Joel H. Benington

Stimulation of A1 adenosine receptors mimics the electroencephalographic effects of sleep deprivation

N6-Cyclopentyladenosine (CPA), an A1 adenosine receptor agonist, increased EEG slow-wave activity in nonREM sleep when administered either systemically (0.1-3 mg/kg) or intracerebroventricularly (3.5-10 micrograms) in the rat. The power spectrum of EEG changes (as calculated by Fourier analysis) matched that produced by total sleep deprivation in the rat. The effects of CPA on the nonREM-sleep EEG were dose-dependent. These findings suggest that adenosine is an endogenous mediator of sleep-deprivation induced increases in EEG slow-wave activity, and therefore that increased adenosine release is a concomitant of accumulation of sleep need and may be involved in homeostatic feedback control of sleep expression.

Cellular and molecular connections between sleep and synaptic plasticity.

The hypothesis that sleep promotes learning and memory has long been a subject of active investigation. This hypothesis implies that sleep must facilitate synaptic plasticity in some way, and recent studies have provided evidence for such a function. Our knowledge of both the cellular neurophysiology of sleep states and of the cellular and molecular mechanisms underlying synaptic plasticity has expanded considerably in recent years. In this article, we review findings in these areas and discuss possible mechanisms whereby the neurophysiological processes characteristic of sleep states may serve to facilitate synaptic plasticity. We address this issue first on the cellular level, considering how activation of T-type Ca(2+) channels in nonREM sleep may promote either long-term depression or long-term potentiation, as well as how cellular events of REM sleep may influence these processes. We then consider how synchronization of neuronal activity in thalamocortical and hippocampal-neocortical networks in nonREM sleep and REM sleep could promote differential strengthening of synapses according to the degree to which activity in one neuron is synchronized with activity in other neurons in the network. Rather than advocating one specific cellular hypothesis, we have intentionally taken a broad approach, describing a range of possible mechanisms whereby sleep may facilitate synaptic plasticity on the cellular and/or network levels. We have also provided a general review of evidence for and against the hypothesis that sleep does indeed facilitate learning, memory, and synaptic plasticity.

The Role of Sleep in Memory Consolidation and Brain Plasticity: Dream or Reality?

The notion that a good night of sleep improves memory is widely accepted by the general public. Among sleep scientists, however, the idea has been hotly debated for decades. In this review, the authors consider current evidence for and against the hypothesis that sleep facilitates memory consolidation and promotes plastic changes in the brain. They find that despite a steady accumulation of positive findings over the past decade, the precise role of sleep in memory and brain plasticity remains elusive. This impasse may be resolved by more integrated approaches that combine behavioral and neurophysiological measurements in well-described in vivo models of synaptic plasticity.

Does the function of REM sleep concern non-REM sleep or waking?

We have hypothesized that REM sleep is functionally and homeostatically related to NREM sleep rather than to waking. In other words, REM sleep rather than to waking. In other words, REM sleep occurs in response to NREM-sleep expression and compensates for some process that takes place during NREM sleep. Under normal conditions, the need for REM sleep does not accrue during waking. The primary basis for this hypothesis is the fact that REM-sleep expression is a function of prior NREM-sleep expression. That is, REM sleep follows NREM sleep within sleep periods, REM-sleep episodes occur at intervals determined by the amount of NREM-sleep time elapsed, and total time spent in REM sleep is consistently about 1/4 of prior NREM-sleep time, regardless of how much time is spent in NREM sleep. Our experimental tests of the hypothesis support it. (1) REM-sleep propensity accumulates quite rapidly during a 2-hr interval spent predominantly in NREM sleep. (2) The timing of individual REM-sleep episodes is controlled homeostatically, by accumulation within NREM sleep of a propensity for REM sleep. The NREM sleep-related model of REM-sleep regulation (Fig. 1) explains a number of phenomena of REM-sleep expression, including the frequent and periodic occurrence of REM-sleep episodes throughout sleep periods, that have been accommodated by the waking-related model but are not functionally accounted for by it. In our opinion, the NREM sleep-related model of REM-sleep regulation recommends itself partly by its simplicity. According to the waking-related model, two independent and competing sleep propensities accumulate during waking and are discharged in two distinct sleep states that perform different waking-related recovery processes. One behaviour, sleep, is thought to perform two independent and competing functions that alternate at regular intervals. In the NREM sleep-related model of REM-sleep regulation, sleep debt simply reflects a need for NREM sleep. That is, the cerebrally less activated state of NREM sleep enables some form of restoration made necessary by the cerebrally activated state of waking. Periodic occurrence of REM-sleep episodes is explained without postulating an oscillatory mechanism to gate expression of NREM sleep versus REM sleep. In assessing the comparative merits of the waking-related and NREM sleep-related models of REM-sleep regulation, one should consider the influence of time-worn habits of thought.(ABSTRACT TRUNCATED AT 400 WORDS)

REM-sleep propensity accumulates during 2-h REM-sleep deprivation in the rest period in rats

Two-hour, highly-selective, rest-period, rapid-eye-movement (REM)-sleep deprivation (RD) was performed on rats to characterize the time-course of the homeostatic response to REM-sleep loss. RD caused a dramatic and progressive increase in the frequency of attempts to enter REM sleep, suppressed non-REM sleep EEG delta power, and (in late rest period trials) was followed by a rebound increase in REM-sleep expression.

