De-May, Claire L.; (2011) Properties of connections made and received by neocortical GABAergic interneurons: Modulation of neurotransmission via cannabinoids and nmda receptors. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Interneurons are a highly diverse population of cell that mediate inhibition within the neocortex, while a relatively uniform population - pyramidal cells - provide excitation. The modulation of neurotransmission between subtypes of interneuron and pyramidal cells by cannabinoids and NMDA receptors was investigated. Dual whole-cell recordings from interneurons and pyramidal cells were obtained from layers II-V of rat (postnatal days 17-22) sensorimotor cortex. During recording, neurons were filled with biocytin for subsequent histological processing to recover the neuroanatomy of recorded cells, allowing for reconstruction and analysis. At excitatory connections, the response in amplitude of EPSPs received by interneurons as a reaction to changes in the holding potential of the postsynaptic cell seemed to coincide with the type of interneuron. NMDA receptors appeared to contribute to EPSPs received by all cell types. Connections from interneurons to pyramidal cells either underwent a DSI protocol during control conditions and in the presence of the CB1 receptor inverse agonist/antagonist AM 251 (8 μM), or were recorded in the presence of the non-selective cannabinoid receptor agonist anandamide (9 μM), followed by AM 251. The reduction in average IPSP amplitude at connections sensitive to DSI was blocked by AM 251, indicating that the effects of DSI were mediated by the CB1 receptor. AM 251 significantly increased the average IPSP amplitude from control in half of the connections tested, suggesting that there is either a tonic activation of CB1 receptors or that they are constitutively active at these pairs. AM 251 did not increase the average IPSP amplitude in two thirds of anandamide sensitive connections, implying that the reduction in average IPSP amplitude was due to a CB1 receptor independent mechanism. To investigate as to whether CB2 receptors were involved in modulating GABAergic inhibition within the neocortex, spontaneous IPSPs were recorded from layer II/III pyramidal cells and challenged with cannabinoid receptor ligands. The results suggest that CB2 receptors modulate GABAA receptor mediated inhibition within the neocortex.

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