinergic neurons.

Evidence for the importance of the basal forebrain cholinergic system in the maintenance of cognitive function has stimulated efforts to identify trophic mechanisms that protect this cell population from atrophy and dysfunction associated with aging and disease. Acidic fibroblast growth factor (aFGF) has been reported to support cholinergic neuronal survival and has been localized in basal forebrain with the use of immunohistochemical techniques. Although these data indicate that aFGF is present in regions containing cholinergic cell bodies, the actual site of synthesis of this factor has yet to be determined. In the present study, in situ hybridization techniques were used to evaluate the distribution and possible colocalization of mRNAs for aFGF and the cholinergic neuron marker choline acetyltransferase (ChAT) in basal forebrain and striatum. In single-labeling preparations, aFGF mRNA-containing neurons were found to be codistributed with ChAT mRNA+ cells throughout all fields of basal forebrain, including the medial septum/diagonal band complex and striatum. By using a double-labeling (colormetric and isotopic) technique, high levels of colocalization (over 85%) of aFGF and ChAT mRNAs were observed in the medial septum, the diagonal bands of Broca, the magnocellular preoptic area, and the nucleus basalis of Meynert. The degree of colocalization was lower in the striatum, with 64% of the cholinergic cells in the caudate and 33% in the ventral striatum and olfactory tubercle labeled by the aFGF cRNA. These data demonstrate substantial regionally specific patterns of colocalization and support the hypothesis that, via an autocrine mechanism, aFGF provides local trophic support for cholinergic neurons in the basal forebrain and the striatum.

Animals↗

PubMed1996

Relative concentrations and seizure-induced changes in mRNAs encoding three AMPA receptor subunits in hippocampus and cortex.

In situ hybridization was used to determine 1) the relative concentrations of mRNAs encoding different subunits of the alpha-amino 3-hydroxy-5-methyl-4- isoxazolepropionate receptor family in select regions of rat forebrain and 2) whether limbic seizures alter the balances of the subunit mRNAs. GluR1 and GluR2 mRNA levels were about equal and were much greater than GluR3 mRNA levels in the principal neurons of each hippocampal subdivision. Probable interneurons in hippocampal molecular layers had much higher levels of GluR1 mRNA than of either GluR2 or GluR3 mRNA. Pyramidal cell layers in neo- and paleocortex had a balance of mRNAs that was significantly different from the balance in hippocampus: GluR1 mRNA and GluR3 mRNA levels were about equal and were substantially lower than those of GluR2 mRNA. Lesion-induced limbic seizures caused transient changes in mRNA levels that were differentiated with regard to subunit and brain region. All three mRNAs were decreased in the pyramidal layers of cortex, and changes in hippocampal pyramidal cells were smaller. Seizure-induced changes in granule cells of the dentate gyrus differed from all other regions examined: GluR1 mRNA was reduced to a greater degree than GluR2 mRNA, whereas GluR3 mRNA content was markedly increased. These data strongly suggest that the subunit composition of alpha-amino 3-hydroxy-5-methyl-4-isoxazolepropionate receptors differs significantly between areas of the cortical telencephalon. Furthermore, the data indicate that aberrant patterns of physiological activity differentially influence the expression of subunit mRNAs in a region-specific and/or cell-type-specific manner.

Animals↗

PubMed1995

Odors increase Fos in olfactory bulb neurons including dopaminergic cells.

Neuronal activity may lead to long lasting changes in cell phenotype through induction of genes such as c-fos which encode transcriptional regulatory factors. Odor-activated olfactory bulb cells exhibit increases in c-fos mRNA expression. The present study examined whether odor stimulation of awake rats also leads to increases in Fos protein in these cells. The phenotype of Fos-immunoreactive cells was partially characterized using double-immunoperoxidase staining. Odor exposure increased Fos-immunoreactivity (IR) in specific sets of olfactory bulb neurons. Fos-IR was not co-localized with IR for glial fibrillary acidic protein, but was co-localized with tyrosine hydroxylase (TH)-IR in a subpopulation of dopaminergic neurons, suggesting that bulbar TH expression may be regulated in part by a Fos mechanism.

