Prefrontal-Hippocampal Pathways Through the Nucleus Reuniens Are Functionally Biased by Brain State.

Brandon E Hauer,Silvia Pagliardini,Clayton T Dickson

doi:10.3389/fnana.2021.804872

Brandon E Hauer, Silvia Pagliardini + Show 1 more

Open Access

https://doi.org/10.3389/fnana.2021.804872

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Abstract

Circuit-level communication between disparate brain regions is fundamental for the complexities of the central nervous system operation. Co-ordinated bouts of rhythmic activity between the prefrontal cortex (PFC) and hippocampus (HPC), in particular, are important for mnemonic processes. This is true during awake behavior, as well as during offline states like sleep. We have recently shown that the anatomically interposed thalamic nucleus reuniens (RE) has a role in coordinating slow-wave activity between the PFC and HPC. Here, we took advantage of spontaneous brain state changes occurring during urethane anesthesia in order to assess if PFC-HPC communication was modified during activated (theta) vs. deactivated (slow oscillation: SO) states. These forebrain states are highly similar to those expressed during rapid eye movement (REM) and non-REM stages of natural sleep, respectively. Evoked potentials and excitatory current sinks in the HPC were consistently larger during SO states, regardless of whether PFC or RE afferents were stimulated. Interestingly, PFC stimulation during theta appeared to preferentially use a cortico-cortical pathway, presumably involving the entorhinal cortex as opposed to the more direct RE to HPC conduit. Optogenetic and chemogenetic manipulations of the RE suggested that this state-dependent biasing was mediated by responding in the RE itself. Finally, the phase of both ongoing rhythms also appeared to be an important factor in modulating HPC responses, with maximal field excitatory postsynaptic potentials (EPSPs) occurring during the negative-going phase of both rhythms. Thus, forebrain state plays an important role in how communication takes place across the PFC and HPC, with the RE as a determining factor in how this is shaped. Furthermore, ongoing sleep-like rhythms influence the coordination and perhaps potentiate excitatory processing in this extended episodic memory circuit. Our results have direct implications for activity-dependent processes relevant to sleep-dependent memory consolidation.

Highlights

Coordinated neural activity is vital for mnemonic processes (Buzsaki, 1996; Siapas and Wilson, 1998)
Our results demonstrate that prefrontal cortex (PFC)-HPC communication is fundamentally different between states and that the RE has a critical role in mediating this disparity
Have we documented striking changes in terms of neural responding in the medial prefrontal cortex (mPFC) to HPC circuit that depend on state, but we have shown that ongoing cycles of circuit rhythms expressed within these states are another significant aspect of altered responsiveness

Summary

Introduction

Coordinated neural activity is vital for mnemonic processes (Buzsaki, 1996; Siapas and Wilson, 1998). One of the most widely studied phenomena in memory-relevant brain areas is the emergence (and prevalence) of collective oscillatory activity These rhythmic patterns and their inter-regional synchrony are thought to modulate and constrain information processing, especially in key memory centers including the hippocampus (HPC) and medial prefrontal cortex (mPFC). Decades of research have indicated a decisive role of both HPC and mPFC in episodic mnemonic processes (Jin and Maren, 2015). Communication between these disparate structures is essential for the proper encoding and retrieval of episodic memories (Simons and Spiers, 2003; Preston and Eichenbaum, 2013). Information relayed from the mPFC to the HPC aids in guiding both memory acquisition and retrieval, while in turn, the HPC sends signals to the mPFC to provide remembered episodes with goals, rules, and procedural representations (Morris, 2001; Dolleman-van der Weel et al, 2019)

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