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Brozka, H.

Publications and source records attributed to Brozka, H..

3 recordsLinked to original sources

Partial lesions of hypocretin neurons of the rat lateral hypothalamus affect wake and sleep regulation under increased sleep pressure

Hypocretin(orexin)-producing neurons in the lateral hypothalamic area are important for sleep and wake regulation in mammals and their damage in humans manifests clinically as narcolepsy. While in previous studies experimentally induced massive loss of these neurons revealed their physiological importance, small lesions and their manifestations can uncover more subtle features of sleep regulation and help understand the delicate processes in early stages of pathogenesis of narcolepsy. We studied the effects of partial lesions (approximately 30%) of hypocretin producing neurons in the lateral hypothalamus on sleep patterns and EEG in rats. The lesions did not change the normal sleep and wake pattern in undisturbed rats. The effects of lesions manifested under increased sleep pressure after six hours of sleep deprivation, when they led to accelerated dynamics of compensatory slow wave sleep. The lesions also led to a slight decrease in theta frequency in wakefulness and in REM sleep, which we observed during undisturbed sleep and wake behavior as well as after sleep deprivation.

neuroscience↗

Genetic Modulation of Protein Expression in Rat Brain

Genetic variations in protein expression are implicated in a broad spectrum of common diseases and complex traits. However, the fundamental genetic architecture and variation of protein expression have received comparatively less attention than either mRNA or classical phenotypes. In this study, we systematically quantified proteins in the brains of a large family of rats using tandem mass tag (TMT)-based quantitative mass-spectrometry (MS) technology. We identified and quantified a comprehensive proteome of 8,119 proteins from Spontaneously Hypertensive (SHR/Olalpcv), Brown Norway with polydactyly-luxate (BN-Lx/Cub), and 29 of their fully inbred HXB/BXH progeny. Differential expression (DE) analysis identified 597 proteins with significant differences in expression between the parental strains (fold change > 2 and FDR < 0.01). We characterized 95 variant peptides by proteogenomics approach and discovered 464 proteins linked to strong cis-acting quantitative trait loci (pQTLs, FDR < 0.05). We also explored the linkage of pQTLs with behavioral phenotypes in rats and examined the sex-specific pQTLs to reveal both distinct and shared cis-pQTLs between sexes. Furthermore, by creating a novel view of the rat pangenome, we improved the ability to pinpoint candidate genes underlying pQTL. Finally, we explored the connection between the pQTLs in rat and human disorders, underscoring the translational potential of our findings. Collectively, this work demonstrates the value of large and systematic proteo-genetic datasets in understanding protein modulation in the brain and its functional linkage to complex central nervous system (CNS) traits.

genetics↗

Incidental Temporal Binding in Rats: A Novel Behavioral Task Relevant to Episodic Memory

We designed a behavioral task called One-Trial Trace Escape Reaction (OTTER), in which rats incidentally associate two temporally discontinuous stimuli: a neutral acoustic cue (CS) with an aversive stimulus (US) which occurs two seconds later (CS-2s-US sequence). Rats are first habituated to two similar environmental contexts (A and B), each consisting of an interconnected dark and light chamber. Next, rats experience the CS-2s-US sequence in the dark chamber of one of the contexts (either A or B); the US is terminated immediately after a rat escapes into the light chamber. The CS-2s-US sequence is presented only once to ensure the incidental acquisition of the association. The recall is tested 24 h later when rats are presented with only the CS in the alternate context (B or A), and their behavioral response is observed. Our results show that 59 % of the rats responded to the CS by escaping to the light chamber, although they experienced only one CS-2s-US pairing. The OTTER task offers a flexible high throughput tool to study memory acquired incidentally after a single experience. Incidental acquisition of association between temporally discontinuous events is highly relevant to episodic memory formation.

animal behavior and cognition↗