Biology subjects

Kiseleva, A.

Publications and source records attributed to Kiseleva, A..

6 recordsLinked to original sources

bioRxiv2025

Disruption of theta-timescale spiking impairs learning but spares hippocampal replay

The ability to rapidly learn and retrieve salient information about new environments is critical for survival. In mammals, the hippocampus plays a crucial role in that learning. Specialized features of hippocampal population coding, including network-level theta oscillatory activity, location-specific firing of principal cells, and reactivation of experience during immobility (replay), have been implicated in rapid storage and retrieval of spatial information. Disruptions of theta and replay jointly, or replay alone, are sufficient to impair learning; however, the specific contribution of theta-associated temporal structure during locomotion remains unknown. In this study, we manipulated hippocampal spiking activity in rats specifically during locomotion by optogenetically activating septal parvalbumin-expressing GABAergic neurons. We developed a closed-loop, theta phase-specific stimulation protocol that reliably reduced theta power shortly after stimulation onset. This manipulation preserved the place codes of individual cells but disrupted the fine temporal structure of endogenous spatio-temporal representations (i.e., theta sequences) at the pairwise and population level. Theta disruption during locomotion was also sufficient to cause pronounced deficits in learning the more cognitively challenging component of a spatial alternation task, even though disruption was applied on only [~]66% of trials. Notably, network effects accompanying theta disruption were restricted to locomotor periods; we did not observe changes in replay rate, length, or content during immobility. Together, these results demonstrate the importance of the precise temporal microstructure of locomotion-associated spatial representations in the hippocampus for learning.

neuroscience↗

bioRxiv2024

Olfactory facilitation of visual categorization in the 4-month-old brain depends on visual demand

To navigate their environment, infants rely on intersensory facilitation when unisensory perceptual demand is high, a principle known as inverse effectiveness. Given that this principle was mainly documented in the context of audiovisual stimulations, here we aim to determine whether it applies to olfactory-to-visual facilitation. We build on previous evidence that the mothers body odor facilitates face categorization in the 4-month-old brain, and investigate whether this effect depends on visual demand. Scalp electroencephalogram (EEG) was recorded in 2 groups of 4-month-old infants while they watched 6-Hz streams of visual stimuli with faces displayed every 6th stimulus to tag a face-selective response at 1 Hz. We used variable natural stimuli in one group (Nat Group), while stimuli were simplified in the other group (Simp Group) to reduce perceptual categorization demand. During visual stimulation, infants were alternatively exposed to their mothers vs. a baseline odor. For both groups, we found an occipito-temporal face-selective response, but with a larger amplitude for the simplified stimuli, reflecting less demanding visual categorization. Importantly, the mothers body odor enhances the response to natural, but not to simplified, face stimuli, indicating that maternal odor improves face categorization when it is most demanding for the 4-month-old brain. Overall, this study demonstrates that the inverse effectiveness of intersensory facilitation applies to the sense of smell during early perceptual development. Highlights- Intersensory facilitation is a function of unisensory perceptual demand in infants (inverse effectiveness). - This inverse relation between multisensory and unisensory perception has been mainly documented using audiovisual stimulations. - Here we show that olfactory-to-visual facilitation depends on visual demand in 4-month-old infants. - The inverse effectiveness of intersensory facilitation during early perceptual development applies to the sense of smell.

neuroscience↗

bioRxiv2023

Olfactory-to-visual facilitation in the infant brain declines gradually from 4 to 12 months

During infant development, intersensory facilitation declines gradually as unisensory perception improves. However, this developmental trade-off has been mainly investigated using audiovisual stimulations. Here, fifty 4- to 12-month-old infants were tested to determine whether the facilitating effect of their mothers body odor on neural face categorization, as previously observed at 4 months, decreases with age. In a baseline odor context, results revealed a face-selective electroencephalographic (EEG) response that increases and changes qualitatively between 4 and 12 months, marking improved face categorization. At the same time, the benefit of adding maternal odor fades gradually with age, indicating an inverse relation with the strength of the sole visual response, and generalizing to olfactory-visual interactions previous evidence from the audiovisual domain.

