Closed-loop brain stimulation to reduce pathologic fear DOI Open Access
Rodrigo O. Sierra, Lizeth K. Pedraza, Lívia Barcsai

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 24, 2022

ABSTRACT Maladaptive processing of trauma related memory engrams leads to dysregulated fear reactions. In post-traumatic stress disorder (PTSD), dysfunctional extinction learning prevents discretization trauma-related and generalized responses. PTSD is postulated as a mnemonic-based disorder, but we lack markers or treatments targeting pathological processing. Hippocampal sharp wave-ripples (SWRs) concurrent neocortical oscillations are scaffolds consolidate contextual memory, their role during remains poorly understood. We demonstrate that closed-loop SWRs triggered neuromodulation the medial forebrain bundle (MFB) can enhance consolidation extinction. It modified memories became resistant induced recall (i.e., ‘renewal’ ‘reinstatement’) did not reemerge spontaneously PTSD-like phenotype. The effects mediated by D2 receptor signaling synaptic remodeling in basolateral amygdala. These results suggest help consolidating memories. Furthermore, enhancing SWR-triggered induction reward signals alleviate pathologic reactions rodent model PSTD. No adverse were seen, suggesting this potential therapy for anxiety disorders.

Language: Английский

Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear DOI Creative Commons
Michael S. Totty, Tuğçe Tuna, Karthik R. Ramanathan

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 17, 2023

Traumatic events result in vivid and enduring fear memories. Suppressing the retrieval of these memories is central to behavioral therapies for pathological fear. The medial prefrontal cortex (mPFC) hippocampus (HPC) have been implicated suppression, but how mPFC-HPC activity coordinated during extinction unclear. Here we show that after training, coherent theta oscillations (6-9 Hz) HPC mPFC are correlated with suppression conditioned freezing male female rats. Inactivation nucleus reuniens (RE), a thalamic hub interconnecting HPC, reduces extinction-related Fos expression both dampens coherence, impairs retrieval. Conversely, theta-paced optogenetic stimulation RE augments relapse extinguished Collectively, results demonstrate role coordinating interactions suppress extinction.

Language: Английский

Citations

31
Neural circuits for the adaptive regulation of fear and extinction memory DOI Creative Commons
Samantha L. Plas, Tuğçe Tuna, Hugo Bayer

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 2, 2024

The regulation of fear memories is critical for adaptive behaviors and dysregulation these processes implicated in trauma- stress-related disorders. Treatments disorders include pharmacological interventions as well exposure-based therapies, which rely upon extinction learning. Considerable attention has been directed toward elucidating the neural mechanisms underlying In this review, we will discuss historic discoveries emerging evidence on memories. We focus circuits regulating acquisition Pavlovian conditioning rodent models, particularly role medial prefrontal cortex hippocampus contextual control extinguished also consider new work revealing an important thalamic nucleus reuniens modulation prefrontal-hippocampal interactions learning memory. Finally, explore effects stress circuit clinical implications findings.

Language: Английский

Citations

16
Synchronized LFP rhythmicity in the social brain reflects the context of social encounters DOI Creative Commons
Alok Nath Mohapatra,

David Peles,

Shai Netser

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Jan. 2, 2024

Abstract Mammalian social behavior is highly context-sensitive. Yet, little known about the mechanisms that modulate according to its context. Recent studies have revealed a network of mostly limbic brain regions which regulates behavior. We hypothesize coherent theta and gamma rhythms reflect organization this into functional sub-networks in context-dependent manner. To test concept, we simultaneously record local field potential (LFP) from multiple adult male mice performing three discrimination tasks. While LFP rhythmicity across all tasks dominated by global internal state, pattern coherence between various behavioral task more than other variables. Moreover, Granger causality analysis implicate ventral dentate gyrus as main player coordinating context-specific rhythmic activity. Thus, our results suggest coordinated activity within reflects subject’s

Language: Английский

Citations

11
Basal forebrain innervation of the amygdala: an anatomical and computational exploration DOI Creative Commons
Tuğçe Tuna, Tyler Banks, Gregory Glickert

et al.

Brain Structure and Function, Journal Year: 2025, Volume and Issue: 230(1)

Published: Jan. 13, 2025

Abstract Theta oscillations of the mammalian amygdala are associated with processing, encoding and retrieval aversive memories. In hippocampus, power network theta oscillation is modulated by basal forebrain (BF) GABAergic projections. Here, we combine anatomical computational approaches to investigate if similar BF projections amygdaloid complex provide an analogous modulation local activity. We used retrograde tracing fluorescent immunohistochemistry identify cholinergic non-cholinergic parvalbumin- or calbindin-immunoreactive neuronal subgroups targeting input (lateral basolateral nuclei) output (central nucleus central bed stria terminalis) regions complex. observed a dense non-cholinergic, putative projection from ventral pallidum (VP) substantia innominata (SI) (BLA). The VP/SI axonal BLA were confirmed using viral anterograde transsynaptic labeling. tested potential function this VP/SI-BLA pathway in 1000-cell biophysically realistic model, which incorporated principal neurons three major interneuron groups BLA, together extrinsic glutamatergic, cholinergic, inputs. silico that theta-modulation enhanced via their selective innervation parvalbumin-expressing interneurons. Ablation parvalbumin-, but not somatostatin- calretinin-expressing, interneurons reduced model. These results suggest long-range may modulate activity at target through formation common interneuron-type oscillatory phase-specific disinhibitory motif.

Language: Английский

Citations

1
Dynamic Routing of Theta-Frequency Synchrony in the Amygdalo-Hippocampal-Entorhinal Circuit Coordinates Retrieval of Competing Memories DOI
Jie Zheng,

Yiqi Sun,

Fei Wang

et al.

