Functional significance of hippocampal plasticity in epileptic brain: Electrophysiological changes of the dentate granule cells associated with mossy fiber sprouting

Dudek, F. Edward; Obenaus, André; Schweitzer, Jeffrey S.; Wuarin, Jean Pierre

doi:10.1002/hipo.450040306

Cited by 82 publications

(52 citation statements)

References 36 publications

(49 reference statements)

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“…These data argue that infrapyramidal blade excitability may relate, or even depend, on the anatomic differences. Indeed, this possibility supports the hypothesis in the literature that mossy fiber sprouting increases dentate gyrus excitability, based on anatomic (Frotscher and Zimmer, 1983;Represa et al, 1993;Franck et al, 1995;Okazaki et al, 1995;Sutula et al, 1998;Wenzel et al, 2000) and physiological data (Tauck and Nadler, 1985;Sutula et al, 1992Sutula et al, , 1998Dudek et al, 1994;Pollard et al, 1996;Wuarin and Dudek, 1996;Patrylo and Dudek, 1998;Molnar and Nadler, 1999;Okazaki et al, 1999).…”

Section: Epileptic Ratssupporting

confidence: 84%

Structural and functional asymmetry in the normal and epileptic rat dentate gyrus

Scharfman

Sollas

Smith

et al. 2002

J of Comparative Neurology

128

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The rat dentate gyrus is usually described as relatively homogeneous. Here, we present anatomic and physiological data which demonstrate that there are striking differences between the supra-and infrapyramidal blades after status epilepticus and recurrent seizures. These differences appear to be an accentuation of a subtle asymmetry present in normal rats. In both pilocarpine and kainic acid models, there was greater mossy fiber sprouting in the infrapyramidal blade. This occurred primarily in the middle third of the hippocampus. Asymmetric sprouting was evident both with Timm stain as well as antisera to brain-derived neurotrophic factor (BDNF) or neuropeptide Y (NPY). In addition, surviving NPY-immunoreactive hilar neurons were distributed preferentially in the suprapyramidal region of the hilus. Extracellular recordings from infrapyramidal sites in hippocampal slices of pilocarpine-treated rats showed larger population spikes and weaker paired-pulse inhibition in response to perforant path stimulation relative to suprapyramidal recordings. A single stimulus could evoke burst discharges in infrapyramidal granule cells but not suprapyramidal blade neurons. BDNF exposure led to spontaneous epileptiform discharges that were larger in amplitude and longer lasting in the infrapyramidal blade. Stimulation of the infrapyramidal molecular layer evoked larger responses in area CA3 than suprapyramidal stimulation. In slices from the temporal pole, in which anatomic evidence of asymmetry waned, there was little evidence of physiological asymmetry either. Of interest, some normal rats also showed signs of greater evoked responses in the infrapyramidal blade, and this could be detected with both microelectrode recording and optical imaging techniques. Although there were no signs of hyperexcitability in normal rats, the data suggest that there is some asymmetry in the normal dentate gyrus and this asymmetry is enhanced by seizures. Taken together, the results suggest that supra-and infrapyramidal blades of the dentate gyrus could have different circuit functions and that the infrapyramidal blade may play a greater role in activating the hippocampus. The rat dentate gyrus is a laminar structure that consists of a dense layer of granule cells, an adjacent molecular layer, and a polymorphic layer (the hilus). The granule cell layer is usually described as relatively homogeneous, i.e., structurally and functionally similar along its entire length. Thus, the width of the layer and the properties of the cells within it are similar from the lateral tip of the "suprapyramidal" blade (i.e., the area closest to CA1, also referred to as the upper, dorsal, or inner blade), to the lateral tip of the "infrapyramidal" blade. The organization of the molecular layer also appears to be homogeneous. Hilar neurons appear to be distributed in a random manner, with no preference for any particular area of the hilus (Amaral, 1978). Granule cell axons, the mossy fibers, appear to be homogeneous in general (Blackstad et al., 1970;Gaarskjae...

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Section: Epileptic Ratssupporting

confidence: 84%

Structural and functional asymmetry in the normal and epileptic rat dentate gyrus

Scharfman

Sollas

Smith

et al. 2002

J of Comparative Neurology

128

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“…This cell loss has been found to be progressive (Sutula, 1991;Kalviainen et al, 1998), and associated with -in fact, probably required for (Schauwecker et al, 2000) -synaptic reorganization and increased excitability in the involved circuits (Dudek et al, 1994;Scharfman et al, 2000).…”

Section: Introductionmentioning

confidence: 94%

“…The striking cell loss in specific hippocampal regions and layers found in humans with temporal lobe epilepsy has suggested that seizures may cause epilepsy by killing neurons, leading to reduced inhibition or to the development of excitatory synapses and circuits (e.g., Sloviter, 1991;Dudek et al, 1994;Scharfman, 1999).…”

Section: Introductionmentioning

confidence: 99%

Is neuronal death required for seizure-induced epileptogenesis in the immature brain?

