Synaptic plasticity

Mechanisms of Synaptic Plasticity in the Hippocampus

Over the past 20 years, one of the major research interests in our lab has been to comprehend the induction and modulation of synaptic

plasticity involved in the storage of memory in the hippocampus. Using various electrophysiological, imaging, and molecular techniques, we

found that Acetylcholine (Ach) can potentiate the response of the hippocampus to afferent stimulation by interaction with several types of

excitatory neurotransmitter receptors via second-messenger pathways. We also found that Serotonin (5-HT) and Norepinephrine interact with glutamate

and GABA to produce marked changes in response of hippocampal neurons to afferent stimulation. More recently, we found that Ach alone can

produce a long lasting, age-dependent potentiation of response to afferent stimulation, comparable to more commonly known LTP.

In studying mechanisms of plasticity, we adopted, in collaboration with Dr. Yoram Groner of the WIS, a transgenic (Tg) mouse model of oxidative

stress. The Tg mice exhibit a marked deficiency in the ability to express various types of long lasting plasticity, which has been shown to

arise, in part, from an increased GABA-ergic drive in the hippocampus. We are currently studying the cellular and molecular mechanisms that

may lead to this phenomenon and the subsequent imparement in plasticity.

These studies have a direct relevance to the understanding of aging and Alzheimer's disease. For example, we have found that aged rats show

reduced ability to use Ach and 5-HT to enhance the response of hippocampal cells to afferent stimulation. Defining  the molecular and

subcellular events underlying memory formation and storage are of tremendous importance for understanding the cognitive function of the brain.

                  


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