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File085 - Role of NT3/TrkC in the regulation of fear2019-032023-07

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2018
Location: BF-GMS
Title:
2018 Grants
Start date: 2019-01

Reference code: PT/FB/BL-2018-085
Location: BF-GMS
Title:
085 - Role of NT3/TrkC in the regulation of fear
Duration: 2019-03 - 2023-07
Researcher(s):
Mónica Santos
Institution(s): Center for Neuroscience and Cell Biology, University of Coimbra (Portugal)
Contents: Contents:
Application form
Correspondence
Research Funding Agreement
Progress report
Final report
Article
Language: eng
Author:
Santos, M.
Number of reproductions:
1
Keywords:
Neurotrophin 3 / Fear conditioning / TrkC / Fear extinction / Psychophysiology

DocumentMale-specific features are reduced in Mecp2-null mice: Analyses of vasopressinergic innervation, pheromone production and social behaviour2020

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2018
Location: BF-GMS
Title:
2018 Grants
Start date: 2019-01

Reference code: PT/FB/BL-2018-085
Location: BF-GMS
Title:
085 - Role of NT3/TrkC in the regulation of fear
Duration: 2019-03 - 2023-07
Researcher(s):
Mónica Santos
Institution(s): Center for Neuroscience and Cell Biology, University of Coimbra (Portugal)
Contents: Contents:
Application form
Correspondence
Research Funding Agreement
Progress report
Final report
Article
Language: eng
Author:
Santos, M.
Number of reproductions:
1
Keywords:
Neurotrophin 3 / Fear conditioning / TrkC / Fear extinction / Psychophysiology

Reference code: PT/FB/BL-2018-085.02
Location: BF-GMS
Title:
Male-specific features are reduced in Mecp2-null mice: Analyses of vasopressinergic innervation, pheromone production and social behaviour
Publication year: 2020
URL:
https://link.springer.com/article/10.1007/s00429-020-02122-6#citeas
Abstract/Results: ABSTRACT:
Deficits in arginine vasopressin (AVP) and oxytocin (OT), two neuropeptides closely implicated in the modulation of social behaviours, have been reported in some early developmental disorders and autism spectrum disorders. Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene are associated to Rett syndrome and other neuropsychiatric conditions. Thus, we first analysed AVP and OT expression in the brain of Mecp2-mutant mice by immunohistochemistry. Our results revealed no significant differences in these systems in young adult Mecp2-heterozygous females, as compared to WT littermates. By contrast, we found a significant reduction in the sexually dimorphic, testosterone-dependent, vasopressinergic innervation in several nuclei of the social brain network and oxytocinergic innervation in the lateral habenula of Mecp2-null males, as compared to WT littermates. Analysis of urinary production of pheromones shows that Mecp2-null males lack the testosterone-dependent pheromone darcin, strongly suggesting low levels of androgens in these males. In addition, resident-intruder tests revealed lack of aggressive behaviour in Mecp2-null males and decreased chemoinvestigation of the intruder. By contrast, Mecp2-null males exhibited enhanced social approach, as compared to WT animals, in a 3-chamber social interaction test. In summary, Mecp2-null males, which display internal testicles, display a significant reduction of some male-specific features, such as vasopressinergic innervation within the social brain network, male pheromone production and aggressive behaviour. Thus, atypical social behaviours in Mecp2-null males may be caused, at least in part, by the effect of lack of MeCP2 over sexual differentiation.
Accessibility: Document exists in file
Copyright/Reproduction:
By permission
Language:
eng
Author:
Martínez-Rodríguez, E.
Secondary author(s):
Martín-Sánchez, A., Kul, E., Bose, A., Martínez-Martínez, F. J., Stork, O., Martínez-García, F., Lanuza, E., Santos, M., Agustín-Pavón, C.
Document type:
Article
Number of reproductions:
1
Percentiles:
7
Reference:
Martínez-Rodríguez, E., Martín-Sánchez, A., Kul, E., Bose, A., Martínez-Martínez, F. J., Stork, O., ... Agustín-Pavón, C. (2020). Male-specific features are reduced in Mecp2-null mice: Analyses of vasopressinergic innervation, pheromone production and social behaviour. Brain Structure and Function, 225(7), 2219-2238. https://doi.org/10.1007/s00429-020-02122-6
2-year Impact Factor: 3.270|2020
Times cited: 5|2024-02-13
Indexed document: Yes
Quartile: Q1
Keywords: Aggression / Autism spectrum disorders / Methyl-CpG-binding protein 2 / Nonapeptides / Rett syndrome / Social behaviour

DocumentTrkC intracellular signalling in the brain fear network during the formation of a contextual fear memory2023

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2018
Location: BF-GMS
Title:
2018 Grants
Start date: 2019-01

