GABA-induced potentiation of neuronal excitability occurs during contiguous pairings with intracellular calcium elevation

The temporal convergence of neuronal signals is commonly considered as a likely prerequisite for enhanced neuronal excitability underlying the induction of associative memories. Here we report that transmitter application on presynaptic terminals of the Hermissenda Type B photoreceptors, when paired with depolarization, results in a potentiation of the excitability of the B-cell which derives from an increase in input resistance across the B-cell soma membrane. Pressure microapplication of γ-aminobutyric acid (GABA) (12.5 μM) on the terminal branches of the Hermissenda Type B photoreceptors results in the fast (< 1 s) activation of an inward Cl^- conductance, characterized by a decrease in neuronal membrane resistance and an accompanying hyperpolarization (3-6 mV) of the B-cell. A slower effect of GABA, characterized by a slight depolarization (2-4 mV) and increase in resistance was observed approximately 2 min after GABA application. Following bath application of the Cl^- channel blocker picrotoxin (100 μM), this increase in resistance was observed within 20 s of GABA application, suggesting that it was normally masked by the faster Cl^- conductance. The magnitude of the resistance increase in response to GABA was enhanced when the B-cell was held at depolarized membrane potentials (-40 to -20 mV), but was eliminated if Ca²⁺ was removed from the extracellular bath, or if the non-specific protein kinase inhibitor H7 (100 μM) was added to the extracellular bath. In a final experiment, GABA application was paired with a transient (10 s) depolarization of the B-cell (to -20 mV). No initial effect of this pairing (at 30 s) could be detected, although an increase in resistance in the B-cell was observed after 5 min and persisted for at least 10 min. This persistent increase in resistance was not observed in response to GABA application without depolarization or in response to depolarization without GABA application. These findings suggest a mechanism whereby enhanced excitability of single neurons may result from converging neuronal signals (i.e. transmitter application and postsynaptic depolarization), and share many similarities with mechanisms underlying long-term potentiation, particularly like that seen in hippocampal mossy fiber synapses in the mammalian brain.