Skip to main content
main-content
Erschienen in: Brain Structure and Function 7/2021

27.06.2021 | Original Article

Increased mGlu5 mRNA expression in BLA glutamate neurons facilitates resilience to the long-term effects of a single predator scent stress exposure

verfasst von: John Shallcross, Lizhen Wu, Courtney S. Wilkinson, Lori A. Knackstedt, Marek Schwendt

Erschienen in: Brain Structure and Function | Ausgabe 7/2021

Einloggen, um Zugang zu erhalten

Abstract

Post-traumatic stress disorder (PTSD) develops in a subset of individuals exposed to a trauma with core features being increased anxiety and impaired fear extinction. To model the heterogeneity of PTSD behavioral responses, we exposed male Sprague–Dawley rats to predator scent stress once for 10 min and then assessed anxiety-like behavior 7 days later using the elevated plus maze and acoustic startle response. Rats displaying anxiety-like behavior in both tasks were classified as stress Susceptible, and rats exhibiting behavior no different from un-exposed Controls were classified as stress Resilient. In Resilient rats, we previously found increased mRNA expression of mGlu5 in the amygdala and prefrontal cortex (PFC) and CB1 in the amygdala. Here, we performed fluorescent in situ hybridization (FISH) to determine the subregion and cell-type-specific expression of these genes in Resilient rats 3 weeks after TMT exposure. Resilient rats displayed increased mGlu5 mRNA expression in the basolateral amygdala (BLA) and the infralimbic and prelimbic regions of the PFC and increased BLA CB1 mRNA. These increases were limited to glutamatergic cells. To test the necessity of mGlu5 for attenuating TMT-conditioned contextual fear 3 weeks after TMT conditioning, intra-BLA infusions of the mGlu5 negative allosteric modulator MTEP were administered prior to context re-exposure. In TMT-exposed Resilient rats, but not Controls, MTEP increased freezing on the day of administration, which extinguished over two additional un-drugged sessions. These results suggest that increased mGlu5 expression in BLA glutamate neurons contributes to the behavioral flexibility observed in stress-Resilient animals by facilitating a capacity for extinguishing contextual fear associations.
Literatur
Zurück zum Zitat Abraham WC (2008) Metaplasticity: tuning synapses and networks for plasticity. Nat Rev Neurosci 9:387–399 CrossRef Abraham WC (2008) Metaplasticity: tuning synapses and networks for plasticity. Nat Rev Neurosci 9:387–399 CrossRef
Zurück zum Zitat Bouton ME, Westbrook RF, Corcoran KA, Maren S (2006) Contextual and temporal modulation of extinction: behavioral and biological mechanisms. Biol Psychiatry 60:352–360 CrossRef Bouton ME, Westbrook RF, Corcoran KA, Maren S (2006) Contextual and temporal modulation of extinction: behavioral and biological mechanisms. Biol Psychiatry 60:352–360 CrossRef
Zurück zum Zitat Castillo PE, Younts TJ, Chávez AE, Hashimotodani Y (2012) Endocannabinoid signaling and synaptic function. Neuron 76:70–81 CrossRef Castillo PE, Younts TJ, Chávez AE, Hashimotodani Y (2012) Endocannabinoid signaling and synaptic function. Neuron 76:70–81 CrossRef
Zurück zum Zitat Duvarci S, Pare D (2014) Amygdala microcircuits controlling learned fear. Neuron 82:966–980 CrossRef Duvarci S, Pare D (2014) Amygdala microcircuits controlling learned fear. Neuron 82:966–980 CrossRef
Zurück zum Zitat Ehrlich I, Humeau Y, Grenier F et al (2009) Amygdala inhibitory circuits and the control of fear memory. Neuron 62:757–771 CrossRef Ehrlich I, Humeau Y, Grenier F et al (2009) Amygdala inhibitory circuits and the control of fear memory. Neuron 62:757–771 CrossRef
Zurück zum Zitat Ferraguti F, Shigemoto R (2006) Metabotropic glutamate receptors. Cell Tissue Res 326:483–504 CrossRef Ferraguti F, Shigemoto R (2006) Metabotropic glutamate receptors. Cell Tissue Res 326:483–504 CrossRef
Zurück zum Zitat Kano M, Ohno-Shosaku T, Hashimotodani Y et al (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89:309–380 CrossRef Kano M, Ohno-Shosaku T, Hashimotodani Y et al (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89:309–380 CrossRef
Zurück zum Zitat Koenigs M, Grafman J (2009) Posttraumatic stress disorder: the role of medial prefrontal cortex and amygdala. Neuroscientist 15:540–548 CrossRef Koenigs M, Grafman J (2009) Posttraumatic stress disorder: the role of medial prefrontal cortex and amygdala. Neuroscientist 15:540–548 CrossRef
Zurück zum Zitat Krabbe S, Gründemann J, Lüthi A (2018) Amygdala inhibitory circuits regulate associative fear conditioning. Biol Psychiatry 83:800–809 CrossRef Krabbe S, Gründemann J, Lüthi A (2018) Amygdala inhibitory circuits regulate associative fear conditioning. Biol Psychiatry 83:800–809 CrossRef
Zurück zum Zitat Pape HC, Pare D (2010) Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol Rev 90:419–463 CrossRef Pape HC, Pare D (2010) Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol Rev 90:419–463 CrossRef
Zurück zum Zitat Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, London Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, London
Zurück zum Zitat Sah P, Faber ESL, De Armentia ML, Power J (2003) The amygdaloid complex: anatomy and physiology. Physiol Rev 83:803–834 CrossRef Sah P, Faber ESL, De Armentia ML, Power J (2003) The amygdaloid complex: anatomy and physiology. Physiol Rev 83:803–834 CrossRef
Zurück zum Zitat Sareen J (2014) Posttraumatic stress disorder in adults: impact, comorbidity, risk factors, and treatment. Can J Psychiatry 59:460–467 CrossRef Sareen J (2014) Posttraumatic stress disorder in adults: impact, comorbidity, risk factors, and treatment. Can J Psychiatry 59:460–467 CrossRef
Zurück zum Zitat Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671–675 CrossRef Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671–675 CrossRef
Zurück zum Zitat Sotres-Bayon F, Cain CK, LeDoux JE (2006) Brain mechanisms of fear extinction: historical perspectives on the contribution of prefrontal cortex. Biol Psychiatry 60:329–336 CrossRef Sotres-Bayon F, Cain CK, LeDoux JE (2006) Brain mechanisms of fear extinction: historical perspectives on the contribution of prefrontal cortex. Biol Psychiatry 60:329–336 CrossRef
Metadaten
Titel
Increased mGlu5 mRNA expression in BLA glutamate neurons facilitates resilience to the long-term effects of a single predator scent stress exposure
verfasst von
John Shallcross
Lizhen Wu
Courtney S. Wilkinson
Lori A. Knackstedt
Marek Schwendt
Publikationsdatum
27.06.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
Brain Structure and Function / Ausgabe 7/2021
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-021-02326-4