Prelimbic proBDNF facilitates memory destabilization by regulation of neuronal function in juveniles

Fear regulation changes as a function of age and adolescence is a key developmental period for the continued maturation of fear neural circuitry. The involvement of prelimbic proBDNF in fear memory extinction and its mediated signaling were reported previously. Given the inherent high level of proBDNF during juvenile period, we tested whether prelimbic proBDNF regulated synaptic and neuronal functions allowing to influencing retrieval-dependent memory processing. By examining freezing behavior of auditory fear conditioned rats, we found high levels of prelimbic proBDNF in juvenile rats enhanced destabilization of the retrieval-dependent weak but not strong fear memory through activating p75NTR-GluN2B signaling. This modification was attributed to the increment in proportion of thin type spine and promotion in synaptic function, as evidence by facilitation of NMDA-mediated EPSCs and GluN2B-dependent synaptic depression. The strong prelimbic theta- and gamma-oscillation coupling predicted the suppressive effect of proBDNF on the recall of post-retrieval memory. Our results critically emphasize the importance of developmental proBDNF for modification of retrieval-dependent memory and provide a potential critical targeting to inhibit threaten memories associated with neurodevelopment disorders.

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Plastic Synaptic Networks of the Amygdala for the Acquisition, Expression, and Extinction of Conditioned Fear

Physiological Reviews ◽

10.1152/physrev.00037.2009 ◽

2010 ◽

Vol 90 (2) ◽

pp. 419-463 ◽

Cited By ~ 595

Author(s):

Hans-Christian Pape ◽

Denis Pare

Keyword(s):

Conditioned Fear ◽

Fear Memory ◽

Network Activity ◽

Fear Learning ◽

Learning Mechanisms ◽

Memory Extinction ◽

Basic Biology ◽

Learned Fear ◽

Neuronal Systems ◽

Neuronal Functions

The last 10 years have witnessed a surge of interest for the mechanisms underlying the acquisition and extinction of classically conditioned fear responses. In part, this results from the realization that abnormalities in fear learning mechanisms likely participate in the development and/or maintenance of human anxiety disorders. The simplicity and robustness of this learning paradigm, coupled with the fact that the underlying circuitry is evolutionarily well conserved, make it an ideal model to study the basic biology of memory and identify genetic factors and neuronal systems that regulate the normal and pathological expressions of learned fear. Critical advances have been made in determining how modified neuronal functions upon fear acquisition become stabilized during fear memory consolidation and how these processes are controlled in the course of fear memory extinction. With these advances came the realization that activity in remote neuronal networks must be coordinated for these events to take place. In this paper, we review these mechanisms of coordinated network activity and the molecular cascades leading to enduring fear memory, and allowing for their extinction. We will focus on Pavlovian fear conditioning as a model and the amygdala as a key component for the acquisition and extinction of fear responses.

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Environmental enrichment prevents the late effect of acute stress-induced fear extinction deficit: the role of hippocampal AMPA-GluA1 phosphorylation

Translational Psychiatry ◽

10.1038/s41398-020-01140-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Leonardo Santana Novaes ◽

Letícia Morais Bueno-de-Camargo ◽

Carolina Demarchi Munhoz

Keyword(s):

Environmental Enrichment ◽

Basolateral Amygdala ◽

Acute Stress ◽

Fear Memory ◽

Fear Extinction ◽

Post Traumatic Stress ◽

Related Disorder ◽

Memory Extinction ◽

Post Traumatic

AbstractThe persistence of anxiety and the deficit of fear memory extinction are both phenomena related to the symptoms of a trauma-related disorder, such as post-traumatic stress disorder (PTSD). Recently we have shown that single acute restraint stress (2 h) in rats induces a late anxiety-related behavior (observed ten days after stress), whereas, in the present work, we found that the same stress impaired fear extinction in animals conditioned ten days after stress. Fourteen days of environmental enrichment (EE) prevented the deleterious effect of stress on fear memory extinction. Additionally, we observed that EE prevented the stress-induced increase in AMPA receptor GluA1 subunit phosphorylation in the hippocampus, but not in the basolateral amygdala complex and the frontal cortex, indicating a potential mechanism by which it exerts its protective effect against the stress-induced behavioral outcome.

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Role of Amygdala-Infralimbic Cortex Circuitry in Glucocorticoid-Induced Facilitation of Auditory Fear Memory Extinction

Basic and Clinical Neuroscience Journal ◽

10.32598/bcn.2021.2161.1 ◽

2021 ◽

pp. 1-22

Author(s):

Masoomeh Dadkhah ◽

◽

Abbas Ali Vafaei ◽

Ali Rashidy-Pour ◽

Parnia Trahomi ◽

...

