A contextual fear conditioning paradigm in head-fixed mice exploring virtual reality. DOI Creative Commons
Seetha Krishnan, Can Dong,

Heather Ratigan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 27, 2024

ABSTRACT Contextual fear conditioning is a classical laboratory task that tests associative memory formation and recall. Techniques such as multi-photon microscopy holographic stimulation offer tremendous opportunities to understand the neural underpinnings of these memories. However, techniques generally require animals be head-fixed. There are few paradigms test contextual in head-fixed mice, none where behavioral outcome following freezing, most common measure freely moving animals. To address this gap, we developed paradigm mice using virtual reality (VR) environments. We designed an apparatus deliver tail shocks (unconditioned stimulus, US) while navigated VR environment (conditioned CS). The acquisition was tested when were reintroduced shock-paired day. three different variations and, all them, observed increased conditioned response characterized by freezing behavior. This especially prominent during first trial environment, compared neutral received no shocks. Our results demonstrate can VR, discriminate between feared context, display response, similar behaving Furthermore, two-photon microscope, imaged from large populations hippocampal CA1 neurons before, during, conditioning. findings reconfirmed those literature on animals, showing place cells undergo remapping show narrower fields approach offers new study mechanisms underlying formation, recall, extinction As preparation compatible with stimulation, it enables long-term tracking manipulation throughout distinct stages provides subcellular resolution for investigating axonal, dendritic, synaptic dynamics real-time.

Language: Английский

A thalamic-hippocampal CA1 signal for contextual fear memory suppression, extinction, and discrimination DOI Creative Commons

Heather Ratigan,

Seetha Krishnan, Shai Smith

et al.

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

Published: Oct. 24, 2023

Abstract The adaptive regulation of fear memories is a crucial neural function that prevents inappropriate expression. Fear can be acquired through contextual conditioning (CFC) which relies on the hippocampus. thalamic nucleus reuniens (NR) necessary to extinguish and innervates hippocampal CA1. However, role NR-CA1 pathway in unknown. We developed head-restrained virtual reality CFC paradigm, demonstrate mice acquire context-dependent responses. found inhibiting following lengthens duration fearful freezing epochs, increases generalization, delays extinction. Using vivo imaging, we recorded NR-axons innervating CA1 become tuned CFC. conclude actively suppresses by disrupting memory retrieval during behavior, process also reduces generalization accelerates

Language: Английский

Citations

27
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

14
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
Projections from thalamic nucleus reuniens to medial septum enable extinction of remote fear memory DOI Creative Commons
Kamil F. Tomaszewski, Magdalena Ziółkowska, Kacper Łukasiewicz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 20, 2024

Abstract Aversive experiences lead to the formation of long-lasting memories. Despite need better understand how enduring fear memories can be attenuated, underlying brain circuits remain largely unknown. In this study, employing a combination genetic manipulations, neuronal circuit mapping, and chemogenetics in mice, we identify new projection from thalamic nucleus reuniens (RE) medial septum (MS), show that is involved extinction remote (30-day old), but not recent (1-day These findings provide first functional description RE→MS highlight significance thalamo-septal regions memory organization as function age, phenomenon known systems consolidation.

Language: Английский

Citations

5
MK-801 attenuates one-trial tolerance in the elevated plus maze via the thalamic nucleus reuniens DOI
Xue Xu, Qian Gong, Xiao‐Dong Wang

et al.

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110318 - 110318

Published: Jan. 1, 2025

Language: Английский

Citations

0
Projections from thalamic nucleus reuniens to hippocampal CA1 area participate in context fear extinction by affecting extinction-induced molecular remodeling of excitatory synapses DOI Creative Commons
Magdalena Ziółkowska, Narges Sotoudeh, Anna Cały

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 23, 2025

The ability to extinguish contextual fear in a changing environment is crucial for animal survival. Recent data support the role of thalamic nucleus reuniens (RE) and its projections dorsal hippocampal CA1 area (RE→dCA1) this process. However, it remains poorly understood how RE impacts dCA1 neurons during extinction (CFE). Here, we reveal that RE→dCA1 pathway contributes by affecting CFE-induced molecular remodeling excitatory synapses. Anatomical tracing chemogenetic manipulation mice demonstrate form synapses regulate synaptic transmission stratum oriens (SO) lacunosum-moleculare (SLM) area, but not radiatum (SR). We also observe CFE-specific structural changes expression scaffold protein, PSD-95, both strata innervated RE, SR. Interestingly, only SLM are specific dendrites RE. To further projection CFE, brief inhibition CFE session persistently impairs formation memory PSD-95 levels SLM. Thus, our indicate participates regulating

Language: Английский

Citations

0
A contextual fear conditioning paradigm in head-fixed mice exploring virtual reality DOI Open Access
Seetha Krishnan, Can Dong,

Heather Ratigan

et al.

