Postnatal development of retrograde endocannabinoid modulation of inhibitory transmission in monkey prefrontal cortex

GONZALEZ-BURGOS G; YOSHINO H; MIYAMAE T; PAFUNDO DE; ROTARU D; LEWIS DA

San Diego, CA

Congreso; 40th annual meeting of the Society for Neuroscience; 2010

Society for Neuroscience

Endocannabinoid (eCB) retrograde modulation of synaptic transmission in dorsolateral prefrontal cortex (DLPFC) may be critical for cognition. Despite its functional relevance, the postnatal development of eCB retrograde modulation remains largely unexplored. Because the eCB system is the primary target of exogenous cannabinoids, developmental changes in the strength of eCB modulation may determine an age-dependent sensitivity of neocortical circuits to cannabis abuse. Importantly, heavy cannabis use during adolescence is a risk factor for schizophrenia and drug addiction. We examined the postnatal development of the eCB system in primate DLPFC, studying depolarization-induced suppression of inhibition (DSI) in layer 3 pyramidal neurons of macaque monkey DLPFC. IPSCs were evoked at 0.2 Hz by focal extracellular stimulation applied near the soma of the recorded neurons after adding agatoxin IVA (250 nM, a P/Q type Ca2+ channel blocker) to minimize eCB-insensitive GABA release. We induced DSI applying depolarizing steps (4 s, -80 to 0 mV) to pyramidal cells in slices from neonatal (1 month-old, two animals), pre-adolescent (12 month-old), adolescent (34 and 35 month old) and adult (74 month-old) animals. In experiments in which significant DSI was induced (residual IPSC: 33.7 ± 4.7 %), subsequent application of the eCB Receptor 1 (CB1R) antagonist SR141617A (10 µM) significantly attenuated DSI (residual IPSC: 83.7 ± 3.9 %, p < 0.05), showing that DSI in monkey DLPFC requires CB1R activation. A One-Way ANOVA analysis showed a significant effect of age group on the magnitude of DSI in DLPFC (F = 3.115, p