Retrograde signalling with nitric oxide at neocortical synapses

Long-term changes of synaptic transmission in slices of rat visual cortex w ere induced by intracellular tetanization: bursts of short depolarizing pul ses applied through the intracellular electrode without concomitant presyna ptic stimulation. Long-term synaptic changes after this purely postsynaptic induction were associated with alterations of release indices, thus provid ing a case for retrograde signalling at neocortical synapses. Both long-ter m potentiation and long-term depression were accompanied by presynaptic cha nges, indicating that retrograde signalling can achieve both up- and down-r egulation of transmitter release. The direction and the magnitude of the am plitude changes induced by a prolonged intracellular tetanization depended on the initial properties of the input. The inputs with initially high pair ed-pulse facilitation (PPF) ratio, indicative of low release probability, w ere most often potentiated. The inputs with initially low PPF ratio, indica tive of high release probability, were usually depressed or did not change. Thus, prolonged postsynaptic activity can lead to normalization of the wei ghts of nonactivated synapses. The dependence of polarity of synaptic modif ications on initial PPF disappeared when plastic changes were induced with a shorter intracellular tetanization, or when the NO signalling pathway was interrupted by inhibition of NO synthase activity or by application of NO scavengers. This indicates that the NO-dependent retrograde signalling syst em has a relatively high activation threshold. Long-term synaptic modificat ions, induced by a weak postsynaptic challenge or under blockade of NO sign alling, were nevertheless associated with presynaptic changes. This suggest s the existence of another retrograde signalling system, additional to the high threshold, NO-dependent system. Therefore, our data provide a clear ca se for retrograde signalling at neocortical synapses and indicate that mult iple retrograde signalling systems, part of which are NO-dependent, are inv olved.