SR2-INDUCED SUPPRESSION OF INHIBITION AND PROVIDES NEW EVIDENCE FOR APRESYNAPTIC EXPRESSION MECHANISM IN RAT HIPPOCAMPAL SLICES( SUPPORTS DEPOLARIZATION)

1. We studied the transient suppression of evoked GABA(A)ergic inhibit ory postsynaptic currents (eIPSCs) that follows brief membrane depolar ization in rat CA1 hippocampal pyramidal cells, a process called depol arization-induced suppression of inhibition (DSI). We used whole-cell patch electrodes filled with a CsCl-based solution to voltage clamp th e currents. All experiments were done in the presence of 50 mu M 2-ami no-5-phosphonovaleric acid (APV) and 20 mu M 8-cyano-'7-nitroquinoxali ne-2,3-dione (CNQX) to block ionotropic glutamate-induced currents and polysynaptic transmission in the slice preparation. 0 2. Substituting strontium (Sr2+) for extracellular calcium (Ca2+) led to the appearan ce of numerous 'asynchronous' small IPSCs following an eIPSC. These as ynchronous IPSCs were indistinguishable from TTX-insensitive quantal I PSCs. 3. Although somewhat less effective than Ca2+, Sr2+ was capable of supporting DSI, and both asynchronous and synchronous IPSCs were bl ocked by the DSI process. 4. During DSI, quantal content of eIPSCs, bu t not quantal size, was significantly reduced. 5. Sr2+ converted paire d-pulse depression (PPD) of eIPSCs to a paired-pulse facilitation (PPF ), presumably br altering the probability of release at inhibitory ner ve terminals. DSI had no effect on either PPD or PPF. 6. The results s how that Sr2+ induces asynchronous release of GABA as it does of other neurotransmitters and changes the probability of release at GABA(A)er gic terminals as well. Most importantly, the results support the hypot hesis that, despite being induced postsynaptically, DSI is expressed p resynaptically as a decrease in GABA release, possibly by acting at a site other than the Ca2+-dependent release step.