11月4日のNeuroClubでは以下の論文を紹介いたします。
よろしくお願いいたします。

Dos Santos et al. (2026)
Soluble α2δ-1, altered in disease CSF, modulates network homeostasis and
rescues deficits in a neuropsychiatric mouse model
https://doi.org/10.1016/j.neuron.2026.02.004

Summary
Excitation-inhibition (E/I) balance depends on dynamic communication
between neuronal subtypes, potentially beyond classical
neurotransmission. While membrane-bound ion channels are essential for
neuronal function, their potential roles as extracellular regulators of
network dynamics remain largely unexplored. Here, we identify a soluble
form of the voltage-gated Ca2+ channel subunit α2δ-1 in human
cerebrospinal fluid (CSF) and show that it acts as an activity-regulated
intercellular modulator of network homeostasis. Soluble α2δ-1 is reduced
in the CSF of individuals with schizophrenia (SZ). Its synthetic analog,
synthetic ectodomain of Alpha2Delta-1 (SEAD1), modulates cortical
activity by enhancing the function of parvalbumin-positive (PV+)
interneurons and restoring E/I balance. A single SEAD1 injection into
the prefrontal cortex of a genetic mouse model of SZ reversed synaptic
and behavioral deficits, including memory and social impairments. These
findings reveal soluble synaptic ectodomains as a previously
underappreciated class of extracellular signaling molecules with
therapeutic potential in neuropsychiatric disorders.