Sleep problems are classical complaints in depressed patients. Polygraphie recordings performed in drug free depressed patients during an acute episode of the illness have allowed description of sleep continuity, architecture and REM sleep disturbances. While the specificity of these abnormalities is not fully established, these perturbations appear to be core symptoms of the depressive episode. Antidepressants drugs, whatever their pharmacological profile have been shown to suppress or at least to reduce REM sleep. However, the effects of these drugs on sleep continuity and architecture seem to be related to their specific pharmacological action.

The adult human typically exhibits a monophasic sleep-wake cycle, i.e., remains awake and alert for approximately 16 hours and then sleeps for 8 hours. Recent experiments have provided new insights in the role of the endogenous circadian pacemaker in this consolidation of sleep and wakefulness.

Sleep deprivation studies had shown previously that sleepiness and alertness are co-determined by a process which keeps track of the history of sleep and wakefulness and the circadian pacemaker, which keeps track of time. During every day life and during sleep deprivation both processes change simultaneously and their relative contribution to alertness and sleep propensity cannot be assessed under these conditions.

Despite huge efforts from public sectors to educate society as to the deleterious physiological consequences of smoking while pregnant, 12–25% of all babies worldwide are born to mothers who smoked during their pregnancies. Chief among the negative legacies bestowed to the exposed individual is an enhanced proclivity postnatally to addict to drugs of abuse, which suggests that the drug exposure during gestation changed the developing brain in such a way that biased it towards addiction. Glutamate signalling has been shown to be altered by prenatal nicotine exposure (PNE) and glutamate is the major excitatory neurotransmitter within the laterodorsal tegmental nucleus (LDT), which is a brainstem region importantly involved in responding to motivational stimuli and critical in development of drug addiction-associated behaviours, however, it is unknown whether PNE alters glutamate signalling within this nucleus. Accordingly, we used calcium imaging, to evaluate AMPA and NMDA receptor-mediated calcium responses in LDT brain slices from control and PNE mice. We also investigated whether the positive AMPA receptor modulator cyclothiazide (CYZ) had differential actions on calcium in the LDT following PNE. Our data indicated that PNE significantly decreased AMPA receptor-mediated calcium responses, and altered the neuronal calcium response to consecutive NMDA applications within the LDT. Furthermore, CYZ strongly potentiated AMPA-induced responses, however, this action was significantly reduced in the LDT of PNE mice when compared with enhancements in responses in control LDT cells. Immunohistochemical processing confirmed that calcium imaging recordings were obtained from the LDT nucleus as determined by presence of cholinergic neurons. Our results contribute to the body of evidence suggesting that neurobiological changes are induced if gestation is accompanied by nicotine exposure. We conclude that in light of the role played by the LDT in motivated behaviour, the cellular changes in the LDT induced by exposures to nicotine prenatally, when combined with alterations in other reward-related regions, could contribute to the increased susceptibility to smoking observed in the offspring.

Prenatal nicotine exposure (PNE) is a risk factor for developing an addiction to nicotine at a later stage in life. Understanding the neurobiological changes in reward related circuitry induced by exposure to nicotine prenatally is vital if we are to combat the heightened addiction liability in these vulnerable individuals. The laterodorsal tegmental nucleus (LDT), which is comprised of cholinergic, GABAergic and glutamatergic neurons, is importantly involved in reward mediation via demonstrated excitatory projections to dopamine-containing ventral tegmental neurons. PNE could lead to alterations in LDT neurons that would be expected to alter responses to later-life nicotine exposure. To examine this issue, we monitored nicotine-induced responses of LDT neurons in brain slices of PNE and drug naive mice using calcium imaging and whole-cell patch clamping. Nicotine was found to induce rises in calcium in a smaller proportion of LDT cells in PNE mice aged 7–15 days and smaller rises in calcium in PNE animals from postnatal ages 11–21 days when compared with age-matched control animals. While inward currents induced by nicotine were not found to be different, nicotine did induce larger amplitude excitatory postsynaptic currents in PNE animals in the oldest age group when compared with amplitudes induced in similar-aged control animals. Immunohistochemically identified cholinergic LDT cells from PNE animals exhibited slower spike rise and decay slopes, which likely contributed to the wider action potential observed. Further, PNE was associated with a more negative action potential afterhyperpolarization in cholinergic cells. Interestingly, the changes found in these parameters in animals exposed prenatally to nicotine were age related, in that they were not apparent in animals from the oldest age group examined. Taken together, our data suggest that PNE induces changes in cholinergic LDT cells that would be expected to alter cellular excitability. As the changes are age related, these PNE-associated alterations could contribute differentially across ontogeny to nicotine-mediated reward and may contribute to the particular susceptibility of in utero nicotine exposed individuals to addict to nicotine upon nicotine exposure in the juvenile period.