Animals↗

PubMed1995

NGF mRNA is expressed by GABAergic but not cholinergic neurons in rat basal forebrain.

Nerve growth factor (NGF) supports the survival and biosynthetic activities of basal forebrain cholinergic neurons and is expressed by neurons within lateral aspects of this system including the horizontal limb of the diagonal bands and magnocellular preoptic areas. In the present study, colormetric and isotopic in situ hybridization techniques were combined to identify the neurotransmitter phenotype of the NGF-producing cells in these two areas. Adult rat forebrain tissue was processed for the colocalization of mRNA for NGF with mRNA for either choline acetyltransferase, a cholinergic cell marker, or glutamic acid decarboxylase, a GABAergic cell marker. In both regions, many neurons were single-labeled for choline acetyltransferase mRNA, but cells containing both choline acetyltransferase and NGF mRNA were not detected. In these fields, virtually all NGF mRNA-positive neurons contained glutamic acid decarboxylase mRNA. The double-labeled cells comprised a subpopulation of GABAergic neurons; numerous cells labeled with glutamic acid decarboxylase cRNA alone were codistributed with the double-labeled neurons. These data demonstrate that in basal forebrain GABAergic neurons are the principal source of locally produced NGF.

Acetylcholine↗

PubMed1995

Insulin-like growth factor-1 mRNA is increased in deafferented hippocampus: spatiotemporal correspondence of a trophic event with axon sprouting.

Deafferentation is known to induce axonal sprouting in adult brain, but the signals that direct this response are not understood. To evaluate the possible roles of insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) in central axonal sprouting, the present study used in situ hybridization to evaluate IGF-1 and bFGF mRNA expression in entorhinal deafferented rat hippocampus. Alternate tissue sections were processed for Fink-Heimer impregnation of axonal degeneration, Bandeiraea simplicifolia (BS-1) labeling of microglia, and glial fibrillary acidic protein immunocytochemistry. In control hippocampus, IGF-1 mRNA was localized to a few neurons, with no labeled cells in the dentate gyrus molecular layer; bFGF cRNA hybridization was diffuse in dendritic fields but was dense in CA2 stratum pyramidale. Both mRNA species were increased by deafferentation. The distribution of elevated IGF-1 mRNA corresponded precisely to fields of axonal degeneration and was greatest in the dentate gyrus outer molecular layer and stratum lacunosum moleculare. In these fields, IGF-1 mRNA was elevated by 2 days, reached maximal levels at 4 days, and declined by 10 days postlesion. Double labeling revealed that the majority of IGF-1 cRNA-labeled cells were microglia. In deafferented hippocampus, bFGF mRNA was broadly increased across fields both containing and lacking axonal degeneration. In the dentate, bFGF mRNA levels peaked at 5 days postlesion and remained elevated through 14 days. These results demonstrate that reactive microglia within deafferented hippocampal laminae express IGF-1 mRNA just prior to and during the period of reactive axonal growth and suggest that IGF-1 plays a role in directing the sprouting of spared afferents into these fields.

Animals↗

PubMed1995

Proliferative zones of postnatal rat brain express epidermal growth factor receptor mRNA.

