Neuropsychological studies have established the brain's limbic system as critically important for human learning and memory processes, and limbic system degeneration is centrally involved in the etiology of Alzheimer's and Korsakoff's disease. The highly diffuse character of degenerative change in these conditions has made difficult the discovery of links between specific forms and sites of damage on the one hand and specific mnemonic and behavioral impairments on the other. Knowledge of the specific mnemonic functions and dynamic interactions of limbic brain circuits may prove helpful to the discovery of such links. Yet, little is known of these functions. The overall objective of this project is to specify completely these functions in an animal model. Past work of this project established the critical relevance of limbic circuits in relation to discriminative avoidance learning in rabbits. Studies of the neuronal activity in the behaving animal, selective lesioning, and neurochemical manipulations have fostered substantial progress toward this specification. Of particular value has been multi-channel recording, which allows documentation of learning-related neuronal activity simultaneously in six brain areas. This approach has yielded many unprecedented findings and a theoretical working model of the dynamic interactions of the cerebral cortical and thalamic limbic structures subserving learning. Studies proposed here afford major strides toward the elaboration of a veridical model. These studies will indicate: a) how the convergence of tegmental cholinergic and mammillothalamic afferents brings about training-induced neuronal plasticity in limbic thalamus; b) the pathway whereby cue-driven auditory information that triggers the learned response accesses the sites of critical learning-relevant plasticity in limbic thalamus; c) the functional relevance of training-stage related peaks of learning-relevant plasticity in subdivisions of the anterior thalamus; d) the dynamic interactions of hippocampal with limbic cortical and thalamic circuits that govern the training-stage related peaks of plasticity and suppression of learned behavior in response to unexpected events; e) the pathways whereby learning-relevant plasticity in limbic circuits accesses the motor system to produce output of the learned behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS026736-11
Application #
3412718
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Project Start
1982-08-21
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
11
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Talk, Andrew; Kang, Eunjoo; Gabriel, Michael (2004) Independent generation of theta rhythm in the hippocampus and posterior cingulate cortex. Brain Res 1015:15-24
Talk, Andrew; Kashef, Alireza; Gabriel, Michael (2004) Effects of conditioning during amygdalar inactivation on training-induced neuronal plasticity in the medial geniculate nucleus and cingulate cortex in rabbits (Oryctolagus cuniculus). Behav Neurosci 118:944-55
Smith, David M; Wakeman, Derek; Patel, Jay et al. (2004) Fornix lesions impair context-related cingulothalamic neuronal patterns and concurrent discrimination learning in rabbits (Oryctolagus cuniculus). Behav Neurosci 118:1225-39
Poremba, A; Gabriel, M (2001) Amygdalar efferents initiate auditory thalamic discriminative training-induced neuronal activity. J Neurosci 21:270-8
Duvel, A D; Smith, D M; Talk, A et al. (2001) Medial geniculate, amygdalar and cingulate cortical training-induced neuronal activity during discriminative avoidance learning in rabbits with auditory cortical lesions. J Neurosci 21:3271-81
Freeman Jr, J H; Gabriel, M (1999) Changes of cingulothalamic topographic excitation patterns and avoidance response incubation over time following initial discriminative conditioning in rabbits. Neurobiol Learn Mem 72:259-72
Taylor, C L; Freeman Jr, J H; Holt, W et al. (1999) Impairment of cingulothalamic learning-related neuronal coding in rabbits exposed to cocaine in utero: general and sex-specific effects. Behav Neurosci 113:62-77
Poremba, A; Gabriel, M (1999) Amygdala neurons mediate acquisition but not maintenance of instrumental avoidance behavior in rabbits. J Neurosci 19:9635-41
Kang, E; Gabriel, M (1998) Hippocampal modulation of cingulo-thalamic neuronal activity and discriminative avoidance learning in rabbits. Hippocampus 8:491-510
Hart, M; Poremba, A; Gabriel, M (1997) The nomadic engram: overtraining eliminates the impairment of discriminative avoidance behavior produced by limbic thalamic lesions. Behav Brain Res 82:169-77

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