Knowledge of the input-output characteristics of various neuronal types is a necessary first step toward an understanding of cellular events related to waking and sleep. In spite of the oversimplification involved, the dichotomy in terms of type I (long-axoned, output) neurons and type II (short-axoned, local) interneurons is helpful in functionally delineating the neuronal circuits involved in the genesis and epiphenomena of waking and sleep states. The possibility is envisaged that cortical interneurons, which are particularly related to higher neuronal activity and have been found in previous experiments to be more active during sleep than during wakefulness, might be involved in complex integrative processes occurring during certain sleep stages. Electrophysiological criteria for the identification of output cells and interneurons are developed, with emphasis on various possibilities and difficulties involved in recognizing interneurons of the mammalian brain. The high-frequency repetitive activity of interneurons is discussed, together with various possibilities of error to be avoided when interpreting data from bursting cells. Data first show opposite changes in spontaneous and evoked discharges of identified output cells versus putative interneurons recorded from motor and parietal association cortical areas in behaving monkeys and cats during wakefulness (W) compared to sleep with synchronized EEG activity (S): significantly increased rates of spontaneous firing, enhanced antidromic or synaptic responsiveness, associated with shorter periods of inhibition in type I (pyramidal tract, cortico-thalamic and cortico-pontine) cells during W versus significantly decreased frequencies of spontaneous discharge and depression of synaptically elicited reponses of type II cells during W compared to S. These findings are partly explained on the basis of recent iontophoretic studies showing that acetylcholine, viewed as a synaptic transmitter of the arousal system, excites output-type neurons and inhibits high-frequency bursting cells. Comparing W and S to the deepest stage of sleep with desynchronized EEG activity (D) in type I and type II cells revealed that: (a) the increased firing rates of output cells in D, over those in W and S, is substantially due to a tonic excitation during this state, and rapid eye movements (REMs) only contribute to the further increase of discharge frequencies; (b) in contrast, the increased rates of discharge in interneurons during D is entirely ascribable to REM-related firing. On the basis of experiments reporting that increased duration of D has beneficial effects upon retention of information acquired during W, the suggestion is made that increased firing rates of association cortical interneurons during REM epochs of D sleep are an important factor in maintaining the soundness of a memory trace.

Background: Dementia with Lewy bodies (DLB) is often associated with REM sleep behavior disorders (RBD) characterized, in contrast to the usual paralysis of REM sleep, by violent motor and verbal activity. Patients and Methods: The pharmacological management of RBD was investigated in three DLB patients treated with clonazepam, a benzodiazepine used as an antiepileptic, or donepezil, a cholinesterase inhibitor. Results: All three patients had marked improvement. The pharmacodynamic mechanisms underlying the efficacy of the two drugs might be due to facilitator effect on the pedunculopontine nucleus, a key structure in the physiology of REM sleep.

