Necl-4/CADM4 regulates GABAergic synaptic strength on GABAergic inhibitory neurons via ErbB4 activation and prevents neuronal impairments.

ABSTRACT: Neural networks comprise excitatory and inhibitory neurons, linked through excitatory and inhibitory synapses. Synaptic excitation/inhibition balance is controlled for brain development and functions, and its dysregulations are implicated in aging-dependent neuronal impairments. Here, we found that Necl-4/CADM4, an immunoglobulin superfamily cell adhesion molecule, is expressed in γ-aminobutyric acidergic (GABAergic) inhibitory neurons and localizes at GABAergic synapses on inhibitory neurons in cultured hippocampal neurons and the mouse hippocampus. Necl-4 genetic ablation induced neuronal loss with synaptic degenerations in the hippocampus, and cultured Necl-4-knockout (KO) hippocampal neurons were more susceptible to death. Prior to the neuronal death, the Necl-4-KO hippocampal neurons

SUBMITTER: Komaki R 

PROVIDER: S-EPMC12559063 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature