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|Title: ||Investigating the role of fast-spiking interneurons in neocortical dynamics|
|Authors: ||Papasavvas, Christoforos A|
|Issue Date: ||2017 |
|Publisher: ||Newcastle University|
|Abstract: ||Fast-spiking interneurons are the largest interneuronal population in neocortex. It is
well documented that this population is crucial in many functions of the neocortex by
subserving all aspects of neural computation, like gain control, and by enabling
dynamic phenomena, like the generation of high frequency oscillations. Fast-spiking
interneurons, which represent mainly the parvalbumin-expressing, soma-targeting
basket cells, are also implicated in pathological dynamics, like the propagation of
seizures or the impaired coordination of activity in schizophrenia. In the present thesis,
I investigate the role of fast-spiking interneurons in such dynamic phenomena by using
computational and experimental techniques.
First, I introduce a neural mass model of the neocortical microcircuit featuring divisive
inhibition, a gain control mechanism, which is thought to be delivered mainly by the
soma-targeting interneurons. Its dynamics were analysed at the onset of chaos and
during the phenomena of entrainment and long-range synchronization. It is
demonstrated that the mechanism of divisive inhibition reduces the sensitivity of the
network to parameter changes and enhances the stability and
exibility of oscillations.
Next, in vitro electrophysiology was used to investigate the propagation of activity in
the network of electrically coupled fast-spiking interneurons. Experimental evidence
suggests that these interneurons and their gap junctions are involved in the propagation
of seizures. Using multi-electrode array recordings and optogenetics, I investigated the
possibility of such propagating activity under the conditions of raised extracellular K+
concentration which applies during seizures. Propagated activity was recorded and the
involvement of gap junctions was con rmed by pharmacological manipulations.
Finally, the interaction between two oscillations was investigated. Two oscillations with di erent frequencies were induced in cortical slices by directly activating the pyramidal
cells using optogenetics. Their interaction suggested the possibility of a coincidence
detection mechanism at the circuit level. Pharmacological manipulations were used to
explore the role of the inhibitory interneurons during this phenomenon. The results,
however, showed that the observed phenomenon was not a result of synaptic activity.
Nevertheless, the experiments provided some insights about the excitability of the
tissue through scattered light while using optogenetics.
This investigation provides new insights into the role of fast-spiking interneurons in the
neocortex. In particular, it is suggested that the gain control mechanism is important
for the physiological oscillatory dynamics of the network and that the gap junctions
between these interneurons can potentially contribute to the inhibitory restraint during
|Description: ||PhD Thesis|
|Appears in Collections:||Institute of Neuroscience|
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