Oyrer, J; (2015) Calcium-permeable AMPA receptors in layer 5 interneurons of the mouse visual cortex. Doctoral thesis , UCL (University College London).

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Abstract

Cortical sensory processing is widely studied in the visual cortex. Such processing depends on specific neuronal connectivity, and the reliable activation of inhibitory interneurons. Excitatory connections onto both excitatory and inhibitory neurons exhibit synaptic plasticity thought to underlie circuit refinement and function. The mechanisms of induction and expression of short- and long-term plasticity can differ between neurons and depend on synapse-specific differences in molecular machinery. Compared to synapses onto principal cells, less is known about plasticity at synapses onto inhibitory neurons. In part, this reflects difficulties of classifying these diverse cells. Mechanistically, postsynaptic N-methyl-D-aspartate-type glutamate receptors are necessary for most forms of plasticity. However, in the hippocampus, postsynaptic amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors (AMPARs) of the calcium-permeable (CP-) subtype are thought to underlie a form of non-Hebbian plasticity. I sought to examine the expression of CP-AMPARs at synapses onto the two major classes of inhibitory interneuron in layer 5 of the mouse visual cortex, Basket cells (BCs) and Martinotti cells (MCs). I made patch-clamp recordings from cells in acute brain slices from wild-type and transgenic animals. Interneurons were distinguished using laser scanning two-photon microscopy to characterize their defining patterns of axonal arborisation, and voltage recording to determine their characteristic firing properties. To examine synaptic AMPARs, I recorded miniature excitatory postsynaptic currents, determined their kinetic properties, their rectification due to voltage-dependent block by intracellular polyamines, and their sensitivity to the selective blocker of CP-AMPARs, 1-naphthyl acetyl spermine. I also used antibody labelling to examine the presence of the GluA2 subunit in the two interneuron classes. Although MCs proved less amenable to voltage-clamp recording than did BCs, my findings indicate the presence of CP-AMPARs in BCs but not in MCs, suggesting distinct activation of these two inhibitory inputs to Pyramidal cells. I conclude by discussing the likely influence of differential CP-AMPAR expression on the dynamics of the cortical network.

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