Short-term potentiation of miniature excitatory synaptic currents causes excitation of supraoptic neurons

Magnocellular neurons (MCNs) of the hypothalamic supraoptic nucleus (SON) s ecrete vasopressin and oxytocin. With the use of whole-cell and nystatin-pe rforated patch recordings of MCNs in current- and voltage-clamp modes, we s how that high-frequency stimulation (HFS, 10-200 Hz) of excitatory afferent s induces increases in the frequency and amplitude of 2,3-dioxo-6-nitro-1,2 ,3,4-tetrahydrobenzo(f)quinoxaline-7-sulfonamide (NBQX)-sensitive miniature excitatory postsynaptic currents (mEPSCs) lasting up to 20 min. This synap tic enhancement, referred to as short-term potentiation (STP), could be ind uced repeatedly; required tetrodotoxin (TTX)-dependent action potentials to initiate, but not to maintain; and was independent of postsynaptic membran e potential, N-methyl-D-aspartate (NMDA) receptors. or retrograde neurohypo physeal neuropeptide release. STP was nor accompanied by changes in the con ductance of the MCNs or in the responsiveness of the postsynaptic non-NMDA receptors, as revealed by brief application of alpha-amino3-hydroxy-5-methy l-4-isoxazolepropionic acid (AMPA) and kainate. mEPSCs showed similar rise times before and after HFS and analysis of amplitude distributions of mEPSC s revealed one or more peaks pre-HFS and the appearance of additional peaks post-HFS. which were equidistant from the first peak. STP of mEPSCs was no t associated with enhanced evoked responses, but was associated with an NBQ X-sensitive increase in spontaneous activity of MCNs. Thus we have identifi ed a particularly long-lasting potentiation of excitatory synapses in the S ON, which has a presynaptic locus, is dissociated from changes in evoked re lease, and which regulates postsynaptic cell excitability.