The long-term objectives of the proposed research are to determine the functional role of acetylcholine in sensory processing and to determine the importance of acetylcholine input to the cortex in cortical plasticity during aging. To attain these objectives, the specific aims of the proposed research are the following: 1) to determine if SI neurons with receptive fields can reorganize in an aged brain as in a young brain; 2) to establish how acetylcholine input from the nucleus basalis of Meynert (NBM) to SI may be important in cortical plasticity of SI cortical maps following trimming of the rat's whiskers in young and aged rats; and 3) if cholinergic input to SI is necessary for plasticity in response to whisker trimming, to see if the effects of a loss of acetylcholine input can be reversed. To reach these goals, the following experimental design and methods will be done. In young and aged rats, extracellular recordings will be used to map receptive fields in SI under the following: l) phosphate buffered- saline injections into the NBM (eleven to fourteen days prior to recording) and whisker trimming (six days prior to recording) to determine if whisker trimming alters cortical maps (control group); 2) a combination of ibotenic acid lesions of the NBM (eleven to fourteen days prior to recording) and whisker trimming to determine if a loss of acetylcholine input to SI reduces or prevents cortical plasticity in response to whisker trimming (experimental group); and 3) if plasticity is prevented by method 2 above, chronic acetylcholine or agonist treatment after NBM lesions and whisker trimming to see if the effects of NBM lesioning after whisker trimming can be reversed. This study is expected to show that acetylcholine input to SI is essential for cortical plasticity in response to altered sensory experiences during the aging process and that the plastic changes can be reestablished by the chronic infusion of acetylcholine into the SI cortex. This study may have relevance to age-related disorders such as Alzheimer's disease.
Baskerville, K A; Schweitzer, J B; Herron, P (1997) Effects of cholinergic depletion on experience-dependent plasticity in the cortex of the rat. Neuroscience 80:1159-69 |