Microglial P2Y12 receptor regulates ventral hippocampal CA1 neuronal excitability and innate fear in mice

Jiyun Peng, Yong Liu, Anthony D. Umpierre, Manling Xie, Dai Shi Tian, Jason R. Richardson, Long Jun Wu

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


The P2Y12 receptor (P2Y12R) is a purinoceptor that is selectively expressed in microglia in the central nervous system. As a signature receptor, microglial P2Y12R mediates process chemotaxis towards ADP/ATP gradients and is engaged in several neurological diseases including chronic pain, stroke and seizures. However, the role of microglial P2Y12R in regulating neuronal excitability and innate behaviors is not fully understood. Here, we generated P2Y12-floxed mice to delete microglial P2Y12R beginning in development (CX3CR1Cre/+:P2Y12f/f; "constitutive knockout"), or after normal development in adult mice (CX3CR1CreER/+:P2Y12f/f; "induced knockout"). Using a battery of behavioral tests, we found that both constitutive and induced P2Y12R knockout mice exhibited innate fear but not learned fear behaviors. After mice were exposed to the elevated plus maze, the c-fos expression in ventral hippocampus CA1 neurons was robustly increased in P2Y12R knockout mice compared with wild-type mice. Consistently, using whole cell patch clamp recording, we found the excitability of ventral hippocampus CA1 neurons was increased in the P2Y12R knockout mice. The results suggest that microglial P2Y12R regulates neuronal excitability and innate fear behaviors in developing and adult mice.

Original languageEnglish (US)
Article number71
JournalMolecular brain
Issue number1
StatePublished - Aug 19 2019


  • Anxiety
  • Conditional knockout
  • Hippocampus
  • Innate fear
  • Microglia
  • P2Y12 receptors

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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