Endocannabinoid signaling and long-term synaptic plasticity

Boris D. Heifets, Pablo E. Castillo

Research output: Contribution to journalReview articlepeer-review

381 Scopus citations


Endocannabinoids (eCBs) are key activity-dependent signals regulating synaptic transmission throughout the central nervous system. Accordingly, eCBs are involved in neural functions ranging from feeding homeostasis to cognition. There is great interest in understanding how exogenous (e.g., cannabis) and endogenous cannabinoids affect behavior. Because behavioral adaptations are widely considered to rely on changes in synaptic strength, the prevalence of eCB-mediated longterm depression (eCB-LTD) at synapses throughout the brain merits close attention. The induction and expression of eCB-LTD, although remarkably similar at various synapses, are controlled by an array of regulatory influences that we are just beginning to uncover. This complexity endows eCB-LTD with important computational properties, such as coincidence detection and input specificity, critical for higher CNS functions like learning and memory. In this article, we review the major molecular and cellular mechanisms underlying eCB-LTD, as well as the potential physiological relevance of this widespread form of synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)283-306
Number of pages24
JournalAnnual review of physiology
StatePublished - Mar 2009


  • CB1
  • Cannabinoid
  • Drug addiction
  • LTD
  • LTP
  • Learning
  • Parkinson's disease
  • STDP
  • Synaptic transmission

ASJC Scopus subject areas

  • Physiology


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