The lateral neocortex is critical for contextual fear memory reconsolidation

Verónica De La Fuente,Germán Falasco,Silvia Vázquez,Alexxai V Kravitz,Francisco J Urbano,Leandro Urrutia,Candela Medina,María Eugenia Pedreira,Arturo Romano

doi:10.1038/s41598-019-48340-9

Abstract

Memories are a product of the concerted activity of many brain areas. Deregulation of consolidation and reprocessing of mnemonic traces that encode fearful experiences might result in fear-related psychopathologies. Here, we assessed how pre-established memories change with experience, particularly the labilization/reconsolidation of memory, using the whole-brain analysis technique of positron emission tomography in male mice. We found differences in glucose consumption in the lateral neocortex, hippocampus and amygdala in mice that underwent labilization/reconsolidation processes compared to animals that did not reactivate a fear memory. We used chemogenetics to obtain insight into the role of cortical areas in these phases of memory and found that the lateral neocortex is necessary for fear memory reconsolidation. Inhibition of lateral neocortex during reconsolidation altered glucose consumption levels in the amygdala. Using an optogenetic/neuronal recording-based strategy we observed that the lateral neocortex is functionally connected with the amygdala, which, along with retrograde labeling using fluorophore-conjugated cholera toxin subunit B, support a monosynaptic connection between these areas and poses this connection as a hot-spot in the circuits involved in reactivation of fear memories.

Highlights

Consolidation is the process by which new information is encoded in neural circuits
We found differences in glucose consumption in different regions including the temporal association cortex (TeA, known as TEa), auditory areas (AUD), the perirhinal cortex (PER, referred to as PRh or PERI), somatosensory cortex, hippocampus and amygdala in animals that underwent labilization/reconsolidation processes compared to animals that did not express the fear memory
Using retrograde labeling and an optogenetic/electrode array-based strategy we demonstrate that the lateral neocortex projects to the amygdala, which is a key structure for the processing of emotional information[25]

Summary

Introduction

Consolidation is the process by which new information is encoded in neural circuits. most consolidated memories do not remain immutable indefinitely[1,2,3]; instead, they may change over time and with experience. No in vivo whole-brain studies have been performed to elucidate the neural circuits and brain areas that subserve memory dynamics during these processes in small animals, despite its relevance in improving our understanding of fear-related dysfunctions in humans, such as phobias and post-traumatic stress disorders[16,17,18]. Functional imaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) are very powerful tools to investigate brain areas involved in different tasks, primarily because of their minimal invasiveness[19], and are widely applied in humans and non-human primates[20,21]. Using retrograde labeling and an optogenetic/electrode array-based strategy we demonstrate that the lateral neocortex projects to the amygdala, which is a key structure for the processing of emotional information[25]

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