Numerous studies have replicated the finding of mentation in both rapid eye movement (REM) and nonrapid eye movement (NREM) sleep. However, two different theoretical models have been proposed to account for this finding: (1) a one-generator model, in which mentation is generated by a single set of processes regardless of physiological differences between REM and NREM sleep; and (2) a two-generator model, in which qualitatively different generators produce cognitive activity in the two states. First, research is reviewed demonstrating conclusively that mentation can occur in NREM sleep; global estimates show an average mentation recall rate of about 50% from NREM sleep – a value that has increased substantially over the years. Second, nine different types of research on REM and NREM cognitive activity are examined for evidence supporting or refuting the two models. The evidence largely, but not completely, favors the two-generator model. Finally, in a preliminary attempt to reconcile the two models, an alternative model is proposed that assumes the existence of covert REM sleep processes during NREM sleep. Such covert activity may be responsible for much of the dreamlike cognitive activity occurring in NREM sleep.

We present evidence disputing the hypothesis that memories are processed or consolidated in REM sleep. A review of REM deprivation (REMD) studies in animals shows these reports to be about equally divided in showing that REMD does, or does not, disrupt learning/memory. The studies supporting a relationship between REM sleep and memory have been strongly criticized for the confounding effects of very stressful REM deprivation techniques. The three major classes of antidepressant drugs, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and selective serotonin reuptake inhibitors (SSRIs), profoundly suppress REM sleep. The MAOIs virtually abolish REM sleep, and the TCAs and SSRIs have been shown to produce immediate (40–85%) and sustained (30–50%) reductions in REM sleep. Despite marked suppression of REM sleep, these classes of antidepressants on the whole do not disrupt learning/memory. There have been a few reports of patients who have survived bilateral lesions of the pons with few lingering complications. Although these lesions essentially abolished REM sleep, the patients reportedly led normal lives. Recent functional imaging studies in humans have revealed patterns of brain activity in REM sleep that are consistent with dream processes but not with memory consolidation. We propose that the primary function of REM sleep is to provide periodic endogenous stimulation to the brain which serves to maintain requisite levels of central nervous system (CNS) activity throughout sleep. REM is the mechanism used by the brain to promote recovery from sleep. We believe that the cumulative evidence indicates that REM sleep serves no role in the processing or consolidation of memory.

In a repetitive auditory stimulus sequence, deviant infrequent tones typically elicit a component of auditory event-related potentials termed mismatch negativity (MMN). The elicitation of MMN is assumed to reflect the existence of a memory trace of the standard stimulus that has a decay time of about 10 s and is strengthened by repetition of the standards. The main aim of the present study was to test the decay time of the sensory memory trace during rapid-eye movement (REM) sleep vs. wakefulness, as indexed by the MMN. Subjects were presented 10 tone trains, separated by 3, 6, or 9 s of silence, during waking and REM sleep. Each train consisted of 9 standards of 1000 Hz and 1 deviant of 2000 Hz that occurred at position 1, 2, 4, or 6. The waking deviants elicited a frontocentral negativity with a scalp topography equivalent to the MMN component. During REM sleep, the negative component showed the same scalp distribution only for the 3-s intertrain interval (ITI). In this brain state, the MMN amplitude was smaller and decreased with prolongation of the ITI. These results suggest a weaker sensory memory trace formation and a premature decay time of such a memory trace during REM sleep as compared with wakefulness.

Asymmetry of waking electroencephalography (EEG) alpha power in frontal regions has been correlated with waking emotional reactivity and the emotional content of dream reports. Little is known regarding alpha asymmetry during sleep. The present study was performed to compare alpha power and alpha power asymmetry in various brain regions across states of sleep and wakefulness. Waking and sleep EEG were recorded in a group of patients undergoing polysomnographic evaluation for possible sleep disorders. Alpha EEG asymmetry in frontal and temporal regions was significantly correlated in waking versus sleep, particularly during rapid eye movement (REM) sleep. These results suggest that patterns of frontal alpha asymmetry are stable across sleep and waking and may be related to emotional reactivity during dreaming. During sleep, alpha power was highest during slow-wave sleep and lowest during REM sleep. Implications of these data for understanding the functional significance of alpha power during waking and sleeping are considered.