Monoaminergic and cholinergic modulation of REM-sleep timing in rats

The effects on sleep structure of systemic administration of benchmark cholinergic, serotonergic, and noradrenergic antagonists (QNB, ritanserin, metergoline, and prazosin) were characterized in rats using a new technique for identifying transitions (NRTs) from non-REM (NREM) sleep to REM sleep. In agreement with previous studies, all agents tested reduced REM-sleep expression (by 36-86%). In addition, the serotonergic and noradrenergic antagonists reduced NRT frequency (by 58-81%). The cholinergic antagonist QNB had no effect on NRT frequency. These findings suggest that blockade of serotonergic or noradrenergic receptors increases the interval between REM-sleep episodes, perhaps reducing the rate of accumulation of REM-sleep propensity. Blockade of cholinergic receptors, by contrast, decreases REM-sleep expression by interfering with REM-sleep maintenance, not by modulating REM-sleep timing. These conclusions are contrary to the predictions of a number of published models of REM-sleep timing.

Apamin, a selective SK potassium channel blocker, suppresses REM sleep without a compensatory rebound

To determine the role of neuronal potassium conductance in rapid-eye-movement (REM)-sleep homeostasis, we have administered small doses of apamin (2-5 ng), a selective blocker of the calcium-dependent SK potassium channel, injected into the lateral ventricle in rats, and characterized the resultant effects on REM-sleep expression. Apamin produces a dose-dependent reduction in REM-sleep expression without an increase in the frequency of attempts to enter REM sleep, suggesting that accumulation of REM-sleep propensity is suppressed. The vast majority (84-95%) of lost REM sleep is not recovered 40 h after apamin administration. These findings suggest that accumulation of REM-sleep propensity is linked to the increased neuronal potassium conductance in nonREM sleep.

Debating how REM sleep is regulated (and by what)

Paul Franken has published in the March 2002 issue of this journal (pp. 17–28) an interesting article in which he re-analyzes two of his datasets to test a new model of rapid eye movement sleep (REMS) regulation. In Franken’s model, REMS timing is regulated in the short term by the accumulation of a REMS propensity during non-rapid eye movement sleep (NREMS). This part of Franken’s model builds on a publication of Benington and Heller (1994), which in turn was based on a number of studies showing that REMS timing is a NREMS dependent process (reviewed by Benington and Heller 1994). Additionally, Franken has posited the long-term accumulation of another form of REMS propensity in both waking and NREMS, which he feels is necessary to account for REMS rebounds following total sleep deprivation (TSD). In Franken’s words, ‘the differences in REMS during recovery cannot be explained by assuming that the need for REMS increases exclusively during NREMS.’ This part of Franken’s model is in effect rather similar to mainstream views of REMS regulation, according to which REMS expression is controlled by accumulation of a REMS propensity during waking. In this commentary, I will discuss the strengths and weaknesses of interpreting the effects of TSD in terms either of a REMS propensity accumulating during waking, during NREMS, or as in Franken’s model during both waking and NREMS. In my opinion, none of these models accounts for the available data in a decisive and entirely unproblematic way, yet all are at least broadly consistent with the available data and so remain viable models. However, we should not restrict our consideration of this question to abstract analyses of such models. REMS, NREMS and waking are physiological states of the brain and body. The homeostatic regulation of REMS presumably involves physiological changes as a propensity for REMS accumulates and is discharged. As I will discuss later in this commentary, my own support for the idea that REMS is regulated by the accumulation of a REMS propensity in NREMS derives primarily from a consideration of the neurophysiological characteristics of waking, NREMS and REMS, not from purely phenomenological analyses of arousal state distributions. FRANKEN’S MODEL OF LONG-TERM REMS REGULATION

A Protocol for Using Electronic Messaging To Facilitate Academic Committee Deliberations.

In this paper we offer a protocol for electronic deliberations that honors the rights of committee members and is consistent with Roberts Rules of Order. Implementing a formal protocol for electronic deliberations by academic committees ensures that all committee members will have an opportunity to participate fully in the committees deliberations. In this way, electronic deliberations can provide as much opportunity for achieving a consensus as in-person meetings, while also offering the convenience associated with electronic communication. Should electronic deliberations not appear to be working in a particular situation, this protocol provides a mechanism for calling an in-person meeting, thereby providing the best of both worlds.