Translational Model of Infant PTSD Induction: Methods for Infant Fear Conditioning DOI

Roseanna M. Zanca,

Sara Stanciu,

Islam Ahmed

et al.

Neuromethods, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 22

Published: Jan. 1, 2023

Across species such as humans and rodents, pathological fear expression occurs in PTSD, early life trauma has been shown to cause PTSD but also lays the foundation for later-life vulnerability PTSD. Fear conditioning rodents an important source better understanding neurobehavioral features of yet technical difficulties required adapt very young pups age-specific challenges working with a vulnerable population have presented major roadblocks some labs. Here we present infant rodent methods rats understand both its use tool how experiences capture specific neural events that can initiate pathway pathology. These include experimental framework incorporates infant’s developmental environment warmth maternal presence. We detailed handling procedures enable consistent, replicable learning these infants. Finally, introduce maltreatment method termed Scarcity-Adversity model low bedding, which induces harsh treatment pups, mimics one more robust predictors humans. The incorporation following typical atypical care provide comprehensive animal explore characteristics define causal link between

Language: Английский

How adverse childhood experiences get under the skin: A systematic review, integration and methodological discussion on threat and reward learning mechanisms DOI Creative Commons
Julia Ruge, Mana R. Ehlers, Alexandros Kastrinogiannis

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: July 16, 2024

Adverse childhood experiences (ACEs) are a major risk factor for the development of multiple psychopathological conditions, but mechanisms underlying this link poorly understood. Associative learning encompasses key through which individuals learn to important environmental inputs emotional and behavioral responses. ACEs may impact normative maturation associative processes, resulting in their enduring maladaptive expression manifesting psychopathology. In review, we lay out systematic methodological overview integration available evidence proposed association between threat reward processes. We summarize results from literature search (following PRISMA guidelines) yielded total 81 articles (threat: n=38, reward: n=43). Across fields, behaviorally, observed converging pattern aberrant with history ACEs, independent other sample characteristics, specific ACE types, outcome measures. Specifically, blunted was reflected reduced discrimination safety cues, primarily driven by diminished responding conditioned cues. Furthermore, attenuated manifested accuracy rate tasks involving acquisition contingencies. Importantly, emerged despite substantial heterogeneity assessment operationalization across both fields. conclude that represent mechanistic route become physiologically neurobiologically embedded ultimately confer greater closing, discuss potentially fruitful future directions research field, including considerations.

Language: Английский

Citations

10
Safety learning during development: Implications for development of psychopathology DOI
Lana Ruvolo Grasser, Tanja Jovanović

Behavioural Brain Research, Journal Year: 2021, Volume and Issue: 408, P. 113297 - 113297

Published: April 18, 2021

Language: Английский

Citations

43
A legacy of fear: Physiological evidence for intergenerational effects of trauma exposure on fear and safety signal learning among African Americans DOI
Anaïs F. Stenson, Sanne J.H. van Rooij, Sierra Carter

et al.

Behavioural Brain Research, Journal Year: 2020, Volume and Issue: 402, P. 113017 - 113017

Published: Nov. 13, 2020

Language: Английский

Citations

44
PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus DOI Creative Commons
Eric Raúl Velasco, Antonio Florido, África Flores

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 28, 2022

Exposure to traumatic stress can lead fear dysregulation, which has been associated with posttraumatic disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is PTSD risk women, and PACAP (ADCYAP1)-PAC1R (ADCYAP1R1) are highly expressed hypothalamus. Here, we show female mice subjected acute immobilization (IMO) have extinction impairments related Adcyap1 Adcyap1r1 mRNA upregulation hypothalamus, PACAP-c-Fos downregulation Medial Amygdala (MeA), PACAP-FosB/ΔFosB Ventromedial Hypothalamus dorsomedial part (VMHdm). DREADD-mediated inhibition of MeA neurons projecting VMHdm during IMO rescues both impairment. We also found women genotype ADCYAP1R1 rs2267735 impaired extinction.

Language: Английский

Citations

23
The functional heterogeneity of PACAP: Stress, learning, and pathology DOI Creative Commons
Abha K. Rajbhandari, Jessica R. Barson, Marieke R. Gilmartin

et al.

Neurobiology of Learning and Memory, Journal Year: 2023, Volume and Issue: 203, P. 107792 - 107792

Published: June 25, 2023

Language: Английский

Citations

11
Uncertain in the face of change: Lack of contingency shift awareness during extinction is associated with higher fear-potentiated startle and PTSD symptoms in children DOI Creative Commons
Tanja Jovanović, Charis Wiltshire, Mariam Reda

et al.

International Journal of Psychophysiology, Journal Year: 2022, Volume and Issue: 178, P. 90 - 98

Published: June 16, 2022

Language: Английский

Citations

17
PACAP‐expressing neurons in the lateral habenula diminish negative emotional valence DOI
Marjorie R. Levinstein, David Bergkamp, Zoë K. Lewis

et al.

