title: Reactivating fear memory under propranolol resets pre-trauma levels of dendritic spines in basolateral amygdala but not dorsal hippocampus neurons.
abstract: Fear memory enhances connectivity in cortical and limbic circuits but whether treatments disrupting fear reset connectivity to pre-trauma level is unknown. Here we report that C56BL/6J mice exposed to a tone-shock association in context A (conditioning), and briefly re-exposed to the same tone-shock association in context B (reactivation), exhibit strong freezing to the tone alone delivered 48 h later in context B (long term fear memory). This intense fear response is associated with a massive increase in dendritic spines and phospho-Erk (p-ERK) signaling in basolateral amygdala (BLA) but neurons. We then show that propranolol (a central/peripheral β-adrenergic receptor blocker) administered before, but not after, the reactivation trial attenuates long term fear memory assessed drug free 48 h later, and completely prevents the increase in spines and p-ERK signaling in BLA neurons. An increase in spines, but not of p-ERK, was also detected in the dorsal hippocampus (DH) of the conditioned mice. DH spines, however, were unaffected by propranolol suggesting their independence from the ERK/β-ARs cascade. We conclude that propranolol selectively blocks dendritic spines and p-ERK signaling enhancement in the BLA; its effect on fear memory is, however, less pronounced suggesting that the persistence of spines at other brain sites decreases the sensitivity of the fear memory trace to treatments selectively targeting β ARs in the BLA.
authors.affiliation: IRCCS Santa Lucia Foundation Rome, Italy ; Institute of Cell Biology and Neurobiology, National Research Council (CNR) Rome, Italy.
authors.forename: Gisella
authors.initials: G
authors.lastname: Vetere
authors.affiliation: Institute of Cell Biology and Neurobiology, National Research Council (CNR) Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Piserchia
authors.affiliation: IRCCS Santa Lucia Foundation Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Borreca
authors.affiliation: Institute of Cell Biology and Neurobiology, National Research Council (CNR) Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Novembre
authors.affiliation: IRCCS Santa Lucia Foundation Rome, Italy ; Institute of Cell Biology and Neurobiology, National Research Council (CNR) Rome, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Aceti
authors.affiliation: IRCCS Santa Lucia Foundation Rome, Italy ; Institute of Cell Biology and Neurobiology, National Research Council (CNR) Rome, Italy.
authors.forename: Martine
authors.initials: M
authors.lastname: Ammassari-Teule
keywords: amygdala; dendritic spines; fear memory reactivation; hippocampus; p-ERK; propranolol