Reconstruction and simulation of thalamoreticular microcircuitry

Thalamoreticular circuitry is central to sensory processing, attention, and sleep, and is implicated in numerous brain disorders, but the cellular and synaptic mechanisms remain intractable. Therefore, we developed the first detailed microcircuit model of mouse thalamus and thalamic reticular nucleus that captures morphological and biophysical properties of ∼14,000 neurons connected via ∼6M synapses, and recreates biological synaptic and gap junction connectivity. Realistic spontaneous and evoked activity during wakefulness and sleep emerge allowing dissection of cellular and synaptic contributions. Computer simulations suggest that reticular inhibition shapes thalamic responses and cortex can drive frequency-selective thalamic enhancement during wakefulness, whereas in sleep, reticular inhibition and cortical UP-states can trigger thalamic bursts and spindles. Gap junctions and short-term synaptic plasticity underlie spindle properties such as waxing and waning, and neuromodulation influences the occurrence of spindles. The model is openly available to support testing hypotheses of thalamoreticular circuitry in normal brain function and in disease. ### Competing Interest Statement The authors have declared no competing interest.