Two ligands for the epidermal growth factor receptor (EGF-R), EGF and transforming growth factor-alpha (TGF alpha), have recently been shown to influence the proliferation, differentiation or survival of diverse populations of fetal and neonatal neuronal and glial cells in culture. These findings suggest that EGF, TGF alpha, or another EGF-R ligand play a role in the regulation of similar cellular developmental events in vivo. In the present study, in situ hybridization with an 35S-labeled cRNA probe was used to determine if mRNA for EGF-R is expressed in two principal germinal zones of the postnatal rat brain, the forebrain ventricular/subventricular zone and the cerebellar external granule layer. Cells labeled with the EGF-R cRNA were distributed throughout the subventricular zone, particularly in the dorsolateral aspect, from birth to adulthood, although the numbers of labeled cells as well as the density of hybridization diminished during development. In the developing cerebellum, virtually all cells in the external granule layer were densely labeled with the EGF-R cRNA, as were numerous perikarya throughout the molecular layer. EGF-R mRNA was also transiently expressed at lower levels by neurons of the internal granule layer and deep cerebellar nuclei. By adulthood, cerebellar expression of EGF-R mRNA was not detected. These results demonstrate prominent expression of EGF-R mRNA within germinal zones of the developing brain and indicate a role for EGF, TGF alpha, or another member of the EGF-related family in regulating the activities of neuronal and glial progenitor cells in vivo.

Animals↗

PubMed1995

Decreased expression of the alpha subunit of Ca2+/ calmodulin-dependent protein kinase type II mRNA in the adult rat CNS following recurrent limbic seizures.

Calcium/calmodulin-dependent protein kinase type II (CamKII) is a ubiquitous brain enzyme implicated in a wide variety of neuronal processes. Understanding CamKII has become increasingly complicated with the recent identification of multiple gene transcripts coding for separate subunits. Previous studies have shown that mRNA for the alpha subunit of CamKII can be increased by reduction of afferent input. In this study we have examined the regulation of alpha CamKII mRNA following increased activity due to seizures. Using in situ hybridization with a cRNA probe against the rat alpha CamKII sequence we found reduced levels of hybridization following limbic seizures induced by lesions of the hilus of the dentate gyrus. Hybridization was most dramatically reduced in the granule cells of the dentate gyrus and the pyramidal cells of hippocampal region CA1. There were also significant reductions in hybridization in the superficial layers of neocortex and piriform cortex. In each of these region hybridization was decreased in the molecular layers which is consistent with the reported dendritic localization of alpha CamKII mRNA. All changes in mRNA content were transient, with maximal reductions at 24 h following lesion placement and a return to control levels by 96 h. These findings demonstrate the negative regulation of alpha CamKII mRNA by seizure activity and raise the possibility that synthesis of this kinase may be regulated by normal physiological activity.

Animals↗

PubMed1995

Expression of agrin mRNA is altered following seizures in adult rat brain.

Agrin mRNA is broadly distributed throughout the adult rat brain, consistent with its proposed role in synaptogenesis and the organization of synaptic proteins in the central nervous system. The present study examined the effect of neuronal activity on agrin mRNA expression in adult rat forebrain using the hilus lesion paradigm for seizure induction and in situ hybridization and polymerase chain reaction techniques for quantification and characterization of agrin mRNA content. Seizures induced rapid, prolonged, and region-specific changes in agrin mRNA expression with the most prominent alterations occurring in hippocampal and cortical neurons. However, there were no detectable perturbations in the relative abundance of alternatively spliced agrin transcripts in affected brain regions. Activity-dependent changes in agrin expression suggest a role for this protein in modifications of synaptic structure associated with functional synaptic plasticity.

Agrin↗

PubMed1995

A subpopulation of striatal gabaergic neurons expresses the epidermal growth factor receptor.

