Biophysical and circuit properties underlying population dynamics in neocortical networks

The neocortex of awake animals displays an activated state in whichcortical activity manifests highly complex, seemingly noisybehavior. At the level of single neurons the activity is characterizedby strong subthreshold fluctuations and irregular firing at lowrate. At the network level, the activity is weakly synchronized andexhibits a chaotic dynamics. Yet, it is within this regime thatinformation is processed reliably through neural networks. This regimeis thus crucial to neural computation. In this thesis, we contributeto its understanding by investigating how the biophysical propertiesat the cellular level combined with the properties of the networkarchitecture shapes this asynchronous dynamics.This thesis builds up on the so-called mean-field models of networkdynamics, a theoretical formalism that describes population dynamicsvia a self-consistency approach. At the core of this formalism lie theneuronal transfer function: the input-output description of individualneurons. The first part of this thesis focuses on derivingbiologically-realistic neuronal transfer functions. We firstformulate a two step procedure to incorporate biological details (suchas an extended dendritic structure and the effect of various ionicchannels) into this transfer function based on experimentalcharacterizations.First, we investigated in vitro how layer V pyramidal neocorticalneurons respond to membrane potential fluctuations on a cell-by-cellbasis. We found that, not only individual neurons strongly differ interms of their excitability, but also, and unexpectedly, in theirsensitivities to fluctuations. In addition, using theoreticalmodeling, we attempted to reproduce these results. The model predictsthat heterogeneous levels of biophysical properties such as sodiuminactivation, sharpness of sodium activation and spike frequencyadaptation account for the observed diversity of firing rateresponses.Then, we studied theoretically how dendritic integration in branchedstructures shape the membrane potential fluctuations at the soma. Wefound that, depending on the type of presynaptic activity, variouscomodulations of the membrane potential fluctuations could beachieved. We showed that, when combining this observation with theheterogeneous firing responses found experimentally, individual neuronsdifferentially responded to the different types of presynapticactivities. We thus propose that, because this mechanism offers a wayto produce specific activation as a function of the input properties,biophysical heterogeneity might contribute to the encoding of the stimulusproperties during sensory processing in neural networks.The second part of this thesis investigates how circuit properties,such as recurrent connectivity and lateral connectivity, combine withbiophysical properties to impact sensory responses through effectsmediated by population dynamics.We first investigated what was the effect of a high level of ongoingdynamics (the Up-state compared to the Down-state) on the scaling ofpost-synaptic responses. We found that the competition between therecruitment within the active recurrent network (in favor of highresponses in the Up-state) and the increased conductance level due tobackground activity (in favor of reduced responses in the Up-state)predicted a non trivial stimulus-response relationship as a functionof the intensity of the stimulation. This prediction was shown toaccurately capture measurements of post-synaptic membrane potentialresponses in response to cortical, thalamic or auditory stimulation inrat auditory cortex in vivo.Finally, by taking advantage of the mean-field approach, weconstructed a tractable large-scale model of the layer II-III networkincluding the horizontal fiber network. We investigate thespatio-temporal properties of this large-scale model and we compareits predictions with voltage sensitive dye imaging in awake fixatingmonkey.