Introduction to slow synaptic potentials and their neuromodulation by dopamine.

The existence of two muscarinically mediated slow postsynaptic potentials (PSPs) and a noncholinergic (peptidergic) late-slow PSP was established in the 1960s. These have synaptic delays and PSP durations 100-10,000 times those for the nicotinic (fast) excitatory post-synaptic potential (EPSP). Evidence is reviewed for an against the proposal that, in rabbit superior cervical ganglia, the slow (s-) inhibitory postsynaptic potential requires a second transmitter, dopamine, released by muscarinic action on interneurones (the small, intensely fluorescent cells). The s-EPSP in frog ganglia appears only in already depolarized cells by a muscarinic closure of the M (voltage-sensitive K+) channels. But the large s-EPSP in mammalian neurones, not depolarized, is generated largely via other mechanisms, especially one involving cyclic GMP. Dopamine also produces a long-term enhancement (LTE) of the muscarinic slow PSPs in rabbit superior cervical ganglia, whether dopamine is applied exogenously or released intraganglionically by preganglionic nerve impulses at 10 s-1. LTE is producible heterosynaptically, and it persists well over 3 h; a noncholinergic (peptide?) transmitter may contribute to the initial 30 min of LTE. LTE is mediated by a D1 receptor coupled to cyclic AMP; it is blocked by cyclic GMP or low Ca2+ or calmidazolium (a calmodulin inhibitor). The modulatory process of LTE has certain similarities to, but also fundamental differences from, the long-term potentiation known in the hippocampus.