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Inhibitory circuits of the cortex : control of rhythmic and stimulus evoked activity


We are surrounded by a world, which makes sense, only because we make sense of it. At every instant in our waking life we estimate the state of the world based on sensory data, then we reshape the world to meet our goals. How are these sensations encoded, goals represented and action computed? To answer these questions we dissect the biological circuitry in our brains that seamlessly performs these computations. To study the dynamics of neural circuits, we specifically focus on the role inhibition in shaping signal processing. This work examines how inhibitory circuits process increasingly complex forms of afferent input. First, we characterize and model local circuit responses to brief impulses of afferent activity. We find that local circuits generate feedforward inhibition in the first few milliseconds after an afferent impulse. This inhibition adjusts the excitability of the local population normalizing it to the afferent excitation level. Then, in the next few milliseconds, as individual local pyramidal cells spike they immediately recruit a distinct recurrent inhibitory circuit. This feedback circuit is extremely sensitive responding with negative feedback when even a single local pyramidal cell is active. By modeling the circuit dynamics during these stages in cortical processing we quantitatively demonstrate that the feedforward and feedback inhibitory circuits are tuned to be both sensitive to sparse activity and yet maintain fidelity with which a cortical circuit represents inputs at high activity levels. Next, the role inhibition during spontaneous rhythmic activity is dissected. Our results demonstrate that by rapidly balancing excitation with inhibition, cortical networks can swiftly modulate rhythms over a wide band of frequencies. Finally, we investigate the role of a distinct type of inhibitory interneuron during the first stage of cortical visual processing. Using optogenetics to either enhance or suppress parvalbumin positive interneurons spiking, we demonstrate that these neurons play a key role in modulating the selectivity of responses in primary visual cortex. Together, these results demonstrate the multifaceted role inhibitory circuits play in signal processing and shaping cortical computation; adding to our communal effort to develop a complete picture of how neural circuitry performs computations and encodes sensation

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