Functional optical probing of the hippocampal trisynaptic circuit in vitro: network dynamics, filter properties, and polysynaptic induction of CA1 LTP.

Jens Stepan,Matthias Eder,Julien Dine

doi:10.3389/fnins.2015.00160

Jens Stepan, Matthias Eder + Show 1 more

Open Access

https://doi.org/10.3389/fnins.2015.00160

Copy DOI

Abstract

Decades of brain research have identified various parallel loops linking the hippocampus with neocortical areas, enabling the acquisition of spatial and episodic memories. Especially the hippocampal trisynaptic circuit [entorhinal cortex layer II → dentate gyrus (DG) → cornu ammonis (CA)-3 → CA1] was studied in great detail because of its seemingly simple connectivity and characteristic structures that are experimentally well accessible. While numerous researchers focused on functional aspects, obtained from a limited number of cells in distinct hippocampal subregions, little is known about the neuronal network dynamics which drive information across multiple synapses for subsequent long-term storage. Fast voltage-sensitive dye imaging in vitro allows real-time recording of activity patterns in large/meso-scale neuronal networks with high spatial resolution. In this way, we recently found that entorhinal theta-frequency input to the DG most effectively passes filter mechanisms of the trisynaptic circuit network, generating activity waves which propagate across the entire DG-CA axis. These “trisynaptic circuit waves” involve high-frequency firing of CA3 pyramidal neurons, leading to a rapid induction of classical NMDA receptor-dependent long-term potentiation (LTP) at CA3-CA1 synapses (CA1 LTP). CA1 LTP has been substantially evidenced to be essential for some forms of explicit learning in mammals. Here, we review data with particular reference to whole network-level approaches, illustrating how activity propagation can take place within the trisynaptic circuit to drive formation of CA1 LTP.

Highlights

Accumulating evidence points to a major role of the hippocampal formation in the acquisition and recall of episodic and spatial memories in mammals (Whitlock et al, 2006; van Strien et al, 2009)
These “trisynaptic circuit waves” involve high-frequency firing of CA3 pyramidal neurons, leading to a rapid induction of classical NMDA receptor-dependent long-term potentiation (LTP) at CA3-CA1 synapses (CA1 Long-term potentiation (LTP))
Together with the fact that frequency facilitation at mossy fiber synapses develops stronger with higher frequencies (Toth et al, 2000), these results suggest that, regarding neuronal activity propagation from the entorhinal cortex (EC) to area CA1, the dentate gyrus (DG)-CA3 complex operates as a kind of “loworder band-pass filter,” wherein the DG network serves as the “low-pass unit” and the CA3 mossy fiber system as the “high-pass device” (Neural band-pass filter; Figure 2)

Summary

Introduction

Accumulating evidence points to a major role of the hippocampal formation in the acquisition and recall of episodic and spatial memories in mammals (Whitlock et al, 2006; van Strien et al, 2009). Functional optical probing of the hippocampal trisynaptic circuit in vitro: network dynamics, filter properties, and polysynaptic induction of CA1 LTP

Results

Conclusion