Cortical Up states induce the selective weakening of subthreshold synaptic inputs

Area of Science:

• Neuroscience
• Cellular Biology
• Sleep Research

Background:

• Slow-wave sleep is crucial for synaptic plasticity and memory consolidation.
• Cortical neurons exhibit synchronized Up and Down states during slow-wave activity.
• The precise cellular mechanisms governing synaptic changes during sleep remain unclear.

Purpose of the Study:

• To investigate the cellular mechanisms of synaptic plasticity during cortical Up and Down states.
• To determine how synaptic inputs are modified during different phases of slow-wave activity.
• To elucidate the role of postsynaptic factors in regulating synaptic strength during sleep.

Main Methods:

• Electrophysiological recordings from LIII pyramidal neurons in acute mouse medial entorhinal cortex slices.
• Analysis of synaptic input responses during simulated Up and Down states.
• Investigation of postsynaptic factors including NMDA receptor and GSK3β activity.
• Measurement of synaptically evoked spine Ca2+ responses.

Main Results:

• Subthreshold synaptic inputs weaken during Up states, independent of global synaptic downscaling.
• Synaptic weakening is dependent on presynaptic spiking and postsynaptic control.
• Postsynaptic NMDA receptors and GSK3β activity are critical for inducing synaptic weakening.
• Suprathreshold inputs are preserved or strengthened during Up states.

Conclusions:

• Up states actively induce synaptic weakening of subthreshold inputs via postsynaptic mechanisms.
• This process selectively modifies synaptic connections, preserving active neuronal assemblies.
• Provides a cellular mechanism for synaptic homeostasis and network maintenance during slow-wave sleep.