Reference code: PT/FB/BL-2018-085
Location: BF-GMS
Title:
085 - Role of NT3/TrkC in the regulation of fear
Duration: 2019-03 - 2023-07
Researcher(s):
Mónica Santos
Institution(s): Center for Neuroscience and Cell Biology, University of Coimbra (Portugal)
Contents: Contents:
Application form
Correspondence
Research Funding Agreement
Progress report
Final report
Article
Language: eng
Author:
Santos, M.
Number of reproductions:
1
Keywords:
Neurotrophin 3 / Fear conditioning / TrkC / Fear extinction / Psychophysiology

Reference code: PT/FB/BL-2018-085.03
Location: BF-GMS
Title:
TrkC intracellular signalling in the brain fear network during the formation of a contextual fear memory
Publication year: 2023
URL:
https://link.springer.com/article/10.1007/s12035-023-03292-0
Abstract/Results: ABSTRACT:
Learned fear is orchestrated by a brain fear network that comprises the amygdala, hippocampus and the medial prefrontal cortex. Synaptic plasticity within this network is critical for the formation of proper fear memories. Known for their role in the promotion of synaptic plasticity, neurotrophins position as obvious candidates in the regulation of fear processes. Indeed, recent evidence from our laboratory and others associates dysregulated signalling through neurotrophin-3 and its receptor TrkC with the pathophysiology of anxiety and fear-related disorders. Here, we put wild-type C57Bl/6J mice through a contextual fear conditioning paradigm in order to characterize TrkC activation and expression in the main brain regions involved in (learned) fear – amygdala, hippocampus, and prefrontal cortex – during the formation of a fear memory. We report an overall decreased activation of TrkC in the fear network during fear consolidation and reconsolidation. During reconsolidation, hippocampal TrkC downregulation was accompanied by a decrease in the expression and activation of Erk, a critical signalling pathway in fear conditioning. Moreover, we did not find evidence that the observed decrease of TrkC activation was caused by altered expression of dominant negative form of TrkC, neurotrophin-3, or the PTP1B phosphatase. Our results indicate hippocampal TrkC inactivation through Erk signalling as a potential mechanism in the regulation of contextual fear memory formation.
Accessibility: Document exists in file
Language:
eng
Author:
Silva, F.
Secondary author(s):
Masella, G., Madeira, M. F., Duarte, C. B., Santos, M.
Document type:
Article
Number of reproductions:
1
Percentiles:
6
Reference:
Silva, F., Masella, G., Madeira, M. F., Duarte, C. B., & Santos, M. (2023). TrkC Intracellular Signalling in the Brain Fear Network During the Formation of a Contextual Fear Memory. Molecular Neurobiology, 60(6), 3507–3521. https://doi.org/10.1007/s12035-023-03292-0
2-year Impact Factor: 5.100|2022
Impact factor notes: Impact factor not available yet for 2023
Times cited: 1|2024-02-16
Indexed document: Yes
Quartile: Q2
Keywords: Fear conditioning / Neurotrophin 3 / Erk / Akt / PLC

TrkC intracellular signalling in the brain fear network during the formation of a contextual fear memory

TrkC intracellular signalling in the brain fear network during the formation of a contextual fear memory

DocumentFinal report - Role of NT3/TrkC in the regulation of fear2023

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2018
Location: BF-GMS
Title:
2018 Grants
Start date: 2019-01

Reference code: PT/FB/BL-2018-085
Location: BF-GMS
Title:
085 - Role of NT3/TrkC in the regulation of fear
Duration: 2019-03 - 2023-07
Researcher(s):
Mónica Santos
Institution(s): Center for Neuroscience and Cell Biology, University of Coimbra (Portugal)
Contents: Contents:
Application form
Correspondence
Research Funding Agreement
Progress report
Final report
Article
Language: eng
Author:
Santos, M.
Number of reproductions:
1
Keywords:
Neurotrophin 3 / Fear conditioning / TrkC / Fear extinction / Psychophysiology

