Thalamic control of sensory processing and spindles in a biophysical somatosensory thalamoreticular circuit model of wakefulness and sleep.

Thalamoreticular circuitry plays a key role in arousal, attention, cognition, and sleep spindles, and is linked to several brain disorders. A detailed computational model of mouse somatosensory thalamus and thalamic reticular nucleus has been developed to capture the properties of over 14,000 neurons connected by 6 million synapses. The model recreates the biological connectivity of these neurons, and simulations of the model reproduce multiple experimental findings in different brain states. The model shows that inhibitory rebound produces frequency-selective enhancement of thalamic responses during wakefulness. We find that thalamic interactions are responsible for the characteristic waxing and waning of spindle oscillations. In addition, we find that changes in thalamic excitability control spindle frequency and their incidence. The model is made openly available to provide a new tool for studying the function and dysfunction of the thalamoreticular circuitry in various brain states.

Morphology, physiology and synaptic connectivity of local interneurons in the mouse somatosensory thalamus.

The thalamic reticular nucleus (TRN) neurons, projecting across the external medullary lamina, have long been considered to be the only significant source of inhibition of the somatosensory ventral posterior (VP) nuclei of the thalamus. Here we report for the first time effective local inhibition and disinhibition in the VP. Inhibitory interneurons were found in GAD67-GFP-expressing mice and studied using in vitro multiple patch clamp. Inhibitory interneurons have expansive bipolar or tripolar morphologies, reach across most of the VP nucleus and display low threshold bursting behaviour. They form triadic and non-triadic synaptic connections onto thalamocortical relay neurons and other interneurons, mediating feedforward inhibition and disinhibition. Synaptic inputs arrive before those expected from the TRN neurons, suggesting that local inhibition plays an early and significant role in the functioning of the somatosensory thalamus. KEY POINTS: The physiology and structure of local interneurons in the mouse somatosensory thalamus is described for the first time. Inhibitory interneurons have extensive dendritic arborization providing significant local dendro-dendritic inhibition in the somatosensory thalamus. Triadic and non-triadic synaptic connectivity onto thalamic relay neurons and other interneurons provides both local feedforward inhibition and disinhibition. Interneurons of the somatosensory thalamus provide inhibition before the thalamic reticular nucleus, suggesting they play an important role in sensory perception.