This research identifies calneuron-1 as a critical regulator of the M1 muscarinic acetylcholine receptor, linking its overexpression to the pathophysiology of schizophrenia. The study demonstrates that high levels of this protein disrupt G-protein coupling, which shifts the balance of neural activity toward excitation and impairs communication between the prefrontal cortex and hippocampus. These molecular changes result in significant cognitive deficits, including impaired memory and reduced flexibility, in both developing and adult mice. Crucially, the researchers found that the drug xanomeline can break the interaction between calneuron-1 and the receptor. This intervention restores normal network signaling and reverses behavioral symptoms, highlighting a promising therapeutic target for treating the complex symptoms of the disorder.

References:

• Oelschlegel A M, Pöpplau J A, Ryzynski A, et al. Elevated calneuron-1, an accessory subunit of muscarinic receptors, induces frontotemporal dysconnectivity and schizophrenia-like deficits[J]. Neuron, 2025.