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

Abstract

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...

Modulation of vascular endothelial growth factor (VEGF) expression in motor neurons and its electrophysiological effects

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Changes in neuropeptide Y protein expression following photothrombotic brain infarction and epileptogenesis

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Compensatory Neurogenesis in the Injured Adult Brain

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