Experimental and theoretical analysis of multivesicular release at a sensory synapse

James, Ben (2021) Experimental and theoretical analysis of multivesicular release at a sensory synapse. Doctoral thesis (PhD), University of Sussex.

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Traditionally, neurons were believed to transmit information between one another by action potentials and the release of synaptic vesicles, both of which thought to be binary processes. In this framework, an action potential (or change in membrane potential for graded neurons) elicits the release of at most a single vesicle per active zone (AZ), the site of vesicular release. Information, then, is conveyed in this system simply be altering the probability of a single vesicle being released, and thus altering the total rate of release.
In recent years, however, evidence has demonstrated that many cells, particularly those in the early sensory systems, are capable of multivesicular release (MVR), wherein multiple synaptic vesicles are released nearly simultaneously, with precision of up to 10 microseconds. As most neurons have a temporal integration window on the millisecond range, it is thus likely the postsynaptic cell could represent these events as distinct symbols in a non-binary digital system, allowing for information transmission not only in the rate of vesicular events, but also their amplitude. While evidence for MVR has existed for decades, considerably less attention has been paid to its functional significance – how does MVR affect processing in intact circuits? Is it utilized to transmit information? How efficiently does it operate?
In this work I attempt to answer these questions, first by developing a method with which one can decompose 2p glutamate recordings from intact zebrafish BC terminals into units of individual vesicles – essentially ‘counting’ vesicles. In doing so, I show that MVR is used in the early visual system to transmit temporal contrast information, one of the most basic aspects of the visual scene. Finally, I create a model of vesicle release and postsynaptic activity that allows for directly comparing how information transmission can be influenced by either rate or amplitude coding. Here, by systematically altering the parameters of the postsynaptic cell, I demonstrate in which circumstances either rate coding or amplitude coding are beneficial for transmission. MVR, rather than being some obscure phenomenon, plays a fundamental part in processing and transmitting information in early sensory systems.

Item Type: Thesis (Doctoral)
Schools and Departments: School of Life Sciences > Neuroscience
Subjects: Q Science > QP Physiology > QP0351 Neurophysiology and neuropsychology > QP0361 Nervous system > QP0364 Synapses
Depositing User: Library Cataloguing
Date Deposited: 27 May 2021 10:59
Last Modified: 27 May 2021 10:59
URI: http://sro.sussex.ac.uk/id/eprint/99407

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