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

Bourgognon, J.-M. et al. (2013) Regulation of neuronal plasticity and fear by a dynamic change in PAR1–G protein coupling in the amygdala. Molecular Psychiatry, 18(10), pp. 1136-1145. (doi: 10.1038/mp.2012.133) (PMID:23032873) (PMCID:PMC3690134)

Abstract

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 Gαq/11 and Gαo proteins, while after fear conditioning coupling to Gαo 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.

• Item Type: Articles
• Additional Information: This work was supported by a Medical Research Council project grant (G0500231/ 73852), and a Marie Curie Excellence grant (MEXT-CT-2006-042265 from European Commission) to Robert Pawlak. We acknowledge the support of ECMNet (COST BM1001).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bourgognon, Dr Julie-Myrtille
• Authors: Bourgognon, J.-M., Schiavon, E., Salah-Uddin, H., Skrzypiec, A. E., Attwood, B. K., Shah, R. S., Patel, S. G., Mucha, M., John Challiss, R. A., Forsythe, I. D., and Pawlak, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
• Journal Name: Molecular Psychiatry
• Publisher: Nature Publishing Group
• ISSN: 1359-4184
• Published Online: 02 October 2012