Epidermal growth factor and transforming growth factor alpha are mitogenic polypeptides that act at the epidermal growth factor receptor, a protein tyrosine kinase.10,16,18,24 Studies have shown that epidermal growth factor and transforming growth factor alpha support the survival and promote the differentiation of central nervous system neurons in vitro.13,21,33 Messenger RNAs for both transforming growth factor alpha and the epidermal growth factor receptor have been identified in the adult and developing mammalian central nervous system, particularly within the neostriatum of young animals.11,15,27,28,30 However, the cell types that synthesize these messenger RNAs in striatum are not well understood. The present study investigates the hypothesis that epidermal growth factor receptor and transforming growth factor alpha are synthesized by striatal GABAergic neurons using double-labeling in situ hybridization in the rat. Most neurons within the neostriatum that intensely expressed messenger RNA for the 67,000 mol. wt isoform of glutamate decarboxylase also expressed messenger RNA for the epidermal growth factor receptor. Scattered striatal cells with neuronal morphology were immunoreactive for epidermal growth factor receptor protein, indicating that epidermal growth factor receptor messenger RNA expressed by striatal neurons is translated. Striatal neurons that expressed high levels of the 67,000 mol. wt isoform of glutamate decarboxylate messenger RNA did not appear to express transforming growth factor alpha messenger RNA. The present study indicates that epidermal growth factor receptor is synthesized by a subpopulation of GABAergic striatal neurons, supporting the hypothesis that transforming growth factor alpha and epidermal growth factor act directly upon neurons to produce their neurotrophic effects. These neurons may be GABAergic interneurons, which have been shown to be relatively resistant to degeneration in Huntington's disease and excitotoxic models of this disease.6,1,9

Animals↗

PubMed1995

Functional mapping of odor-activated neurons in the olfactory bulb.

Induction of immediate-early gene expression, in particular c-fos, can be used to map neural activity in many brain areas, including the olfactory system. By making use of the resolution provided by cellular localization of c-fos mRNA or Fos protein, those neurons activated by a particular odor stimulus can be identified. Odor presentation to awake rats increases c-fos expression by bulb neurons located in discrete portions of the glomerular layer and in the underlying mitral and granule cell layers. The translaminar distribution of co-ordinately activated cells corresponds to the 'functional unit' predicted by the synaptic organization of the bulb, and the distribution of these units throughout the bulb as a whole differs for different odors. The bulbar pattern of activity is spatially altered by changes in odor intensity and during the course of postnatal development. These findings support the idea that distributed patterns of odor-induced neuronal activity contribute to the encoding of olfactory information. Moreover, the role of c-fos in the transcriptional regulation of other genes suggests a mechanism whereby odor experience can lead to long-term changes in the olfactory system.

Animals↗

PubMed1995

Changes in c-fos mRNA expression in rat brain during odor discrimination learning: differential involvement of hippocampal subfields CA1 and CA3.

Levels of c-fos mRNA were measured with in situ hybridization to test for behaviorally dependent changes in neuronal activity in three subdivisions of hippocampus and in components of the olfactory and visual systems. In rats that performed a well-learned nose-poke response for water reward, c-fos mRNA levels were broadly increased, relative to values in home cage-control rats, in visual cortex, superior colliculus, olfactory bulb, and, to comparable levels, regions CA3 and CA1 of hippocampus; hybridization was not increased in the dentate gyrus. In rats first trained on the nose-poke behavior and then required to discriminate between two odors for water reward, the increase in c-fos mRNA was generally not as great and was more regionally differentiated. Thus, in olfactory bulb, hybridization was more greatly elevated in lateral than medial fields, thereby exhibiting regional activation corresponding to the topographic representation of the predominant odor sampled in the discrimination task. In hippocampus of odor-discrimination rats, c-fos mRNA levels were far greater in the region CA3 than region CA1, but remained at cage control values in stratum granulosum. Interestingly, c-fos mRNA levels in each hippocampal subdivision were highly correlated with levels in other regions (e.g., visual cortex) for home cage controls but not for rats in the two behavioral groups. Thus, c-fos mRNA levels in cage-control rats appeared to be regulated by some generalized factor acting throughout much of the brain (e.g., arousal), while odor-discrimination performance changed the pattern of expression within hippocampus, and allowed for a differentiated response by olfactory regions to emerge. These findings suggest that hippocampus possesses multiple modes of functioning and makes contributions to behavior that vary according to task demands.

Animals↗

PubMed1995

Cellular localization of thrombin receptor mRNA in rat brain: expression by mesencephalic dopaminergic neurons and codistribution with prothrombin mRNA.

