Journal Article

Fmr1-KO mice failure to detect object novelty associates with a post-test decrease of structural and synaptic plasticity upstream of the hippocampus

Martire, Alberto, Boussadia, Zaira, Borreca, Antonella, Pignataro, Annabella, De Luca, Mariassunta, Ferrante, Antonella, Ammassari-Teule, Martine

2023

Overview

Mice with deletion of the FMR1 gene show episodic memory impairments and exhibit dendritic spines and synaptic plasticity defects prevalently identified in non-training conditions. Based on evidence that synaptic changes associated with normal or abnormal memory emerge when mice are cognitively challenged, here we examine whether, and how, fragile entorhinal and hippocampal synapses are remodeled when mice succeed or fail to learn. We trained Fmr1 knockout (KO) and wild-type C57BL/6J (WT) mice in the novel object recognition (NOR) paradigm with 1 h or 24 h training-to-test intervals and then assessed whether varying the time between the presentation of similar and different objects modulates NOR performance and plasticity along the entorhinal cortex-hippocampus axis. At the 1 h-interval, KO mice failed to discriminate the novel object, showed a collapse of spines in the lateral entorhinal cortex (LEC), and of long-term potentiation (LTP) in the lateral perforant path (LPP), but a normal increase in hippocampal spines. At the 24 h, they exhibited intact NOR performance, typical LEC and hippocampal spines, and exaggerated LPP-LTP. Our findings reveal that the inability of mice to detect object novelty primarily stands in their impediment to elaborate, and convey to the hippocampus, sensory/perceptive object representations.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/378/1689 / 631/378/2649 / Animal cognition / Animals / Cortex (entorhinal) / Councils / Dendritic plasticity / Dendritic spines / Episodic memory / FMR1 gene / FMR1 protein / Fragile X Mental Retardation Protein - genetics / Gene deletion / Hippocampal plasticity / Hippocampus / Hippocampus - metabolism / Humanities and Social Sciences / Long-term potentiation / Long-Term Potentiation - genetics / Memory / Mice / Mice, Inbred C57BL / Mice, Knockout / multidisciplinary / Neuronal Plasticity - genetics / Pattern recognition / Plasticity / Science / Science (multidisciplinary) / Sensory perception / Somatosensory cortex / Synapses / Synapses - metabolism / Synaptic plasticity / Training