Alterations of AMPA-selected glutamate subtype immunoreactivity in the dentate gyrus after perforant pathway lesion.

Immunocytochemical techniques were employed to examine the changes in immunolabeling of the alpha-amino-3-hydroxy-5-methyl-4-isoaxolepropionate (AMPA) receptor subunits GluR1 and GluR2/3 within the dentate gyrus 1, 3, 7, 14, 30, and 90 days after a unilateral perforant pathway lesion in the rat brain. Completeness of the lesion was confirmed following examination of Nissl-stained tissue sections at all times post-lesion and acetylcholinesterase (AChE)-stained sections 14, 30 and 90 days post-lesion, the latter providing evidence of compensatory sprouting of cholinergic fibers in the outer molecular layer of the dentate gyrus. Compared to the non-lesioned hippocampus there was no difference in the staining pattern of AMPA receptor subunits in the dentate gyrus of the deafferented hippocampus 1, 3, 7 and 14 days following lesioning of the perforant pathway. In contrast, 30 and 90 days post-lesion, GluR1 immunolabeling was increased in the outer molecular layer of the dentate gyrus (i.e., deafferented zone) ipsilateral to lesion. Likewise, GluR2/3 immunolabeling was increased within the same region although the intensity of the response was less than that which was observed for GluR1. These data suggest that the loss of the perforant pathway fibers results in a compensatory increase in GluR1 and to a lesser extent GluR2/3 immunolabeling of the outer molecular layer at 30 and 90 days post-lesion and further suggest that AMPA receptor subunits play a role in perforant pathway signal transduction.

Alterations of GABA(A)beta2/3 immunoreactivity in the dentate gyrus after perforant pathway lesion.

Immunocytochemical techniques were employed to examine the changes in the GABA receptor subunits beta2/3 within the dentate gyrus of the rat brain 1, 3, 7, 14, 30 and 90 days after a unilateral perforant pathway lesion. Three days post-lesion we observed a decrease in beta2/3 immunolabeling in the inner molecular layer of the dentate gyrus followed by a comparable decrease in the outer molecular layer 7 days post-lesion. These decreases were transient; 30 and 90 days post-lesion, beta2/3 immunolabeling appeared similar to controls in the inner portion of the molecular layer, while in the outer region the labeling was increased. In this latter region we also observed a dense band of AChE fibers. Following survival times of 3 days we observed a diffuse staining of the neuropil in the hilar region, and a dense amorphous accumulation of peroxidase reaction product in the polymorphic region. These responses were transient and by 14 days the hilar/polymorphic region appeared indistinguishable from controls. These data suggest a unique pattern of immunoabeling in the molecular and polymorphic region in response to perforant pathway lesion. A putative explanation for this response is discussed.