TY - JOUR
T1 - β-adrenergic enhancement of neuronal excitability in the lateral amygdala is developmentally gated
AU - Fink, Ann E.
AU - LeDoux, Joseph E.
N1 - Funding Information:
This work was supported by National Institute of Mental Health (NIMH) Grant MH-0465 to J. E. LeDoux, National Institute on Drug Abuse Training Grant DA-007254-18, and NIMH Grant F32 MH-100856 to A. E. Fink.
Publisher Copyright:
© 2018 American Physiological Society. All rights reserved.
PY - 2018/5
Y1 - 2018/5
N2 - Noradrenergic signaling in the amygdala is important for processing threats and other emotionally salient stimuli, and β-adrenergic receptor activation is known to enhance neuronal spiking in the lateral amygdala (LA) of juvenile animals. Nevertheless, intracellular recordings have not yet been conducted to determine the effect of β-adrenergic receptor activation on spike properties in the adult LA, despite the potential significance of developmental changes between adolescence and adulthood. Here we demonstrate that the β-adrenergic agonist isoproterenol (15 μM) enhances spike frequency in dorsal LA principal neurons of juvenile male C57BL/6 mice and fails to do so in strain- and sex-matched adults. Furthermore, we find that the age-dependent effect of isoproterenol on spike frequency is occluded by the GABA A receptor blocker picrotoxin (75 μM), suggesting that β-adrenergic receptors downregulate tonic inhibition specifically in juvenile animals. These findings indicate a significant shift during adolescence in the cellular mechanisms of β-adrenergic modulation in the amygdala. NEW & NOTEWORTHY β-Adrenergic receptors (β-ARs) in amygdala are important in processing emotionally salient stimuli. Most cellular recordings have examined juvenile animals, while behavioral data are often obtained from adults. We replicate findings showing that _-ARs enhance spiking of principal cells in the lateral amygdala of juveniles, but we fail to find this in adults. These findings have notable scientific and clinical implications regarding the noradrenergic modulation of threat processing, alterations of which underlie fear and anxiety disorders.
AB - Noradrenergic signaling in the amygdala is important for processing threats and other emotionally salient stimuli, and β-adrenergic receptor activation is known to enhance neuronal spiking in the lateral amygdala (LA) of juvenile animals. Nevertheless, intracellular recordings have not yet been conducted to determine the effect of β-adrenergic receptor activation on spike properties in the adult LA, despite the potential significance of developmental changes between adolescence and adulthood. Here we demonstrate that the β-adrenergic agonist isoproterenol (15 μM) enhances spike frequency in dorsal LA principal neurons of juvenile male C57BL/6 mice and fails to do so in strain- and sex-matched adults. Furthermore, we find that the age-dependent effect of isoproterenol on spike frequency is occluded by the GABA A receptor blocker picrotoxin (75 μM), suggesting that β-adrenergic receptors downregulate tonic inhibition specifically in juvenile animals. These findings indicate a significant shift during adolescence in the cellular mechanisms of β-adrenergic modulation in the amygdala. NEW & NOTEWORTHY β-Adrenergic receptors (β-ARs) in amygdala are important in processing emotionally salient stimuli. Most cellular recordings have examined juvenile animals, while behavioral data are often obtained from adults. We replicate findings showing that _-ARs enhance spiking of principal cells in the lateral amygdala of juveniles, but we fail to find this in adults. These findings have notable scientific and clinical implications regarding the noradrenergic modulation of threat processing, alterations of which underlie fear and anxiety disorders.
KW - Amygdala
KW - Developmental gating
KW - Isoproterenol
KW - Patch clamp
KW - Threat and fear
KW - β-adrenergic receptors
KW - Basolateral Nuclear Complex/drug effects
KW - Isoproterenol/pharmacology
KW - Age Factors
KW - Picrotoxin/pharmacology
KW - Receptors, Adrenergic, beta/drug effects
KW - Mice, Inbred C57BL
KW - Male
KW - GABA-A Receptor Antagonists/pharmacology
KW - Adrenergic beta-Agonists/pharmacology
KW - Patch-Clamp Techniques
KW - Animals
KW - Electrophysiological Phenomena/drug effects
UR - http://www.scopus.com/inward/record.url?scp=85046852932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046852932&partnerID=8YFLogxK
U2 - 10.1152/jn.00853.2017
DO - 10.1152/jn.00853.2017
M3 - Article
C2 - 29361666
AN - SCOPUS:85046852932
SN - 0022-3077
VL - 119
SP - 1658
EP - 1664
JO - Journal of neurophysiology
JF - Journal of neurophysiology
IS - 5
ER -