Low acetylcholine during early sleep is important for motor memory consolidation

Abstract

The synaptic homeostasis theory of sleep proposes that low neurotransmitter activity in sleep is optimal for memory consolidation. We tested this theory by asking whether increasing acetylcholine levels during early sleep would disrupt motor memory consolidation. We trained separate groups of adult mice on the rotarod walking and skilled reaching for food tasks, and after training, administered physostigmine, an acetylcholinesterase inhibitor, to increase cholinergic tone in subsequent sleep. Post-sleep testing suggested that physostigmine impaired motor skill acquisition. Home-cage video monitoring and electrophysiology revealed that physostigmine disrupted sleep structure, delayed non-rapid-eyemovement sleep onset, and reduced slow-wave power in the hippocampus and cortex. The impaired motor performance with physostigmine, however, was not solely due to its effects on sleep structure, as one hour of sleep deprivation after training did not impair rotarod performance. A reduction in cholinergic tone by inactivation of cholinergic neurons during early sleep also affected rotarod performance. Administration of agonists and antagonists of muscarinic and nicotinic acetylcholine receptors revealed that activation of muscarinic receptors during early sleep impaired rotarod performance. The experiments suggest that the increased slow wave activity and inactivation of muscarinic receptors during early sleep due to reduced acetylcholine contribute to motor memory consolidation.

Sleep loss drives acetylcholine- and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation

“…Behavioral data from both human subjects ( 38 , 39 ) and animal models ( 55 ) demonstrate that reduced acetylcholine signaling is essential for the benefits of sleep for memory consolidation ( 37 – 39 ). MS cholinergic neurons send the majority of their output to the hippocampus, although a smaller subset provide cholinergic input to neocortical sites, including entorhinal and primary sensory cortices ( 56 , 57 ).…”

Do Nicotinic Receptors Modulate High-Order Cognitive Processing?

“…Recently, machine learning approaches combined with in vivo neurochemical data demonstrated that concentrations of neurotransmitters such as ACh and norepinephrine in prefrontal cortex can predict the levels of cortical and behavioral arousal [22]. Low levels of ACh during NREM sleep have been suggested to enhance synapse formation and episodic/motor memory consolidation mechanisms [23,24].…”