Long-term depression in the developing hippocampus: low induction threshold and synapse nonspecificity.

It was observed that the use of paired-pulse afferent stimulation as test stimulation (0.1-0.02 Hz) in the hippocampal CA1 area in young (1-2 week) rats, but not in older ones, led to declining synaptic activity. We show that such very low-frequency stimulation leads to long-term depression (LTD) initiated by activation of NMDA receptor channels and/or T-type voltage-dependent calcium channels. The depression is initiated within three or four such stimuli, and <10 are sufficient to induce a notable long-term effect. When the paired-pulse stimulation exceeded threshold for postsynaptic spike activation, the depression was preceded by an NMDA receptor-dependent potentiation. Irrespective of whether homosynaptic potentiation or depression occurred, the paired pulse stimulation also induced depression in neighboring synapses alternately activated by single stimuli. These results point to a very high sensitivity for induction of synaptic depression during the neonatal period. They also support the notion that a brief rise in postsynaptic calcium can induce long-term potentiation (LTP) or LTD, a larger rise more likely to induce LTP, as well as that a prolonged modest increase produces selectively only LTD.