1. Locus Coeruleus Norepinephrine Drives Stress-Induced Increases in Basolateral Amygdala Firing and Impairs Extinction Learning.
- Author
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Giustino, Thomas F., Ramanathan, Karthik R., Totty, Michael S., Miles, Olivia W., and Maren, Stephen
- Subjects
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LOCUS coeruleus , *FIREFIGHTING , *AMYGDALOID body , *NORADRENALINE , *CONDITIONED response - Abstract
Stress impairs extinction learning, and these deficits depend, in part, on stress-induced norepinephrine (NE) release in the basolateral amygdala (BLA). For example, systemic or intra-BLA administration of propranolol reduces the immediate extinction deficit (IED), an impairment in extinction learning that occurs when extinction trials are administered soon after fear conditioning. Here, we explored whether locus coeruleus (LC)-NE regulates stress-induced changes in spike firing in the BLA and consequent extinction learning impairments. Rats were implanted with recording arrays in the BLA and, after recovery from surgery, underwent a standard auditory fear conditioning procedure. Fear conditioning produced an immediate and dramatic increase in the spontaneous firing of BLA neurons that persisted (and in some units, increased further) up to an hour after conditioning. This stress-induced increase in BLA firing was prevented by systemic administration of propranolol. Conditioning with a weaker footshock caused smaller increases in BLA firing rate, but this could be augmented by chemogenetic activation of the LC. Conditioned freezing in response to a tone paired with a weak footshock was immune to the IED, but chemogenetic activation of the LC before the weak conditioning protocol increased conditioned freezing behavior and induced an IED; this effect was blocked with intra-BLA infusions of propranolol. These data suggest that stressinduced activation of the LC increases BLA spike firing and causes impairments in extinction learning. Stress-induced increases in BLA activity mediated by LC-NE may be a viable therapeutic target for individuals with stress- and trauma-related disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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