Sleep and Memory Consolidation Dysfunction in Psychiatric Disorders: Evidence for the Involvement of Extracellular Matrix Molecules

Abstract

Sleep disturbances and memory dysfunction are key characteristics across psychiatric disorders. Recent advances have revealed insight into the role of sleep in memory consolidation, pointing to key overlap between memory consolidation processes and structural and molecular abnormalities in psychiatric disorders. Ongoing research regarding the molecular mechanisms involved in memory consolidation has the potential to identify therapeutic targets for memory dysfunction in psychiatric disorders and aging. Recent evidence from our group and others points to extracellular matrix molecules, including chondroitin sulfate proteoglycans and their endogenous proteases, as molecules that may underlie synaptic dysfunction in psychiatric disorders and memory consolidation during sleep. These molecules may provide a therapeutic targets for decreasing strength of reward memories in addiction and traumatic memories in PTSD, as well as restoring deficits in memory consolidation in schizophrenia and aging. We review the evidence for sleep and memory consolidation dysfunction in psychiatric disorders and aging in the context of current evidence pointing to the involvement of extracellular matrix molecules in these processes.

Benchmarking brain organoid recapitulation of fetal corticogenesis

“…They have high expression in germinal zones and maturing/mature astrocytes 52–55 and are important for the evolution of the human brain, with progenitor cells expressing ECM components at higher levels than in mice 56 . ECM also plays critical roles in synaptic plasticity and electrophysiological properties 57,58 , and its alteration has been linked to neuropsychiatric disorders 59,60 . Our exposure of the differential regulation of ECM genes in BO compared to fetal cortex provides therefore a new relevant insight to consider when interpreting neuropsychiatric disease modelling datasets.…”

In vitro cell models merging circadian rhythms and brain waves for personalized neuromedicine

“…This thalamic crosstalk between sleep and sensorimotor integration supports the involvement of sleep in fundamental functions such as memory consolidation, brain clearance and plasticity, and energy conservation. Noteworthy attention to the process of memory consolidation is found both in the review of Fields, 16 focusing on the pivotal role of specific brain waves oscillating at different frequencies during the various stages of NREM and REM sleep for long-term memory retention, and the review of Gisabella et al., 17 pointing to the involvement of extracellular matrix molecules in synaptic regulation during sleep. In these processes, sleep is involved in changes in strength or efficacy of synapses formed during wakefulness for selective memories, i.e., experiences accumulated throughout the day are reactivated during slow-wave sleep in a process called systemic consolidation, 17 where memories are deleted or sorted for short-term storage sites such as the hippocampus, and then transferred to long-term storage in neocortical areas to be integrated into existing knowledge schemas, which can mark them as potentially useful or unnecessary in the future.…”

“…Noteworthy attention to the process of memory consolidation is found both in the review of Fields, 16 focusing on the pivotal role of specific brain waves oscillating at different frequencies during the various stages of NREM and REM sleep for long-term memory retention, and the review of Gisabella et al., 17 pointing to the involvement of extracellular matrix molecules in synaptic regulation during sleep. In these processes, sleep is involved in changes in strength or efficacy of synapses formed during wakefulness for selective memories, i.e., experiences accumulated throughout the day are reactivated during slow-wave sleep in a process called systemic consolidation, 17 where memories are deleted or sorted for short-term storage sites such as the hippocampus, and then transferred to long-term storage in neocortical areas to be integrated into existing knowledge schemas, which can mark them as potentially useful or unnecessary in the future. 16 , 17 Memories are then strengthened in these long-term storage areas during REM sleep, in a process called synaptic consolidation, while the short-term storage memories are removed via synaptic pruning, greatly reducing the signal-to-noise ratio and restoring the capacity to form new synapses.…”

“…In these processes, sleep is involved in changes in strength or efficacy of synapses formed during wakefulness for selective memories, i.e., experiences accumulated throughout the day are reactivated during slow-wave sleep in a process called systemic consolidation, 17 where memories are deleted or sorted for short-term storage sites such as the hippocampus, and then transferred to long-term storage in neocortical areas to be integrated into existing knowledge schemas, which can mark them as potentially useful or unnecessary in the future. 16 , 17 Memories are then strengthened in these long-term storage areas during REM sleep, in a process called synaptic consolidation, while the short-term storage memories are removed via synaptic pruning, greatly reducing the signal-to-noise ratio and restoring the capacity to form new synapses. 17 To this aim, the activity of millions of neurons in many different regions of the brain must be linked to produce a coherent memory that intertwines emotions, sights, sounds, smells, sequences of events, and other stored experiences.…”

“…16 , 17 Memories are then strengthened in these long-term storage areas during REM sleep, in a process called synaptic consolidation, while the short-term storage memories are removed via synaptic pruning, greatly reducing the signal-to-noise ratio and restoring the capacity to form new synapses. 17 To this aim, the activity of millions of neurons in many different regions of the brain must be linked to produce a coherent memory that intertwines emotions, sights, sounds, smells, sequences of events, and other stored experiences. In this way, several neurons are activated together; they send impulses at the same time and strengthen their synaptic connections, where learning takes place.…”