Biology subjects

Sosa, M.

Publications and source records attributed to Sosa, M..

9 recordsLinked to original sources

bioRxiv2026

Differential Transcription of Escherichia Coli K-12 Genes Under Hypomagnetic and Geomagnetic Conditions

The transcriptomic response of Escherichia coli to hypomagnetic versus geomagnetic exposure was examined using RNA sequencing across seven pairwise comparisons of differently conditioned cultures. Eighty-one genes were reproducibly differentially expressed, meeting significance and fold-change criteria in at least four of seven comparisons. The direction of differential expression tracked the 90-minute magnetic field exposure condition rather than the magnetic field conditions to which the seed cultures were exposed, indicating that the response is driven by acute field exposure rather than culture history. The affected genes point to a distinct metabolic state layered on top of lag phase, marked by atypical iron stress, downregulation of the flagellar regulon, and a phosphotransferase-mediated carbon-metabolism program favoring rapid energy acquisition over growth.

microbiology↗

bioRxiv2026

Structured navigation in a goal-directed task reveals flexible spatial coding

Animal survival depends on accurate navigation. The last several decades have revealed that neurons encoding position and orientation can support navigation through the construction of an internal map of space for the external world. However, current experimental approaches for studying this system require tradeoffs between behavioral richness and experimental control; open field tasks often lack structured trials or trajectories and virtual reality paradigms constrain natural movement variables. Here, we introduce a platform that combines freely moving behavior with control over environmental stimuli, trajectories, and reward locations. This platform is compatible with chronic Neuropixels recordings, dynamic optical projection of visual stimuli and real-time pose estimation. Using this platform, we show rats can learn a multistage spatial targeting task and that high density Neuropixels recordings can be performed in conjunction. Recordings in medial entorhinal cortex revealed canonical spatial and head direction tuning, along with population-level activity that tracked distance to task-relevant goals. Together, this platform provides a powerful approach for examining the neural basis of flexible navigation under experimentally controlled yet naturalistic conditions.

neuroscience↗

bioRxiv2023

Hippocampal sequences span experience relative to rewards

Hippocampal place cells fire in sequences that span spatial environments and non-spatial modalities, suggesting that hippocampal activity can anchor to the most behaviorally salient aspects of experience. As reward is a highly salient event, we hypothesized that sequences of hippocampal activity can anchor to rewards. To test this, we performed two-photon imaging of hippocampal CA1 neurons as mice navigated virtual environments with changing hidden reward locations. When the reward moved, the firing fields of a subpopulation of cells moved to the same relative position with respect to reward, constructing a sequence of reward-relative cells that spanned the entire task structure. The density of these reward- relative sequences increased with task experience as additional neurons were recruited to the reward- relative population. Conversely, a largely separate subpopulation maintained a spatially-based place code. These findings thus reveal separate hippocampal ensembles can flexibly encode multiple behaviorally salient reference frames, reflecting the structure of the experience.

neuroscience↗

bioRxiv2022

Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform

We introduce a massively parallel novel sequencing platform that combines an open flow cell design on a circular wafer with a large surface area and mostly natural nucleotides that allow optical end-point detection without reversible terminators. This platform enables sequencing billions of reads with longer read length ([~]300bp) and fast runs times (<20hrs) with high base accuracy (Q30 > 85%), at a low cost of $1/Gb. We establish system performance by whole-genome sequencing of the Genome-In-A-Bottle reference samples HG001-7, demonstrating high accuracy for SNPs (99.6%) and Indels in homopolymers up to length 10 (96.4%) across the vast majority (>98%) of the defined high-confidence regions of these samples. We demonstrate scalability of the whole-genome sequencing workflow by sequencing an additional 224 selected samples from the 1000 Genomes project achieving high concordance with reference data.

genomics↗

bioRxiv2020

Hippocampal replay of experience at real-world speeds

Representations related to past experiences play a critical role in memory and decision-making processes. The rat hippocampus expresses these types of representations during sharp-wave ripple (SWR) events, and previous work identified a minority of SWRs that contain "replay" of spatial trajectories at ~20x the movement speed of the animal. Efforts to understand replay typically make multiple assumptions about which events to examine and what sorts of representations constitute replay. We therefore lack a clear understanding of both the prevalence and the range of representational dynamics associated with replay. Here we develop a state space model that uses a combination of movement dynamics of different speeds to capture the spatial content and time evolution of replay during SWRs. Using this model, we find that the large majority of replay events contain spatially coherent, interpretable content. Furthermore, many events progress at real-world, rather than accelerated, movement speeds, consistent with actual experiences.

neuroscience↗

bioRxiv2020

Multiple, independent, common variants overlapping known and putative gut enhancers at RET, SEMA3 and NRG1 underlie Hirschsprung disease risk in European ancestry subjects

