Archival ReportDiminished Fear Extinction in Adolescents Is Associated With an Altered Somatostatin Interneuron–Mediated Inhibition in the Infralimbic Cortex
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Animals
The following mouse lines were purchased from Jackson Laboratory (Bar Harbor, ME) and subsequently bred in the Skirball division of New York University Medical School animal facility: B6 PVcre (017320, C57BL/6J), sttm2.1(cre)Zjh/J (013044, C57BL/6/129S4SvJae/C57BL/6J), Ai32(RCL-ChR2(H134R)/ EYFP) (024109, C57BL/6J), B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J (007914, C57BL/6J), and GAD67/GAD67-EGFP (G42, 007677, BALBc/C57BL/6J) mice. PV-channelrhodopsin-2 (PV-ChR2) mice were generated from
Suppression of Fear Extinction in Adolescent Mice
To compare FE in preadolescent, adolescent, and adult mice, we have pooled together behavioral data from PV-ChR2 (Supplemental Figure S1) and SST-ChR2 mice (Supplemental Figure S2). There were 3 treatment groups: TA, FC, and FE. In preadolescent mice, FC resulted in a robust freezing behavior compared with the TA group (Figure 1A). Furthermore, FE caused a significant reduction in freezing compared with the FC group (Figure 1A). Similar to the preadolescent group, adolescent mice exhibited a
Discussion
Our current study reports the changes in the membrane properties, glutamatergic input, and GABAergic output of PVINs and SSTINs in the IL-mPFC during the transition from preadolescence to adulthood in mice. While PVINs undergo a protracted development and reach maturity only by adulthood, SSTINs are developed early but exhibit an adolescence-specific GABAergic plasticity. The surge in SSTIN-mediated inhibition of pyramidal neurons during adolescence and an irreversible suppression of this
Acknowledgments and Disclosures
This work was supported by National Institutes of Health Grant No. HD076914 (to IN).
The authors report no biomedical financial interests or potential conflicts of interest.
References (57)
- et al.
Posttraumatic stress disorder may be associated with impaired fear inhibition: Relation to symptom severity
Psychiatry Res
(2009) - et al.
Evidence for retarded extinction of aversive learning in anxious children
Behav Res Ther
(2006) - et al.
How inhibition shapes cortical activity
Neuron
(2011) The adolescent brain and age-related behavioral manifestations
Neurosci Biobehav Rev
(2000)- et al.
Adaptation to synaptic inactivity in hippocampal neurons
Neuron
(2005) - et al.
A cooperative mechanism involving Ca2+-permeable AMPA receptors and retrograde activation of GABAB receptors in interpeduncular nucleus plasticity
Cell Rep
(2017) - et al.
Neocortical somatostatin neurons reversibly silence excitatory transmission via GABAb receptors
Curr Biol
(2015) - et al.
Prefrontal mechanisms in extinction of conditioned fear
Biol Psychiatry
(2006) - et al.
Prefrontal cortical parvalbumin and somatostatin expression and cell density increase during adolescence and are modified by BDNF and sex
Mol Cell Neurosci
(2018) - et al.
The impact of NMDA receptor hypofunction on GABAergic neurons in the pathophysiology of schizophrenia
Schizophr Res
(2015)