Fear Learning Enhances Prefrontal Cortical Suppression of Auditory Thalamic Inputs to the Amygdala in Adults, but Not Adolescents.

Nicole C Ferrara,Eliska Mrackova,Maxine K Loh,Mallika Padival,J Amiel Rosenkranz

doi:10.3390/ijms21083008

Abstract

Adolescence is characterized by increased susceptibility to the development of fear- and anxiety-related disorders. Adolescents also show elevated fear responding and aversive learning that is resistant to behavioral interventions, which may be related to alterations in the circuitry supporting fear learning. These features are linked to ongoing adolescent development of medial prefrontal cortical (PFC) inputs to the basolateral amygdala (BLA) that regulate neural activity and contribute to the refinement of fear responses. Here, we tested the hypothesis that the extent of PFC inhibition of the BLA following fear learning is greater in adults than in adolescents, using anesthetized in vivo recordings to measure local field potentials (LFPs) evoked by stimulation of PFC or auditory thalamic (MgN) inputs to BLA. We found that BLA LFPs evoked by stimulation of MgN inputs were enhanced in adults following fear conditioning. Fear conditioning also led to reduced summation of BLA LFPs evoked in response to PFC train stimulation, and increased the capacity of PFC inhibition of MgN inputs in adults. These data suggest that fear conditioning recruits additional inhibitory capacity by PFC inputs to BLA in adults, but that this capacity is weaker in adolescents. These results provide insight into how the development of PFC inputs may relate to age differences in memory retention and persistence following aversive learning.

Highlights

Adolescents are vulnerable to stressors that can result in lasting maladaptive behavioral effects associated with increased risk for fear- and anxiety-related disorders [1]
Developmental changes in the prefrontal cortical (PFC)–basolateral amygdala (BLA) pathway are believed to contribute to alterations in the balanScye noafpetxiccitinatpiountsafnrodminahuibdititioonryinthtahleamBLicAc. ePnrteesresntcoe tohfePBFLCAinapreutsstrteontghtehBeLneAdafroellroewlaitnivgellyeasrtnaibnleg farnodm deaurrliyngadmoleemscoernycectoonasodluidltahtoioond.; hPoFwCesvteimr, iunlcarteioansesreignuinlahtiebsitBoLryAsyanctaipvtiitcytrinanasnmiasgsieo-ndecpoenntidneunet umnatnilnmeri,da-anddotlhesisceonncgeo(iPnNg Dma3t0u)r[a1t3io].n Tdhuirsinisgsaudpoploesrcteedncbeymparyiorcownotrrikbudteemtoonthsterarteignuglainticorneaosfesfeianr srpesopnotannseeosuasftienrhfiebairtolreyarpnoinstgsy[6n,1a3p,t1i8c]c.uHrreerne,t wfreeqpureonvciydeunevtiildPeNncDe 3fo0,ruhneliigkhetespneodntPanFeCoruesgeuxlcaittiaotnoroyf the medial geniculate nucleus (MgN)–BLA responses following fear learning in adults, but not adolescents
We found that PFC stimulation reduces MgN–BLA responses following fear conditioning in adults

Summary

Introduction

Adolescents are vulnerable to stressors that can result in lasting maladaptive behavioral effects associated with increased risk for fear- and anxiety-related disorders [1]. Exposure to stressors during adolescence often results in heightened expression of learned fear and an inability to appropriately suppress fear [2,3,4] This is frequently reported using aversive learning experiences, where the pairing of a neutral conditional stimulus (CS) with an aversive unconditional stimulus (UCS) forms a memory, and the strength of this memory can be measured with a fear response (e.g., freezing [5]) to the CS in the absence of the UCS during a subsequent test. Using these procedures, adolescents exhibit heightened fear expression during learning as well as at long-term retention tests when compared with adults [6]. This highlights a need to understand the brain circuit differences that underlie learning-related changes over the course of development

Methods

Results

Conclusion