Cell culture studies demonstrating that the serine protease thrombin can induce neuronal and glial process retraction, glial proliferation, and changes in gene expression suggest a role for thrombin in CNS development, plasticity, and response to injury. Most cellular responses to thrombin are mediated by proteolytic activation of the cloned thrombin receptor (TR), a member of the seven transmembrane domain, G-protein-coupled receptor superfamily. As a step toward understanding the role of thrombin and its receptor in the CNS, Northern blot, in situ hybridization, and immunohistochemical techniques were used to analyze the cellular localization of TR mRNA in weanling-age rat brain. TR mRNA was broadly distributed across the neuraxis, although expression was very focal and often anatomically limited within specific neural structures. The greatest hybridization was associated with individual neurons in neocortex, cingulate/retrosplenial cortex, and subiculum, subsets of nuclei in hypothalamus, thalamus, pretectum, and ventral mesencephalon, and discrete cell layers in the hippocampus, cerebellum, and olfactory bulb. Patterns of hybridization included neuronal, glial, and ependymal cells, although white matter was uniformly negative, as were most cerebrovascular endothelial cells. Expression of TR mRNA by astroglia and dopaminergic neurons was confirmed by colocalization with immunoreactivity for glial fibrillary acidic protein (GFAP) in hippocampus and tyrosine hydroxylase in the substantia nigra. Comparison between TR and prothrombin (thrombin's precursor) cRNA hybridization demonstrated distinct but overlapping brain distributions of these transcripts, most clearly evident in postnatally developing, laminated structures. These results suggest widespread utilization of, and multiple physiologic, and possibly pathophysiologic, functions for, the thrombin/TR cell signaling system in the CNS.

Animals↗

PubMed1995

Regional patterns of c-fos mRNA expression in rat hippocampus following exploration of a novel environment versus performance of a well-learned discrimination.

Previous studies using c-fos cRNA in situ hybridization demonstrated a differential involvement of hippocampal subfields CA1 and CA3 in the acquisition of an olfactory discrimination (Hess et al., 1995). The present experiments employed the same method to examine changes in neuronal activity associated with two related behaviors: (1) initial exploration of the training apparatus and (2) performance of a well-learned odor discrimination. Rats in the two groups had similar labeling patterns within hippocampus indicating increased expression in all three major subfields with the greatest effect being in CA1. This pattern of "CA1 dominance" was notably different from that produced during early stages of two-odor discrimination learning in prior experiments. Hippocampal labeling in exploration and performance rats differed in that (1) hybridization was greater in CA1, CA3, and dentate gyrus in the former group and (2) a tendency for labeled cells to occur in clusters was more evident in exploration animals. Levels of c-fos mRNA in olfactory and visual structures were not predictive of expression patterns within hippocampus although labeling in piriform cortex and dentate gyrus was correlated in rats performing a well-practiced discrimination. Moreover, the pattern of hybridization in olfactory bulb was found to be behaviorally dependent. These results, together with those from previous studies, indicate that hippocampus has multiple patterns of regional activation but that one of these is common to very different behavioral circumstances. It is hypothesized that this common pattern emerges whenever the animal responds to distant cues using species-specific or well-learned behaviors and involves coordinated temporal convergence of sensory and septal/brainstem inputs.

Animals↗

PubMed1994

Expression of EGF receptor mRNA in rat nigrostriatal system.

In situ hybridization with a cRNA probe was used to determine the cellular expression of mRNA for the epidermal growth factor receptor (EGF-R) within the rat dopaminergic nigrostriatal system. Hybridization for EGF-R mRNA was distributed throughout the ventral mesencephalon within cells of the substantia nigra pars compacta and ventral tegmental area (VTA). Unilateral lesion of the nigrostriatal pathway with the neurotoxin 6-hydroxydopamine resulted in substantial elimination of EGF-R cRNA hybridization in the ipsilateral substantia nigra and VTA. EGF-R mRNA was also demonstrated within a population of striatal somata, with highest levels of expression detected neonatally. These results indicate that a subpopulation of ventral midbrain dopaminergic neurons, as well as striatal perikarya, express the EGF-R and, thus, may be directly responsive to endogenous EGF, transforming growth factor-alpha, or another EGF-R ligand in vivo.

