TY - JOUR
T1 - Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala
AU - Krishnan, Balaji
AU - Scott, Michael T.
AU - Pollandt, Sebastian
AU - Schroeder, Bradley
AU - Kurosky, Alexander
AU - Shinnick-Gallagher, Patricia
N1 - Funding Information:
This study was funded by the FP7-DIGISOIL project (FP7-ENV-2007- 1 N°211523) that was financed by the EC under the 7th Framework Programme for Research and Technological Development, Area “Environment”, Activity 6.3 “Environmental Technologies”. The authors particularly thank J.L. Belotti for this assistance with the soil analysis.
Funding Information:
This work was supported by NRSA F32 Ruth L. Kirschstein postdoctoral Grant DA023316 , and NIDA R03 DA033428 to B.K., and an NHLBI Proteomics Center Award N01-HV-00245 . The authors acknowledge Robert Fox, David V. Herin (deceased), Luis F. Orozco-Cabal for technical assistance with survival surgeries. The authors acknowledge Kelly Dineley and especially Gladys Ko, Anusha Srinivasan for their suggestions and critical reading of the manuscript. The authors declare no competing financial interests.
Publisher Copyright:
© 2015.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Long-term memory (LTM) of fear stores activity dependent modifications that include changes in amygdala signaling. Previously, we identified an enhanced probability of release of glutamate mediated signaling to be important in rat fear potentiated startle (FPS), a well-established translational behavioral measure of fear. Here, we investigated short- and long-term synaptic plasticity in FPS involving metabotropic glutamate receptors (mGluRs) and associated downstream proteomic changes in the thalamic-lateral amygdala pathway (Th-LA). Aldolase A, an inhibitor of phospholipase D (PLD), expression was reduced, concurrent with significantly elevated PLD protein expression. Blocking the PLD-mGluR signaling significantly reduced PLD activity. While transmitter release probability increased in FPS, PLD-mGluR agonist and antagonist actions were occluded. In the unpaired group (UNP), blocking the PLD-mGluR increased while activating the receptor decreased transmitter release probability, consistent with decreased synaptic potentials during tetanic stimulation. FPS Post-tetanic potentiation (PTP) immediately following long-term potentiation (LTP) induction was significantly increased. Blocking PLD-mGluR signaling prevented PTP and reduced cumulative PTP probability but not LTP maintenance in both groups. These effects are similar to those mediated through mGluR7, which is co-immunoprecipitated with PLD in FPS. Lastly, blocking mGluR-PLD in the rat amygdala was sufficient to prevent behavioral expression of fear memory. Thus, our study in the Th-LA pathway provides the first evidence for PLD as an important target of mGluR signaling in amygdala fear-associated memory. Importantly, the PLD-mGluR provides a novel therapeutic target for treating maladaptive fear memories in posttraumatic stress and anxiety disorders.
AB - Long-term memory (LTM) of fear stores activity dependent modifications that include changes in amygdala signaling. Previously, we identified an enhanced probability of release of glutamate mediated signaling to be important in rat fear potentiated startle (FPS), a well-established translational behavioral measure of fear. Here, we investigated short- and long-term synaptic plasticity in FPS involving metabotropic glutamate receptors (mGluRs) and associated downstream proteomic changes in the thalamic-lateral amygdala pathway (Th-LA). Aldolase A, an inhibitor of phospholipase D (PLD), expression was reduced, concurrent with significantly elevated PLD protein expression. Blocking the PLD-mGluR signaling significantly reduced PLD activity. While transmitter release probability increased in FPS, PLD-mGluR agonist and antagonist actions were occluded. In the unpaired group (UNP), blocking the PLD-mGluR increased while activating the receptor decreased transmitter release probability, consistent with decreased synaptic potentials during tetanic stimulation. FPS Post-tetanic potentiation (PTP) immediately following long-term potentiation (LTP) induction was significantly increased. Blocking PLD-mGluR signaling prevented PTP and reduced cumulative PTP probability but not LTP maintenance in both groups. These effects are similar to those mediated through mGluR7, which is co-immunoprecipitated with PLD in FPS. Lastly, blocking mGluR-PLD in the rat amygdala was sufficient to prevent behavioral expression of fear memory. Thus, our study in the Th-LA pathway provides the first evidence for PLD as an important target of mGluR signaling in amygdala fear-associated memory. Importantly, the PLD-mGluR provides a novel therapeutic target for treating maladaptive fear memories in posttraumatic stress and anxiety disorders.
KW - Amygdala memory mechanisms
KW - Fear potentiated startle
KW - Neuropharmacology
KW - Neurophysiology
KW - Phospholipase D
KW - Proteomic studies
UR - http://www.scopus.com/inward/record.url?scp=84953720341&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84953720341&partnerID=8YFLogxK
U2 - 10.1016/j.nlm.2015.12.009
DO - 10.1016/j.nlm.2015.12.009
M3 - Article
C2 - 26748024
AN - SCOPUS:84953720341
VL - 128
SP - 65
EP - 79
JO - Communications in behavioral biology. Part A: [Original articles]
JF - Communications in behavioral biology. Part A: [Original articles]
SN - 1074-7427
ER -