Published: Feb. 14, 2025

Contextual fear conditioning is a classical laboratory task that tests associative memory formation and recall. Techniques such as multi-photon microscopy holographic stimulation offer tremendous opportunities to understand the neural underpinnings of these memories. However, techniques generally require animals be head-fixed. There are few paradigms test contextual in head-fixed mice, none where behavioral outcome following freezing, most common measure freely moving animals. To address this gap, we developed paradigm mice using virtual reality (VR) environments. We designed an apparatus deliver tail shocks (unconditioned stimulus, US) while navigated VR environment (conditioned CS). The acquisition was tested when were reintroduced shock-paired day. three different variations and, all them, observed increased conditioned response characterized by freezing behavior. This especially prominent during first trial environment, compared neutral received no shocks. Our results demonstrate can VR, discriminate between feared context, display response, similar behaving Furthermore, two-photon microscope, imaged from large populations hippocampal CA1 neurons before, during, conditioning. findings reconfirmed those literature on animals, showing place cells undergo remapping show narrower fields approach offers new study mechanisms underlying formation, recall, extinction As preparation compatible with stimulation, it enables long-term tracking manipulation throughout distinct stages provides subcellular resolution for investigating axonal, dendritic, synaptic dynamics real-time.

Language: Английский

Citations

0
A contextual fear conditioning paradigm in head-fixed mice exploring virtual reality DOI Open Access
Seetha Krishnan, Can Dong,

Heather Ratigan

et al.

Published: Feb. 14, 2025

Contextual fear conditioning is a classical laboratory task that tests associative memory formation and recall. Techniques such as multi-photon microscopy holographic stimulation offer tremendous opportunities to understand the neural underpinnings of these memories. However, techniques generally require animals be head-fixed. There are few paradigms test contextual in head-fixed mice, none where behavioral outcome following freezing, most common measure freely moving animals. To address this gap, we developed paradigm mice using virtual reality (VR) environments. We designed an apparatus deliver tail shocks (unconditioned stimulus, US) while navigated VR environment (conditioned CS). The acquisition was tested when were reintroduced shock-paired day. three different variations and, all them, observed increased conditioned response characterized by freezing behavior. This especially prominent during first trial environment, compared neutral received no shocks. Our results demonstrate can VR, discriminate between feared context, display response, similar behaving Furthermore, two-photon microscope, imaged from large populations hippocampal CA1 neurons before, during, conditioning. findings reconfirmed those literature on animals, showing place cells undergo remapping show narrower fields approach offers new study mechanisms underlying formation, recall, extinction As preparation compatible with stimulation, it enables long-term tracking manipulation throughout distinct stages provides subcellular resolution for investigating axonal, dendritic, synaptic dynamics real-time.

Language: Английский

Citations

0
Distinct neural responses of ventromedial prefrontal cortex-projecting nucleus reuniens neurons during aversive memory extinction DOI Creative Commons

Y. Mochizuki,

Asuka Joji-Nishino,

Kazuo Emoto

et al.

Molecular Brain, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 5, 2025

Animals adaptively regulate aversive memories in safe environments through extinction, a process central to exposure therapy for anxiety disorders. The limbic thalamus controls cognitive function concert with interconnected cortical and structures. Though medial prefrontal (mPFC) afferents the memory, functional role of efferents mPFC is unclear. Here, we investigated roles thalamic nuclei, reuniens (RE) mediodorsal (MD) thalamus, projecting cortex memory conditioning extinction male mice. Using retrograde tracing, demonstrated that ventromedial PFC (vmPFC)- dorsomedial (dmPFC)-projecting neurons are topologically segregated within RE MD. Fiber photometry revealed both RE→vmPFC MD→vmPFC respond stimuli. Notably, develop shock-associated cue (CS+) response during conditioning. During exhibited biphasic CS+, while showed no cue-evoked activity. Neither optogenetic activation nor inactivation these populations altered freezing behavior compared controls. Collectively, findings indicate encode information but dispensable behavioral modulation. This study highlights distinct contributions thalamus-PFC circuits processing.

Language: Английский

Citations

0
In relentless pursuit of the white whale: A role for the ventral midline thalamus in behavioral flexibility and adaption? DOI Creative Commons

Élodie Panzer,

Isabella Guimares-Olmo,

Anne Pereira de Vasconcelos

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 163, P. 105762 - 105762

Published: June 12, 2024

The reuniens (Re) nucleus is located in the ventral midline thalamus. It has fostered increasing interest, not only for its participation a variety of cognitive functions (e.g., spatial working memory, systemic consolidation, reconsolidation, extinction fear or generalization), but also neuroanatomical positioning as bidirectional relay between prefrontal cortex (PFC) and hippocampus (HIP). In this review we compile discuss recent studies having tackled possible implication Re behavioral flexibility, major PFC-dependent executive function controlling goal-directed behaviors. Experiments considered explored role perseveration, reversal learning, extinction, set-shifting. They point to contribution mainly by connections with PFC, possibly those hippocampus, even amygdala, at least fear-related behavior. As such, could be crucial crossroad supporting PFC-orchestrated ability cope new, potentially unpredictable environmental contingencies, thus flexibility adaption.

Language: Английский

Citations

3