Key Parameters Required to Perform Contextual Fear Conditioning and Extinction in Adult Rats DOI
Mónica Navarro-Sánchez, Isis Gil‐Miravet,

Daniel Montero-Caballero

et al.

Published: Jan. 1, 2023

Contextual fear conditioning is a behavioral paradigm used to assess hippocampal-dependent memory in experimental animals. Perception of the context depends on activation distinct population neurons hippocampus and hippocampal-related areas that process discrete aspects perception. In absence any putatively associated cue, becomes salient element may warn an upcoming aversive event; particular conditions, animals generalize this warning new or similar context. these studies we evaluated effects number sessions, unconditioned stimuli per acquisition session distribution extinction sessions determine under which conditions generalization occurred adult male female rats. We observed organization spacing were relevant factors contextual memories. Extinction with significantly greater robustness when spread over two days. Furthermore, results indicated exposure single 0.3 mA 0.5 s footshock different could produce context-specific fear, while more footshocks within produced response Notably, occurred, successive re-exposure generalized way paired exposure. Together, present findings identify clear procedural parameters amenable neural systems analysis three clinically outcomes conditioning, i.e., acquisition, storage extinction.

Language: Английский

Darting across space and time: parametric modulators of sex-biased conditioned fear responses DOI Open Access
J. Mitchell, Sean G. Trettel, Anna J. Li

et al.

Learning & Memory, Journal Year: 2022, Volume and Issue: 29(7), P. 171 - 180

Published: June 16, 2022

Pavlovian fear conditioning is a widely used behavioral paradigm for studying associative learning in rodents. Despite early recognition that subjects may engage variety of both conditioned and unconditioned responses, the last several decades have seen field narrow its focus to measure freezing as sole indicator fear. We previously reported female rats were more likely than males darting, an escape-like response associated with heightened shock reactivity. To determine how experimental parameters contribute frequency darting females, we manipulated factors such chamber size, intensity, number trials. better capture fear-related repertoires our animals, developed ScaredyRat, open-source custom Python tool analyzes Noldus Ethovision-generated raw data files identify darters quantify responses. found that, like freezing, occurrences scale alterations. While most occurs extended training protocol, can emerge well. Collectively, suggest reflects switch responding product individual animal's sex, reactivity, parameters, underscoring need careful consideration sex biological variable classic paradigms.

Language: Английский

Citations

62
Some key parameters in contextual fear conditioning and extinction in adult rats DOI Creative Commons
Mónica Navarro-Sánchez, Isis Gil‐Miravet,

Daniel Montero-Caballero

et al.

Behavioural Brain Research, Journal Year: 2024, Volume and Issue: 462, P. 114874 - 114874

Published: Jan. 22, 2024

Contextual fear conditioning is a behavioral paradigm used to assess hippocampal-dependent memory in experimental animals. Perception of the context depends on activation distinct population neurons hippocampus and hippocampal-related areas that process discrete aspects perception. In absence any putatively associated cue, becomes salient element may warn an upcoming aversive event; particular conditions, animals generalize this warning new or similar context. study we evaluated effects number sessions, unconditioned stimuli per acquisition session distribution extinction sessions determine under which conditions generalization occurred adult, male rats. We observed organization spacing were relevant factors contextual memories. Extinction with significantly greater robustness when spread over two days. Furthermore, results indicated exposure single 0.3 mA, 0.5 s footshock different could produce context-specific fear, while more footshocks within produced response Notably, occurred, successive re-exposure generalized way paired exposure. Together, present findings identify clear procedural parameters amenable neural systems analysis three clinically outcomes conditioning, i.e., acquisition, storage extinction.

Language: Английский

Citations

11
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
Preliminary pharmacokinetics and in vivo studies indicate analgesic and stress mitigation effects of a novel NMDA receptor modulator DOI
Blaise M. Costa,

De'Yana Hines,

Nakia Phillip

et al.

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2025, Volume and Issue: 392(4), P. 103401 - 103401

Published: Feb. 27, 2025

N-methyl D-aspartate receptor (NMDAR) channel blockers produce analgesic and antidepressant effects by preferentially inhibiting the GluN2D subtype at lower doses. Given distinct physiological role of GluN2 subunits, we hypothesized that compounds capable simultaneously modulating GluN2A subtypes in opposite directions could serve as effective analgesics with minimal cognitive adverse effects. In this translational study, investigated vivo costa NMDAR stimulator 4 (CNS4), a recently discovered glutamate concentration-dependent modulator. Pharmacokinetic data revealed CNS4 reaches peak plasma brain concentrations within 0.25 hours after intraperitoneal injection, reaching values up to 8.4% those (64.9 vs 5.47 μg/mL). Preliminary results showed CNS4, nonopioid compound, increased escape latency mice during hotplate assay 1.74-fold compared saline. fear conditioning experiment, anecdotally reduced electric shock sensation significantly decreased stress-related defecation (fecal pellets: males, 21 1; females, 19 3). also improved hyperarousal behavior (25 jumps), without affecting memory parameters such freezing episodes, duration, or latency. caused no changes locomotion across 8 9 studied. Remarkably, approximately 50 training, prevented stress-induced excessive sucrose drinking more than 2-fold both male female mice. These findings suggest penetrates tissue produces pharmacological NMDAR-targeting drugs but mechanism, avoiding undesirable side typical traditional blockers. Therefore, holds potential novel analgesic, warranting further investigation. SIGNIFICANCE STATEMENT: (NMDA)-subtype receptors are an attractive target for chronic pain posttraumatic stress disorder treatments because they play critical forming emotional memories stressful events. pharmacology work, demonstrate central stress-mitigating characteristics concentration-biased NMDA modulator, 4.

