Phosphorylation Signals in Striatal Medium Spiny Neurons

Trends Pharmacol Sci. 2016 Oct;37(10):858-871. doi: 10.1016/j.tips.2016.07.003. Epub 2016 Aug 18.

Abstract

Dopamine signaling in the brain is a complex phenomenon that strongly contributes to emotional behaviors. Medium spiny neurons (MSNs) play a major role in dopamine signaling through dopamine D1 receptors (D1Rs) or dopamine D2 receptors (D2Rs) in the striatum. cAMP/protein kinase A (PKA) regulates phosphorylation signals downstream of D1Rs, which affects the excitability of MSNs, leading to reward-associated emotional expression and memory formation. A combination of phosphoproteomic approaches and the curated KANPHOS database can be used to elucidate the physiological and pathophysiological functions of dopamine signaling and other monoamines. Emerging evidence from these techniques suggests that the Rap1 pathway plays a crucial role in the excitability of MSNs, leading to the expression of emotional behaviors.

Keywords: database; dopamine; excitability; phosphoproteomics; protein kinase A; reward-associated behaviors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Emotions / physiology*
  • Humans
  • Memory / physiology
  • Neurons / metabolism*
  • Phosphorylation / physiology
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Reward
  • Signal Transduction / physiology

Substances

  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Dopamine