The impact of chronic intermittent hypoxia on enzymatic activity in memory-associated brain regions of male and female rats

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

Published: Dec. 13, 2024

Background Obstructive sleep apnea (OSA) is an intermittent hypoxia disorder associated with cognitive dysfunction, including learning and memory impairments. There evidence that alterations in protease activity neuronal activation as are dependent on sex, may be brain region-specific. However, the mechanisms mediating OSA-induced impairments unclear. Therefore, we used a rat model of OSA, chronic (CIH), to investigate (e.g., calpain caspase-3) (early growth response protein 1, EGR-1) regions memory. We OSA known (CIH) (calpain Methods Male female Sprague Dawley rats were exposed CIH or room air (normoxic) for 14 days. quantified cleaved spectrin products, along EGR-1 expression hippocampal subregions (CA1, CA3), cortical [entorhinal cortex (ETC), retrosplenial (RSC), cerebellar (CC)], subcortical [raphe nucleus (RN), locus coeruleus (LC)] Within each group, Pearson correlations activity, caspase-3 performed between regions. Sex differences within normoxic examined. Results dysregulated male ETC CA1 RSC. RN decreased cleavage products ETC. calpain-cleaved RSC but increased these was RN. Correlational analysis revealed excitatory connections males inhibitory females. shifted from negative positive correlations. Conclusions Overall, data show dysregulates impairs function region- sex-dependent manner. This indicates females exhibit sex-specific vulnerabilities mild OSA. These findings concur our previous behavioral studies demonstrated impairment CIH-exposed rats.

Language: Английский

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A superior colliculus-originating circuit prevents cocaine reinstatement via VR-based eye movement desensitization treatment

National Science Review, Journal Year: 2024, Volume and Issue: 12(4)

Published: Dec. 26, 2024

ABSTRACT While Virtual Reality (VR) technology shows promise in the management of substance use disorders, development an effective VR-based extinction procedure remains lacking. In this study, we developed a eye movement desensitization and reprocessing training program tailored for mice. We found that VR treatment during cocaine prevents reinstatement by suppressing hyperactivation glutamatergic excitatory neurons intermediate layers superior colliculus (SCiCaMKIIα) exposure to environmental cues. Additionally, SCiCaMKIIα innervate tyrosine hydroxylase-positive locus coeruleus (LCTH). Environmental cues trigger stronger phasic activation LCTH through SCiCaMKIIα→LCTH projection, leading increased dopamine release onto dorsal CA3 (dCA3) region, thereby facilitating reinstatement. Furthermore, demonstrate effectively inhibits neural circuitry involving SCiCaMKIIα→LCTH→dCA3 response cues, thus preventing Our findings suggest may represent promising strategy achieving drug abstinence.

Language: Английский

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A locus coeruleus to dorsal hippocampus pathway mediates cue-induced reinstatement of opioid self-administration in male and female rats

Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 49(6), P. 915 - 923

Published: Feb. 19, 2024

Language: Английский

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50 Years of Research on Dopamine’s Role in Passive Aversive Conditioning and Extinction: A Systematic Review

Authorea (Authorea), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 15, 2023

Dopamine, a catecholamine neurotransmitter, has historically been associated with the encoding of reward, whereas its role in aversion received less attention. Here, we systematically gather vast evidence for dopamine simplest form aversive learning: passive conditioning and extinction. In past, crude methods were used to augment or inhibit order study relationship fear More advanced techniques such as conditional genetic, chemogenic, optogenetic approaches now provide causal dopamine’s these learning processes. Dopamine neurons encode extinction-related information convey signal via activation D1, D2, D3, D4 receptor sites particularly amygdala, prefrontal cortex, striatum continuously form, consolidate, retrieve, update extinction memory dynamic reciprocal manner. Based on reviewed literature, conclude that is crucial contributes way comparable reward.

Language: Английский

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Partial or complete loss of norepinephrine differentially alters contextual fear and catecholamine release dynamics in hippocampal CA1

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

Published: March 27, 2023

ABSTRACT Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, precise temporal dynamics of their release in hippocampus during behavior unknown. In addition, new animal models are required probe effects altered catecholamine synthesis learning. Utilizing GRAB NE DA sensors, vivo fiber photometry, two mouse locus coeruleus norepinephrine (LC-NE) synthesis, we investigate (NE) dopamine (DA) dorsal hippocampal CA1 conditioning. We report aversive foot-shock increases both CA1, while freezing associated with recall accompanied by decreased release. Partial loss LC-NE reveals modulated sex. Moreover, find recent sensitive partial complete throughout prenatal postnatal development, similar prior observations mice global beginning postnatally. contrast, remote compromised only prenatally. Overall, these findings provide novel insights into role behavior, highlight a complex relationship between genotype, sex, signaling.

Language: Английский

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