29. Postsynaptic activity-dependent modulation of unitary IPSPs by specific presynaptic cannabinoid receptors in rat neocortex

Claire De-May claire.de-may@pharmacy.ac.uk Marina Todorova marina.todorova@pharmacy.ac.uk Afia Ali afia.ali@pharmacy.ac.uk

Department of Pharmacology, School of Pharmacy, University of London, UK

Endogenous cannabinoids (CB) can serve as retrograde modulators and their receptors are expressed in a subset of neocortical interneurones. The aim of the present study was to investigate the modulation of inhibition by CB receptors in two populations of interneurones. Dual whole-cell recordings combined with biocytin labelling were performed in acute slices of rat neocortex (postnatal day 17-22). Layer II/III accommodating multipolar and bitufted interneurones were recorded simultaneously with postsynaptic pyramidal cells. The axons of multipolar interneurones projected horizontally within layer II/III, while the axons of bitufted interneurones were more vertically oriented, spanning layers V to I. Unitary IPSPs elicited in postsynaptic pyramidal cells by multipolar and bitufted interneurones were reduced by the CB receptor agonist anandamide. Depolarisation-induced suppression of inhibition (DSI) was evident in the IPSPs activated by both proximally targeting multipolar and dendrite-preferring bitufted interneurones. Unitary IPSP amplitudes were reduced by approximately 50% compared with control recordings in both populations, accompanied by an increase in the proportion of apparent failures of transmission. Following addition of the selective CB1 receptor antagonist AM-251, these effects were blocked in the multipolar interneurones; however bitufted cell IPSPs remained depressed. We propose that another type of CB receptor is involved here. Our data suggest postsynaptic activity-dependent interneurone-specific and selective insertion of presynaptic CB receptors that differentially modulate inhibition in layer II/III of the neocortex.