Neurobiology of Associative Learning
My laboratory is studying the neurobiology of associative learning in the young and aging mammalian brain with in vivo and in vitro techniques using eyeblink conditioning, spatial learning and fear conditioning as behavioral model systems.
Many of our ongoing experiments focus on the hippocampus, a paleocortical region involved in transferring information during learning from short- to long-term memory storage. Single-neuron ensemble recording in the conscious animal is used to localize and functionally characterize the cell types involved in laying down the “memory trace” in the hippocampus and associated regions. In parallel experiments, biophysical measurements are made from hippocampal brain slices taken from trained animals to define ionic mechanisms for the conditioning-specific alterations in postsynaptic intrinsic currents that have been observed. Synaptic alterations related to conditioning are also being explored in brain slices. Cellular and systems alterations in aging brain that may underlie learning deficits and agents which may be useful in enhancing learning rates in aging are being studied.
Recent experiments are focusing on the manner that prefrontal and sensory system neocortical regions, and the caudate nucleus of the basal ganglia change during eyeblink conditioning. We are also using transgenic mouse models of Alzheimer’s Disease along with behavioral and biophysical approaches to better understand the cellular and systems changes that occur as Alzheimer’s Disease develops. The goal of these experiments is to use them to assist in developing better treatments for AD.
Other ongoing and developing experimental lines include functional magnetic resonance imaging in rabbits and humans; eyeblink conditioning combined with other cognitive evaluations in young, aging, and neurologically impaired humans to understand parallels between the brain substrates of associative learning in the animal and human brain; development of eyeblink conditioning and other behavioral tasks in mice so that we may examine aged, transgenic and knockout strains of mice behaviorally, biophysically, and with pharmacological agents.