Figure 1.

Neurotransmitter and receptor roles in striatal LTP and LTD. A) Diagram showing types of long-term synaptic plasticity at glutamatergic striatal synapses, and the general paradigm for inducing plasticity and examining effects of pharmacological treatments. The white bar indicates time periods during which pharmacological agents can be given to modify induction or expression of LTP or LTD. B) Schematic diagram of mechanisms thought to be involved in striatal LTP. Induction of LTP involves activation of NMDARs, along with either D1 or A2A receptor activation in direct and indirect pathway neurons, respectively. Increases in intracellular calcium trigger biochemical changes, possibly including activation of the calmodulin-dependent protein kinase type II (CAMKIIa). The GPCRs stimulate adenylyl cyclase activity and phosphorylation of DARPP-32 (not shown), but the mechanisms of linking these signaling pathways to LTP expression are not yet known. Expression of LTP is thought to involve AMPAR insertion at the synapse. C) Schematic diagram of mechanisms involved in striatal LTD. Postsynaptic depolarization activates Cav1.3-type voltage-gated calcium channels, while glutamate activates group I mGluRs. The calcium and metabotropic signals converege to stimulate endocannabinoid (EC) synthesis and release. The EC acts on presynaptic CB1 receptors. Combined CB1 activation and presynaptic activity produces a long-lasting decrease in presynaptic release probability (possibly through decreased calcium channel function or more direct effects on vesicle fusion). Arrowheads indicate stimulation, while circular line endings indicate inhibition. D) Listing of neurotransmitter receptor subtypes implicated in LTP and LTD induction. Note that these receptors do not appear to be necessary for maintenance of LTP or LTD once plasticity has been induced.