Electronic Theses and Dissertations Uc San Diego Title: Cannabinoid-dependent Plasticity in Rodent Somatosensory Cortex Cannabiniod-dependent Plasticity in Rodent Somatosensory Cortex

Abstract: Cortical long-term depression (LTD) and long-term potentiation (LTP) are thought to be important mechanisms for the plasticity of topographic sensory maps, especially in rodent somatosensory (barrel) cortex. At the layer (L) 4 to L2/3 synapse in rat barrel cortex, LTP and LTD can be induced by spike timing-dependent plasticity (STDP) in which the precise, millisecond-scale timing of preand postsynaptic spikes drive LTP and LTD (Dan and Poo, 2004). The cellular mechanisms underlying STDP are unknown but widely debated (Karmarkar et al., 2002; Shouval et al., 2002; Johnston et al., 2003; Dan and Poo 2004). In chapter 2, we describe a form of spike timingdependent LTD (tLTD) that has mechanisms that differ from those classically described in hippocampus. It does not require postsynaptic NMDA receptors but instead requires voltagegated calcium channels, calcium release from IP3-sensitive stores, metabotropic glutamate receptor activation, and endogenous cannabinoid signaling. Endogenous cannabinoid signaling is an important mechanism for both short and long-term forms of plasticity in many areas of the brain (Wilson and Nicoll, 2002; Chevaleyre et al., 2006). The cannabinoid type 1 (CB1) receptor is widely expressed and it is thought that the endogenous cannabinoid system acts primarily through this receptor in the brain. However, there is some evidence that non-CB1 cannabinoid receptors also exist in the brain and could mediate some effects of endogenous cannabinoids (Breivogel et al., 2001; Hajos and Freund, 2002; Begg et al., 2005). In chapter 3, we examine a form of short-term plasticity at inhibitory synapses termed depolarization-induced suppression of inhibition, or DSI, and provide evidence that this phenomenon can be mediated by a novel, non-CB1 cannabinoid receptor in somatosensory cortex. In chapter 4, we further explore the cannabinoid dependence of t-LTD in a CB1 receptor knockout mouse. We show that in somatosensory cortex, a novel cannabinoid receptor can mediate t-LTD in the absence of the CB1 receptor