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

Abstract

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 (P) 8, 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.

Active Sleep Promotes Functional Connectivity in Developing Sensorimotor Networks

“…Moreover, sensory feedback from twitches reliably triggers synchronized neural oscillations across the neuraxis, suggesting that these oscillations also contribute to the development of long‐range network connectivity. More broadly, independently of twitching, active sleep may provide a context that promotes functional connectivity in the sensorimotor system including, as recently shown in 12‐day‐old rats, highly synchronized oscillatory activity between the hippocampus and red nucleus …”

“…Early oscillatory activity in vivo has been most extensively – but not exclusively – described in the cortex and hippocampus . In these forebrain structures, fragmented oscillatory activity is thought to assist in the development of local neuronal networks, with effects on synapse formation, neuronal differentiation and migration, programmed cell death (apoptosis), and formation and refinement of topographic maps …”

“…Although different from the continuous oscillatory patterns of adults, these early oscillations appear to have important functions for the development of the nervous system . In addition, temporal coupling or coactivation of brief oscillatory events is indicative of connectivity among functionally related neural structures …”

“…The functional roles of neural oscillations have been predominantly examined in the adult forebrain, although brain rhythms are present throughout the neuraxis and emerge in early development . In the cerebral cortex of humans and rodents, the earliest neural activity is characterized by the presence of brief oscillatory bursts interposed with periods of silence; this pattern of fragmented activity is referred to as discontinuous .…”

“…Based on such studies, one might conclude that the expression of brain rhythms is independent of experience or behavioral state. Within the developing sensorimotor system, however, early neural oscillations are largely triggered by sensory input arising from external stimulation ( exafference ) or sensory feedback arising from self‐generated movements ( reafference ) …”