Fast synaptic transmission and release probability in the vertebrate CNS mediated by multiple nicotinic receptors
Grove, Charlotte Louise
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The ability to quantify the parameters of synaptic transmission, namely release probability, p, the number of vesicles ready to be released, n, and the postsynaptic response to the contents of one vesicle, q, is useful because it enables us to understand the reliability of synaptic transmission, the range of frequencies over which transmission can be maintained and whether the locus of synaptic plasticity is pre- or postsynaptic.;A relatively recent multinomial approach (Silver and Clements. 2000) is employed to characterize release at an axo-axonic connection between the Mauthner axon and the axon of the cranial relay neuron in the goldfish hindbrain. Fast synaptic transmission at a CNS connection mediated by several nicotinic acetylcholine receptors is investigated via paired recordings using this connection.;The overall objective of this thesis is threefold: (1) to establish that a change in release probability is the major cause for rapid depression, (2) to demonstrate that release probability may be heterogeneous and (3) to delineate which factors modify the amplitude, synaptic delay and decay kinetics of the composite EPSPs observed at this connection.;To demonstrate this, I first identified and characterized three classes of CRNs mediated by one, the a7, or a combination of the alpha7, alpha3*beta2 and alpha3*beta4 nicotinic acetylcholine receptors and second showed that these different receptor types are spatially separated.;Further I established that the axo-axonic synapse between the Mauthner axon and the axon of the cranial relay neuron, exhibits primarily a change in release probability as depression is imposed on this circuit by repeated synaptic stimulation over a range of frequencies. This manipulation leads not only to a depression of the EPSP amplitude, but also to longer synaptic delays. Subsequently, I documented a change in the relative weights of the EPSP components as a function of depression to demonstrate that heterogeneity in release probability may be operative at these connections. Spillover, desensitization and saturation are not evident, even though release probability at this connection is high.