Reference code: PT/FB/BL-2018-085.01
Location: BF-GMS
Title:
Final report - Role of NT3/TrkC in the regulation of fear
Publication year: 2023
Abstract/Results:
ABSTRACT:
Background
Anxiety disorders are among the most prevalent psychiatric conditions, sharing exaggerated fear and resistance to extinction. A role for NT3-TrkC pathway in the regulation of pathological fear has been described, though its role in physiological conditions has never been investigated.
Aims
The aim of this project was to investigate the contribution of the NT3-TrkC pathway to the formation and extinction of physiological fear memories.
Method
Young adult male mice were trained in the contextual fear conditioning and extinction paradigm, a flagship model to study learned fear and extinction. We used a multidisciplinary approach that combined rodent behavior with pharmacological and molecular tools, and ex vivo electrophysiological recordings, to investigate the cellular and molecular mechanisms underlying the role of NT3-TrkC in fear memories.
Results
We found that a strict spatio-temporal regulation of TrkC activation is necessary for the proper formation and extinction of fear memories. Moreover, we identified a role for the amygdalar NT3-TrkC pathway in the naturally existing inter-individual variation in fear extinction in mice. Amygdalar TrkC activation is sufficient to rescue fear extinction deficits through modulation of synaptic plasticity. In particular, activation of TrkC induces LTD, weakens LTP and results in the synaptic accumulation of GluN2B-containing NMDA receptors.
Conclusions
Data obtained proves a role for the NT3-TrkC pathway in the formation and extinction of fear memories. This study puts forward TrkC as a molecule of interest in the research of mechanism-based drugs towards patients with fear-related disorders.
Accessibility: Document exists in file
Language:
eng
Author:
Santos, M.
Document type:
Final report
Number of reproductions:
1
Reference:
Santos, M. (2023). Final report - Role of NT3/TrkC in the regulation of fear.
Indexed document: No
Keywords: Neurotrophins / Fear extinction / Anxiety disorders / Synaptic plasticity

Final report - Role of NT3/TrkC in the regulation of fear

Final report - Role of NT3/TrkC in the regulation of fear

DocumentThe amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity2024

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2018
Location: BF-GMS
Title:
2018 Grants
Start date: 2019-01

Reference code: PT/FB/BL-2018-085
Location: BF-GMS
Title:
085 - Role of NT3/TrkC in the regulation of fear
Duration: 2019-03 - 2023-07
Researcher(s):
Mónica Santos
Institution(s): Center for Neuroscience and Cell Biology, University of Coimbra (Portugal)
Contents: Contents:
Application form
Correspondence
Research Funding Agreement
Progress report
Final report
Article
Language: eng
Author:
Santos, M.
Number of reproductions:
1
Keywords:
Neurotrophin 3 / Fear conditioning / TrkC / Fear extinction / Psychophysiology

Reference code: PT/FB/BL-2018-085.04
Location: BF-GMS
Title:
The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity
Publication year: 2024
URL:
https://doi.org/10.1038/s41380-024-02412-z
Abstract/Results: ABSTRACT:
Fear-related pathologies are among the most prevalent psychiatric conditions, having inappropriate learned fear and resistance to extinction as cardinal features. Exposure therapy represents a promising therapeutic approach, the efficiency of which depends on inter-individual variation in fear extinction learning, which neurobiological basis is unknown. We characterized a model of extinction learning, whereby fear-conditioned mice were categorized as extinction (EXT)-success or EXT-failure, according to their inherent ability to extinguish fear. In the lateral amygdala, GluN2A-containing NMDAR are required for LTP and stabilization of fear memories, while GluN2B-containing NMDAR are required for LTD and fear extinction. EXT-success mice showed attenuated LTP, strong LTD and higher levels of synaptic GluN2B, while EXT-failure mice showed strong LTP, no LTD and higher levels of synaptic GluN2A. Neurotrophin 3 (NT3) infusion in the lateral amygdala was sufficient to rescue extinction deficits in EXT-failure mice. Mechanistically, activation of tropomyosin receptor kinase C (TrkC) with NT3 in EXT-failure slices attenuated lateral amygdala LTP, in a GluN2B-dependent manner. Conversely, blocking endogenous NT3-TrkC signaling with TrkC-Fc chimera in EXT-success slices strengthened lateral amygdala LTP. Our data support a key role for the NT3-TrkC system in inter-individual differences in fear extinction in rodents, through modulation of amygdalar NMDAR composition and synaptic plasticity.
Accessibility: Document exists in file
Language:
eng
Author:
Masella, G.
Secondary author(s):
Silva, F., Corti, E., Azkona, G., Madeira, M. F., Tomé, Â. R., Ferreira, S. G., Cunha, R. A., Duarte, C. B., Santos, M
Document type:
Article
Number of reproductions:
1
Reference:
Masella, G., Silva, F., Corti, E., Azkona, G., Madeira, M. F., Tomé, Â. R., Ferreira, S. G., Cunha, R. A., Duarte, C. B., & Santos, M. (2024). The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity. Molecular Psychiatry, 10.1038/s41380-024-02412-z. Advance online publication. https://doi.org/10.1038/s41380-024-02412-z
2-year Impact Factor: 11|2022
Impact factor notes: Impact factor not available yet for 2024
Times cited: 0|2024-02-19
Indexed document: Yes
Quartile: Q1
Keywords: Fear extinction learning / GluN2B-containing NMDAR / amygdala NT3-TrkC

The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity

The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity