Effects of cholinergic depletion in the nucleus basalis of Meynert on neurotransmitters and synaptic markers in the somatosensory cortex

The research in this dissertation investigates the effects of cholinergic depletion of inputs from nucleus basalis of Meynert (NBM) on neurotransmitters and synaptic markers in the somatosensory cortex. The purpose of these studies was to understand the effects of cholinergic depletion on the expression of glutamic acid decarboxylase (GAD), N-methyl-D-aspartate (NMDA) receptors, and synaptophysin in the PMBSF cortex.; Chapter 1 details the history of cholinergic lesioning and details the purpose for each experiment. Injections of 192 IgG saporin (IT) were used to selectively lesion cholinergic neurons in the basal forebrain. Experiments in chapter 2 were designed to investigate the effects of cholinergic depletion on ChAT, GAD, NMDA receptor, and synaptophysin at 2 weeks post IT-injection. Results were confirmed with immunocytochemistry and confocal microscopy. Results demonstrate that ChAT, GAD, NMDA, and synaptophysin levels are all significantly decreased in the PMBSF cortex two weeks post-injection.; Experiments in chapter 3 were designed to understand the long-term effects of cholinergic depletion on the expression of GAD, NMDA receptors, and synaptophysin, and to determine if these proteins spontaneously recover to control levels. Data show that ChAT levels transiently increase at 1 month post-injection, and then remain significantly decreased at 2 and 4 months when compared to PBS-injected controls. GAD and NMDA receptor expression were significantly decreased at all time points compared to PBS-injected controls. Synaptophysin levels initially decreased, however by 4 months, levels were approaching control levels.; The experiments in chapter 4 were carried out to determine the efficacy of neurotrophins in promoting recovery of PMBSF cortical neurons. In addition, a behavioral task was included in this study to determine if discrimination learning and performance improved in animals that received neurotrophins. Data from chapter 4 show that following neurotrophin application, animals experience a significant increase in ChAT, GAD, and synaptophysin levels. While NMDA levels were increased in the neurotrophin implanted animals, the change was not significant. Synaptophysin expression was increased following neurotrophin application compared to saline implanted controls in IT-injected animals. These experiments indicate that neurotrophins may be able to remediate some of the effects of cholinergic depletion in the PMBSF cortex.