Presynaptic inhibition produced by an identified presynaptic inhibitory neuron. I. Physiological mechanisms.

We have examined the synaptic conductance mechanisms underlying presynaptic inhibition in Aplysia californica in a circuit in which all the neural elements are identified cells (Fig. 1). L10 makes connections to identified follower cells (RB and left upper quadrant cells, L2-L6). These connections are presynaptically inhibited by stimulating cells of the L32 cluster (4). L32 cells produce a slow inhibitory synaptic potential on L10. This inhibitory synaptic potential is associated with an apparent increased membrane conductance in L10. Both the inhibitory postsynaptic potential (IPSP) and the conductance increase are voltage dependent; the IPSP could not be reversed by hyperpolarizing the membrane potentials to - 120 mV. The hyperpolarization of L10 induced by L32 reduces the transmitter output of L10 and thereby contributes to presynaptic inhibition. However, this hyperpolarization accounts for about 30% of the effect because presynaptic inhibition can still be observed even when the hyperpolarization of L10 by L32 is prevented by voltage clamping. When L10 is voltage clamped, stimulation of L32 produces a slow outward synaptic current associated with an apparent increased conductance. Both the synaptic current and conductance change measured under clamp are voltage dependent, and the outward current could not be reversed. This synaptic current is not mediated by an increase in C1- conductance. It is sensitive to external K+ concentration, especially at hyperpolarized membrane potentials. With L10 under voltage clamp, stimulation of L32 also reduces a slow inward current in L10. This current has time and voltage characteristics similar to those of the Ca2+ current. Presynaptic inhibition is still produced by L32 when L10 is voltage clamped, and transmitter release is elicited by depolarizing voltage-clamp pulses. This component of presynaptic inhibition, which accounts for approximately 70% of the inhibition, appears to be due to a decrease in the Ca2+ current in the presynaptic neuron.