Evidence for common expression mechanisms underlying heterosynaptic and associative long-term depression in the dentate gyrus.

1. The extent to which heterosynaptic and prime-associative stimulation protocols generate different forms of long-term depression (LTD) was assessed in the lateral perforant path synapses terminating on dentate gyrus granule cells in pentobarbital-anesthetized rats. 2. Heterosynaptic LTD was induced in the lateral path by repeated tetanization of the medial path. Prime-associative LTD of the lateral path was induced by alternating high-frequency conditioning trains to the medial path and single shocks to the lateral path at 100-ms intervals, all occurring 10 min after priming stimulation of the lateral path (5 Hz, 80 pulses). 3. Induction of LTD by one administration of the prime-associative protocol was normally greater in magnitude than the LTD induced by the heterosynaptic protocol. Saturation of LTD by repeated delivery of the prime-associative protocol completely occluded the subsequent induction of LTD by the heterosynaptic protocol. Saturation of LTD by repeated delivery of the heterosynaptic protocol produced an 80% occlusion of the LTD generated by the prime-associative protocol. 4. These data support the hypothesis that activity-dependent (associative) and activity-independent (heterosynaptic) LTD involve overlapping expression mechanisms, despite having demonstrably different induction mechanisms.