Early remodeling of the neocortex upon episodic memory encoding

Abstract

Understanding the mechanisms by which long-term memories are formed and stored in the brain represents a central aim of neuroscience. Prevailing theory suggests that long-term memory encoding involves early plasticity within hippocampal circuits, whereas reorganization of the neocortex is thought to occur weeks to months later to subserve remote memory storage. Here we report that long-term memory encoding can elicit early transcriptional, structural, and functional remodeling of the neocortex. Parallel studies using genome-wide RNA sequencing, ultrastructural imaging, and whole-cell recording in wild-type mice suggest that contextual fear conditioning initiates a transcriptional program in the medial prefrontal cortex (mPFC) that is accompanied by rapid expansion of the synaptic active zone and postsynaptic density, enhanced dendritic spine plasticity, and increased synaptic efficacy. To address the real-time contribution of the mPFC to long-term memory encoding, we performed temporally precise optogenetic inhibition of excitatory mPFC neurons during contextual fear conditioning. Using this approach, we found that real-time inhibition of the mPFC inhibited activation of the entorhinal-hippocampal circuit and impaired the formation of long-term associative memory. These findings suggest that encoding of long-term episodic memory is associated with early remodeling of neocortical circuits, identify the prefrontal cortex as a critical regulator of encoding-induced hippocampal activation and long-term memory formation, and have important implications for understanding memory processing in healthy and diseased brain states.learning | transcriptome | neuroplasticity | optogenetics | hippocampus

Brain aerobic glycolysis and motor adaptation learning

“…Thus, it is not surprising that BA44 might show extensive involvement in the brain's adaptation to the visual-motor adaptation task. That an area of cerebral cortex should be involved early in the learning process is consistent with recent work by Bero et al (55).…”

Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits

“…Moreover, contextual fear memory consolidation can elicit early transcriptional, structural, and functional remodeling of PFC cells few hours after conditioning (Vetere et al, 2011;Bero et al, 2014). These observations are consistent with the demonstration that PFC neurons are reactivated during encoding of associative memories (Lesburgue`res et al, 2011).…”

“…A possible mechanism involves the synthesis of new proteins required for strengthening synaptic connections in fear-related circuits. In addition, microstructural changes (Sandku¨hler and Lee, 2013) and activity-dependent gene expression have particular time-courses during memory consolidation (Bero et al, 2014;Aceti et al, 2015). These findings suggest that post-learning ''sensitive" periods are windows of opportunity during which traumatic memories can be manipulated.…”

Optogenetics: Applications in neurobiology

“…Bero et al found that optogenetic excitation of mPFC neurons inhibits the activation of entorhinal-hippocampal circuits and impairs the encoding of long-term associative memory (Bero et al, 2014). Since the development of optogenetics, there have also been some new discoveries about the mechanism of memory retrieval.…”