Author: Minh-Son To
To, Minh-Son, 2017 On the Properties and Behaviour of Single Neurons in the Cortex, Flinders University, School of Medicine
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Neurons are the building blocks of the nervous system, and the computations they perform underlie our thoughts, emotions and behaviour. The thesis begins in vivo in the mouse binocular visual cortex. This system provides a convenient setting for studying how different inputs are combined in single neurons. We investigate the mechanisms underlying sublinear summation of visual information in pyramidal neurons of the binocular visual cortex and reveal the critical role of balanced excitation and inhibition. Our methods involve use of the somatic voltage-clamp technique. However, we show that distortions due to poor space-clamp affect the estimation of excitatory and inhibitory conductances. We therefore next use numerical simulations in silico to determine how space-clamp errors affect the measurement of combined excitatory and inhibitory inputs, including the estimated temporal relationship between excitation and inhibition. We also explore how the somatic or dendritic location of inhibition affects neuronal output. These simulations show that the site and nature of excitatory synaptic input to a neuron play a fundamental role in how inhibition modulates the input-output relationship. These findings motivated the development of a two-photon microscope to allow arbitrary activation of distributed synaptic inputs in three-dimensions with high temporal precision. Such a tool provides unprecedented flexibility in dissecting how synaptic inputs are processed in single neurons, but can also be extended to explore network properties including connectivity. Finally the thesis arrives back where it began, in vivo, where we develop a behavioural paradigm involving operant conditioning of single neuron activity recorded in vivo using two-photon microscopy. This system will enable the future study of the mechanisms underlying synaptic plasticity and neuroprosthetic learning in vivo, as well as help to understand how single neurons contribute to behaviour.
Keywords: Neurons, cortex, patch-clamp, voltage-clamp, space-clamp, two-photon, neuroprosthetics
Subject: Medicine thesis
Thesis type: Doctor of Philosophy
Completed: 2017
School: School of Medicine
Supervisor: Damien Keating