A Contextual Fear Conditioning Paradigm in Head-Fixed Mice Exploring Virtual Reality DOI Creative Commons
Seetha Krishnan, Can Dong,

Heather Ratigan

et al.

Published: Dec. 2, 2024

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

Remapping revisited: how the hippocampus represents different spaces DOI
André A. Fenton

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(6), P. 428 - 448

Published: May 7, 2024

Language: Английский

Citations

11
Hippocampal place cell remapping occurs with memory storage of aversive experiences DOI Creative Commons
Garrett J. Blair, Changliang Guo, Shiyun Wang

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 19, 2023

Aversive stimuli can cause hippocampal place cells to remap their firing fields, but it is not known whether remapping plays a role in storing memories of aversive experiences. Here, we addressed this question by performing vivo calcium imaging CA1 freely behaving rats (n = 14). Rats were first trained prefer short path over long for obtaining food reward, then avoid the delivering mild footshock. Remapping was assessed comparing cell population vector similarity before acquisition versus after extinction avoidance. Some received shock systemic injections amnestic drug scopolamine at dose (1 mg/kg) that impaired avoidance learning spared spatial tuning and shock-evoked responses neurons. Place remapped significantly more following remembered than forgotten shocks (drug-free conditions); shock-induced did fields migrate toward or away from shocked location similarly prevalent responsive non-responsive shocks. When exposed neutral barrier rather shock, less response barrier. We conclude occurs events are merely perceived forgotten, suggesting reorganization codes may play events.The human brain able remember experiences occurred specific places times, such as birthday party held particular restaurant. A part hippocampus helps store these episodic memories, how exactly fully understood. Within specialized neurons which ‘label’ locations with unique patterns activity. revisit place, restaurant, recall stored pattern activity allowing us recognize familiar location. It has been shown new negative experience – example, if went back restaurant had terrible meal triggers update label associated However, remains uncertain re-labelling assists memory unpleasant experience. To investigate, Blair et al. used technique monitor moving rats. The given foot previously explored Tiny cameras attached heads record hundreds shock. Initially, avoided where they shocked. Over time, began return location; however, displayed different compared previous visits test change corresponded another group administered amnesia-inducing causing them forget These site show any changes when revisited it. findings imply alter only event remembered, forgotten. This indicates alterations Having better understanding could lead treatments diseases impair memory, Alzheimer’s disease age-related dementia.

Language: Английский

Citations

14
Diminished social memory and hippocampal correlates of social interactions in chronic social defeat stress susceptibility DOI Creative Commons
Amanda Larosa, Tian Rui Zhang, Alice S. Wong

et al.

Biological Psychiatry Global Open Science, Journal Year: 2025, Volume and Issue: unknown, P. 100455 - 100455

Published: Jan. 1, 2025

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
MiniXL: An open-source, large field-of-view epifluorescence miniature microscope for mice capable of single-cell resolution and multi-brain region imaging DOI Creative Commons

Pingping Zhao,

Changliang Guo,

Mian Xie

et al.

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

Published: Aug. 19, 2024

Abstract Capturing the intricate dynamics of neural activity in freely behaving animals is essential for understanding mechanisms underpinning specific behaviors. Miniaturized microscopy enables investigators to track population at cellular level, but field view (FOV) these microscopes have been limited and does not allow multiple-brain region imaging. To fill this technological gap, we developed eXtra Large field-of-view Miniscope (MiniXL), a 3.5g lightweight miniaturized microscope with an FOV measuring 3.5 mm diameter electrically adjustable working distance 1.9 ± 200 μm. We demonstrated capability MiniXL recording large neuronal both subcortical area (hippocampal dorsal CA1) deep brain regions (medial prefrontal cortex, mPFC nucleus accumbens, NAc). The allows simultaneous imaging multiple such as bilateral mPFCs or NAc during complex social behavior tracking cells across sessions. As all UCLA ecosystem, fully open-source will be shared neuroscience community lower barriers adoption technology.

