The Journal of neuroscience : the official journal of the Society for Neuroscience
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Aged rats have impairments in several types of cognitive functions, including spatial working memory (WM), that are dependent upon the septohippocampal cholinergic system. The present series of experiments was designed to assess the effectiveness of pharmacological manipulations of the medial septal area (MSA) in order to influence the physiology of the septohippocampal pathway and, therefore, the brain functions in which this pathway participates. Aged (22MO) and young (4MO) Fischer-344 rats received microinfusions into the MSA with either saline, the muscarinic agonist, oxotremorine (OXO), or the muscarinic antagonist, scopolamine (SCOP). ⋯ SCOP produced a shift of the hippocampal theta to a higher frequency and a lower peak power, and a decrease in the initial slope of pEPSP. In 4MO rats, SCOP altered hippocampal theta similarly to 22MO, but did not affect the pEPSP slope. These results indicate that (1) cholinergic receptors in the MSA are a useful target for drugs to improve WM in aging rats, (2) age-related changes in the activity of the septohippocampal pathway may increase its sensitivity to drugs which alter its activity, and (3) alterations in hippocampal physiology may contribute differently to changes in WM in young and in old rats.
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The developmental stage at which nerve cells initially express specific neurotransmitters and their corresponding receptors remains elusive. In the present study, the distribution patterns of transcripts for the GABA-synthesizing enzyme, glutamate decarboxylase (GAD67), and specific GABAA receptor subunits were examined in the proliferative zone of the rat central nervous system using in situ hybridization. In order to define the DNA synthetic zone of the germinal matrix, tissue sections were taken from embryos whose mothers had been injected with 5-bromo-2'-deoxyuridine (BrdU) and had survived for 1 hr. ⋯ In clear contrast, GAD67 mRNA was abundant in the outer half of the germinal matrix (i.e., TZ or SV), and in the intermediate zone as well. Immunocytochemical staining of E17 neocortex with anti-GABA antibody revealed a well defined band of GABA-immunoreactive cells and processes in the SV and occasional positive cells in the VZ. It appears that cells in the proliferative zone may express GABA at the migratory stage, whereas cells in the VZ may express mRNAs for GABAA receptor alpha 4, beta 1, and gamma 1 subunits at the premigratory stage, just after completing cell division.(ABSTRACT TRUNCATED AT 400 WORDS)