PET Metabolic Imaging of Time-Dependent Reorganization of Olfactory Cued Fear Memory Networks in Rats

Abstract

Memory consolidation involves reorganization at both the synaptic and system levels.The latter involves gradual reorganization of the brain regions that support memory and has been mostly highlighted using hippocampal-dependent tasks. The standard memory consolidation model posits that the hippocampus becomes gradually less important over time in favor of neocortical regions. By contrast, this reorganization of circuits in amygdala-dependent tasks has been less investigated. Moreover, this question has been addressed using primarily lesion or cellular imaging approaches thus precluding the comparison of recent and remote memory networks in the same animals. To overcome this limitation, we used microPET imaging to characterize, in the same animals, the networks activated during the recall of a recent vs remote memory in an olfactory cued fear conditioning paradigm. The data highlighted the drastic difference between the extent of the two networks. Indeed, while the recall of a recent odor fear memory activates a large network of structures spanning from the prefrontal cortex to the cerebellum, significant activations during remote memory retrieval are limited to the piriform cortex. These results strongly support the view that amygdala-dependent memories also undergo system-level reorganization, and that sensory cortical areas might participate in the long-term storage of emotional memories.

Threat Memory in the Sensory Cortex: Insights from Olfaction

“…Moreover, this plasticity also exhibits time-dependent properties, more prominent in long-term threat memory (Hegoburu and others 2014; Mouly and others 2022; You and others 2022) (Fig. 1B).…”

“…1B). Notably, applying neuroimaging methods (fMRI and PET) for large-scale, whole-brain analysis combined with temporal profiling of associative plasticity over a long delay, two new studies (in rodents and humans) demonstrated that the piriform cortex exhibits associative plasticity both soon and long after threat conditioning, in contrast to transitory (or no) plasticity in the amygdala and frontal cortices (Mouly and others 2022; You and others 2022). These effects are consistent with findings from human fMRI and electrophysiologic studies in the visual and auditory cortices, which indicated lasting associative plasticity in the sensory cortex in contrast to transitory plasticity in the amygdala and inferotemporal and orbitofrontal cortices (Apergis-Schoute and others 2014; You and others 2021).…”

Distinct brain networks for remote episodic memory depending on content and emotional value

“…The brain networks recruited in Where rats, that show an incomplete memory, are more restricted and less efficient in terms of functional connectivity and specific to networks of memories with contextual and spatial information (dorsal hippocampus, retrosplenial cortex, and habenula) 46–50 . In contrast, WWW rats that remember all episodic information recruit larger brain networks, including the same spatial network and brain regions that are functionally connected and implicated in olfactory memory (piriform, lateral entorhinal, orbitofrontal, prelimbic and infralimbic cortices) 51–56 . A comparison of the Where and WWW profiles reveals that complete recollection of remote episodic memory recruits a core network of interconnected brain regions (medio-lateral orbitofrontal, ventral CA1 and basolateral amygdala) 57–62 that are implicated in the valence and emotional processing of information and directly correlated with memory accuracy during recall.…”

Reversing Aging: Decline in Complex Olfactory Learning Can be Rectified by Restoring Intrinsic Plasticity of Hippocampal CA1 Pyramidal Neurons

“…Based on these results, we concluded that aged CA1 neurons are more plastic compared to aged PC neurons. As sensory cortices are the more permanent repertoire of long‐term memory, [ 37–39 ] our results may suggest that conversion of short‐term memory (initially encoded in the hippocampus) to long‐term memory storage becomes more challenging in aged animals.…”