Lesion of the hippocampus selectively enhances LEC’s activity during recognition memory based on familiarity

Abstract

The sense of familiarity for events is crucial for successful recognition memory. However, the neural substrate and mechanisms supporting familiarity remain unclear. A major controversy in memory research is whether the parahippocampal areas, especially the lateral entorhinal (LEC) and the perirhinal (PER) cortices, support familiarity or whether the hippocampus (HIP) does. In addition, it is unclear if LEC, PER and HIP interact within this frame. Here, we especially investigate if LEC and PER's contribution to familiarity depends on hippocampal integrity. To do so, we compare LEC and PER neural activity between rats with intact hippocampus performing on a human to rat translational task relying on both recollection and familiarity and rats with hippocampal lesions that have been shown to then rely on familiarity to perform the same task. Using high resolution Immediate Early Gene imaging, we report that hippocampal lesions enhance activity in LEC during familiarity judgments but not PER’s. These findings suggest that different mechanisms support familiarity in LEC and PER and led to the hypothesis that HIP might exert a tonic inhibition on LEC during recognition memory that is released when HIP is compromised, possibly constituting a compensatory mechanism in aging and amnesic patients.

Reevaluating the role of the hippocampus in memory: A meta‐analysis of neurotoxic lesion studies in nonhuman primates

“…Thus, our current data do not permit an accurate conclusion about the relation between effect size and lesion specificity. However, individual reports do support a role for surrounding structures in item recognition (Eichenbaum et al, 2007; Hasselmo, 2006; Mahnke et al, 2021), suggesting future studies into regions like the entorhinal cortex would be valuable.…”

“…The relative sparing of visual recognition memory after selective lesions in the hippocampus may imply adjacent cortical regions have a compensatory role that mitigates loss-of-function in a linear manner. This notion is supported somewhat by a recent finding that hippocampal lesions increase entorhinal cortex activity during a familiarity task (Mahnke et al, 2021) and by previous research reporting facilitative effects of hippocampal lesions (Cheung & Cardinal, 2005;Ito et al, 2006;Schwarting & Busse, 2017). However, this "compensatory" hypothesis does not account for the finding that small lesions predicted large deficits on VPC and DMS/DNMS tasks.…”

“…However, individual reports do support a role for surrounding structures in item recognition (Eichenbaum et al, 2007;Hasselmo, 2006;Mahnke et al, 2021), suggesting future studies into regions like the entorhinal cortex would be valuable.…”

Five discoveries of Volodymyr Betz. Part one. Betz and the islands of entorhinal cortex

“…The LEC/aLEC is a key node of the episodic (Bellmund, Polti, & Doeller, 2020, Vandrey et al, 2020Takehara-Nishiuchi, 2022) and social (Dang et al, 2022;Lopez-Rojas, de Solis, Leroy, Kandel, & Siegelbaum, 2022) memory, provides fast information reproduction under similar context (Pilkiw, Jarovi & Takehara-Nishiuchi, 2022) participates in detecting familiarity for events (Mahnke, Atucha, Pina-Fernàndez, Kitsukawa & Sauvage, 2021), in time association of the stimuli which are applied in a certain sequence (Yu, Yu, Choi & Takehara-Nishiuchi, 2021), in engramming and reproduction of the temporal information, summarized in the LEC according to the acquired behavioral experience (Tsao et al, 2018;Bellmund, Deuker & Doeller, 2019;Bellmund, Polti, & Doeller, 2020), and finaly, in producing the space-time map of the experienced events Bellmund et al, 2019;Montchal, Reagh & Yassa, 2019;Bellmund, Polti, & Doeller, 2020). The LEC may also play a role in the mechanisms of fear memory (East Jr., Brady & Quinn, 2021) and neuropathic pain syndrome (Guida et al, 2022), in the formation of spatial correlates of feeding behavior (Azevedo et al, 2019) and, together with the anterior cingulate cortex -participate in the motivation sphere function and in the network reinforcement correlates formation .…”

Phase-locking of hippocampal CA3 neurons to distal CA1 theta oscillations selectively predicts memory performance

“…To test the non-spatial recognition memory, we used the innate ability of rats to dig and to discriminate between odors. Behavioral training and paradigm have been described in details previously (Ku et al, 2017;Mahnke et al, 2021;. In short, each training session contained a "study" phase, a delay, and a "test" phase.…”