Keyword(s):

Critical Role ◽

Fear Memory ◽

Fear Extinction ◽

Freezing Behavior ◽

Extinction Training ◽

Male Rats ◽

Memory Extinction ◽

The Right ◽

Fear Expression

Purpose: The basolateral amygdala (BLA) and infralimbic area (IL) of medial prefrontal cortex (mPFC) are two inter-connected brain structures that mediate both fear memory expression and extinction. Besides the well-known role of the BLA in the acquisition and expression of fear memory, projections from IL to BLA inhibit fear expression and have a critical role in fear extinction. However, the details of IL-BLA interaction remain unclear. Here, we aimed to investigate the role of functional reciprocal interactions between BLA and IL in mediating fear memory extinction. Methods: Using lidocaine (LID), male rats underwent unilateral or bilateral inactivation of the BLA and then unilateral intra-IL infusion of CORT, prior to extinction training of auditory fear conditioning paradigm. Freezing behavior was reported as an index for the measurement of conditioned fear. Infusions were performed before the extinction training, allowing to examine the effects on fear expression and also further extinction memory. Experiments 1-3 investigated the effects of left or right infusion of CORT into IL, and LID unilaterally into BLA on fear memory extinction. Results: Results showed that intra-IL infusion of CORT in the right hemisphere reduced freezing behavior when administrated before the extinction training. Auditory fear memory extinction was impaired by asymmetric inactivation of BLA and CORT infusion in the right IL; however, the same effect was not observed with symmetric inactivation of BLA. Conclusion: It is concluded that that the IL-BLA neural circuit may provide additional evidence to contribution of this circuit in auditory fear extinction. This study demonstrate dissociable roles for right or left BLA in subserving the auditory fear extinction. Our finding also raise the possibility that left BLA-IL circuitry may contribute in mediating auditory fear memory extinction via underlying mechanisms, however further research is required.

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Activation of mineralocorticoid receptors facilitate the acquisition of fear memory extinction and impair the generalization of fear memory in diabetic animals

Psychopharmacology ◽

10.1007/s00213-019-05388-9 ◽

2019 ◽

Vol 237 (2) ◽

pp. 529-542

Author(s):

Thiago Oliari Ribeiro ◽

Letícia Morais Bueno-de-Camargo ◽

Ana Paula Farias Waltrick ◽

Amanda Ribeiro de Oliveira ◽

Marcus Lira Brandão ◽

...

Keyword(s):

Fear Memory ◽

Mineralocorticoid Receptors ◽

Memory Extinction

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Fear Memory Extinction is Blocked Following Acute Glial Cell Inhibition With Ibudilast: Implications for Targeting Neuroinflammation in Preclinical Traumatic Stress Exposure Models

Biological Psychiatry ◽

10.1016/j.biopsych.2020.02.746 ◽

2020 ◽

Vol 87 (9) ◽

pp. S289

Author(s):

Rachel Taylor ◽

Matthew May ◽

Gabriella Silva ◽

Elizabeth Bergman ◽

Nicole Moore ◽

...

Keyword(s):

Glial Cell ◽

Traumatic Stress ◽

Fear Memory ◽

Stress Exposure ◽

Exposure Models ◽

Memory Extinction ◽

Cell Inhibition

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Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2008.07.001 ◽

2008 ◽

Vol 18 (12) ◽

pp. 849-859 ◽

Cited By ~ 137

Author(s):

Rafael M. Bitencourt ◽

Fabrício A. Pamplona ◽

Reinaldo N. Takahashi

Keyword(s):

Fear Memory ◽

Contextual Fear ◽

Contextual Fear Memory ◽

Memory Extinction

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Rethinking the role of L-type voltage-gated calcium channels in fear memory extinction

Learning & Memory ◽

10.1101/lm.996908 ◽

2008 ◽

Vol 15 (5) ◽

pp. 324-325 ◽

Cited By ~ 5

Author(s):

G. E. Schafe

Keyword(s):

Calcium Channels ◽

Fear Memory ◽

Voltage Gated ◽

Voltage Gated Calcium Channels ◽

Memory Extinction

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Role of voltage-gated L-type Ca2+ channel isoforms for brain function

Biochemical Society Transactions ◽

10.1042/bst0340903 ◽

2006 ◽

Vol 34 (5) ◽

pp. 903-909 ◽

Cited By ~ 107

Author(s):

J. Striessnig ◽

A. Koschak ◽

M.J. Sinnegger-Brauns ◽

A. Hetzenauer ◽

N.K. Nguyen ◽

...

Keyword(s):

Brain Function ◽

Drug Targets ◽

Mouse Strains ◽

Voltage Gated ◽

Brain Functions ◽

Memory Extinction ◽

Individual Contributions ◽

The Individual ◽

Neuronal Functions ◽

Ca2 Channels

Voltage-gated LTCCs (L-type Ca2+ channels) are established drug targets for the treatment of cardiovascular diseases. LTCCs are also expressed outside the cardiovascular system. In the brain, LTCCs control synaptic plasticity in neurons, and DHP (dihydropyridine) LTCC blockers such as nifedipine modulate brain function (such as fear memory extinction and depression-like behaviour). Voltage-sensitive Ca2+ channels Cav1.2 and Cav1.3 are the predominant brain LTCCs. As DHPs and other classes of organic LTCC blockers inhibit both isoforms, their pharmacological distinction is impossible and their individual contributions to defined brain functions remain largely unknown. Here, we summarize our recent experiments with two genetically modified mouse strains, which we generated to explore the individual biophysical features of Cav1.2 and Cav1.3 LTCCs and to determine their relative contributions to various physiological peripheral and neuronal functions. The results described here also allow predictions about the pharmacotherapeutic potential of isoform-selective LTCC modulators.

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