The classically conditioned eyeblink response is one of the most advanced models for understanding the neural mechanisms underlying associative learning and disease states such as Alzheimer's dementia. Classical conditioning is an example of associative learning that occurs when a reinforcing unconditioned stimulus (US) is contingent on the occurrence of a preceding conditioned stimulus (CS). These studies are usually carried out in behaving rabbits which presents numerous challenges for experiments aimed at determining cellular mechanisms that produce conditioning. To facilitate such studies, we have developed an in vitro brain stem preparation from turtles that demonstrates a neural correlate of eyeblink classical conditioning. When auditory nerve electrical stimulation (the """"""""tone"""""""" CS) is paired with trigeminal nerve stimulation (the """"""""airpuff' US) a burst discharge is recorded in the abducens nerve which represents a blink response. The present project is aimed at investigation of the cellular mechanisms underlying conditioning. We will build on our previous findings suggesting that not only is postsynaptic trafficking of glutamate receptor subunits critical to conditioning, but that coordinate presynaptic remodeling occurs to facilitate neurotransmitter release. The following Specific Aims will be examined: To investigate the role of protein kinases CaMKII, PKA, PKC, and MARK in the induction and expression of in vitro abducens conditioning. To examine glutamate receptor trafficking at synaptic sites during in vitro conditioning. To perform intracellular recordings of abducens motor neurons to examine intrinsic properties and synaptic potentials in control and conditioned preparations. And, to determine a role for the immediate early genes (lEGs) Arc and Egr-1 in in vitro conditioning. The insights gained into basic processes of learning and memory will have fundamental implications for understanding memory disorders such as occur in amnesia and Alzheimer's disease.
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