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

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.

Interaction of nucleus reuniens and entorhinal cortex projections in hippocampal field CA1 of the rat

“…However, at IPI 25 ms, EC-induced PPF was hardly noticeable (PPF 1.1 ± 0.2, n=4). These findings are in agreement with those reported in previous studies (Sloviter 1991;Leung et al 1995;Dolleman-van der Weel et al 1997;Eleore et al 2011;Ito and Schuman 2012;Gonzalez et al 2016). …”

Involvement of intracellular Zn2+ signaling in LTP at perforant pathway–CA1 pyramidal cell synapse

“…On the basis of recent establishment of in vivo perforant pathway LTP recording (Aksoy‐Aksel & Manahan‐Vaughan, ; Gonzalez, Villarreal, Morales, & Derrick, ), the role of synaptic Zn 2+ in perforant pathway LTP was examined by our original approach, in which a recording electrode attached to a microdialysis probe was used and the recording region was locally perfused with Zn 2+ chelators in ACSF via the microdialysis probe. Perforant pathway LTP was not attenuated under perfusion with CaEDTA (10 mM), but attenuated under perfusion with ZnAF‐2DA (50 μM), suggesting that intracellular Zn 2+ signaling is required for perforant pathway LTP as well as Schaffer collateral LTP (Takeda et al, ) (Figure ).…”

“…These results suggest that intracellular Zn 2+ signaling, which originates in internal stores/proteins, is involved in LTP at perforant pathway–CA1 pyramidal cell synapses (Figure ). Because perforant pathway LTP may be induced NMDA receptor‐dependently (Gonzalez et al, ), it is likely that NMDA receptor activation triggers off Zn 2+ release from internal stores. Stork and Li () report that Zn 2+ is released from thapsigargin/IP3‐sensitive stores in cultured cortical neurons.…”

Leptin Regulation of Synaptic Function at Hippocampal TA-CA1 and SC-CA1 Synapses: Implications for Health and Disease

“…Recent in vivo studies demonstrate that LTP that lasts in excess of 24 h can be evoked by tetanic stimulation in freely behaving rats [56,64]. Further investigation found that this form of in vivo LTP is dependent on NMDA receptor activation [64]. Moreover, in hippocampal slices (P30-50), stimulation of proximal TA inputs induces LTP at distal SC-CA1 synapses when the two inputs are paired at a precise time interval [65].…”

“…Furthermore, GluA2-lacking AMPA receptors are required for the maintenance, but not induction of HFS-induced LTP at juvenile TA-CA1 synapses [59]. Recent in vivo studies demonstrate that LTP that lasts in excess of 24 h can be evoked by tetanic stimulation in freely behaving rats [56,64]. Further investigation found that this form of in vivo LTP is dependent on NMDA receptor activation [64].…”