The regulation of expression of the 67-kiloDalton form of glutamic acid decarboxylase in the rodent barrel cortex.

摘要

Sensory experience often leads to functional reorganization of peripheral representations in the primary sensory cortices, and evidence exists that gamma-aminobutyric acid (GABA)ergic transmission plays an important role in this cortical reorganization. The 67-kiloDalton form of glutamic acid decarboxylase (GAD67) is responsible for the majority of the GABA synthesis in the mammalian brain, and changes in its expression have been shown to result in corresponding changes in GAD activity and GABA levels. Therefore, GAD67 may play a potential role in sensory-dependent changes in GABAergic transmission occurring with cortical plasticity.; With the underlying premise that experience-dependent alterations in GAD67 expression could potentially play a role in cortical plasticity, this thesis sought to test the hypotheses that whisker stimulation increases both GAD67 mRNA and protein expression in the rodent barrel cortex. This thesis also sought to test the hypotheses that members of the early growth response (EGR) transcription factor family and/or BDNF may play roles in this experience-dependent regulation of cortical GAD67 mRNA expression.; The results of the experiments of this thesis fail to support the proposed hypotheses. The results from some of the experiments of this thesis were not conclusive and failed to demonstrate that sensory stimulation, either by either passive whisker stimulation or by active exploration of novel and/or complex environments, alters barrel cortex GAD67 protein levels. Results of other studies failed to demonstrate that either the EGR transcription factors or BDNF play a role in the regulation of barrel cortex GAD67 mRNA expression. The results of experiments in this thesis however yielded the previously unknown sequence of the rat GAD67 promoter region and may indicate that the EGR transcription factors can affect expression from the rat GAD67 promoter in vitro. Experimental results also indicate that sensory stimulation in our whisker stimulation paradigm, if it does alter GAD67 mRNA expression, most likely decreases, rather than increases, barrel cortex GAD67 mRNA levels.