Reduction of aversive learning rates in Pavlovian conditioning by angiotensin II antagonist losartan: a randomised controlled trial DOI Open Access
Ondrej Zika, Judith E. Appel,

Corinna Klinge

et al.

Published: May 17, 2023

Background: Angiotensin receptor blockade (ARB) has been linked to aspects of aversive learning and memory formation, the prevention post-traumatic stress disorder symptom development. Methods: We investigate influence ARB losartan on Pavlovian conditioning using a probabilistic paradigm. In double-blind, randomised placebo-controlled design, we tested 45 (18 female) healthy volunteers during Baseline session, after application or placebo (Drug session) Follow-up session. On each participants engaged in task where they had predict probability an electrical stimulation every trial while true shock contingencies repeatedly switched between phases high low threat. Computational reinforcement models were used dynamics. Results: Acute administration significantly reduced participants’ adjustment both low-to-high high-to-low threat changes. This was driven by rates group drug session compared baseline. The 50mg dose did not induce reduction blood pressure change reaction times, ruling out general attention engagement. Decreased expectations maintained follow up 24hrs later.Conclusions: study shows that acutely reduces environments. Such decreased may explain previously reported preventive role development anxiety symptoms.

Language: Английский

The Reduced Cortilymph Flow Path in the Short-Wave Region Allows Outer Hair Cells to Produce Focused Traveling-Wave Amplification DOI
John J. Guinan, Nam Hyun Cho, Sunil Puria

et al.

Journal of the Association for Research in Otolaryngology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Language: Английский

Citations

1
Single-Cell Resolution of Individual Variation in Hypothalamic Neurons Allows Targeted Manipulation Affecting Social Motivation DOI Creative Commons
Simona Sarafinovska, Sarah K. Koester,

Li Fang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract Despite decades of research, connecting molecular and cellular phenotypes to complex behavioral traits remains an elusive goal 1 . Social motivation exhibits individual trait variation 2 , which we hypothesize is mediated by variability across hypothalamic neurons. To test this, generated single-nucleus RNA-sequencing profiles 3,4 >120,000 neurons from tuberal hypothalamus adjacent thalamus in 36 mice, balanced sex autism-associated mutation 5 with all mice assessed for social First, show that activation patterns predict behavior individuals: specifically, paraventricular Agtr1a + (angiotensin receptor 1a) predicted reduced behavior. Subsequent inhibition AGTR1A telmisartan—an FDA-approved antihypertensive 6 —improved orienting. Second, natural neuronal proportions—likely arising stochastic developmental events 7 —is sufficient shape adult even among genetically-identical identified multiple populations whose relative abundance reward-seeking Chemogenetic one such population, Nxph4 the postero-lateral 8 suppressed aspects motivation. This work establishes proof-of-principle approach where single-cell genomics precisely maps neural substrates governing revealed variations architecture deterministically influence motivation, enabled identification therapeutically-actionable targets immediate translational potential disorders deficits.

Language: Английский

Citations

1
Angiotensin blockade enhances motivational reward learning via enhancing striatal prediction error signaling and frontostriatal communication DOI
Ting Xu, Xinqi Zhou, Jonathan W. Kanen

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(4), P. 1692 - 1702

Published: Feb. 21, 2023

Language: Английский

Citations

17
The central renin–angiotensin system: A genetic pathway, functional decoding, and selective target engagement characterization in humans DOI
Ting Xu, Zhiyi Chen, Xinqi Zhou

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(8)

Published: Feb. 13, 2024

Accumulating evidence suggests that the brain renin angiotensin system (RAS) plays a pivotal role in regulation of cognition and behavior as well neuropathology neurological mental disorders. The II type 1 receptor (AT1R) mediates most functional neuropathology-relevant actions associated with central RAS. However, an overarching comprehension to guide translation utilize therapeutic potential RAS humans is currently lacking. We conducted comprehensive characterization using innovative combination transcriptomic gene expression mapping, image-based behavioral decoding, pre-registered randomized controlled discovery–replication pharmacological resting-state magnetic resonance imaging (fMRI) trials (N = 132) selective AT1R antagonist. exhibited particular dense subcortical network encompassing thalamus, striatum, amygdalo-hippocampal formation. Behavioral decoding map showed association memory, stress, reward, motivational processes. Transient blockade further decreased neural activity systems characterized by high expression, while increasing connectivity cortico-basal ganglia-thalamo-cortical circuitry. Effects on level were specifically signatures dopaminergic, opioid, acetylcholine, corticotropin-releasing hormone signaling systems. robustness results was supported independent fMRI trial. These findings present biologically informed pathways their relevance humans.

