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Title: Probing network dynamics in barrel cortex
Author: Beeren, L. K.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2012
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Recent studies have demonstrated that a rat can be trained to behaviourally report the electrical stimulation of a single cortical neuron (Houweling and Brecht, 2008). Other studies have reported detection of the optogenetic stimulation of ~300 neurons (Huber et al., 2008). However, although the animal can detect the stimulation, it is unclear what effect this small perturbation is having on the network and to what degree this will alter the animal’s ability to perform a task. This thesis investigates the effect on both the local network and on behaviour of several magnitudes of neuronal perturbation, from a single spike to the excitation of several thousand neurons. Finding the limitations under which a network can function provides powerful insights into how neurons interact to form meaningful networks. I performed simultaneous intra- and multi-unit extracellular recordings from the rat barrel cortex. I introduced a single spike into the patched neuron, and monitored the evolution of network activity via the extracellular probe. I found that the introduction of a single spike in a neuron produces a detectable increase in firing rate in the local network. To extend the investigation, channelrhodopsin-2 (ChR2), a light-sensitive membrane protein, was electroporated under visual control into a small number (1 - 10) of layer 2/3 pyramidal cells in the somatosensory cortex of the adult mouse. After exciting the ChR2-positive neurons, the resulting network activity was measured both by cell-attached and whole-cell patch-clamp recordings from nearby neurons and by monitoring up to 50 nearby cells in different cortical layers using the multi-site silicon probe. I found that excitation of a small number of neurons caused an increase in the spike rate of the local network, which lasted up to 300 ms. On the next level, large-scale perturbations were introduced into the brain by the optogenetic excitation of several thousand neurons in the cortexof transgenic mice expressing ChR2 under the Thy1 promoter. A short (2-20 ms) pulse of blue light produced a strong initial response, measured in both the LFP and spiking activity across supragranular layers of the barrel cortex. This initial response was often followed by ~5 bursts of spikes which resulted in an oscillation in the LFP. This oscillation was found to be of similar frequency and time-scale to an oscillation recorded in the barrel cortex resulting from the deflection of a single whisker. After pharmacologically blocking activity in the thalamus, confirmed by loss of the whisker response, the light-induced oscillations disappeared, indicating that the thalamus is necessary for their propagation. Optogenetic stimulation was also able to generate oscillations in the awake animal. I investigated the effect of such a large perturbation on mice undergoing a simple whisker-deflection discrimination task. It was found that the performance of the mice initially dropped to chance level if a strong perturbation was delivered 100 ms before the sensory stimulation. If the strong perturbation was sustained for every trial, the performance of the mice did not improve. If the perturbing stimulation was removed and then introduced gradually, the animal was able to adapt to the stimulation and learn to perform the task despite the perturbation. In summary, small perturbations have a measurable effect on the local network, implying the use of a rate code for at least some brain states in the barrel cortex. A large perturbation produces a strong cortical response, which often leads to a strong oscillation. The same stimulus interferes with the behaviour of a mouse undergoing a simple task, and yet the mouse can learn to perform accurately despite the noise. Together, these findings suggest a coding regime with high degrees of redundancy and robustness. Although the cortical activity patterns are easily perturbed - even a single spike causes a temporary increase in firing rate - this disturbance does not have debilitating effects on the behaviour or the experience of the animal.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available