TY - JOUR
T1 - Activity-dependent signaling
T2 - Influence on plasticity in circuits controlling fear-related behavior
AU - Hill, Julia L.
AU - Martinowich, Keri
N1 - Funding Information:
Activity-dependent BDNF signaling significantly impacts excitatory/inhibitory (E/I) balance via its regulation of both glutamatergic and GABAergic neurotransmission. As demonstrated in a number of genetic models, proper E/I balance is critical in regulating fear and anxiety [ 35,38,61 ]. While BDNF is primarily expressed in glutamatergic cells, tropomysin receptor kinase B (TrkB), BDNF's cognate receptor, is expressed in both excitatory and inhibitory neurons [ 62,63 ]. BDNF-TrkB signaling is implicated in inhibitory synapse function and controls the maturation of cortical inhibition [ 64 ]. Since BDNF potently regulates GABAergic synapses, BDNF signaling is theorized to be a key mechanism in the homeostatic plasticity that maintains E/I balance [ 65 ]. This idea is supported by the fact that neural activity induces Bdnf expression, and the subsequently produced BDNF promotes inhibition to dampen excitability. Evidence that disrupting activity-dependent Bdnf expression and secretion impairs inhibitory synapses and GABAergic transmission provides additional empirical support for this hypothesis [ 56,66 ]. Genetically altered mice in which activity-dependent BDNF signaling is attenuated have fewer fast-spiking PV interneurons and reduced inhibitory post-synaptic currents (IPSC) in PFC, contributing to impaired GABAergic transmission [ 38,67 ]. Several interneuron subtypes express TrkB, providing a mechanistic basis for controlling inhibitory synaptic potentiation [ 63 ]. This possibility is strengthened by evidence that TrkB deletion in PV-interneurons decreases their action potential generation [ 68 ]. Evidence that heterozygous TrkB deletion in PV-interneurons causes fear extinction deficits suggests that TrkB signaling may contribute to the ability of PV-interneurons to regulate fear [ 61 ]. Thus, BDNF's ability to properly regulate fear learning and extinction may be mediated at least in part by its critical role in inhibitory plasticity and E/I balance.
Publisher Copyright:
© 2015 Elsevier Ltd.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Fear regulation is impaired in anxiety and trauma-related disorders. Patients experience heightened fear expression and reduced ability to extinguish fear memories. Because fear regulation is abnormal in these disorders and extinction recapitulates current treatment strategies, understanding the underlying mechanisms is vital for developing new treatments. This is critical because although extinction-based exposure therapy is a mainstay of treatment, relapse is common. We examine recent findings describing changes in network activity and functional connectivity within limbic circuits during fear regulation, and explore how activity-dependent signaling contributes to the neural activity patterns that control fear and anxiety. We review the role of the prototypical activity-dependent molecule, brain-derived neurotrophic factor (BDNF), whose signaling has been critically linked to regulation of fear behavior.
AB - Fear regulation is impaired in anxiety and trauma-related disorders. Patients experience heightened fear expression and reduced ability to extinguish fear memories. Because fear regulation is abnormal in these disorders and extinction recapitulates current treatment strategies, understanding the underlying mechanisms is vital for developing new treatments. This is critical because although extinction-based exposure therapy is a mainstay of treatment, relapse is common. We examine recent findings describing changes in network activity and functional connectivity within limbic circuits during fear regulation, and explore how activity-dependent signaling contributes to the neural activity patterns that control fear and anxiety. We review the role of the prototypical activity-dependent molecule, brain-derived neurotrophic factor (BDNF), whose signaling has been critically linked to regulation of fear behavior.
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U2 - 10.1016/j.conb.2015.10.001
DO - 10.1016/j.conb.2015.10.001
M3 - Review article
C2 - 26485574
AN - SCOPUS:84944711367
VL - 36
SP - 59
EP - 65
JO - Current Opinion in Neurobiology
JF - Current Opinion in Neurobiology
SN - 0959-4388
ER -