Regulation of neuronal plasticity and fear by a dynamic change in PAR1-G protein coupling in the amygdala

J. M. Bourgognon, E. Schiavon, H. Salah-Uddin, A. E. Skrzypiec, B. K. Attwood, R. S. Shah, S. G. Patel, M. Mucha, R. A. John Challiss, I. D. Forsythe, R. Pawlak

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Fear memories are acquired through neuronal plasticity, an orchestrated sequence of events regulated at circuit and cellular levels. The conventional model of fear acquisition assumes unimodal (for example, excitatory or inhibitory) roles of modulatory receptors in controlling neuronal activity and learning. Contrary to this view, we show that protease-activated receptor-1 (PAR1) promotes contrasting neuronal responses depending on the emotional status of an animal by a dynamic shift between distinct G protein-coupling partners. In the basolateral amygdala of fear-naive mice PAR1 couples to Gα q/11 and Gα o proteins, while after fear conditioning coupling to Gα o increases. Concurrently, stimulation of PAR1 before conditioning enhanced, but afterwards it inhibited firing of basal amygdala neurons. An initial impairment of the long-term potentiation (LTP) in PAR1-deficient mice was transformed into an increase in LTP and enhancement of fear after conditioning. These effects correlated with more frequent 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) receptor-mediated miniature post synaptic events and increased neuronal excitability. Our findings point to experience-specific shifts in PAR1-G protein coupling in the amygdala as a novel mechanism regulating neuronal excitability and fear.

Original languageEnglish
Pages (from-to)1136-1145
Number of pages10
JournalMolecular Psychiatry
Issue number10
StatePublished - Oct 2013
Externally publishedYes


  • G protein-coupled receptors
  • PAR-1
  • amygdala
  • biased agonism
  • experience-directed signaling
  • fear


Dive into the research topics of 'Regulation of neuronal plasticity and fear by a dynamic change in PAR1-G protein coupling in the amygdala'. Together they form a unique fingerprint.

Cite this