The wake-sleep cycle, a spontaneous succession of global brain states that correspond to major overt behaviors, occurs in all higher vertebrates. The transitions between these states, at once rapid and drastic, remain poorly understood. Here, intracranial local field potentials (LFPs) recorded in the cortex, hippocampus, striatum, and thalamus were used to characterize the neurophysiological correlates of the rat wake-sleep cycle. By way of a new method for the objective classification and quantitative investigation of all major brain states, we demonstrate that global brain state transitions occur simultaneously across multiple forebrain areas as specific spectral trajectories with characteristic path, duration, and coherence bandwidth. During state transitions, striking changes in neural synchronization are effected by the prominent narrow-band LFP oscillations that mark state boundaries. Our results demonstrate that distant forebrain areas tightly coordinate the processing of neural information during and between global brain states, indicating a very high degree of functional integration across the entire wake-sleep cycle. We propose that transient oscillatory synchronization of synaptic inputs, which underlie the rapid switching of global brain states, may facilitate the exchange of information within and across brain areas at the boundaries of very distinct neural processing regimens.

Dopaminergic dysregulation can cause motor dysfunction, but the mechanisms underlying dopamine-related motor disorders remain under debate. We used an inducible and reversible pharmacogenetic approach in dopamine transporter knockout mice to investigate the simultaneous activity of neuronal ensembles in the dorsolateral striatum and primary motor cortex during hyperdopaminergia ( approximately 500% of controls) with hyperkinesia, and after rapid and profound dopamine depletion (<0.2%) with akinesia in the same animal. Surprisingly, although most cortical and striatal neurons ( approximately 70%) changed firing rate during the transition between dopamine-related hyperkinesia and akinesia, the overall cortical firing rate remained unchanged. Conversely, neuronal oscillations and ensemble activity coordination within and between cortex and striatum did change rapidly between these periods. During hyperkinesia, corticostriatal activity became largely asynchronous, while during dopamine-depletion the synchronicity increased. Thus, dopamine-related disorders like Parkinson's disease may not stem from changes in the overall levels of cortical activity, but from dysfunctional activity coordination in corticostriatal circuits.

SUMMARY Both reward- and punishment-related stimuli are motivationally salient and attract the attention of animals. However, it remains unclear how motivational salience is processed in the brain. Here we show that both reward- and punishment-predicting stimuli elicited robust bursting of many non-cholinergic basal forebrain (BF) neurons in behaving rats. The same BF neurons also responded with similar bursting to primary reinforcement of both valences. Reinforcement responses were modulated by expectation, with surprising reinforcement eliciting stronger BF bursting. We further demonstrate that BF burst firing predicted successful detection of near-threshold stimuli. Together, our results point to the existence of a salience-encoding system independent of stimulus valence. We propose that the encoding of motivational salience by ensemble bursting of non-cholinergic BF neurons may improve behavioral performance by affecting the activity of widespread cortical circuits, and therefore represents a novel candidate mechanism for top-down attention.

The discovery of experience-dependent brain reactivation during both slow-wave (SW) and rapid eye-movement (REM) sleep led to the notion that the consolidation of recently acquired memory traces requires neural replay during sleep. To date, however, several observations continue to undermine this hypothesis. To address some of these objections, we investigated the effects of a transient novel experience on the long-term evolution of ongoing neuronal activity in the rat forebrain. We observed that spatiotemporal patterns of neuronal ensemble activity originally produced by the tactile exploration of novel objects recurred for up to 48 h in the cerebral cortex, hippocampus, putamen, and thalamus. This novelty-induced recurrence was characterized by low but significant correlations values. Nearly identical results were found for neuronal activity sampled when animals were moving between objects without touching them. In contrast, negligible recurrence was observed for neuronal patterns obtained when animals explored a familiar environment. While the reverberation of past patterns of neuronal activity was strongest during SW sleep, waking was correlated with a decrease of neuronal reverberation. REM sleep showed more variable results across animals. In contrast with data from hippocampal place cells, we found no evidence of time compression or expansion of neuronal reverberation in any of the sampled forebrain areas. Our results indicate that persistent experience-dependent neuronal reverberation is a general property of multiple forebrain structures. It does not consist of an exact replay of previous activity, but instead it defines a mild and consistent bias towards salient neural ensemble firing patterns. These results are compatible with a slow and progressive process of memory consolidation, reflecting novelty-related neuronal ensemble relationships that seem to be context- rather than stimulus-specific. Based on our current and previous results, we propose that the two major phases of sleep play distinct and complementary roles in memory consolidation: pretranscriptional recall during SW sleep and transcriptional storage during REM sleep.

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Episodic and spatial memories engage the hippocampus during acquisition but migrate to the cerebral cortex over time. We have recently proposed that the interplay between slow-wave (SWS) and rapid eye movement (REM) sleep propagates recent synaptic changes from the hippocampus to the cortex. To test this theory, we jointly assessed extracellular neuronal activity, local field potentials (LFP), and expression levels of plasticity-related immediate-early genes (IEG) arc and zif-268 in rats exposed to novel spatio-tactile experience. Post-experience firing rate increases were strongest in SWS and lasted much longer in the cortex (hours) than in the hippocampus (minutes). During REM sleep, firing rates showed strong temporal dependence across brain areas: cortical activation during experience predicted hippocampal activity in the first post-experience hour, while hippocampal activation during experience predicted cortical activity in the third post-experience hour. Four hours after experience, IEG expression was specifically upregulated during REM sleep in the cortex, but not in the hippocampus. Arc gene expression in the cortex was proportional to LFP amplitude in the spindle-range (10–14 Hz) but not to firing rates, as expected from signals more related to dendritic input than to somatic output. The results indicate that hippocampo-cortical activation during waking is followed by multiple waves of cortical plasticity as full sleep cycles recur. The absence of equivalent changes in the hippocampus may explain its mnemonic disengagement over time.

Both acetylcholine (ACh) and theta oscillations are important for learning and memory, but the dynamic interaction between these two processes remains unclear. Recent advances in amperometry techniques have revealed phasic ACh releases in vivo. However, it is unknown whether phasic ACh release co-occurs with theta oscillations. We investigated this issue in the CA1 region of urethaneanesthetized male rats using amperometric and electrophysiological recordings. We found that ACh release was highly correlated with the appearance of both spontaneous and induced theta oscillations. Moreover, the maximal ACh release was observed around or slightly above the pyramidal layer. Interestingly, such release lagged behind theta initiation by 25-60 s. The slow ACh release profile was matched by the slow firing rate increase of a subset of medial-septal low-firing-rate neurons. Together, these results establish, for the first time, the in vivo coupling between phasic ACh release and theta oscillations on spatiotemporal scales much finer than previously known. These findings also suggest that phasic ACh is not required for theta initiation and may instead operate synergistically with theta oscillations to promote neural plasticity in the service of learning and memory.