Journal
CEREBRAL CORTEX
Volume 28, Issue 7, Pages 2253-2266Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhx126
Keywords
cannabinoid receptor 1; lateral perforant path; long-term potentiation; Munc18-1; pregnenolone
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Funding
- National Institutes of Health [NS085709, P01NS045260, HD08949101, MH096847, MH108408, NS064079, DA012413, DA031387]
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH108408] Funding Source: NIH RePORTER
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Endocannabinoids (ECBs) depress transmitter release at sites throughout the brain. Here, we describe another form of ECB signaling that triggers a novel form of long-term potentiation (LTP) localized to the lateral perforant path (LPP) which conveys semantic information from cortex to hippocampus. Two cannabinoid CB1 receptor (CB1R) signaling cascades were identified in hippocampus. The first is pregnenolone sensitive, targets vesicular protein Munc18-1 and depresses transmitter release; this cascade is engaged by CB(1)Rs in Schaffer-Commissural afferents to CA(1) but not in the LPP, and it does not contribute to LTP. The second cascade is pregnenolone insensitive and LPP specific; it entails co-operative CB1R/beta 1-integrin signaling to effect synaptic potentiation via stable enhancement of transmitter release. The latter cascade is engaged during LPP-dependent learning. These results link atypical ECB signaling to the encoding of a fundamental component of episodic memory and suggest a novel route whereby endogenous and exogenous cannabinoids affect cognition.
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