neuroscience↗

bioRxiv2018

Genome-wide chromatin accessibility and transcriptome profiling show minimal epigenome changes and coordinated transcriptional dysregulation of hedgehog signaling in Danforth’s short tail mice

Danforths short tail (Sd) mice provide an excellent model for investigating the underlying etiology of human caudal birth defects, which affect 1 in 10,000 live births. Sd animals exhibit aberrant axial skeleton, urogenital, and gastrointestinal development similar to human caudal malformation syndromes including urorectal septum malformation, caudal regression, VACTERL association, and persistent cloaca. Previous studies have shown that the Sd mutation results from an endogenous retroviral (ERV) insertion upstream of the Ptf1a gene resulting in its ectopic expression at E9.5. Though the genetic lesion has been determined, the resulting epigenomic and transcriptomic changes driving the phenotype have not been investigated. Here, we performed ATAC-seq experiments on isolated E9.5 tailbud tissue, which revealed minimal changes in chromatin accessibility in Sd/Sd mutant embryos. Interestingly, chromatin changes were localized to a small interval adjacent to the Sd ERV insertion overlapping a known Ptf1a enhancer region, which is conserved in mice and humans. Furthermore, mRNA-seq experiments revealed increased transcription of PTF1A target genes and, importantly, downregulation of hedgehog pathway genes. Reduced sonic hedgehog (SHH) signaling was confirmed by in situ hybridization and immunofluorescence suggesting that the Sd phenotype results, in part, from downregulated SHH signaling. Taken together, these data demonstrate substantial transcriptome changes in the Sd mouse, and indicate that the effect of the ERV insertion on Ptf1a expression may be mediated by increased chromatin accessibility at a conserved Ptf1a enhancer. We propose that human caudal dysgenesis disorders may result from dysregulation of hedgehog signaling pathways.

genetics↗

bioRxiv2018

Knock-in rats expressing Cre and Flp recombinases at the Parvalbumin locus.

Rats have the ability to learn and perform sophisticated behavioral tasks, making them very useful for investigating neural circuit functions. In contrast to the extensive mouse genetic toolkit, the paucity of recombinase-expressing rat models has limited the ability to monitor and manipulate molecularly-defined neural populations in this species. Here we report the generation and validation of two knock-in rat strains expressing either Cre or Flp recombinase under the control of Parvalbumin (Pvalb), a gene expressed in the critical \"fast-spiking\" subset of inhibitory interneurons (FSIs). These strains were generated with CRISPR-Cas9 gene editing and show highly specific and penetrant labeling of Pvalb-expressing neurons, as demonstrated by in situ hybridization and immunohistochemistry. We validated these models in both prefrontal cortex and striatum using both ex vivo and in vivo approaches, including whole-cell recording, optogenetics, extracellular physiology and photometry. Our results demonstrate the utility of these new transgenic models for a wide range of neuroscience experiments.

neuroscience↗

bioRxiv2018

Murine SEC24D Can Substitute Functionally for SEC24C in vivo

The COPII component SEC24 mediates the recruitment of transmembrane cargoes or cargo adaptors into newly forming COPII vesicles on the ER membrane. Mammalian genomes encode four Sec24 paralogs (Sec24a-d), with two subfamilies based on sequence homology (SEC24A/B and C/D), though little is known about their comparative functions and cargo-specificities. Complete deficiency for Sec24d results in very early embryonic lethality in mice (before the 8 cell stage), with later embryonic lethality (E 7.5) observed in Sec24c null mice. To test the potential overlap in function between SEC24C/D, we employed dual recombinase mediated cassette exchange to generate a Sec24cc-d allele, in which the C-terminal 90% of SEC24C has been replaced by SEC24D coding sequence. In contrast to the embryonic lethality at E7.5 of SEC24C-deficiency, Sec24cc-d/c-d pups survive to term, though dying shortly after birth. Sec24cc-d/c-d pups are smaller in size, but exhibit no obvious developmental abnormality. These results suggest that tissue-specific and/or stage-specific expression of the Sec24c/d genes rather than differences in cargo function explain the early embryonic requirements for SEC24C and SEC24D.

cell biology↗