Ectopic Granule Cells of the Rat Dentate Gyrus

Scharfman, Helen E.; Goodman, Jeffrey H.; McCloskey, Daniel P.

doi:10.1159/000096208

Cited by 99 publications

(114 citation statements)

References 123 publications

(105 reference statements)

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“…Interneurons in the hilus do as well, although the population of both mossy cells and interneurons is reduced relative to the normal rat, and it is not yet clear which GABAergic neurons are involved of the many types that exist. Granule cells appear to be relatively quiet when CA3 burst discharges occur (Scharfman and McCloskey, 2007) but this is not always the case: some granule cells have depolarizations during the CA3 burst discharges -and do so at a long latency. The long latency suggests that CA3 neurons activate granule cells via mossy cells, similar to the normal rat.…”

Section: Functional Implications Of the Ca3 Backprojectionmentioning

confidence: 99%

The CA3 “backprojection” to the dentate gyrus

Scharfman

2007

The Dentate Gyrus: A Comprehensive Guide to Structure, Function, and Clinical Implications

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The hippocampus is typically described in the context of the trisynaptic circuit, a pathway that relays information from the perforant path to the dentate gyrus, dentate to area CA3, and CA3 to area CA1. Associated with this concept is the assumption that most hippocampal information processing occurs along the trisynaptic circuit. However, the entorhinal cortex may not be the only major extrinsic input to consider, and the trisynaptic circuit may not be the only way information is processed in hippocampus. Area CA3 receives input from a variety of sources, and may be as much of an "entry point" to hippocampus as the dentate gyrus. The axon of CA3 pyramidal cells targets diverse cell types, and has commissural projections, which together make it able to send information to much more of the hippocampus than granule cells. Therefore, CA3 pyramidal cells seem better designed to spread information through hippocampus than the granule cells. From this perspective, CA3 may be a point of entry that receives information which needs to be "broadcasted," whereas the dentate gyrus may be a point of entry that receives information with more selective needs for hippocampal processing.One aspect of the argument that CA3 pyramidal cells have a widespread projection is based on a part of its axonal arbor that has received relatively little attention, the collaterals that project in the opposite direction to the trisynaptic circuit, "back" to the dentate gyrus. The evidence for this "backprojection" to the dentate gyrus is strong, particularly in area CA3c, the region closest to the dentate gyrus, and in temporal hippocampus. The influence on granule cells is indirect, through hilar mossy cells and GABAergic neurons of the dentate gyrus, and appears to include direct projections in the case of CA3c pyramidal cells of ventral hippocampus. Physiological studies suggest that normally area CA3 does not have a robust excitatory influence on granule cells, but serves instead to inhibit it by activating dentate gyrus GABAergic neurons. Thus, GABAergic inhibition normally controls the backprojection to dentate granule cells, analogous to the way GABAergic inhibition appears to control the perforant path input to granule cells. From this perspective, the dentate gyrus has two robust glutamatergic inputs, entorhinal cortex and CA3, and two "gates," or inhibitory filters that reduce the efficacy of both inputs, keeping granule cells relatively quiescent. When GABAergic inhibition is reduced experimentally, or under pathological conditions, CA3 pyramidal cells activate granule cells reliably, and do so primarily by disynaptic excitation that is mediated by mossy cells. We suggest that the backprojection has important functions normally that are dynamically regulated by nonprincipal cells of the dentate gyrus. Slightly reduced GABAergic input would lead to increased polysynaptic associative processing between CA3 and the dentate gyrus. Under pathological conditions associated with loss of GABAergic interneurons, the backprojection ma...

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Section: Functional Implications Of the Ca3 Backprojectionmentioning

confidence: 99%

The CA3 “backprojection” to the dentate gyrus

Scharfman

2007

The Dentate Gyrus: A Comprehensive Guide to Structure, Function, and Clinical Implications

224

250

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“…Therefore, strategies that prevent or reverse abnormal mossy fiber sprouting in the dentate gyrus have received considerable attention as a treatment for TLE (Shetty and Turner, 1997;Shetty et al, 2005;Hattiangady et al, 2006). Furthermore, many studies suggest that anomalous migration of newly developed granule cells from the subgranular zone into the dentate hilus is another key feature of TLE (Houser, 1990;Scharfman et al, 2000;Scharfman et al, 2002b;Scharfman et al, 2003;McCloskey et al, 2006;Parent et al, 2006;Gong et al, 2007;Scharfman et al, 2007). In comparison to granule cells located in the granule cell layer, the ectopically migrated granule cells exhibit abnormal dendritic orientation Ribak, 2005, 2006), aberrant synaptic connectivity (Pierce et al, 2005;Jessberger et al, 2007), spontaneous epileptiform activity (Scharfman et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Is exposure to enriched environment beneficial for functional post-lesional recovery in temporal lobe epilepsy?