Genes Brain & Behavior, Journal Year: 2022, Volume and Issue: 21(7)

Published: March 18, 2022

Abstract The lateral habenula (LHb) is a small, bilateral, epithalamic nucleus which processes aversive information. While primarily glutamatergic, LHb neurons express genes coding for many neuropeptides, such as Adcyap1 the gene encoding pituitary adenylate cyclase‐activating polypeptide (PACAP), itself has been associated with anxiety and stress disorders. Using Cre‐dependent viral vectors, we targeted characterized these based on their anatomical projections found that they projected to both raphe rostromedial tegmentum but only weakly ventral tegmental area. RiboTag capture ribosomal‐associated mRNA from reanalysis of existing single cell RNA sequencing data, did not identify unique molecular phenotype PACAP‐expressing in LHb. In order understand function neurons, conditionally expressed hM 3 Dq DREADD selectively chemogenetically excited during behavioral testing open field test, contextual fear conditioning, sucrose preference, novelty suppressed feeding, conditioned place preference. We Gq activation produce behaviors opposite what expected whole—they decreased anxiety‐like behavior produced conclusion, represents molecularly diverse population cells oppose actions remainder by being rewarding or diminishing negative consequences events.

Language: Английский

Citations

13
How adverse childhood experiences get under the skin: A systematic review, integration and methodological discussion on threat and reward learning mechanisms DOI Open Access
Julia Ruge, Mana R. Ehlers, Alexandros Kastrinogiannis

et al.

Published: May 17, 2023

Adverse childhood experiences (ACEs) are a major risk factor for the development of multiple psychopathological conditions, but mechanisms underlying this link poorly understood. Associative learning encompasses key through which individuals learn to important environmental inputs emotional and behavioral responses. ACEs may impact normative maturation associative processes, resulting in their enduring maladaptive expression manifesting psychopathology. In review, we lay out systematic methodological overview integration available evidence proposed association between threat reward processes. We summarize results from literature search (following PRISMA guidelines) yielded total 81 articles (threat: n=38, reward: n=43). Across fields, behaviorally, observed converging pattern aberrant with history ACEs, independent other sample characteristics, specific ACE types, outcome measures. Specifically, blunted was reflected reduced discrimination safety cues, primarily driven by diminished responding conditioned cues. Furthermore, attenuated manifested accuracy rate tasks involving acquisition contingencies. Importantly, emerged despite substantial heterogeneity assessment operationalization across both fields. conclude that represent mechanistic route become physiologically neurobiologically embedded ultimately confer greater closing, discuss future directions research field, including considerations.

Language: Английский

Citations

7
Effects of Early Maternal Care on Anxiety and Threat Learning in Adolescent Nonhuman Primates DOI Creative Commons
Elyse L. Morin,

Erin R. Siebert,

Brittany Howell

et al.

Developmental Cognitive Neuroscience, Journal Year: 2024, Volume and Issue: 71, P. 101480 - 101480

Published: Nov. 23, 2024

Early life adverse experiences, including childhood maltreatment, are major risk factors for psychopathology, anxiety disorders with dysregulated fear responses. Consistent human studies, maltreatment by the mother (MALT) leads to increased emotional reactivity in rhesus monkey infants. Whether this persists and results altered emotion regulation, due enhanced learning or impaired utilization of safety signals as shown stress-related disorders, is unclear. Here we used a model MALT examine long-term effects on state threat/safety 25 adolescents, using conditioning paradigm (AX+/BX-) acoustic startle amplitude peripheral measure. The AX+/BX- measures baseline startle, fear-potentiated cue discrimination, attenuation signals, extinction. Baseline was higher animals, suggesting elevated anxiety. No differences threat learning, discrimination were detected. However, animals showed generalized blunted responses conditioned cue, regardless presence transfer test, took longer extinguish spontaneously recovered threat. These findings suggest caregiving experiences have impacts adolescent responses, consistent reports children exposure.

Language: Английский

Citations

2
Pituitary Adenylate Cyclase-Activating Polypeptide in Learning and Memory DOI Creative Commons
Marieke R. Gilmartin, Nicole C. Ferrara

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: June 22, 2021

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved neuropeptide that regulates neuronal physiology and transcription through Gs/Gq-coupled receptors. Its actions within hypothalamic, limbic, mnemonic systems underlie its roles in stress regulation, affective processing, neuroprotection, cognition. Recently, elevated PACAP levels genetic disruption of PAC1 receptor signaling humans has been linked to maladaptive threat learning pathological fear post-traumatic disorder (PTSD). positioned integrate memory PTSD for which the traumatic experience central disorder. However, PACAP's role received comparatively less attention than stress. In this review, we consider evidence PACAP-PAC1 plasticity, discuss emerging data on sex differences signaling, raise key questions further study toward elucidating contribution adaptive learning.

Language: Английский

Citations

14