Gq neuromodulation of BLA parvalbumin interneurons induces burst firing and mediates fear-associated network and behavioral state transition in mice

• Published in: Nature communications Vol. 13; no. 1; pp. 1290 - 16
• Main Authors: Fu, Xin, Teboul, Eric, Weiss, Grant L., Antonoudiou, Pantelis, Borkar, Chandrashekhar D., Fadok, Jonathan P., Maguire, Jamie, Tasker, Jeffrey G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14/34; 42; 631/378/1457/1284; 631/378/1697/2602; 64/110; 9/30; 9/74; 96/109; 96/95; Adrenergic receptors; Amygdala; Animals; Basolateral Nuclear Complex - metabolism; Brain; Fear; Fear conditioning; Humanities and Social Sciences; Inhibitory postsynaptic potentials; Inhibitory Postsynaptic Potentials - physiology; Interneurons; Interneurons - metabolism; Memory; Mice; multidisciplinary; Neuromodulation; Neurons; Neurosciences; Oscillations; Parvalbumin; Parvalbumins - metabolism; Recall; Receptor mechanisms; Science; Science (multidisciplinary); Time synchronization
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28928-y

Patterned coordination of network activity in the basolateral amygdala (BLA) is important for fear expression. Neuromodulatory systems play an essential role in regulating changes between behavioral states, however the mechanisms underlying this neuromodulatory control of transitions between brain and behavioral states remain largely unknown. We show that chemogenetic Gq activation and α1 adrenoreceptor activation in mouse BLA parvalbumin (PV) interneurons induces a previously undescribed, stereotyped phasic bursting in PV neurons and time-locked synchronized bursts of inhibitory postsynaptic currents and phasic firing in BLA principal neurons. This Gq-coupled receptor activation in PV neurons suppresses gamma oscillations in vivo and in an ex vivo slice model, and facilitates fear memory recall, which is consistent with BLA gamma suppression during conditioned fear expression. Thus, here we identify a neuromodulatory mechanism in PV inhibitory interneurons of the BLA which regulates BLA network oscillations and fear memory recall. The authors study mechanisms underlying neuromodulatory control of transitions between brain and behavioral states. They identify a mechanism whereby modulation of Gq activity in basolateral amygdala parvalbumin interneurons mediates the transition to a fear-associated network and behavioral state.