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Pharmacology researchers have discovered a key mechanism linking sleep and wake to synaptic plasticity in the brain, shedding light on how learning and memory may be affected by rest. Their study, published by Alfonsa et al. in the journal Current Biology, reveals that intracellular chloride levels shift during sleep and wakefulness, influencing synaptic plasticity processes in the brain’s cortex.

The Akerman group found that changes in chloride ion balance affect the ability of neurons to undergo long-term potentiation (LTP), a process that is critical for learning. With wakefulness, neurons exhibit higher intracellular chloride concentrations, which make it easier to strengthen excitatory synaptic connections. In contrast, decreases in intracellular chloride concentration that accompany sleep make it more difficult to strengthen excitatory synaptic connections.

Experiments demonstrated that depriving mice of sleep altered chloride balance, making cortical neurons more excitable and lowering their threshold for inducing LTP. Conversely, blocking chloride transport mechanisms following periods of wakefulness raised the threshold for inducing LTP. These findings suggest that chloride regulation may play a crucial role in cognitive functions like memory consolidation.

The study contributes to broader theories on how sleep supports learning and brain function. By identifying chloride’s role in regulating excitatory synaptic plasticity, the findings could inform research on sleep disorders, cognitive decline, and conditions like epilepsy. Lead authors Dr Hannah Alfonsa and Professor Colin Akerman suggest that manipulating chloride balance could offer new avenues for enhancing cognitive function and brain health.

See the full paper here