Language: Английский

Citations

6
Common and separable neural alterations in adult and adolescent depression – evidence from neuroimaging meta-analyses DOI
Mercy Chepngetich Bore, Xiqin Liu,

Xiaoqi Huang

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 164, P. 105835 - 105835

Published: July 29, 2024

Language: Английский

Citations

6
Establishing connectivity through microdissections of midbrain stimulation-related neural circuits DOI Creative Commons
Georgios P. Skandalakis, Clemens Neudorfer,

Caitlin A. Payne

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(9), P. 3083 - 3098

Published: May 29, 2024

Abstract Comprehensive understanding of the neural circuits involving ventral tegmental area is essential for elucidating anatomofunctional mechanisms governing human behaviour, in addition to therapeutic and adverse effects deep brain stimulation neuropsychiatric diseases. Although has been targeted successfully with different diseases, axonal connectivity region not fully understood. Here, using fibre microdissections cadaveric hemispheres, population-based high-definition tractography previously reported hotspots, we find that participates an intricate network serotonergic pontine nuclei, basal ganglia, limbic system, forebrain prefrontal cortex, which implicated treatment obsessive–compulsive disorder, major depressive Alzheimer’s disease, cluster headaches aggressive behaviours.

Language: Английский

Citations

4
Dysfunctional mesocorticolimbic circuitry in cluster headache DOI Creative Commons
Stefania Ferraro, Greta Demichelis, Jean Paul Medina

et al.

The Journal of Headache and Pain, Journal Year: 2025, Volume and Issue: 26(1)

Published: May 19, 2025

Language: Английский

Citations

0
Angiotensin II Regulates the Neural Expression of Subjective Fear in Humans: A Precision Pharmaco-Neuroimaging Approach DOI
Ran Zhang, Weihua Zhao, Ziyu Qi

et al.

Biological Psychiatry Cognitive Neuroscience and Neuroimaging, Journal Year: 2022, Volume and Issue: 8(3), P. 262 - 270

Published: Sept. 27, 2022

Language: Английский

Citations

10
The central renin angiotensin II system – a genetic pathway, functional decoding and selective target engagement characterization in humans DOI Creative Commons
Ting Xu, Zhiyi Chen, Xinqi Zhou

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 21, 2023

Abstract The brain renin angiotensin II system plays a pivotal role in cognition and neuropathology via the central type 1 receptor (AT1R), yet lack of biologically informed framework currently impedes translational therapeutic progress. We combined imaging transcriptomic meta-analyses with pharmaco-resting state fMRI employing selective AT1R antagonist discovery-replication design (n=132 individuals). was densely expressed subcortical systems engaged reward, motivation, stress, memory. Pharmacological target engagement suppressed spontaneous neural activity high expression enhanced functional network integration cortico-basal ganglia-thalamo-cortical circuits. AT1R-regulation on further mediated by dopaminergic, opioid corticotrophin-releasing hormone pathways. Overall, this work provides first comprehensive characterization architecture function indicating that AT1R-mediates human behavior regulating specific circuits interacting classical transmitter systems.

Language: Английский

Citations

1
Reduction of Aversive Learning Rates in Pavlovian Conditioning by Angiotensin II Antagonist Losartan: A Randomized Controlled Trial DOI Creative Commons
Ondrej Zika, Judith E. Appel,

Corinna Klinge

et al.

Biological Psychiatry, Journal Year: 2024, Volume and Issue: 96(4), P. 247 - 255

Published: Feb. 2, 2024

BackgroundAngiotensin receptor blockade (ARB) has been linked to aspects of aversive learning and memory formation, the prevention post-traumatic stress disorder symptom development.MethodsWe investigate influence ARB losartan on Pavlovian conditioning using a probabilistic paradigm. In double-blind, randomised placebo-controlled design, we tested 45 (18 female) healthy volunteers during Baseline session, after application or placebo (Drug session) Follow-up session. On each participants engaged in task where they had predict probability an electrical stimulation every trial while true shock contingencies repeatedly switched between phases high low threat. Computational reinforcement models were used dynamics.ResultsAcute administration significantly reduced participants' adjustment both low-to-high high-to-low threat changes. This was driven by rates group drug session compared baseline. The 50mg dose did not induce reduction blood pressure change reaction times, ruling out general attention engagement. Decreased expectations maintained follow up 24hrs later.ConclusionsThis study shows that acutely reduces environments, highlighting potential role renin-angiotensin system anxiety development.

Language: Английский

Citations

0