Hippocampus–Prefrontal Coupling Regulates Recognition Memory for Novelty Discrimination

Abstract

Recognition memory provides the ability to distinguish familiar from novel objects and places, and is important for recording and updating events to guide appropriate behavior. The hippocampus (HPC) and medial prefrontal cortex (mPFC) have both been implicated in recognition memory, but the nature of HPC-mPFC interactions, and its impact on local circuits in mediating this process is not known. Here we show that novelty discrimination is accompanied with higher theta activity (4-10 Hz) and increased c-Fos expression in both these regions. Moreover, theta oscillations were highly coupled between the HPC and mPFC during recognition memory retrieval for novelty discrimination, with the HPC leading the mPFC, but not during initial learning. Principal neurons and interneurons in the mPFC responded more strongly during recognition memory retrieval compared with learning. Optogenetic silencing of HPC input to the mPFC disrupted coupled theta activity between these two structures, as well as the animals' (male Sprague Dawley rats) ability to differentiate novel from familiar objects. These results reveal a key role of monosynaptic connections between the HPC and mPFC in novelty discrimination via theta coupling and identify neural populations that underlie this recognition memory-guided behavior.

Hippocampal-medial prefrontal cortex network dynamics predict performance during retrieval in a context-guided object memory task

“…We found that the power of vHPC theta oscillations increases during object exploration, suggesting that vHPC theta oscillations in this task might be associated with the cognitive processes underlying the behavioral response. In addition, several studies reported an increase of mPFC theta power during decision making, attentional processes, and, recently, in a NOR task ( 23 , 46 , 47 ). We observed an increase in mPFC theta power during the exploration of the contextually incongruent object.…”

“…Based on the anatomical connectivity and pharmacological experiments, we predicted that the resolution of the task would involve tight communication between both structures. Increased theta vHPC-mPFC connectivity has been observed in spatial navigation, working memory ( 17 , 48 ), a NOR task, and rewarded object–context associations ( 25 , 47 , 49 ). Consistently, we found that the vHPC and mPFC share an increase in theta activity irrespective of the explored object.…”

“…Due to the vast projections that arrive at the mPFC from associative regions ( 56 ), the mPFC has been postulated as the orchestrator of memory reactivation in downstream structures for different tasks ( 4 , 23 , 46 , 47 ). We have previously shown that activation of the vHPC, as well as its interaction with the mPFC, affects the labilization of OIC memory traces in the perirhinal cortex ( 29 ).…”

Theta coupling within the medial prefrontal cortex regulates fear extinction and renewal

“…LFP recordings from the mPFC in ex-vivo slices have hinted toward synchronized activity between the PL and IL ( Van Aerde et al., 2008 ). We thus investigated coupled activity between the PL and IL across behavioral states using cross-correlation analysis ( Adhikari et al., 2010 ; Wang et al., 2021 ). This method assumes that functional connectivity between the two structures is accompanied by reasonably coherent activity within a specific frequency range.…”

Activation of the CA2-vCA1 pathway reverses social discrimination dysfunction inShank3Bknockout mice

“…Hippocampal theta and gamma rhythms have been associated with novelty recognition (Penley et al, 2013;Kitanishi et al, 2015;Zheng et al, 2016;Brown et al, 2020;Kragel et al, 2020;Park et al, 2021;Wang et al, 2021). Since social stimuli have been shown to increase hippocampal theta and gamma oscillations (Tendler and Wagner, 2015;Villafranca-Faus et al, 2021;Brown et al, 2020) and mouse models of social dysfunction have been associated with alterations in hippocampal oscillations at both frequencies (Arbab et al, 2018;Aoki et al, 2017;Cheaha and Kumarnsit, 2015), we examined theta and gamma power in the vCA1 of WT and Shank3B KO mice in the presence of a novel mouse.…”