Animal Studies on the Role of Sleep in Memory: From Behavioral Performance to Molecular Mechanisms

Abstract

Although the exact functions of sleep remain a topic of debate, several hypotheses propose that sleep benefits neuronal plasticity, which ultimately supports brain function and cognition . For over a century, researchers have applied a wide variety of behavioral, electrophysiological, biochemical, and molecular approaches to study how memory processes are promoted by sleep and perturbed by sleep loss. Interestingly, experimental studies indicate that cognitive impairments as a consequence of sleep deprivation appear to be most severe with learning and memory processes that require the hippocampus , which suggests that this brain region is particularly sensitive to the consequences of sleep loss. Moreover, recent studies in laboratory rodents indicate that sleep deprivation impairs hippocampal neuronal plasticity and memory processes by attenuating intracellular cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling. Attenuated cAMP-PKA signaling can lead to a reduced activity of the transcription factor cAMP response element binding protein (CREB) and ultimately affect the expression of genes and proteins involved in neuronal plasticity and memory formation. Pharmacogenetic experiments in mice show that memory deficits following sleep deprivation can be prevented by specifically boosting cAMP signaling in excitatory neurons of the hippocampus. Given the high incidence of sleep disturbance and sleep restriction in our 24/7 society, understanding the consequences of sleep loss and unraveling the underlying molecular mechanisms is of great importance.

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

“…The cyclic AMP (c-AMP)/protein kinase A (PKA)/c-AMP response element binding protein (CREB) pathway plays an important role in synaptogenesis and synaptic plasticity [135]. Although the c-AMP /PKA/CREB pathway is not the focus of this review, it is important to note its cross-talk with phospholipase C (PLC)/PKC signaling pathway.…”

The basolateral amygdala can mediate the effects of fear memory on sleep independently of fear behavior and the peripheral stress response

“…Recent work (Wellman et al, 2016) and the current study also demonstrate that individual outbred rats can show either decreases or increases in REM in response to IS, also without differences in freezing or SIH. Thus, while several studies have demonstrated that sleep may play a role in the consolidation of contextual fear memory associated with brief or mild fearful experiences (e.g., Graves, Heller, Pack, and Abel, 2003; Greenwood, Thompson, Opp, and Fleshner, 2014; Hagewoud, Bultsma, Barf, Koolhaas, and Meerlo, 2011; Hellman and Abel, 2007; Kumar and Jha, 2012; Menz, Rihm, and Büchel, 2016; Menz, Rihm, Salari, Born, Kalisch, Pape, Marshall, and Buchel, 2013; Rossi, Tiba, Moreira, Ferreira, Oliveira, and Suchecki, 2014; Silvestri, 2005; for recent review see Havekes, Meerlo, and Abel, 2015), there is no evidence that REM sleep is necessary for the formation of contextual fear memory associated with relatively intense stressful experiences. Interestingly, we found no correlation between freezing and either REM or NREM sleep.…”

Acute Sleep Deprivation Blocks Short- and Long-Term Operant Memory inAplysia

“…[58][59][60][61][62] Sleep also appears necessary for memory, with sleep deprivation leading to decrements in cognitive performance and memory impairments. 4,[63][64][65] Additionally, sleep following learning can enhance memory strength, particularly for hippocampal-dependent learning in humans and animal models. [66][67][68][69] Invertebrates, with their comparatively simple nervous system, have proven invaluable for elucidating the molecular mechanisms underlying complex behavior.…”

“…Acute sleep deprivation and chronic sleep restriction cause significant decrements in short-term and long-term memories in humans and in animal models. [3][4][5][6][7][8][9] In mammals, the consolidation of hippocampal dependent spatial memory is particularly susceptible to the effects of sleep deprivation. [10][11][12] In Drosophila and mouse models, genetic mutants exhibiting reduced sleep also show impairments in memory.…”