Analysis of feedforward mechanisms of multiwhisker receptive field generation in a model of the rat barrel cortex.

There is substantial anatomical segregation in the organization of the rodent barrel system - each whisker on the mystacial pad sends input to TC cells within a dedicated thalamic barreloid, which in turn innervates a corresponding cortical barrel, and RS cells within a barrel respond primarily to deflections of the corresponding whisker at the beginning of the dedicated transmission line (the principal whisker, PW). However, it is also well-established that barrel cells exhibit multiwhisker receptive fields (RFs), and display lower amplitude, longer latency responses to deflections of non-PWs (or adjacent whiskers, AWs). There is considerable controversy regarding the origin of such multiwhisker RFs; three possibilities include: (i) TC cells within a barreloid respond to multiple whiskers, and barrel RS cells simply inherit multiwhisker responses from their aligned barreloid; (ii) TC cells respond only to the PW, but individual barreloids innervate multiple barrels; (iii) multiwhisker responses of barrel cells arise from lateral corticocortical (barrel-to-barrel) synaptic transmission. Ablation studies attempting to pinpoint the source of RS cell AW responses are often contradictory (though experimental work tends to suggest possibilities (i) or (iii) to be most plausible), and hence it is important to carefully evaluate these hypotheses in terms of available physiological data on barreloid and barrel response dynamics. In this work, I employ a biologically detailed model of the rat barrel cortex to evaluate possibility (i), and I show that, within the model, hypothesis (i) is capable of explaining a broad range of the available physiological data on responses to single (PW or AW) deflections and paired whisker deflections (AW deflection followed by PW deflection), as well as the dependence of such responses on the angular direction of whisker deflection. In particular, the model shows that barrel RS cells can exhibit AW direction tuning despite the fact that barreloid to barrel wiring has no systematic dependence on the AW direction preference of TC cells. Future modeling work will examine the other possibilities for the generation of multiwhisker RS cell RFs, and compare and contrast the different possible mechanisms within the context of available experimental data.

Effects of Adaptation on Discrimination of Whisker Deflection Velocity and Angular Direction in a Model of the Barrel Cortex.

Two important stimulus features represented within the rodent barrel cortex are velocity and angular direction of whisker deflection. Each cortical barrel receives information from thalamocortical (TC) cells that relay information from a single whisker, and TC input is decoded by barrel regular-spiking (RS) cells through a feedforward inhibitory architecture (with inhibition delivered by cortical fast-spiking or FS cells). TC cells encode deflection velocity through population synchrony, while deflection direction is encoded through the distribution of spike counts across the TC population. Barrel RS cells encode both deflection direction and velocity with spike rate, and are divided into functional domains by direction preference. Following repetitive whisker stimulation, system adaptation causes a weakening of synaptic inputs to RS cells and diminishes RS cell spike responses, though evidence suggests that stimulus discrimination may improve following adaptation. In this work, I construct a model of the TC, FS, and RS cells comprising a single barrel system-the model incorporates realistic synaptic connectivity and dynamics and simulates both angular direction (through the spatial pattern of TC activation) and velocity (through synchrony of the TC population spikes) of a deflection of the primary whisker, and I use the model to examine direction and velocity selectivity of barrel RS cells before and after adaptation. I find that velocity and direction selectivity of individual RS cells (measured over multiple trials) sharpens following adaptation, but stimulus discrimination using a simple linear classifier by the RS population response during a single trial (a more biologically meaningful measure than single cell discrimination over multiple trials) exhibits strikingly different behavior-velocity discrimination is similar both before and after adaptation, while direction classification improves substantially following adaptation. This is the first model, to my knowledge, that simulates both whisker deflection velocity and angular direction and examines the ability of the RS population response to pinpoint both stimulus features within the context of adaptation.

Spiking and Excitatory/Inhibitory Input Dynamics of Barrel Cells in Response to Whisker Deflections of Varying Velocity and Angular Direction.

The spiking of barrel regular-spiking (RS) cells is tuned for both whisker deflection direction and velocity. Velocity tuning arises due to thalamocortical (TC) synchrony (but not spike quantity) varying with deflection velocity, coupled with feedforward inhibition, while direction selectivity is not fully understood, though may be due partly to direction tuning of TC spiking. Data show that as deflection direction deviates from the preferred direction of an RS cell, excitatory input to the RS cell diminishes minimally, but temporally shifts to coincide with the time-lagged inhibitory input. This work constructs a realistic large-scale model of a barrel; model RS cells exhibit velocity and direction selectivity due to TC input dynamics, with the experimentally observed sharpening of direction tuning with decreasing velocity. The model puts forth the novel proposal that RS→RS synapses can naturally and simply account for the unexplained direction dependence of RS cell inputs - as deflection direction deviates from the preferred direction of an RS cell, and TC input declines, RS→RS synaptic transmission buffers the decline in total excitatory input and causes a shift in timing of the excitatory input peak from the peak in TC input to the delayed peak in RS input. The model also provides several experimentally testable predictions on the velocity dependence of RS cell inputs. This model is the first, to my knowledge, to study the interaction of direction and velocity and propose physiological mechanisms for the stimulus dependence in the timing and amplitude of RS cell inputs.