During sleep and awake rest, the neocortex generates large-scale slow-wave activity. Here we report that the claustrum, a poorly understood subcortical neural structure, coordinates neocortical slow-wave generation. We established a transgenic mouse line allowing genetic and electrophysiological interrogation of a subpopulation of claustral glutamatergic neurons.

The orbitofrontal cortex receives multi-modality sensory inputs, including olfactory input, and is thought to be involved in conscious perception of the olfactory image of objects. Generation of olfactory consciousness may require neuronal circuit mechanisms for the “binding” of distributed neuronal activities, with each constituent neuron representing a specific component of an olfactory percept. The shortest neuronal pathway for odor signals to reach the orbitofrontal cortex is olfactory sensory neuron—olfactory bulb—olfactory cortex—orbitofrontal cortex, but other pathways exist, including transthalamic pathways. Here, we review studies on the structural organization and functional properties of the shortest pathway, and propose a model of neuronal circuit mechanisms underlying the temporal bindings of distributed neuronal activities in the olfactory cortex. We describe a hypothesis that suggests functional roles of gamma oscillations in the bindings. This hypothesis proposes that two types of projection neurons in the olfactory bulb, tufted cells and mitral cells, play distinct functional roles in bindings at neuronal circuits in the olfactory cortex: tufted cells provide specificity-projecting circuits which send odor information with early-onset fast gamma synchronization, while mitral cells give rise to dispersedly-projecting feed-forward binding circuits which transmit the response synchronization timing with later-onset slow gamma synchronization. This hypothesis also suggests a sequence of bindings in the olfactory cortex: a small-scale binding by the early-phase fast gamma synchrony of tufted cell inputs followed by a larger-scale binding due to the later-onset slow gamma synchrony of mitral cell inputs. We discuss that behavioral state, including wakefulness and sleep, regulates gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex.

AbstractDuring sleep and awake rest, the neocortex generates large-scale slow-wave activity. Here we report that the claustrum, a poorly understood subcortical neural structure, coordinates neocortical slow-wave generation. We established a transgenic mouse line allowing genetic and electrophysiological interrogation of a subpopulation of claustral glutamatergic neurons. These claustral excitatory neurons received inputs from glutamatergic neurons in a large neocortical network. Optogenetic activation of claustral neurons in vitro induced excitatory post-synaptic responses in most neocortical neurons, but elicited action potentials primarily in inhibitory interneurons. Optogenetic activation of claustral neurons in vivo induced a Down-state featuring a prolonged silencing of neural acticity in all layers of many cortical areas, followed by a globally synchronized Down-to-Up state transition. These results demonstrate a crucial role of the claustrum in synchronizing inhibitory interneurons across the neocortex for spatiotemporal coordination of brain state. Thus, the claustrum is a major subcortical hub for the synchronization of neocortical slow-wave activity.

During slow-wave sleep, anterior piriform cortex neurons show highly synchronized discharges that accompany olfactory cortex sharp waves (OC-SPWs). The OC-SPW-related synchronized activity of anterior piriform cortex neurons travel down to the olfactory bulb and is thought to be involved in the reorganization of bulbar neuronal circuitry. However, influences of the OC-SPW-related activity on other regions of the central olfactory system are still unknown. Olfactory tubercle is an area of OC and part of ventral striatum that plays a key role in reward-directed motivational behaviors. In this study, we show that in freely behaving rats, olfactory tubercle receives OC-SPW-associated synchronized inputs during slow-wave sleep. Local field potentials in the olfactory tubercle showed SPW-like activities that were in synchrony with OC-SPWs. Single-unit recordings showed that a subpopulation of olfactory tubercle neurons discharged in synchrony with OC-SPWs. Furthermore, correlation analysis of spike activity of anterior piriform cortex and olfactory tubercle neurons revealed that the discharges of anterior piriform cortex neurons tended to precede those of olfactory tubercle neurons. Current source density analysis in urethane-anesthetized rats indicated that the current sink of the OC-SPW-associated input was located in layer III of the olfactory tubercle. These results indicate that OC-SPW-associated synchronized discharges of piriform cortex neurons travel to the deep layer of the olfactory tubercle and drive discharges of olfactory tubercle neurons. The entrainment of olfactory tubercle neurons in the OC-SPWs suggests that OC-SPWs coordinate reorganization of neuronal circuitry across wide areas of the central olfactory system including olfactory tubercle during slow-wave sleep.