The timing of sleep and wakefulness in mammals is governed by a sleep homeostatic process and by the circadian clock of the suprachiasmatic nucleus (SCN), which has a molecular basis for rhythm generation. By combining SCN electrical activity recordings with electroencephalogram (EEG) recordings in the same animal (the Wistar rat), we discovered that changes in vigilance states are paralleled by strong changes in SCN electrophysiological activity. During rapid eye movement (REM) sleep, neuronal activity in the SCN was elevated, and during non-REM (NREM) sleep, it was lowered. We also carried out selective sleep deprivation experiments to confirm that changes in SCN electrical activity are caused by changes in vigilance state. Our results indicate that the 24-hour pattern in electrical activity that is controlled by the molecular machinery of the SCN is substantially modified by afferent information from the central nervous system.
Circadian rhythms in neuronal ensemble, subpopulations, and single unit activity were recorded in the suprachiasmatic nuclei (SCN) of rat hypothalamic slices. Decomposition of the ensemble pattern revealed that neuronal subpopulations and single units within the SCN show surprisingly short periods of enhanced electrical activity of Ϸ5 h and show maximal activity at different phases of the circadian cycle. The summed activity accounts for the neuronal ensemble pattern of the SCN, indicating that circadian waveform of electrical activity is a composed tissue property. The recorded single unit activity pattern was used to simulate the responsiveness of SCN neurons to different photoperiods. We inferred predictions on changes in peak width, amplitude, and peak time in the multiunit activity pattern and confirmed these predictions with hypothalamic slices from animals that had been kept in a short or long photoperiod. We propose that the animals' ability to code for day length derives from plasticity in the neuronal network of oscillating SCN neurons.T he suprachiasmatic nuclei (SCN) contain a major pacemaker of circadian rhythms in mammals (1, 2). The SCN control circadian rhythms in the central nervous system and peripheral organs and as such ensures that organisms are able to anticipate and adjust to predictable changes in the environment that occur with the day-night cycle (3-5). The SCN is also involved in adaptation of the organism to the annual cycle by monitoring seasonal changes in day length (6). As an example, animals will accommodate their daily behavioral activity to the photoperiod. A multioscillator structure has been proposed to fulfill this dual task (7).At least nine candidate genes have been identified that play a role in rhythm generation on the basis of a transcriptionaltranslational feedback loop (8, 9). A number of additional genes may be involved to further refine or shape circadian rhythms (10). Although great progress has been made in understanding the molecular basis for circadian rhythm generation, it is unknown how individual neuronal activity rhythms are integrated to render a functioning pacemaker that is able to code for circadian and seasonal rhythms. The SCN each contain Ϸ10,000 neurons, which are small and densely packed (11). After dissociation, isolated SCN neurons express circadian rhythms in their firing patterns (12, 13). The freerunning periods of the individual neurons vary from 20 to 28 h. The average period matches the behavioral activity pattern of Ϸ24 h. In these cultured dispersals, synaptically coupled neurons can sometimes be observed with synchronized firing patterns (14). In SCN tissue explants cultured on multielectrode plates, the variation in free-running period is considerably smaller (15)(16)(17). In these explants, firing patterns can be observed which are in phase, or 6 -12 h out of phase. The range of phase relationships observed within the SCN in vitro suggests a level of temporal complexity that challenges our understanding of how a singular phase and perio...
The suprachiasmatic nuclei (SCN) of the hypothalamus contain a pacemaker that generates circadian rhythms in many functions. Light is the most important stimulus that synchronizes the circadian pacemaker to the environmental cycle. In this paper we have characterized the baseline neuronal firing patterns of the SCN as well as their response to light in freely moving rats. Multiunit and single-unit recordings showed that SCN neurons increase discharge during daytime and decrease discharge at night. Discharge levels of individual neurons that were followed throughout the circadian cycle appeared in phase with the population and were characterized by low discharge rates (often below 1 Hz), with a twofold increase during the day. The effect of light on the multiunit response was dependent on the duration of light exposure and on light intensity, with light thresholds of approximately 0.1 lux. The light response level showed a strong dependency on time of day, with large responsiveness at night and low responsiveness during day. At both phases of the circadian cycle, the response level could be raised by an increase in light intensity. Single-unit measurements revealed that the time-dependent light response of SCN neurons was present also at the level of single units. The results show that the basic light response characteristics that were observed at the multiunit level result from an integrated response of similarly behaving single units. Research at the single-unit level is therefore a useful approach for investigating the basic principles of photic entrainment.
The basal forebrain (BF) is a heterogeneous structure located in the ventral aspect of the cerebral hemispheres. It contains cholinergic as well as different types of noncholinergic corticopetal neurons and interneurons, including GABAergic and peptidergic cells. The BF constitutes an extrathalamic route to the cortex, and its activity is associated with an increase in cortical release of the neurotransmitter acetylcholine, concomitant with electroencephalographic (EEG) low-voltage fast activity (LVFA). However, the specific role of the different BF cell types has largely remained unknown due to the lack of chemical identification of the recorded neurons. Here we show that the firing rate of immunocytochemically identified cholinergic and parvalbumin-containing neurons increase during cortical LVFA. In contrast, increased neuropeptide Y neuron firing is accompanied by cortical slow waves. Our results, furthermore, indicate that BF neurons posses a distinct temporal relationship to different EEG patterns and suggest a more dynamic interplay within BF as well as between BF and cortical circuitries than previously proposed.
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