Periodic Reporting for period 4 - Opto-Sleep (All-optical deconstruction of thalamic control of sleep-wake states.)
Berichtszeitraum: 2021-12-01 bis 2022-11-30
In a first published study, we showed that spontaneous firing of centromedial thalamus (CMT) neurons is phase-advanced to global cortical UP-states and NREM–wake transitions, and oscillates independently from somato-sensory thalamo-cortical oscillations. Importantly, we showed that tonic optogenetic activation of CMT neurons induces NREM–wake transitions, whereas burst activation mimics UP-states in the cingulate cortex (CING) and enhances brain-wide synchrony of cortical slow waves during sleep.
Our current Opto-Sleep investigations focus on the connectivity, dynamics and functions of synaptic circuits linking the medio-dorsal thalamic neurons to the prefrontal cortex across sleep-wake states (see specific aim #2). We found that amongst cortical microcircuits, CMT projections contact Parvalbumin (PV)-positive inhibitory neurons. 2-photon somatic calcium imaging reveals that the activity of GCaMP6-expressing PV inhibitory neurons is significantly increased during REM. Conversely, the activity of GCaMP6-expressing layer II/III pyramidal neurons is significantly decreased during REM sleep. Our results suggest a tight modulation of the neuronal thalamo-cortical circuits during sleep-wake transitions. This modulation is likely to be exerted by thalamic projections controlling the activity of local inhibitory neurons, which, in turn, modulate principal neuron excitability.