A research group led by Professor Kozo Kaibuchi and Assistant Professor Yasuhiro Funahashi of Nagoya University has clarified the molecular mechanism of dopamine-related behavior / memory formation control that causes emotions such as "pleasure" and "motivation".
It is said that there are about 1,000 billion nerve cells in the human brain, and they form a complicated network (neural circuit) while being interconnected.Among them, one of the neural circuits called "reward system" is activated in response to a stimulus (reward stimulus) that brings fun and comfort.Then, emotions such as pleasure and motivation are triggered, and learning and memorizing as an experience.The main regulator involved in this is a neurotransmitter called dopamine.Dopamine acts on medium spiny neurons in the nucleus accumbens of the brain, causing intracellular changes at the molecular level and regulating cell function.It is also said to be related to the etiology and pathophysiology of psychiatric and neurological disorders such as schizophrenia and drug addiction.
The research group identified the transcription factor "Npas4" as a protein that binds to the multifunctional protein "CBP" involved in reward memory formation.We also found that dopamine activates the protein kinase "MAPK" in the cell to phosphorylate Npas4 and promote the binding between Npas4 and CBP.Furthermore, we found that phosphorylation of Npas4 promotes gene expression involved in neuronal synaptic plasticity and regulates reward-related behavior and memory formation in mice.
This time, it was revealed for the first time in the world that phosphorylation of Npas4 by MAPK is involved in reward-related behavior and memory.This result is expected to lead to the development of treatments for psychiatric and neurological disorders such as schizophrenia and drug addiction caused by dysfunction of the dopamine nervous system.
Paper information:[Cell Reports] Phosphorylation of Npas4 by MAPK regulates reward-related gene expression and behaviors
