Homosynaptic Long-Term Depression: Mechanisms and Role in Learning

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LAY ABSTRACT IBN-9808930 Changes in the strength of connections (synapses) between neurons in the brain are believed by most neuroscientists to underlie learning and memory. Synapses in the brain may increase in strength, or decrease in strength, as a consequence of learning by an animal. One prominent form of a change in synaptic strength that occurs in the mammalian brain is known as homosynaptic long-term depression or LTD. LTD is a decrease in the strength of a synapse, lasting 60 minutes to hours, produced by low-frequency stimulation of a presynaptic neural pathway. Many synapses in a part of the brain known as the hippocampus exhibit LTD. Because the hippocampus plays an important role in learning and memory in mammals, it is thought that LTD might represent a neural mechanism of memory. Despite a half-decade of work on LTD in the hippocampus, however, relatively little is understood about the cellular mechanisms that underlie LTD. Furthermore, even less is understood regarding what role LTD of hippocampal synapses might play in learning and memory. Part of the difficulty is that the hippocampus is a complex structure. Moreover, the types of learning that involve the hippocampus are difficult to understand on a neurobiological level. The goal of the present project is to study the role of LTD in learning and memory in an animal with a simple nervous system. The hope is that the insights gained by studying the cellular mechanisms of LTD, and its role in learning, in a relatively simple organism will help us to understand the mechanisms and learning- related role of LTD in the brains of more complex organisms, including man. Toward this end the PI will study LTD in an invertebrate organism, the marine snail Aplysia californica. This animal possesses a relatively simple nervous system and exhibits several simple forms of learning. Furthermore, a great deal is already known about the neural mechanisms of Aplysia's behavior. The PI has previously shown that synapses between sensory and motor neurons in the nervous system of Aplysia can exhibit LTD. The PI will analyze the cellular mechanisms of LTD of the synapses between sensory and motor neurons in Aplysia. The PI will also determine whether LTD plays a role in a simple form of learning exhibited by Aplysia known as long-term habituation. The results of this project should provide important general insights regarding the cellular mechanisms of LTD and the role that LTD plays in learning. It is expected that these insights will advance knowledge about how nervous systems mediate learning and memory.