Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala

Balaji Krishnan, Michael T. Scott, Sebastian Pollandt, Bradley Schroeder, Alexander Kurosky, Patricia Shinnick-Gallagher

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)65-79
Number of pages15
JournalNeurobiology of Learning and Memory
Volume128
DOIs
StatePublished - Feb 1 2016

Fingerprint

Phospholipase D
Metabotropic Glutamate Receptors
Amygdala
Fear
Long-Term Potentiation
Synaptic Potentials
Fructose-Bisphosphate Aldolase
Neuronal Plasticity
Long-Term Memory
Post-Traumatic Stress Disorders
Anxiety Disorders
Proteomics
Glutamic Acid
Maintenance

Keywords

  • Amygdala memory mechanisms
  • Fear potentiated startle
  • Neuropharmacology
  • Neurophysiology
  • Phospholipase D
  • Proteomic studies

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Experimental and Cognitive Psychology

Cite this

Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala. / Krishnan, Balaji; Scott, Michael T.; Pollandt, Sebastian; Schroeder, Bradley; Kurosky, Alexander; Shinnick-Gallagher, Patricia.

In: Neurobiology of Learning and Memory, Vol. 128, 01.02.2016, p. 65-79.

Research output: Contribution to journalArticle

Krishnan, Balaji ; Scott, Michael T. ; Pollandt, Sebastian ; Schroeder, Bradley ; Kurosky, Alexander ; Shinnick-Gallagher, Patricia. / Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala. In: Neurobiology of Learning and Memory. 2016 ; Vol. 128. pp. 65-79.
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