Dhanushkodi

Shetty

2008

Neuroscience & Biobehavioral Reviews

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Exposure to environmental enrichment has been shown to induce robust neuronal plasticity in both intact and injured adult central nervous system, including up-regulation of multiple neurotrophic factors, enhanced neurogenesis in the dentate gyrus of the hippocampus, and improved spatial learning and memory function. Neuronal plasticity, though mostly adaptive and abnormal, also occurs during certain neurodegenerative conditions such as the temporal lobe epilepsy (TLE). The TLE is characterized by hippocampal neurodegeneration, aberrant mossy fiber sprouting, spontaneous recurrent motor seizures, cognitive deficits, and abnormally enhanced neurogenesis during the early phase and dramatically declined neurogenesis during the chronic phase of the disease. As enrichment has been found to be beneficial for treating animal models of Alzheimer's, Parkinson's, and Huntington's diseases, there is considerable interest in determining the efficacy of this strategy for preventing or treating chronic TLE after the initial precipitating brain injury. This review first discusses the proof of principle behind the potential application of the environmental enrichment strategy for preventing or treating TLE after brain injury. The subsequent chapters confer the portrayed beneficial effects of enrichment for functional post-lesional recovery in TLE and the possible complications which may arise from housing epilepsy-prone or epileptic rats in enriched environmental conditions. The final segment discusses studies that are essential for further understanding the efficacy of this approach for preventing or treating TLE.

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“…This may seem counterintuitive, as it is generally expected that excessive excitatory activity would lead to cell loss. However, numerous studies have reported increased hilar neurons in animal models of TLE and it is speculated that neurogenesis may be a compensatory response to seizure-induced cell death [34][35][36]41]. Characterization of these neurons has revealed that they exhibit properties of dentate granule cells (i.e., ectopic granule cells).…”

Section: Discussionmentioning

confidence: 99%

“…In rats, chemical or electrically induced seizures and status epilepticus result in a number of cytoarchitectural changes in the hippocampus including activation and proliferation of astrocytes [33] and neurogenesis in the dentate hilus associated with the formation of ectopic granule cells [34][35][36]. Our objective in the current study was to determine if similar changes occur in the neonatal DOM model and further to see if such changes are progressive over time by sampling animals at time points earlier than those previously examined (i.e., prior to postnatal day (PND) 90).…”

Section: Introductionmentioning

confidence: 99%

Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat model of epilepsy: implications for understanding presymptomatic epileptogenesis, predictive diagnosis, and targeted treatments

et al. 2017

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Epilepsies affect about 4% of the population and are frequently characterized by a prolonged Bsilent^period before the onset of spontaneous seizures. Most current animal models of epilepsy either involve acute seizure induction or kindling protocols that induce repetitive seizures. We have developed a rat model of epilepsy that is characterized by a slowly progressing series of behavioral abnormalities prior to the onset of behavioral seizures. In the current study, we further describe an accompanying progression of cytoarchitectural changes in the hippocampal formation. Groups of male and female SD rats received serial injections of a low dose of domoic acid (0.020 mg/kg) (or vehicle) throughout the second week of life. Postmortem hippocampal tissue was obtained on postnatal days 29, 64, and 90 and processed for glial fibrillary acidic protein (GFAP), NeuN, and calbindin expression. The data revealed no significant changes on postnatal day (PND) 29 but a significant increase in hilar NeuN-positive cells in some regions on PND 64 and 90 that were identified as ectopic granule cells. Further, an increase in GFAP positive cell counts and evidence of reactive astrogliosis was found on PND 90 but not at earlier time points. We conclude that changes in cellular expression, possibly due to on-going non-convulsive seizures, develop slowly in this model and may contribute to progressive brain dysfunction that culminates in a seizure-prone phenotype.

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Ectopic Granule Cells of the Rat Dentate Gyrus

Cited by 99 publications

References 123 publications

The CA3 “backprojection” to the dentate gyrus

The CA3 “backprojection” to the dentate gyrus

Is exposure to enriched environment beneficial for functional post-lesional recovery in temporal lobe epilepsy?

Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat model of epilepsy: implications for understanding presymptomatic epileptogenesis, predictive diagnosis, and targeted treatments

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