THE CLAUSTRUM: A CENTRAL PATTERN GENERATOR INVOLVED IN SLEEP RHYTHMS?

Slow oscillations (≤1 Hz) during slow-wave sleep, anesthesia, and quiet wakefulness are involved in large-scale cortical synchronization and memory consolidation. While UP states typically initiate locally and propagate across cortex, DOWN states occur nearly simultaneously. This global synchronization suggests the involvement of long-range coordinating mechanisms and recent evidence points to the claustrum as a possible key contributor. The mouse claustrum is extensively reciprocally connected to most cortical regions, strongly active during slow-wave sleep and has been shown to trigger synchronized transitions to neocortical DOWN states. Thus, it is a strong potential orchestrator of widespread cortical network dynamics.
Using intracellular patch clamp and extracellular electrodes arrays, we show in an ex vivo horizontal slice preparation that the claustrum intrinsically generates large-scale synchronized 0.3-1 Hz oscillations in the presence of a low concentration of cholinergic agonist mirroring the low cholinergic tone and thus moderate neuronal excitability present in vivo during sleep.
We investigate the cellular and network mechanisms underlying the claustral oscillation and show that these include the emergence of rhythmic excitatory and/or inhibitory drives received by different cellular subtypes (excitatory projection cells Vglut1/2 and GABAergic interneurons PV/SST/VIP/NPY) resulting in synchronized bursting, but also the presence of intrinsically oscillating neurons that we assume play a role in initiating and maintaining the oscillation.
Finally, we study the potential long-range interactions of the claustral rhythmic activity with other regions in our slice model and establish that this oscillation can be synchronized with sleep-like UP and DOWN states generated independently in the entorhinal cortex.