Language: Английский

Citations

2
Efficient encoding of aversive location by CA3 long-range projections DOI Creative Commons
Negar Nikbakht, Martin Pofahl,

Albert Miguel‐López

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(3), P. 113957 - 113957

Published: March 1, 2024

Memorizing locations that are harmful or dangerous is a key capability of all organisms and requires an integration affective spatial information. In mammals, the dorsal hippocampus mainly processes information, while intermediate to ventral hippocampal divisions receive information via amygdala. However, how aversive integrated currently unknown. To address this question, we recorded activity long-range CA3 axons at single-axon resolution in mice forming memory. We show (i-dCA3) projections rapidly overrepresent areas preceding location stimulus due spatially selective addition new place-coding followed by non-specific stabilization. This sequence significantly improves encoding i-dCA3 axon population. These results suggest transmit precise, denoised, stable signal indicating imminent danger hippocampus.

Language: Английский

Citations

1
Prefrontal multistimulus integration within a dedicated disambiguation circuit guides interleaving contingency judgment learning DOI Creative Commons

Justin Pastore,

Johannes Mayer,

Jordan Steinhauser

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(11), P. 114926 - 114926

Published: Oct. 31, 2024

Understanding how cortical network dynamics support learning is a challenge. This study investigates the role of local neural mechanisms in prefrontal cortex during contingency judgment (CJL). To better understand brain underlying CJL, we introduce ambiguity into associative after fear acquisition, inducing generalized response to an ambiguous stimulus sharing nontrivial similarities with conditioned stimulus. Real-time recordings at single-neuron resolution from prelimbic (PL) show distinct PL across CJL phases. Fear acquisition triggers reorganization, led by disambiguation circuit managing spurious and predictive relationships cue-danger, cue-safety, cue-neutrality contingencies. Mice PL-targeted memory deficiency malfunctioning function, while naive mice lacking unconditioned exposure lack circuit. shows that conditioning induces cognitive map reorganization subsequent relies on circuit's ability learn relationships.

Language: Английский

Citations

1
Early and late place cells during postnatal development of the hippocampus DOI Creative Commons
Chenyue Wang, Hongjiang Yang, Shijie Chen

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 21, 2024

A proportion of hippocampal CA1 neurons function as place cells from the onset navigation, which are referred to early cells. It is not clear whether this subset predisposed become during stages, or if all have potential. Here, we longitudinally imaged activity in developing male rats navigation with both one-photon and two-photon microscopy. Our results suggested that a largely consistent population functioned cells, demonstrating higher spatial coding abilities across environments tendency form more synchronous cell assemblies. Early were present deep superficial layers CA1. Cells layer exhibited greater synchrony than those ages. These support theory an initial cognitive map primarily shaped by predetermined set How encode space development well understood. Using longitudinal calcium imaging, authors show consistently represented information days, while later-developing showed enhanced ability.

Language: Английский

Citations

1
Prefrontal multistimulus integration within a dedicated disambiguation circuit guides interleaving contingency judgment learning DOI Creative Commons
Edward Korzus,

Justin Pastore,

Johannes Mayer

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 31, 2024

Abstract Understanding how cortical network dynamics support learning is a challenge. This study investigates the role of local neural mechanisms in prefrontal cortex during contingency judgment (CJL). To better understand brain underlying CJL, we introduced ambiguity into associative after fear acquisition, inducing generalized response to an ambiguous stimulus sharing nontrivial similarities with conditioned stimulus. Real-time recordings at single-neuron resolution from prelimbic (PL) using miniature microscopes revealed distinct PL across CJL phases. Fear acquisition triggered reorganization, led by disambiguation circuit managing spurious and predictive relationships cue–danger, cue–safety, cue–neutrality contingencies. Subjects PL-targeted memory deficiency showed malfunctioning function, while naive subjects lacking unconditioned exposure lacked CJL-specific circuit. uncovers that conditioning induces cognitive map subsequent relies on circuit's ability learn relationships.

Language: Английский

Citations

0