The contribution of within-amygdala meta-plasticity to stress-related psychopathologies
Final Report Abstract
The amygdala substantially contributes to emotional memory formation, e.g. memory of traumatic experiences. Through trauma, the amygdala by itself, but also other brain regions such as hippocampus and prefrontal cortex become profoundly modulated - a mechanism which is named meta-plasticity. In the past, we have analyzed the impact of amygdala plasticity on emotional behavior and resilience. Experience-dependent meta-plasticity was reproduced by genetic blockage of contributing receptors in the amygdala of rats which selectively address innervation by different classes of interneurons. Here, lentiviral knockdown in the amygdala served to compare the receptor TrkB with EphA7 regarding metaplastic changes essential for the processing of stress and trauma. Reduced EphA7 expression correlated with increased anxiety while fear extinction remained unaffected. In contrast, TrkB knockdown in amygdala impaired fear extinction which relies on mPFC functions while anxiety levels were also increased. Knockdown of both receptors did not modulate the acquisition of fear memory. As a BDNF receptor, TrkB controls shc- and PLC- dependent signaling pathways which in turn control the stability of GABAergic synapses through regulation of gephyrin scaffolds. Point mutants of TrkB were generated to inspect the contribution of the different signalling pathways for synaptic stabilization. Our results revealed that extra-synaptic gephyrin clusters become removed through shc-dependent pathways while intrasynaptic gephyrin is regulated by PLC signaling. Moreover, both shcand PLC-signaling account for inhibitory synaptic plasticity (iLTP) as a homeostatic mechanism. In conclusion, the project contributed to the dissection of TrkB signaling pathways important for the stabilization and plasticity of interneuron synapses. In addition, the selective role of TrkB for fear extinction revealed mechanisms of meta-plasticity after amygdala modulation.
Publications
-
Individual behavioral profiling as a translational approach to assess treatment efficacy in an animal model of post-traumatic stress disorder. Frontiers in Neuroscience, 16.
Sarkar, Ishita; Snippe-Strauss, Maja; Tenenhaus Zamir, Adi; Benhos, Amir & Richter-Levin, Gal
-
Dissection of signaling pathways regulating TrkB-dependent gephyrin clustering. Frontiers in Molecular Neuroscience, 17.
Wüstner, Lisa-Sophie; Beuter, Simone; Kriebel, Martin & Volkmer, Hansjürgen
-
Intra-BLA alteration of interneurons’ modulation of activity in rats, reveals a dissociation between effects on anxiety symptoms and extinction learning. Neurobiology of Stress, 33, 100681.
Saha, Rinki; Wüstner, Lisa-Sophie; Chakraborty, Darpan; Anunu, Rachel; Mandel, Silvia; Hazra, Joyeeta Dutta; Kriebel, Martin; Volkmer, Hansjuergen; Kaphzan, Hanoch & Richter-Levin, Gal
-
Selective knockdown of GABAA‐α2 subunit in the dorsal dentate gyrus in adulthood induces anxiety, learning and memory deficits and impairs synaptic plasticity. European Journal of Neuroscience, 60(4), 4393-4408.
Tripathi, Kuldeep; Hazra, Somoday; Hazra, Joyeeta Dutta; Mandel, Silvia; Anunu, Ruchi; Kriebel, Martin; Volkmer, Hansjurgen & Richter‐Levin, Gal
-
Effects of TrkB-related induced metaplasticity within the BLA on anxiety, extinction learning, and plasticity in BLA-modulated brain regions. Behavioral and Brain Functions, 21(1).
Hazra, Joyeeta Dutta; Shrivastava, Kuldeep; Wüstner, Lisa-Sophie; Anunu, Rachel; Chervinsky, Erez; Hazra, Somoday; Beuter, Simone; Kriebel, Martin; Maroun, Mouna; Volkmer, Hansjuergen & Richter-Levin, Gal
