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Freeman Lab Research

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Developmental Neurobiology of Learning

Much of our current research examines developmental changes in the neural mechanisms of associative learning in rats. We have been using eyeblink classical conditioning procedures to examine associative learning and memory. The cerebellum is necessary for this type of associative learning. The cerebellum receives input about the conditioned stimulus (usually a tone) from the pontine nuclei and input about the unconditioned stimulus (usually periorbital stimulation) from the inferior olive. The cerebellum also sends feedback connections to the afferent systems, regulating its own inputs, and thereby influencing its own learning mechanisms. Recent experiments have used unit recording, electrical brain stimulation, pharmacology, and quantitative neuroanatomy to characterize developmental changes within the cerebellum and developmental changes in its interactions with the inferior olive and pontine nuclei. Our most recent findings indicate that feedback connections from the cerebellum to the pontine nuclei and the inferior olive undergo substantial developmental changes. The development of cerebellar-brainstem regulatory mechanisms influences the ontogeny of plasticity mechanisms in the cerebellum that are necessary for learning.

Neurobiology of Learning in Adult Rats

In excitatory classical conditioning, subjects learn that a conditioned stimulus predicts when an unconditioned stimulus will occur. In inhibitory classical conditioning, subjects learn that a conditioned stimulus predicts when an unconditioned stimulus will not occur. Inhibitory conditioning has been studied behaviorally since Pavlov's initial experiments. Little is known, however, about the neural mechanisms of conditioned inhibition. We are currently examining the neural mechanisms of conditioned inhibition of the eyeblink response using neurophysiological and neuropharmacological techniques.

The Cellular and Molecular Mechanisms of Memory

We have been examining the synaptic mechanisms of memory storage in the cerebellum in collaboration with Jeff Kleim and colleagues at the University of Lethbridge in Alberta. Our initial experiment demonstrated that eyeblink conditioning in rats is associated with a substantial increase in the number of excitatory synapses per neuron in the interpositus nucleus of the cerebellum. Follow up experiments are examining the role of increased excitatory synapses in long-term memory. We have also done work with John Wemmie and Michael Welsh to examine the role of acid-gated ion channels in learning.

Freeman Lab Personnel