Spatial overlap between populations of synapses determines the extent of their associative interaction during the induction of long-term potentiation and depression

Abstract

1. This study evaluates the associative interactions between inputs that lead to long-term potentiation (LTP) and long-term depression (LTD) in the dentate gyrus (DG). Previous studies have revealed that when two inputs are coconditioned, the extent of LTP is greater than when each input is conditioned alone. Moreover, for a weak input that does not show LTP when conditioned alone, LTP can be induced in that weak input if it is coconditioned with a strong input. LTD results when one input is silent when another is conditioned. In the present study, we evaluate whether these associative interactions depend on the extent of overlap of the terminal fields of the different inputs. 2. The experiment took advantage of the topographical organization of the temporodentate pathway from the entorhinal cortex (EC) to the DG. Four stimulating electrodes were placed so as to activate ipsilateral and crossed components of the projections from medial and lateral portions of the EC. Recording electrodes were positioned unilaterally in the DG so as to record field potentials. The localization of the synaptic field that was activated by each electrode was determined by current source density (CSD) analysis. The extent of overlap between the terminal fields of ipsi- and contralateral pathways was assessed, and the pathways were divided into groups where the overlap between current sinks was 0-50 or 51-100%. 3. Conditioning stimulation (400-Hz trains of 8 pulses delivered 8 times) was delivered to pathways alone or in combination with other pathways. The extent of LTP was evaluated after coactivation of pathways that overlapped substantially (51-100%) or minimally (0-50%). The extent of LTD was evaluated in pathways that were silent during conditioning of other overlapping or nonoverlapping pathways. 4. The extent of associative LTP or LTD depended on the extent of overlap between the terminal fields of pathways. Coactivation of two pathways that overlapped by 51-100% led to LTP; coactivation of pathways that overlapped by 0-50% did not. Moreover, LTD was induced in a crossed pathway when an ipsilateral pathway that overlapped by 51-100% was activated, but not when a nonoverlapping (0-50% overlap) ipsilateral pathway was activated. The degree of associative LTP or LTD that was induced in crossed pathways was correlated with the percent overlap with the terminal field of the active ipsilateral pathway. 5. Evaluation of whether LTD was induced when one division (medial or lateral) of the ipsilateral pathway was silent when the other division was conditioned revealed similar relationships.(ABSTRACT TRUNCATED AT 400 WORDS)