Acute exercise enhances the consolidation of fear extinction memory and reduces conditioned fear relapse in a sex-dependent manner

Here we report that the recently discovered mammalian DNA modification N6-methyl-2’-deoxyadenosine (m6dA) is dynamically regulated in primary cortical neurons, and accumulates along promoters and coding sequences within the genome of activated prefrontal cortical neurons of adult C57/BI6 mice in response to fear extinction learning. The deposition of m6dA is generally associated with increased genome-wide occupancy of the mammalian m6dA methyltransferase, N6amt1, and this correlates with fear extinction learning-induced gene expression. Of particular relevance for fear extinction memory, the accumulation of m6dA is associated with an active chromatin state and the recruitment of transcriptional machinery to the brain-derived neurotrophic factor (Bdnf) P4 promoter, which is required for Bdnf exon IV mRNA expression and for the extinction of conditioned fear. These results expand the scope of DNA modifications in the adult brain and highlight changes in m6dA as a novel neuroepigenetic mechanism associated with activity-induced gene expression and the formation of fear extinction memory.

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The effects of transcutaneous vagus nerve stimulation on conditioned fear extinction in humans

10.31234/osf.io/8jsu9 ◽

2017 ◽

Author(s):

Andreas Michael Burger ◽

Bart Verkuil ◽

Ilse van Diest ◽

Willem van der Does ◽

Julian Thayer ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Conditioned Fear ◽

Fear Extinction ◽

Extinction Learning ◽

Transcutaneous Vagus Nerve Stimulation ◽

Extinction Memory ◽

Phase Retention ◽

To Receive

After fear conditioning participants were randomly assigned to receive tVNS or sham stimulation during a fear extinction phase. Retention of extinction memory was tested 24 hours later. tVNS accelerated explicit fear extinction learning (US expectancy ratings), but did not lead to better retention of extinction memory 24 hours later. We did not find a differential physiological conditioning response during the acquisition of fear and thus were unable to assess potential effects of tVNS on the extinction of physiological indices of fear.

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IGF-1 facilitates extinction of conditioned fear

eLife ◽

10.7554/elife.67267 ◽

2021 ◽

Vol 10 ◽

Author(s):

Laura E Maglio ◽

José A Noriega-Prieto ◽

Irene B Maroto ◽

Jesús Martin-Cortecero ◽

Antonio Muñoz-Callejas ◽

...

Keyword(s):

Synaptic Plasticity ◽

Synaptic Transmission ◽

Pyramidal Neurons ◽

Conditioned Fear ◽

Long Term Potentiation ◽

Fear Extinction ◽

Neuronal Firing ◽

Term Potentiation ◽

Extinction Memory

Insulin-like growth factor-1 (IGF-1) plays a key role in synaptic plasticity, spatial learning and anxiety-like behavioral processes. While IGF-1 regulates neuronal firing and synaptic transmission in many areas of the central nervous system, its signaling and consequences on excitability, synaptic plasticity, and animal behavior dependent on the prefrontal cortex remain unexplored. Here, we show that IGF-1 induces a long-lasting depression of the medium and slow post-spike afterhyperpolarization (mAHP and sAHP), increasing the excitability of layer 5 pyramidal neurons of the rat infralimbic cortex. Besides, IGF-1 mediates a presynaptic long-term depression of both inhibitory and excitatory synaptic transmission in these neurons. The net effect of this IGF-1 mediated synaptic plasticity is a long-term potentiation of the postsynaptic potentials. Moreover, we demonstrate that IGF-1 favors the fear extinction memory. These results show novel functional consequences of IGF-1 signaling, revealing IGF-1 as a key element in the control of the fear extinction memory.

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IGF-1 facilitates extinction of conditioned fear

10.1101/2020.04.15.042788 ◽

2020 ◽

Author(s):

José A. Noriega-Prieto ◽

Laura E. Maglio ◽

Irene B. Maroto ◽

Jesús Martin-Cortecero ◽

Antonio Muñoz-Callejas ◽

...

Keyword(s):

Prefrontal Cortex ◽

Synaptic Plasticity ◽

Animal Behavior ◽

Pyramidal Neurons ◽

Conditioned Fear ◽

Fear Extinction ◽

Neuronal Firing ◽

Infralimbic Cortex ◽

Regulatory Processes ◽

Extinction Memory

SUMMARYInsulin-like growth factor-1 (IGF-1) plays a key role in synaptic plasticity, degenerative diseases, spatial learning, and anxiety-like behavioral processes. While IGF-1 regulates neuronal activity in many areas of the brain, its effect on synaptic plasticity and animal behavior dependent on the prefrontal cortex remain unexplored. Here, we show that IGF-1 induces a long-lasting depression of the medium and slow post-spike afterhyperpolarization (mAHP and sAHP), increasing the excitability of layer 5 pyramidal neurons of the infralimbic cortex. Besides, IGF-1 mediates a long-term depression of both inhibitory and excitatory synaptic transmission that results in a longterm potentiation of the postsynaptic potentials. We demonstrate that these synaptic and intrinsic regulatory processes mediated by IGF-1 favor the fear extinction memory. These results show novel functional consequences of IGF-1 signaling on animal behavior tasks dependent on the prefrontal cortex, revealing IGF-1 as a key element in the control of the fear extinction memory.Impact StatementIGF-1 modulates the neuronal firing and synaptic plasticity in infralimbic cortex, favoring the extinction memory

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Amygdala Reward Neurons Form and Store Fear Extinction Memory

10.1101/615096 ◽

2019 ◽

Cited By ~ 1

Author(s):

Xiangyu Zhang ◽

Joshua Kim ◽

Susumu Tonegawa

Keyword(s):

Emotional Disorders ◽

Basolateral Amygdala ◽

Conditioned Fear ◽

Fear Memory ◽

Fear Extinction ◽

Neuronal Population ◽

Post Traumatic Stress ◽

Extinction Memory ◽

Memory Engram ◽

Reward Behaviors

SummaryThe ability to extinguish conditioned fear memory is critical for adaptive control of fear response, and its impairment is a hallmark of emotional disorders like post-traumatic stress disorder (PTSD). Fear extinction is thought to take place when animals form a new memory that suppresses the original fear memory. However, little is known about the nature and the site of formation and storage of the new extinction memory. Here, we demonstrate that a fear extinction memory engram is formed and stored in a genetically distinct basolateral amygdala (BLA) neuronal population that drive reward behaviors and antagonize the BLA’s original fear neurons. The activation of the fear extinction engram neurons and natural reward-responsive neurons overlap extensively in the BLA. Furthermore, these two neuron subsets are mutually interchangeable in driving reward behaviors and fear extinction behaviors. Thus, fear extinction memory is a newly formed reward memory.

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