Cannabinoid receptor suppresses long-term depression in the neonatal brain for consolidation of neuronal circuits for spatial cognition

Abstract

Reduction in the efficacy of induction of long-term depression (LTD) of inhibitory transmission has emerged as a key feature of circuit consolidation. We demonstrate that the endocannabinoid (eCB) system facilitates induction of long-term depression (LTD) of inhibitory transmission in the vestibular nucleus (VN). We found downregulation of cannabinoid receptor type I (CB1R) accompanies developmental decrease of LTD induction efficacy from 70% at P5-7 to 20% after P9. This coincides with emergence of graviceptive negative geotaxis reflex at P9. Blockade of CB1R in the neonatal critical period for VN development decreased LTD induction efficacy to 40% and accelerated emergence of graviceptive reflex from P9 to P7, while activation of CB1R delayed it to P13. Furthermore, chronic activation of CB1R in rats during the neonatal stage precluded development of navigational skills in the adult. These findings highlight eCB as an important regulator of GABAergic transmission efficacy in the VN via the modulation of LTD and regulates developmental consolidation of vestibular circuitry. The results further suggest that adolescent exposure to cannabinoids may have a permanent detrimental effect on the development of brain circuits.