Cell - type specific regulation of inhibition via cannabinoid type 1 receptors in rat 1 neocortex

27 Endogenous cannabinoid type-1 (CB1) receptors demonstrate a cell-type specific expression and are 28 potent modulators of synaptic transmission within the CNS. We aimed to investigate whether two 29 classes of multipolar interneuron in the neocortex displayed a form of short-term synaptic plasticity 30 – depolarization induced suppression of inhibition (DSI), and whether the DSI was mediated by a 31 common receptor. Paired whole-cell recordings combined with biocytin labelling were performed 32 between pyramidal cells and either multipolar adapting or multipolar non-adapting interneurons in 33 layers II–IV of male Wistar rat (P17–22) somatosensory cortex. IPSPs elicited by multipolar adapting 34 interneurons were sensitive to DSI, which was blocked by CB1 receptor antagonist, AM-251 (8 μM), 35 indicating that the suppression of inhibition was mediated by CB1 receptors. Two subpopulations of 36 multipolar non-adapting to pyramidal cell connections were discovered based on their susceptibility 37 to DSI. Whilst 50% were insensitive to DSI, the remaining half was sensitive to DSI, which could not 38 be prevented by AM-251. DSI at these connections was also insensitive to the group I (mGluR1a) 39 and III metabotropic glutamate receptor antagonists AIDA (100 μM) and CPPG (100 μM), and group 40 III agonist L-AP4 (50 μM). However, multipolar-non-adapting interneurons to pyramidal cell 41 connections were sensitive to endocannabinoid, anandamide (9 μM), that mimicked the effects of 42 DSI which also could not be prevented by AM-251, implying a CB1 receptor independent suppression 43 of inhibition. These results reveal an interneuron type specific modulation of synaptic transmission 44 via CB receptors in the neocortex. 45 46 47 48 49 50 51 52