Neuroscience Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Elevated fear states facilitate ventral hippocampal engagement of basolateral amygdala neuronal activity DOI Creative Commons
Alexandra C. Ritger, Rachel K. Parker, Sydney Trask

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 14, 2024

Fear memory formation and retention rely on the activation of distributed neural circuits. The basolateral amygdala (BLA) ventral hippocampus (VH) in particular are two regions that support contextual fear processes share reciprocal connections. VH → BLA pathway is critical for increases after initial learning, both renewal following extinction learning during generalization. This raises possibility functional changes projections to learned fear. In line with this, can also be increased alterations original content via reconsolidation, as elevation procedures. However, very little known about supporting reconsolidation-related this study, we used vivo extracellular electrophysiology examine neuronal within a result standard retrieval Elevated expression was accompanied by higher spontaneous firing compared condition. Across range stimulation frequencies, found evoked retrieval. These results suggest associated an capacity drive activity BLA, highlighting potential circuit involved strengthening existing memories.

Language: Английский

Citations

3
Neuromodulation of inhibitory synaptic transmission in the basolateral amygdala during fear and anxiety DOI Creative Commons
Xin Fu, Jeffrey G. Tasker

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: June 27, 2024

The basolateral amygdala plays pivotal roles in the regulation of fear and anxiety these processes are profoundly modulated by different neuromodulatory systems that recruited during emotional arousal. Recent studies suggest activities BLA interneurons inhibitory synaptic transmission principal cells regulated neuromodulators to influence output oscillatory network states BLA, ultimately behavioral expression anxiety. In this review, we first summarize a cellular mechanism stress-induced anxiogenesis mediated interaction glucocorticoid endocannabinoid signaling at synapses BLA. Then discuss cell type-specific activity patterns induced converging on Gq pathway perisomatic parvalbumin-expressing (PV) cholecystokinin-expressing (CCK) basket their effects oscillations learning.

Language: Английский

Citations

3
Integrative genomics analysis highlights functionally relevant genes for equine behaviour DOI Creative Commons

Amy R. Holtby,

Thomas J. Hall, Beatrice A. McGivney

et al.

Animal Genetics, Journal Year: 2023, Volume and Issue: 54(4), P. 457 - 469

Published: March 27, 2023

Behavioural plasticity enables horses entering an exercise training programme to adapt with reduced stress. We characterised SNPs associated behaviour in yearling Thoroughbred using genomics analyses for two phenotypes: (1) handler-assessed coping early events [coping] (n = 96); and (2) variation salivary cortisol concentration at the first backing event [cortisol] 34). Using RNA-seq derived gene expression data amygdala hippocampus tissues from n 2 stallions, we refined those functional relevance by cross-referencing 500 most highly expressed genes each tissue. The of high significance (q < 0.01) were proximity (coping - GABARAP, NDM, OAZ1, RPS15A, SPARCL1, VAMP2; CEBPA, COA3, DUSP1, HNRNPH1, RACK1) biological functions social behaviour, autism spectrum disorder, suicide, stress-induced anxiety depression, Alzheimer's disease, neurodevelopmental disorders, neuroinflammatory fear-induced behaviours alcohol cocaine addiction. strongest association 0.0002) was NDN, a previously temperament cattle. This approach highlights functionally relevant behavioural adaptation that will contribute development genetic markers improve racehorse welfare.

Language: Английский

Citations

7
Closed-loop brain stimulation augments fear extinction in male rats DOI Creative Commons
Rodrigo O. Sierra, Lizeth K. Pedraza, Lívia Barcsai

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 5, 2023

Abstract Dysregulated fear reactions can result from maladaptive processing of trauma-related memories. In post-traumatic stress disorder (PTSD) and other psychiatric disorders, dysfunctional extinction learning prevents discretization memory engrams generalizes responses. Although PTSD may be viewed as a memory-based disorder, no approved treatments target pathological processing. Hippocampal sharp wave-ripples (SWRs) concurrent neocortical oscillations are scaffolds to consolidate contextual memory, but their role during remains poorly understood. Here, we show that closed-loop, SWR triggered neuromodulation the medial forebrain bundle (MFB) enhance consolidation in male rats. The modified memories became resistant induced recall (i.e., ‘renewal’ ‘reinstatement’) did not reemerge spontaneously. These effects were mediated by D2 receptor signaling-induced synaptic remodeling basolateral amygdala. Our results demonstrate SWR-triggered closed-loop stimulation MFB reward system enhances fearful reducing expression across different contexts preventing excessive persistent findings highlight potential augment provide new avenue develop for anxiety disorders.

Language: Английский

Citations

7
Ventral Hippocampal CA1 Pyramidal Neurons Encode Nociceptive Information DOI Creative Commons
Yue Wang,

Naizheng Liu,

Longyu Ma

et al.

Neuroscience Bulletin, Journal Year: 2023, Volume and Issue: 40(2), P. 201 - 217

Published: July 13, 2023

Abstract As a main structure of the limbic system, hippocampus plays critical role in pain perception and chronicity. The ventral hippocampal CA1 (vCA1) is closely associated with negative emotions such as anxiety, stress, fear, yet how vCA1 neurons encode nociceptive information remains unclear. Using vivo electrophysiological recording, we characterized pyramidal neuron subpopulations that exhibited inhibitory or excitatory responses to plantar stimuli were implicated encoding modalities naïve rats. Functional heterogeneity was further identified neuropathic conditions: proportion magnitude response paralleled mechanical allodynia contributed confounded innocuous noxious stimuli, whereas still instrumental discrimination stimulus properties. Increased theta power theta-spike coupling correlated behaviors. Optogenetic inhibition induced rats, chemogenetic reversal overall suppressed activity had analgesic effects rats pain. These results provide direct evidence for representations vCA1.

Language: Английский

Citations

6