Language: Английский

Citations

0
Fear-Conditioning to Unpredictable Threats Reveals Sex and Strain Differences in Rat Fear-Potentiated Startle (FPS) DOI Creative Commons

Valentina Olivera-Pasilio,

Joanna Dabrowska

Neuroscience, Journal Year: 2023, Volume and Issue: 530, P. 108 - 132

Published: Aug. 26, 2023

Language: Английский

Citations

9
Proteomic Analysis Reveals Sex-Specific Protein Degradation Targets in the Amygdala During Fear Memory Formation DOI Creative Commons
Kayla Farrell,

Madeline Musaus,

Shaghayegh Navabpour

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2021, Volume and Issue: 14

Published: Sept. 29, 2021

Ubiquitin-proteasome mediated protein degradation has been widely implicated in fear memory formation the amygdala. However, to date, targets of proteasome remain largely unknown, limiting our understanding functional significance for formation. Additionally, whether similar proteins are targeted by between sexes yet be explored. Here, we combined a degradation-specific K48 Tandem Ubiquitin Binding Entity (TUBE) with liquid chromatography mass spectrometry (LC/MS) identify target substrates process amygdala male and female rats following contextual conditioning. We found that males (43) females (77) differed total number had significant changes polyubiquitin targeting Many identified (106) significantly reduced levels K48-purified samples 1 h after conditioning, suggesting active substrate due learning. Interestingly, only 3 overlapped sexes, may sex-specific. In females, many altered abundance were involved vesicle transport or associated microtubules. Conversely, males, cytoskeleton, ATP synthesis cell signaling have abundance. Only an opposite directional change LENG1, which was enhanced while lower females. This suggests more rapid this during GFAP, critical component astrocyte structure, polyubiquitination both indicating is likely occurring astrocytes Western blot assays revealed these conditioning confirming degradation. Collectively, study provides strong evidence sex differences exist information regarding how ubiquitin-proteasome contribute brain.

Language: Английский

Citations

20
Cognitive Sequelae and Hippocampal Dysfunction in Chronic Kidney Disease following 5/6 Nephrectomy DOI Creative Commons

Yeon Hee Yu,

Seong-Wook Kim, Hyuna Im

et al.

Brain Sciences, Journal Year: 2022, Volume and Issue: 12(7), P. 905 - 905

Published: July 11, 2022

Neurological disorders are prevalent in patients with chronic kidney disease (CKD). Vascular factors and uremic toxins involved cognitive impairment CKD. In addition, vascular dementia-induced alterations the structure function of hippocampus can lead to deficits hippocampal synaptic plasticity function. However, regardless this clinical evidence, pathophysiology CKD is not fully understood. We used male Sprague Dawley rats performed 5/6 nephrectomy observe changes behavior, field excitatory postsynaptic potential, immunostaining following progression. measured volume on magnetic resonance imaging scans controls (n = 34) end-stage renal (ESRD) hemodialysis 42). four cognition-related behavior assays, including novel object recognition, Y-maze, Barnes maze, classical contextual fear conditioning, we identified spatial working memory, learning as well ability distinguish familiar new objects, Immunohistochemical staining Na+/H+ exchanger1 was increased rat models. double immunofluorescent for aquaporin-4 glial fibrillary acidic protein then verified high coexpression model. Furthermore, results from recoding potential (fEPSP) showed reduced amplitude slope fEPSP rats. ESRD a significant decrease compared without or controls. Our findings suggest that uremia resulting decreased may cause destruction blood-brain barrier hippocampus-related

Language: Английский

Citations

13
ChAT::Cre transgenic rats show sex‐dependent altered fear behaviors, ultrasonic vocalizations and cholinergic marker expression DOI Creative Commons

Sarah C. Tryon,

Iris M. Sakamoto,

Kris F. Kaigler

et al.

Genes Brain & Behavior, Journal Year: 2023, Volume and Issue: 22(1)

Published: Jan. 13, 2023

Abstract The cholinergic system is a critical regulator of Pavlovian fear learning and extinction. As such, we have begun investigating the system's involvement in individual differences cued extinction using transgenic ChAT::Cre rat model. current study extends behavioral phenotyping line by examining both freezing behavior ultrasonic vocalizations (USVs) during paradigm. Freezing, 22 kHz USVs, 50 USVs were compared between male female ChAT::Cre+ rats their wildtype (Cre‐) littermates learning, contextual cue‐conditioned recall, extinction, generalization to novel tone. During recall froze slightly more than Cre‐ littermates, displayed significant sex freezing, USVs. Females showed males trials, but fewer distress calls recall. also produced exposure testing chambers prior tone (or shock) presentation with males, this effect was blunted females. Corroborating previous studies, overexpressed vesicular acetylcholine transporter immunolabeling basal forebrain, striatum, basolateral amygdala, hippocampus, had similar levels acetylcholinesterase numbers ChAT+ neurons as rats. This suggests that variance dependent advances theories distinct neural circuits processes regulate sexually divergent responses.

Language: Английский

Citations

5
Unraveling Sex Differences in Affect Processing: Unique Oscillatory Signaling Dynamics in the Infralimbic Cortex and Nucleus Accumbens Shell DOI Creative Commons
Joaquin E. Douton, Regina M. Carelli

Biological Psychiatry Global Open Science, Journal Year: 2023, Volume and Issue: 4(1), P. 354 - 362

Published: Aug. 30, 2023

Negative affect is prevalent in psychiatric diseases such as depression and addiction. Projections from the infralimbic cortex (IL) to nucleus accumbens shell (NAcSh) are causally linked learned negative 20 Hz optogenetic stimulation of this circuit reduces conditioned taste aversion (CTA) male but not female rats. However, prior study did provide insight into how innate versus processed these areas across sex.

Language: Английский

Citations

4