The aims of this research program are to use the whisker barrel cortex and pons as anchor points 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 (EC) and/or perirhinal (PR) cortex, 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. 1. Recordings from the pontine nuclei will determine if activity patterns from neurons after conditioning change relative to baseline and to pseudoconditioning. The forebrain afferents to pontine regions that change will also be defined with retrograde tract tracing. 2. Barrel columns in somatosensory cortex will be studied to determine how neurons in different layers of this sensory neocortex change during learning and after memory consolidation. Descriptions of the structure and function of the whisker barrel microcircuit are used to predict the sequence of change that will be seen. Single neuron activity in thalamic barreloids will define the role of thalamic input to the cortex during learning. 3. Reversible lesions in SI barrel cortex will be done after behavioral consolidation to confirm and extend our pilot data indicating that such lesions block the performance of consolidated conditioned responses. 4. EC interfaces hippocampus and SI cortex via PR and may transfer functional changes between them during learning and consolidation. 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. Since PR is the cortical node between EC and somatosensory cortex, it will be explored as a site for consolidated responses if the EC experiments are negative. 5. Single neuron recordings of different neuron classes in caudate nucleus during learning will be completed to determine the role of this region in mediating the procedural aspects of trace EBC. Reversible lesions will be done to determine if the caudate nucleus is required for retention of trace CRs after behavioral consolidation and the activity patterns of caudate neurons will be studied after consolidation of trace EBC. The well defined somatotopic arrangement of the whisker 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 and temporal neocortical processing of a learned response signaled by a whisker stimulation CS. A common hypothesis is that permanent storage of learning resides in the neocortex following hippocampal processing. Data supporting this hypothesis are rare. This proposed research program will address this issue by defining nodes mediating a well studied forebrain mediated learned response. PUBLIC HEALTH RELEVANCE: The well defined map of the whisker representation in the rabbit sensory cortex makes it useful for examining neocortical mechanisms mediating consolidation and memory storage of a learned response signaled by whisker stimulation. Our eyeblink conditioning paradigm will allow us to examine the cortical and striatal mechanisms involved in conditioned responding. This learning should have common mechanisms with the neural basis of maladaptive behaviors such as drug addiction, and the data gathered here will also be useful for understanding and treating deficits in learning and memory in young and aging persons.