Endocannabinoids in synaptic plasticity and neuroprotection

Jian Yi Xu, Chu Chen

Research output: Contribution to journalReview articlepeer-review

92 Scopus citations

Abstract

Endocannabinoids (eCBs) are endogenous lipid mediators involved in a variety of physiological, pharmacological, and pathological processes. While activation of the eCB system primarily induces inhibitory effects on both GABAergic and glutamatergic synaptic transmission and plasticity through acting on presynaptically expressed CB1 receptors in the brain, accumulated information suggests that eCB signaling is also capable of facilitating or potentiating excitatory synaptic transmission in the hippocampus. Recent studies show that a long-lasting potentiation of excitatory synaptic transmission at Schaffer collateral (SC)-CA1 synapses is induced by spatiotemporally primed inputs, accompanying with a long-term depression of inhibitory synaptic transmission (I-LTD) in hippocampal CA1 pyramidal neurons. This input timing-dependent long-lasting synaptic potentiation at SC-CA1 synapses is mediated by 2-arachidonoylglycerol (2-AG) signaling triggered by activation of postsynaptic N-methyl-d-aspartate receptors, group I metabotropic glutamate receptors (mGluRs), and a concurrent rise in intracellular Ca2+. Emerging evidence now also indicates that 2-AG is an important signaling mediator keeping brain homeostasis by exerting its anti-inflammatory and neuroprotective effects in response to harmful insults through CB1/2 receptor-dependent and/or -independent mechanisms. Activation of the nuclear receptor protein peroxisome proliferator-activated receptor apparently is one of the important mechanisms in resolving neuroinflammation and protecting neurons produced by 2-AG signaling. Thus, the information summarized in this review suggests that the role of eCB signaling in maintaining integrity of brain function is greater than what we thought previously.

Original languageEnglish (US)
Pages (from-to)152-168
Number of pages17
JournalNeuroscientist
Volume21
Issue number2
DOIs
StatePublished - Apr 19 2015
Externally publishedYes

Keywords

  • Alzheimer's disease
  • PPAR
  • chronic traumatic encephalopathy
  • input timing-dependent plasticity
  • long-term depression of inhibitory synaptic transmission
  • monoacylglycerol lipase

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology

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