Neocortical Activation of the Hippocampus during Sleep in Infant Rats

Abstract

We recently reported that the majority of hippocampal neurons in newborn rats increase their activity in association with myoclonic twitches, which are indicative of active sleep. Because spindle bursts in the developing somatosensory neocortex occur in response to sensory feedback from myoclonic twitching, we hypothesized that the state-dependent activity of the newborn hippocampus arises from sensory feedback that sequentially activates the neocortex and then hippocampus, constituting an early form of neocortical-hippocampal communication. Here, in unanesthetized 5-to 6-d-old rats, we test this hypothesis by recording simultaneously from forelimb and barrel regions of somatosensory neocortex and dorsal hippocampus during periods of spontaneous sleep and wakefulness and in response to peripheral stimulation. Myoclonic twitches were consistently followed by neocortical spindle bursts, which were in turn consistently followed by bursts of hippocampal unit activity; moreover, spindle burst power was positively correlated with hippocampal unit activity. In addition, exogenous stimulation consistently evoked this neocortical-to-hippocampal sequence of activation. Finally, parahippocampal lesions that disrupted functional connections between the neocortex and hippocampus effectively disrupted the transmission of both spontaneous and evoked neocortical activity to the hippocampus. These findings suggest that sleep-related motor activity contributes to the development of neocortical and hippocampal circuits and provides a foundation on which coordinated activity between these two forebrain structures develops.

Self-Generated Movements with “Unexpected” Sensory Consequences

“…Across all pups, there was a significant increase in mean rates of spindle bursts ( t 10 = 9.2, P < 0.01) and mean unit firing rates ( t 16 = 3.2, P < 0.01, n = 17 units, 1–2 units per pup) during sleep (Figure 1D). Moreover, LFP power and unit activity increased significantly after twitches with a latency of at least 100–125 ms (Figure 1E), consistent with previous reports of twitch-related reafference in cerebral cortex [21, 22]. Finally, these results were replicated in P4 and P12 rats, demonstrating the stability of the effect across early development (Figure S1).…”

“…Twitch movements may be particularly well suited to this task because, unlike wake movements, they are produced discretely against a background of muscle atonia, both of which enhance signal-to-noise ratio [19]. Our results further suggest that the high fidelity of twitching depends upon the suspension of corollary discharge mechanisms, providing the infant with ideal conditions for activity-dependent development of the spinal cord [35], cerebellum [23], and forebrain [20–22, 36]. The information provided by twitching limbs may also enable the construction and calibration of internal models and predictive codes, which are thought to be essential for flexible and efficient sensorimotor control throughout the lifespan [37–39].…”

“…The apparatus and methods for recording and analyzing neural and muscle activity in head-fixed pups have been described previously [18, 21, 22]. All surgeries were performed under isoflurane anesthesia and data were collected from unanesthetized subjects; brain temperature was maintained at 36–37°C.…”

“…As described previously [23], spike sorting was performed in Spike2 (Cambridge Electronic Design, Cambridge, UK). Sleep and wake states were determined by analyzing the nuchal EMG in conjunction with behavioral scoring [18, 21, 22]. Active sleep was characterized by the occurrence of myoclonic twitches against a background of muscle atonia [40].…”

Perchance to dream? Primordial motor activity patterns in vertebrates from fish to mammals: their prenatal origin, postnatal persistence during sleep, and pathological reemergence during REM sleep behavior disorder

“…This could be an important clue to the neurological abnormalities underlying the clinical condition of 'REM sleep behavior disorder' (RBD), in which coordinated body movements during sleep surface later in life [23,27] . Since spontaneous motility is reflected all the way up to the cerebral cortex level by virtue of proprioceptive feedback evoked by each movement [49,50] , these could contribute to activity-dependent maturational processes at many levels of the developing central nervous system. It would be of great theoretical importance to find out what the relative contributions of these sleep-like behavior patterns ( Fig.…”