Animals↗

PubMed1994

Dopaminergic neurons in rat ventral midbrain express brain-derived neurotrophic factor and neurotrophin-3 mRNAs.

Studies of the trophic activities of brain-derived neurotrophic factor and neurotrophin-3 indicate that both molecules support the survival of a number of different embryonic cell types in culture. We have shown that mRNAs for brain-derived neurotrophic factor and neurotrophin-3 are localized to specific ventral mesencephalic regions containing dopaminergic cell bodies, including the substantia nigra and ventral tegmental area. In the present study, in situ hybridization with 35S-labeled cRNA probes for the neurotrophin mRNAs was combined with neurotoxin lesions or with immunocytochemistry for the catecholamine-synthesizing enzyme tyrosine hydroxylase to determine whether the dopaminergic neurons, themselves, synthesize the neurotrophins in adult rat midbrain. Following unilateral destruction of the midbrain dopamine cells with 6-hydroxydopamine, a substantial, but incomplete, depletion of brain-derived neurotrophic factor and neurotrophin-3 mRNA-containing cells was observed in the ipsilateral substantia nigra pars compacta and ventral tegmental area. In other rats, combined in situ hybridization and tyrosine hydroxylase immunocytochemistry demonstrated that the vast majority of the neurotrophin mRNA-containing neurons in the substantia nigra and ventral tegmental area were tyrosine hydroxylase immunoreactive. Of the total population of tyrosine hydroxylase-positive cells, double-labeled neurons constituted 25-50% in the ventral tegmental area and 10-30% in the substantia nigra pars compacta, with the proportion being greater in medial pars compacta. In addition, tyrosine hydroxylase/neurotrophin mRNA coexistence was observed in neurons in other mesencephalic regions including the retrorubral field, interfascicular nucleus, rostral and central linear nuclei, dorsal raphe nucleus, and supramammillary region. The present results demonstrate brain-derived neurotrophic factor and neurotrophin-3 expression by adult midbrain dopamine neurons and support the suggestion that these neurotrophins influence dopamine neurons via autocrine or paracrine mechanisms. These data raise the additional possibility that inappropriate expression of the neurotrophins by dopaminergic neurons could contribute to the neuropathology of disease states such as Parkinson's disease and schizophrenia.

Animals↗

PubMed1994

Ultrastructural plasticity of the dentate gyrus granule cells following recurrent limbic seizures: I. Increase in somatic spines.

Various paradigms have been used to assess the capacity of the adult brain to undergo activity-dependent morphological plasticity. In this report we have employed recurrent limbic seizures as a means of studying the effects of this form of enhanced neuronal activity on cellular morphology and, in particular, on the incidence of somatic spines on the dentate gyrus granule cells. Seizure activity was induced by the placement of focal, unilateral electrolytic lesions in the dentate gyrus hilus of adult rats. At various intervals postlesion, rats with behaviorally verified seizures were sacrificed, and the hippocampi contralateral to the lesions were removed and prepared for electron microscopy. Quantitative analysis showed that as early as 5 hours postlesion there was a dramatic increase in the density and morphological complexity of spines on the perikarya of the granule cells in rats that received seizure-producing hilus lesions when compared to granule cells from control rats. Many of the somatic spines received asymmetric synapses. The increase in somatic spines was dependent on seizure activity and persisted for at least 1 month following a single recurrent seizure episode. CA1 pyramidal neurons, which exhibit changes in gene expression in response to hilus lesion-induced seizures but do not normally possess somatic spines, did not exhibit an activity-dependent elaboration of somatic spines. Thus, the seizure-induced elaboration of somatic spines represents an amplification of an existing feature of the granule cells and not an effect occurring throughout hippocampus. These data provide evidence for very rapid and long-lasting structural plasticity in response to brief episodes of seizure activity in the adult brain.

Animals↗