Theta Oscillations during Active Sleep Synchronize the Developing Rubro-Hippocampal Sensorimotor Network

Highlights

• Theta oscillations occur in the infant rat red nucleus (RN) during active sleep

• RN theta is first expressed as brief bursts associated with myoclonic twitching

• When tonic RN theta emerges at P12, it is tightly coupled with hippocampal theta

• Inactivation of the medial septum blocks sleep-related, but not twitch-related, theta

Summary

Neuronal oscillations comprise a fundamental mechanism by which distant neural structures establish and express functional connectivity. Long-range functional connectivity between the hippocampus and other forebrain structures is enabled by theta oscillations. Here, we show for the first time that the infant rat red nucleus (RN)—a brainstem sensorimotor structure—exhibits theta (4–7 Hz) oscillations restricted primarily to periods of active (REM) sleep. At postnatal day 8 (P8), theta is expressed as brief bursts immediately following myoclonic twitches; by P12, theta oscillations are expressed continuously across bouts of active sleep. Simultaneous recordings from the hippocampus and RN at P12 show that theta oscillations in both structures are coherent, co-modulated, and mutually interactive during active sleep. Critically, at P12, inactivation of the medial septum eliminates theta in both structures. The developmental emergence of theta-dependent functional coupling between the hippocampus and RN parallels that between the hippocampus and prefrontal cortex. Accordingly, disruptions in the early expression of theta could underlie the cognitive and sensorimotor deficits associated with neurodevelopmental disorders such as autism and schizophrenia.