Multiple forms of long-term synaptic plasticity at hippocampal mossy fiber synapses on interneurons

The hippocampal mossy fiber (MF) pathway originates from the dentate gyrus granule cells and provides a powerful excitatory synaptic drive to neurons in the dentate gyrus hilus and area CA3. Much of the early work on the MF pathway focused on its electrophysiological properties, and ability to drive CA3 pyramidal cell activity. Over the last ten years, however, a new focus on the synaptic interaction between granule cells and inhibitory interneurons has emerged. These data have revealed an immense heterogeneity of long-term plasticity at MF synapses on various interneuron targets. Interestingly, these studies also indicate that the mechanisms of MF long-term plasticity in some interneuron subtypes may be more similar to pyramidal cells than previously appreciated. In this review, we first define the synapse types at each of the interneuron targets based on the receptors present. We then describe the different forms of long-term plasticity observed, and the mechanisms underlying each form as they are currently understood. Finally we highlight various open questions surrounding MF long-term plasticity in interneurons, focusing specifically on the induction and maintenance of LTP, and what the functional impact of persistent changes in efficacy at MF–interneuron synapses might be on the emergent properties of the inhibitory network dynamics in area CA3.This article is part of a Special Issue entitled ‘Synaptic Plasticity & Interneurons’.

Research highlights
► Hippocampal mossy fibers provide synaptic excitation to dentate gyrus and area CA3.
► Mossy fiber synapses are more numerous on interneurons than on pyramidal cells.
► Mossy fiber synaptic plasticity on interneurons is target-cell specific.
► Depending on the interneuron subtype, mossy fiber synapses express LTP and/or LTP.
► Future research directions in mossy fiber plasticity on interneurons are outlined.