Presynaptic plasticity and memory : a behavioral analysis of short and long-term plasticity at the nerve terminal

Abstract

The ability to learn and remember enables animals and humans to adapt to their environment, avoid dangerous situations and adjust to social situations. Most neuroscientists agree that information storage in the brain is probably encoded by changes at the connections between neurons (the synapses). However, the mechanisms involved are poorly understood. In this thesis, the role of presynaptic plasticity in learning and memory was studied. Presynaptic plasticity is a change in the secretion of neurotransmitter from the nerve terminal. Presynaptic plasticity can be short-lasting (tens of milliseconds), intermediate-lasting (seconds to minutes) or long-lasting (hours to days), and may either depress or enhance neurotransmitter release. Consequently, these types of synaptic plasticity can, in theory, have a major role in neuronal communication and information storage. Until recently it was not possible to test the role of presynaptic plasticity in memory using conventional (pharmacological) means. Fortunately, the development of genetic manipulation in mice has provided new scientific tools. In this thesis, appropriate mutant mice with deficits in different forms of presynaptic plasticity were selected, and tested in a variety of learning tasks. The results show that working memory, a short-lasting form of memory, may be regulated by post-tetanic potentiation, a short-lasting form of presynaptic plasticity. Long-lasting memory appears regulated by two types of long-lasting synaptic plasticity, a post-synaptic form and a presynaptic form, that are able to compensate for each other in a mutually exclusive fashion. If either one is blocked then long-lasting memory is not impaired but if both are blocked, long-lasting memory is gone.