Neuromodulator regulation and emotions: insights from the crosstalk of cell signaling

Front Mol Neurosci. 2024 Mar 7:17:1376762. doi: 10.3389/fnmol.2024.1376762. eCollection 2024.

Abstract

The unraveling of the regulatory mechanisms that govern neuronal excitability is a major challenge for neuroscientists worldwide. Neurotransmitters play a critical role in maintaining the balance between excitatory and inhibitory activity in the brain. The balance controls cognitive functions and emotional responses. Glutamate and γ-aminobutyric acid (GABA) are the primary excitatory and inhibitory neurotransmitters of the brain, respectively. Disruptions in the balance between excitatory and inhibitory transmission are implicated in several psychiatric disorders, including anxiety disorders, depression, and schizophrenia. Neuromodulators such as dopamine and acetylcholine control cognition and emotion by regulating the excitatory/inhibitory balance initiated by glutamate and GABA. Dopamine is closely associated with reward-related behaviors, while acetylcholine plays a role in aversive and attentional behaviors. Although the physiological roles of neuromodulators have been extensively studied neuroanatomically and electrophysiologically, few researchers have explored the interplay between neuronal excitability and cell signaling and the resulting impact on emotion regulation. This review provides an in-depth understanding of "cell signaling crosstalk" in the context of neuronal excitability and emotion regulation. It also anticipates that the next generation of neurochemical analyses, facilitated by integrated phosphorylation studies, will shed more light on this topic.

Keywords: KiOSS; cell signaling; emotional behavior; neuromodulator; protein database.

Publication types

  • Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the following funding sources: AMED grant numbers: JP21dm0207075 (KK), JP21wm0425017 (TN and JY), and JP23wm0425008 (DT and JY); JSPS KAKENHI grant number JP17H01380 (KK) and JP21K06427 (DT); MEXT KAKENHI grant numbers; the Uehara Memorial Foundation (KK); the Takeda Science Foundation (KK); and the Hori Sciences and Arts Foundation (DT).