Baram

Eghbal-Ahmadi

Bender

2002

Progress in Brain Research

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Do seizures cause neuronal death? At least in the immature hippocampus, this may not be the critical question for determining the mechanisms of epileptogenesis. Neuronal injury and death have clearly been shown to occur in most epilepsy models in the mature brain, and are widely considered a prerequisite to seizure-induced epilepsy. In contrast, little neuronal death occurs after even a severe and prolonged seizure prior to the third postnatal week. However, seizures early in life, for example prolonged experimental febrile seizures, can profoundly and permanently change the hippocampal circuit in a pro-epileptogenic direction. These seizure-induced alterations of limbic excitability may require transient structural injury, but are mainly due to functional changes in expression of gene coding for specific receptors and channels, leading to altered functional properties of hippocampal neurons. Thus, in some pro-epileptogenic models in the developing brain, neither the death of neurons nor death-induced abnormalities of surviving neurons may underlie the formation of an epileptic circuit. Rather, findings in the experimental prolonged febrile seizure model suggest that persistent functional alterations of gene expression ('neuroplasticity') in diverse hippocampal neuronal populations may promote pro-epileptogenic processes induced by these seizures. These findings also suggest that during development, relatively short, intense bursts of neuronal activity may disrupt 'normal' programmed maturational processes to result in permanent, selective alterations of gene expression, with profound functional consequences. Therefore, determining the cascade of changes in the programmed expression of pertinent genes, including their temporal and cell-specific spatial profiles, may provide important information for understanding the process of transformation of an evolving, maturing hippocampal network into one which is hyperexcitable.

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“…Indeed, physiological studies report the presence of hyperexcitability in both of these regions following CA3 region injury (Tauck and Nadler, 1985;Turner and Wheal, 1991;Perez et al, 1996). The mechanisms responsible for persistent hyperexcitability in the dentate gyrus and the CA1 subfield of the CA3-lesioned hippocampus likely include an aberrant reorganization of the disrupted circuitry, decreased afferent circuitry leading to interneurons, loss of the physiological efficacy of interneurons, and reductions in the number of GABA synthesizing interneurons (Mathern et al, 1993;Mello et al, 1993;Dudek et al, 1994;Okazaki et al, 1995;Shetty andTurner, 2000, 2001;Wuarin and Dudek, 2001;Buckmaster et al, 2002;Scharfman et al, 2003;Shetty et al, 2005) Therefore, strategies that facilitate appropriate reorganization of the disrupted circuitry may be critical for easing hyperexcitability in the injured hippocampus. Replacing the degenerated host neurons with grafting of specific fetal neural cells may be particularly beneficial in this regard.…”

Section: Introductionmentioning

confidence: 99%

Restoration of calbindin after fetal hippocampal CA3 cell grafting into the injured hippocampus in a rat model of temporal lobe epilepsy

Shetty

Hattiangady

2007

Hippocampus

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Degeneration of the CA3 pyramidal and dentate hilar neurons in the adult rat hippocampus after an intracerebroventricular kainic acid (KA) administration, a model of temporal lobe epilepsy, leads to permanent loss of the calcium binding protein calbindin in major fractions of dentate granule cells and CA1 pyramidal neurons. We hypothesize that the enduring loss of calbindin in the dentate gyrus and the CA1 subfield after CA3-lesion is due to disruption of the hippocampal circuitry leading to hyperexcitability in these regions; therefore, specific cell grafts that are capable of both reconstructing the disrupted circuitry and suppressing hyper-excitability in the injured hippocampus can restore calbindin. We compared the effects of fetal CA3 or CA1 cell grafting into the injured CA3 region of adult rats at 45 days after KA-induced injury on the hippocampal calbindin. The calbindin immunoreactivity in the dentate granule cells and the CA1 pyramidal neurons of grafted animals was evaluated at 6 months after injury (i.e. at 4.5 months post-grafting). Compared with the intact hippocampus, the calbindin in "lesion-only" hippocampus was dramatically reduced at 6 months post-lesion. However, calbindin expression was restored in the lesioned hippocampus receiving CA3 cell grafts. In contrast, in the lesioned hippocampus receiving CA1 cell grafts, calbindin expression remained less than the intact hippocampus. Thus, specific cell grafting restores the injury-induced loss of calbindin in the adult hippocampus, likely via restitution of the disrupted circuitry. Since loss of calbindin after hippocampal injury is linked to hyperexcitability, re-expression of calbindin in both dentate gyrus and CA1 subfield following CA3 cell grafting may suggest that specific cell grafting is efficacious for ameliorating injury-induced hyperexcitability in the adult hippocampus. However, electrophysiological studies of KA-lesioned hippocampus receiving CA3 cell grafts are required in future to validate this possibility.

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Functional significance of hippocampal plasticity in epileptic brain: Electrophysiological changes of the dentate granule cells associated with mossy fiber sprouting

Cited by 82 publications

References 36 publications

Structural and functional asymmetry in the normal and epileptic rat dentate gyrus

Structural and functional asymmetry in the normal and epileptic rat dentate gyrus

Is neuronal death required for seizure-induced epileptogenesis in the immature brain?

Restoration of calbindin after fetal hippocampal CA3 cell grafting into the injured hippocampus in a rat model of temporal lobe epilepsy

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