Our overall objective is to investigate, at both behavioral and electrophysiological levels, cognitive dysfunctions which are concomitants of aging. Two such age-related phenomena have emerged in our current studies upon which we propose to focus in the next three year period. Impairment of associative learning, i.e., the conditioned eye-blink response, appears to be a consistent behavioral correlate of aging in the cat. Marked abnormalities have also been consistently found in the endogenous """"""""P300"""""""" potential of the aged cat, similar to the P300 abnormalities reported for aged human subjects and for Alzheimer's presenile dementia. (In contrast to these cognitive dysfunctions, auditory brainstem responses (ABRs) showed no significant difference in latency or central transmission time in aged cats when stimulus intensity was normalized against ABR click threshold.) We propose to investigate the deficient conditionability of the old cat by focusing upon the medial geniculate body (MG) as a model system, which will allow direct comparison of functions within a center which contains both a primary sensory (MGp) and a plastic, reticular-like (MGm) component. Evoked potential and unit recordings will be carried out in the awake restrained cat under a variety of conditions to test the hypothesis that conditioned associative learning is impaired in the aged brain due to deficient functioning at subcortical levels and that such deficiencies will appear in the MGm but not in the MGp. We propose to compare differences in latency, amplitude and topographical distribution of the endogenous P300 potential between old and young cats to test the hypothesis that aging changes are predictably reflected in the cat P300, as in the human aged and Alzheimer P300s. Evoked potential and unit recordings will be carried out in the hippocampus and correlated with the vertex recorded P300 of old and young cats to test the corollary hypothesis that aging changes in abrain system, possibly involving the hippocampus, are predictably reflected in the cat P300. These studies may provide a means of relating a cognition potential, which becomes abnormal with age, to a particular neurophysiological system.
| Kaga, K; Harrison, J B; Butcher, L L et al. (1992) Cat 'P300' and cholinergic septohippocampal neurons: depth recordings, lesions, and choline acetyltransferase immunohistochemistry. Neurosci Res 13:53-71 |
| Harrison, J B; Dickerson, L W; Song, S et al. (1990) Cat-P300 present after association cortex ablation. Brain Res Bull 24:551-60 |
| Harrison, J B; Buchwald, J S; Kaga, K et al. (1988) 'Cat P300' disappears after septal lesions. Electroencephalogr Clin Neurophysiol 69:55-64 |
| Harrison, J B; Buchwald, J S (1987) A cat model of the P300: searching for generator substrates in the auditory cortex and medial septal area. Electroencephalogr Clin Neurophysiol Suppl 40:473-80 |
| Harrison, J; Buchwald, J; Kaga, K (1986) Cat P300 present after primary auditory cortex ablation. Electroencephalogr Clin Neurophysiol 63:180-7 |
| Chen, B M; Buchwald, J S (1986) Midlatency auditory evoked responses: differential effects of sleep in the cat. Electroencephalogr Clin Neurophysiol 65:373-82 |
| Harrison, J; Buchwald, J (1985) Aging changes in the cat P300 mimic the human. Electroencephalogr Clin Neurophysiol 62:227-34 |