PurposeHirschsprung disease (HSCR) is a developmental disorder of the enteric nervous system (ENS) characterized by congenital aganglionosis, and where individual cases harbor coding risk variants in ENS genes. Low-penetrance, common, noncoding variants at RET, SEMA3 and NRG1 loci have been associated in HSCR as well, implicating variable gene expression mediated by cis-regulatory element (CRE) variants as the causal mechanism. However, the extent and combinatorial effects of all putative CRE variants within and across these loci on HSCR is unknown. MethodsUsing 583 HSCR subjects, one of the largest samples of European ancestry studied, and genotyping 56 tag variants we evaluated association of all common variants overlapping putative gut CREs and fine-mapped variants at RET, SEMA3 and NRG1. ResultsWe demonstrate that 28 and 8 tag variants, several of which are independent, overlapping putative-enhancers at the RET and SEMA3 loci, respectively, and, 2 fine-mapped tag variants at NRG1 locus, are associated with HSCR. We demonstrate that risk increases with increasing risk allele dosage from multiple variants within and across these loci and varies >25- fold. ConclusionGene regulatory networks in HSCR-relevant cell types quantify the total burden of risk alleles through sensing reduced gene expression of multiple genes on disease.

genetics↗

bioRxiv2020

A Variable Clock Underlies Internally Generated Hippocampal Sequences

Humans have the ability to store and retrieve memories with various degrees of specificity, and recent advances in reinforcement learning have identified benefits to learning when past experience is represented at different levels of temporal abstraction. How this flexibility might be implemented in the brain remains unclear. We analyzed the temporal organization of rat hippocampal population spiking to identify potential substrates for temporally flexible representations. We examined activity both during locomotion and during memory-associated population events known as sharp wave-ripples (SWRs). We found that spiking during SWRs is rhythmically organized with higher event-to-event variability than spiking during locomotion-associated population events. Decoding analyses using clusterless methods further indidate that similar spatial experience can be replayed in multiple SWRs, each time with a different rhythmic structure whose periodicity is sampled from a lognormal distribution. This variability increases with experience despite the decline in SWR rates that occurs as environments become more familiar. We hypothesize that the variability in temporal organization of hippocampal spiking provides a mechanism for storing experiences with various degrees of specificity.

neuroscience↗

bioRxiv2019

Dorsal and ventral hippocampus engage opposing networks in the nucleus accumbens

Memories of positive experiences require the brain to link places, events, and reward outcomes. Neural processing underlying the association of spatial experiences with reward is thought to depend on interactions between the hippocampus and the nucleus accumbens (NAc)1-9. Hippocampal projections to the NAc arise from both the ventral hippocampus (vH) and the dorsal hippocampus (dH)6-12, and studies using optogenetic interventions have demonstrated that either vH5, 6 or dH7 input to the NAc can support behaviors dependent on spatial-reward associations. It remains unclear, however, whether dH, vH, or both coordinate memory processing of spatial-reward information in the hippocampal-NAc circuit under normal conditions. Times of memory reactivation within and outside the hippocampus are marked by hippocampal sharp-wave ripples (SWRs)13-19, discrete events which facilitate investigation of inter-regional information processing. It is unknown whether dH and vH SWRs act in concert or separately to engage NAc neuronal networks, and whether either dH or vH SWRs are preferentially linked to spatial-reward representations. Here we show that dH and vH SWRs occur asynchronously in the awake state and that NAc spatial-reward representations are selectively activated during dH SWRs. We performed simultaneous extracellular recordings in the dH, vH, and NAc of rats learning and performing an appetitive spatial task and during sleep. We found that individual NAc neurons activated during SWRs from one subdivision of the hippocampus were typically suppressed or unmodulated during SWRs from the other. NAc neurons activated during dH versus vH SWRs showed markedly different task-related firing patterns. Only dH SWR-activated neurons were tuned to similarities across spatial paths and past reward, indicating a specialization for the dH-NAc, but not vH-NAc, network in linking reward to discrete spatial paths. These temporally and anatomically separable hippocampal-NAc interactions suggest that dH and vH coordinate opposing channels of mnemonic processing in the NAc.

neuroscience↗

bioRxiv2019

Regular cycling between representations of alternatives in the hippocampus

Cognitive faculties such as imagination, planning, and decision-making require the ability to represent alternative scenarios. In animals, split-second decision-making implies that the brain can represent alternatives at a commensurate speed. Yet despite this insight, it has remained unknown whether there exists neural activity that can consistently represent alternatives in <1 s. Here we report that neural activity in the hippocampus, a brain structure vital to cognition, can regularly cycle between representations of alternative locations (bifurcating paths in a maze) at 8 Hz. This cycling dynamic was paced by the internally generated 8 Hz theta rhythm, often occurred in the absence of overt deliberative behavior, and unexpectedly also governed an additional hippocampal representation defined by alternatives (heading direction). These findings implicate a fast, regular, and generalized neural mechanism underlying the representation of competing possibilities.

neuroscience↗