Necl-4/CADM4 regulates GABAergic synaptic strength on GABAergic inhibitory neurons via ErbB4 activation and prevents neuronal impairments
Ryouhei Komaki, Hajime Shiotani, Toshihiko Kuriu, Takeshi Kameyama, Muneaki Miyata, Shin Kedashiro, Kimitaka Katanazaka, Shota Nishii, Norio Chihara, Riki Matsumoto, Michinori Koebis, Atsu Aiba, Kiyohito Mizutani, Yoshimi Takai
TL;DR
Necl-4/CADM4 helps regulate GABAergic synapses on inhibitory neurons through ErbB4 activation, preventing neuronal damage and death.
Contribution
Necl-4/CADM4's role in regulating GABAergic synaptic strength and preventing neuronal impairments is newly identified.
Findings
Necl-4 is expressed in GABAergic inhibitory neurons and localizes at their synapses.
Necl-4 genetic ablation increases GABAergic synapse density and synaptic molecules via ErbB4 activation.
Necl-4 deficiency leads to excitotoxicity and neuronal death in hippocampal cultures.
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 showed an increase in GABAergic synapse density on inhibitory neurons and in synaptic molecules at…
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Taxonomy
TopicsNeuroscience and Neuropharmacology Research · Neurogenesis and neuroplasticity mechanisms · Receptor Mechanisms and Signaling