Forebrain-Cerebellar Interaction During Learning

Northwestern University At Chicago, Evanston IL

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Abstract

The aims of this research program are to use the whisker cortex and pons as [unreadable]anchor points[unreadable] to examine information processing loops within the forebrain during whisker signaled trace eyeblink conditioning (EBC). These aims will be done to test our hypothesis that permanent representations of the conditioning network are located in SI cortex, entorhinal cortex (EC), and caudate nucleus. Five specific aims will determine if there are increases in activity suitable to potentiate the input to the pontine nuclei that mediate forebrain facilitation of cerebellar dependent learning as we hypothesize. 1. Recordings from the pontine nuclei will determine if activity patterns from neurons during conditioning change relative to baseline and to pseudoconditioning. The forebrain afferents to pontine regions that change will also be defined with retrograde tracing. 2. Barrel columns in somatosensory cortex will be studied to determine how this region changes during learning and after memory consolidation. Single neuron activity in thalamic barreloids will define the role of thalamic input to the cortex during learning. Nucleus basalis (nBM) activity will define the role of cholinergic input on neocortex during learning. 3. Pretraining lesions of barrel cortex prevented acquisition of CRs, but post training lesions produced a transient impairment. Reversible lesions in SI barrel and eye cortex will be done to test hypotheses explaining the recovery, including that memories are stored in SI cortex after learning. 4. EC interfaces hippocampus and SI cortex and may transfer functional changes between them during learning. We will test the hypothesis that EC is required for consolidation of trace CRs with reversible lesions. An EC layer analysis will be done with single neuron recording. 5. Reversible lesions will be done to determine if the caudate nucleus is required for acquisition or retention of trace CRs. If the lesions indicate caudate nucleus involvement, the activity patterns of neurons within the caudate nucleus during trace EBC will be defined while monitoring the activity level of dopaminergic neurons in the substantia nigra to determine the role of dopamine neuromodulation upon the caudate neurons. The well defined somatotopic arrangement of the whisker/periorbital representation in the rabbit sensory cortex makes it a useful region on which to focus while examining neocortical mechanisms mediating consolidation and memory storage following hippocampal processing of a learned response signaled by a whisker stimulation CS. A better understanding of striatal mechanisms involved in conditioned responding will help to understand the role of the striatum in mediating associative learning that should have common mechanisms with the neural basis of maladaptive behaviors such as drug addiction. The data gathered here will also be useful for understanding and treating deficits in learning and memory in young and aging persons.