scholarly journals The Medial Prefrontal Cortex and Fear Memory: Dynamics, Connectivity, and Engrams

2021 ◽  
Vol 22 (22) ◽  
pp. 12113
Author(s):  
Lucie Dixsaut ◽  
Johannes Gräff

It is becoming increasingly apparent that long-term memory formation relies on a distributed network of brain areas. While the hippocampus has been at the center of attention for decades, it is now clear that other regions, in particular the medial prefrontal cortex (mPFC), are taking an active part as well. Recent evidence suggests that the mPFC—traditionally implicated in the long-term storage of memories—is already critical for the early phases of memory formation such as encoding. In this review, we summarize these findings, relate them to the functional importance of the mPFC connectivity, and discuss the role of the mPFC during memory consolidation with respect to the different theories of memory storage. Owing to its high functional connectivity to other brain areas subserving memory formation and storage, the mPFC emerges as a central hub across the lifetime of a memory, although much still remains to be discovered.

Hippocampus ◽  
2014 ◽  
Vol 24 (12) ◽  
pp. 1482-1492 ◽  
Author(s):  
María Cecilia Martínez ◽  
María Eugenia Villar ◽  
Fabricio Ballarini ◽  
Haydée Viola

2021 ◽  
Author(s):  
Francisco Tomas Gallo ◽  
Maria Belen Zanoni-Saad ◽  
Juan Facundo Morici ◽  
Magdalena Miranda ◽  
Michael C Anderson ◽  
...  

Active forgetting occurs in many species, but how the mechanisms that control behavior contribute to determining which memories are forgotten is still unknown. We previously found that when rats need to retrieve particular memories to guide exploration, it reduces later retention of other memories encoded in that environment. As with humans, this retrieval-induced forgetting relies on prefrontal control processes. The dopaminergic input to the prefrontal cortex is important for executive functions and cognitive flexibility. We found that, in a similar way, prefrontal dopamine signaling through D1 receptors is required for retrieval-induced forgetting in rats. Blockade of medial prefrontal cortex D1 receptors as animals encountered a familiar object impaired forgetting of the memory of a competing object in a subsequent long-term memory test. Inactivation of the ventral tegmental area produced the same pattern of behavior, a pattern that could be reversed by concomitant activation of prefrontal D1 receptors. We observed a bidirectional modulation of retrieval-induced forgetting by agonists and antagonists of D1 receptors in the medial prefrontal cortex. These findings establish the essential role of prefrontal dopamine in the active forgetting of competing memories, contributing to the shaping of retention in response to an organism behavioral goals.


2019 ◽  
Author(s):  
Michelle B. Chen ◽  
Xian Jiang ◽  
Stephen R. Quake ◽  
Thomas C. Südhof

AbstractIt is thought that memory is stored in ‘engrams’, a subset of neurons that undergo learning-induced alterations. The role of gene-expression during learning and short-term memory has been studied extensively, but little is known about remote memory that can persist for a lifetime. Using long-term contextual fear memory as a paradigm, an activity-dependent transgenic model for engram-specific labeling, and single-cell transcriptomics we probed the gene-expression landscape underlying remote memory consolidation and recall in the medial prefrontal cortex. Remarkably, we find sustained activity-specific transcriptional alterations in diverse populations of neurons that persist even weeks after fear-learning and are distinct from those previously identified in learning. Out of a vast plasticity-coding space, we uncover select membrane-fusion genes that could play important roles in maintaining remote memory traces. Unexpectedly, astrocytes and microglia also acquire new persistent gene signatures upon recall of remote memory, suggesting that they actively contribute to memory circuits. Our discovery of novel distinct gene-expression programs involved in long term memory adds an important dimension of activity-dependent cellular states to existing brain taxonomy atlases and sheds light on the elusive mechanisms of remote memory storage.


2018 ◽  
Vol 40 (5) ◽  
pp. 12-15
Author(s):  
Alexis Bédécarrats ◽  
David L. Glanzman

A fundamental assumption in modern psychology and neuroscience is that memory is stored as physical changes in the brain. More than a century ago, the famous neuroanatomist Ramón Y Cajal (see the article entitled “Santiago Ramón y Cajal, the ultimate scientist?” in this issue of The Biochemist) postulated that changes in the strength of synaptic connections between neurons were the physical substrate for memory. Extensive experimental evidence has since established the dominance of this connectionist view, referred to as the “synaptic plasticity” model. However, although the synaptic plasticity model broadly accords with the results of neurobiological studies of learning and memory, it does not fully account for the extraordinary resilience of memory despite the significant loss of synapses during such phenomena as development, trauma and ageing. Here, we will focus on the newly discovered role of small non-coding RNAs (ncRNAs) as potential master regulators of learning-induced epigenesis, neuronal plasticity and, ultimately, memory. In support of this idea, recent data from our lab indicate that RNA can promote the transfer of long-term memory from a trained to an untrained (naïve) animal.


2020 ◽  
Vol 24 (8) ◽  
pp. 885-896
Author(s):  
L. N. Grinkevich

The mechanisms of long-term memory formation and ways to improve it (in the case of its impairment) remain an extremely difficult problem yet to be solved. Over the recent years, much attention has been paid to microRNAs in this regard. MicroRNAs are unique endogenous non-coding RNAs about 22 nucleotides in length; each can regulate translation of hundreds of messenger RNA targets, thereby controlling entire gene networks. MicroRNAs are widely represented in the central nervous system. A large number of studies are currently being conducted to investigate the role of microRNAs in the brain functioning. A number of microRNAs have been shown to be involved in the process of synaptic plasticity, as well as in the long-term memory formation. Disruption of microRNA biogenesis leads to significant cognitive dysfunctions. Moreover, impaired microRNA biogenesis is one of the causes of the pathogenesis of mental disorders, neurodegenerative illnesses and senile dementia, which are often accompanied by deterioration in the learning ability and by memory impairment. Optimistic predictions are made that microRNAs can be used as targets for therapeutic treatment and for diagnosing the above pathologies. The importance of applications related to microRNAs significantly raises interest in studying their functions in the brain. Thus, this review is focused on the role of microRNAs in cognitive processes. It describes microRNA biogenesis and the role of miRNAs in the regulation of gene expression, as well as the latest achievements in studying the functional role of microRNAs in learning and in long-term memory formation, depending on the activation or inhibition of their expression. The review presents summarized data on the effect of impaired microRNA biogenesis on long-term memory formation, including those associated with sleep deprivation. In addition, analysis is provided of the current literature related to the prospects of improving cognitive processes by influencing microRNA biogenesis via the use of CRISPR/Cas9 technologies and active mental and physical exercises.


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