UC San Diego

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 pre- and 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 timing-dependent LTD (t- LTD) that has mechanisms that differ from those classically described in hippocampus. It does not require postsynaptic NMDA receptors but instead requires voltage- gated 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