Studies of human neuropathology have implicated the limbic system in the mediation of learning and memory processes. In accord with this result, our studies of unit activity in behaving animals have shown differentiation of neuronal responses to stimuli with varied associative significance. These effects occur in a triad of reciprocally interconnected limbic structures (the cingulate cortex, anteroventral thalamic nucleus [AVN], and hippocampal formation). Neurons in the deep cingulate cortical layers manifest discriminative firing in the early training stages, but the AVN and the superficial layers do not discriminate until discriminative behavior is well established. Similar relationships hold in the relative prefrontal corticothalamic system, but in this instance, the development of discriminative firing is accelerated, relative to the limbic triad. These results form the basis of a theory in which it is posited that the function of limbic forebrain in learning processes is the encoding and """"""""extraction"""""""" of que significance. The sequential character of the developing differential responses provided the rationale for the model's hypotheses about the causal relationships among the involved structures. Recent tests supported the model's hypotheses that the late discriminative code in the upper cortical layers originates in the AVN, and that the hippocampal formation (subiculum) exerts a tonic suppressive influence over neuronal firing in the cingulate cortex. This suppressive control, predicted by the model, provides a mechanisms to account for the behavioral hyperreactivity shown by animals with hippocampal damage. A major breakthrough has been the realization that the structures of the limbic triad produce an """"""""automatic"""""""" neural code relevant to the performance of well learned behavior, but not to its original acquisition. The analogous code in the prefrontal system is the """"""""leading edge"""""""" code subserving acquisition. Thus our studies identify separate neurobiological substrates for original discriminative acquisition, and for the maintenance of well learned behavior. Most importantly, the recent work indicates that selective removal of afferents yields selective neuronal effects in the recipient structures, and selective behavioral deficits. This general result supports the efficacy of our strategy for the functional analysis of interacting brain systems in relation to ongoing behavior. The proposed studies continue the analytic strategy by investigating the contributions to the significance coding process in the limbic triad made by afferents from the prefrontal system, the noradrenergic and basal forebrain cholinergic projections, the mammillothalamic projection, and possible influences of the pontine reticular formation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH037915-04
Application #
3376397
Study Section
(BPNB)
Project Start
1982-08-21
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
4
Fiscal Year
1985
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
Gabriel, M; Kang, E; Poremba, A et al. (1996) Neural substrates of discriminative avoidance learning and classical eyeblink conditioning in rabbits: a double dissociation. Behav Brain Res 82:23-30
Gabriel, M; Cuppernell, C; Shenker, J I et al. (1995) Mamillothalamic tract transection blocks anterior thalamic training-induced neuronal plasticity and impairs discriminative offidance behavior in rabbits. J Neurosci 15:1437-45
Kubota, Y; Gabriel, M (1995) Studies of the limbic comparator: limbic circuit training-induced unit activity and avoidance behavior in rabbits with anterior dorsal thalamic lesions. Behav Neurosci 109:258-77
Poremba, A; Kubota, Y; Gabriel, M (1994) Afferent connections of the anterior thalamus in rabbits. Brain Res Bull 33:361-5
Henzi, V; Kubota, Y; Gabriel, M (1990) Scopolamine but not haloperidol disrupts training-induced neuronal activity in cingulate cortex and limbic thalamus during learning in rabbits. Brain Res 518:107-14
Gabriel, M (1990) Functions of anterior and posterior cingulate cortex during avoidance learning in rabbits. Prog Brain Res 85:467-82;discussion 482-3
Sparenborg, S; Gabriel, M (1990) Neuronal encoding of conditional stimulus duration in the cingulate cortex and the limbic thalamus of rabbits. Behav Neurosci 104:919-33
Stolar, N; Sparenborg, S; Donchin, E et al. (1989) Conditional stimulus probability and activity of hippocampal, cingulate cortical, and limbic thalamic neurons during avoidance conditioning in rabbits. Behav Neurosci 103:919-34
Gabriel, M; Sparenborg, S; Kubota, Y (1989) Anterior and medial thalamic lesions, discriminative avoidance learning, and cingulate cortical neuronal activity in rabbits. Exp Brain Res 76:441-57
Gabriel, M; Sparenborg, S (1987) Posterior cingulate cortical lesions eliminate learning-related unit activity in the anterior cingulate cortex. Brain Res 409:151-7

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