Astrocyte cell volume dynamics across cortical states and transitions

Area of Science:

• Neuroscience
• Cellular Biology

Background:

• The sleep-wake cycle significantly impacts brain function, altering neural activity, fluid transport, and interstitial volume.
• Cortical astrocytes, crucial glial cells, play roles in regulating the brain microenvironment.

Purpose of the Study:

• To investigate whether cortical astrocytes exhibit state-dependent volume changes.
• To explore the role of norepinephrine and adrenergic signaling in regulating astrocyte volume during different sleep-wake states.

Main Methods:

• In vivo two-photon imaging in mice to monitor astrocyte volume.
• Pharmacological manipulation of adrenergic receptors.
• Chemogenetic and optogenetic stimulation of locus coeruleus neurons.

Main Results:

• Astrocyte volume significantly expands during wakefulness and shrinks during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep.
• Norepinephrine (NE) levels showed state-dependent fluctuations correlating with astrocyte volume.
• Blockage of alpha-1 adrenergic receptors, but not alpha-2 or beta-adrenergic receptors, induced astrocyte shrinkage.
• Stimulation of locus coeruleus (LC) tyrosine hydroxylase (TH)-positive neurons increased astrocyte volume, an effect abolished by the alpha-1 receptor antagonist prazosin.

Conclusions:

• Astrocyte volume is dynamically regulated by the sleep-wake cycle.
• Norepinephrine signaling through alpha-1 adrenergic receptors is a key mechanism driving astrocyte expansion during wakefulness.
• Wakefulness-driven astrocyte expansion may reduce interstitial volume, influencing neuroglia interactions and suppressing glymphatic flow.