Long-term Potentiation at Temporoammonic Path-CA1 Synapses in Freely Moving Rats.

Jossina Gonzalez,Brian E Derrick,Desiree M Villarreal,Isaiah S Morales

doi:10.3389/fncir.2016.00002

Abstract

Hippocampal area CA1 receives direct entorhinal layer III input via the temporoammonic path (TAP) and recent studies implicate TAP-CA1 synapses are important for some aspects of hippocampal memory function. Nonetheless, as few studies have examined TAP-CA1 synaptic plasticity in vivo, the induction and longevity of TAP-CA1 long-term potentiation (LTP) has not been fully characterized. We analyzed CA1 responses following stimulation of the medial aspect of the angular bundle and investigated LTP at medial temporoammonic path (mTAP)-CA1 synapses in freely moving rats. We demonstrate monosynaptic mTAP-CA1 responses can be isolated in vivo as evidenced by observations of independent current sinks in the stratum lacunosum moleculare of both areas CA1 and CA3 following angular bundle stimulation. Contrasting prior indications that TAP input rarely elicits CA1 discharge, we observed mTAP-CA1 responses that appeared to contain putative population spikes in 40% of our behaving animals. Theta burst high frequency stimulation of mTAP afferents resulted in an input specific and N-methyl-D-aspartate (NMDA) receptor-dependent LTP of mTAP-CA1 responses in behaving animals. LTP of mTAP-CA1 responses decayed as a function of two exponential decay curves with time constants (τ) of 2.7 and 148 days to decay 63.2% of maximal LTP. In contrast, mTAP-CA1 population spike potentiation longevity demonstrated a τ of 9.6 days. To our knowledge, these studies provide the first description of mTAP-CA1 LTP longevity in vivo. These data indicate TAP input to area CA1 is a physiologically relevant afferent system that displays robust synaptic plasticity.

Highlights

Hippocampal memory function is thought to involve the relay of entorhinal layer II perforant path (PP) input to the dentate gyrus (DG) and the subsequent activation of the hippocampal ‘‘tri-synaptic loop’’ (Andersen et al, 1966, 1971a)
Both negative-going and positive-going temporoammonic path (TAP)-CA1 field excitatory postsynaptic potentials (EPSPs) were respectively examined via local field recordings in dendritic and somatic regions of an intact hippocampal formation, allowing evaluations of responses evoked near the site of synaptic activation and TAP-CA1 putative population spikes, respectively
CA3 sinks and field EPSP peak latency evoked by perforant path afferents occurred approximately 0.5–1 ms earlier than CA1 sinks and field EPSP peak latency produced by TAP afferents, suggesting distal dendritic CA3 and CA1 sinks are locally generated via independent afferent fibers originating from medial entorhinal cortex layer II stellate cells or layer III pyramidal cells (Steward and Scoville, 1976)

Summary

Introduction

Hippocampal memory function is thought to involve the relay of entorhinal layer II perforant path (PP) input to the dentate gyrus (DG) and the subsequent activation of the hippocampal ‘‘tri-synaptic loop’’ (Andersen et al, 1966, 1971a). As LTP exhibits longevity and input specificity, this form of synaptic plasticity may represent a mechanism for memory storage and learning (Bliss and Gardner-Medwin, 1973; Bliss and Lømo, 1973; Teyler and Discenna, 1984; Bliss and Collingridge, 1993; Martinez and Derrick, 1996). Despite increasing evidence TAP-CA1 synapses are involved in some forms of memory, previous observations of TAP-CA1 LTP largely reflect in vitro investigations (Doller and Weight, 1985; Colbert and Levy, 1993; Dvorak-Carbone and Schuman, 1999b; Remondes and Schuman, 2002, 2003) that were unable to characterize LTP induction and longevity at specific medial or lateral TAP-CA1 synapses

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Conclusion