Biology subjects

Lindo, S.

Publications and source records attributed to Lindo, S..

4 recordsLinked to original sources

bioRxiv2025

Reconstructing a physiological state space via chronic jugular microdialysis in freely moving mice

Maintaining physiological homeostasis requires a complex interplay among endocrine organs, peripheral tissues, and distributed neuroendocrine control circuits, all of which are coupled through feedback loops that operate over minutes to hours. Although many physiological needs are broadcast through hormones, metabolites, and other chemical compounds circulating in the bloodstream, we rarely observe more than a few of these messengers together and at high cadence during behavior. To address this, we developed a minimally disruptive workflow to measure the free fraction of hundreds of amines and small peptides at a 7.5-minute cadence for [~]8 hrs in freely moving mice using chronic jugular microdialysis implants and chemical isotope labeling Liquid Chromatography-Mass Spectrometry. Single-compound profiles behave according to known physiology, such as purine turnover correlating with movement, delayed histamine/5-HIAA changes, and coordinated amino-acid dynamics. Our multiplexed measures enable high-dimensional analyses that uncover properties of the underlying dynamics. For example, systems-level analyses show that 10 dimensions explain over 70% of the variance in hormone/metabolite covariation, consistent with a low rank description of the physiological state space, with projections aligned to locomotion state transitions. Our work opens avenues for the discovery of hormonal dynamics, compound interactions, and their effects on behavior.

physiology↗

bioRxiv2025

Transcriptomic analysis of perirhinal and lateral entorhinal Cortex sub-regions in male mice

The perirhinal cortex (PER) is crucial for object recognition memory and comprises areas 35 and 36. The lateral entorhinal cortex (LEC), subdivided into dorsolateral (DLE) and ventral intermediate (VIE) regions, plays a key role in encoding representations of objects, events, contextual details, and sequential information. Despite their anatomical distinctions, gene expression profiling of these subregions remains limited. To address this gap, we conducted transcriptome analysis of these regions in C57BL/6 mice. Tissue samples were collected using laser microdissection, isolating PER areas 35 and 36, as well as DLE and VIE subregions of the LEC, and subsequently analyzed via RNA sequencing. Our results revealed no significant gene expression differences between PER areas 35 and 36, yet substantial molecular divergence emerged when comparing PER to LEC subregions. The PER exhibited higher expression of genes related to nutritional state sensitivity compared to the LEC, while the DLE showed elevated expression of genes implicated in axonal guidance, neurotrophic support, and glutamatergic neurotransmission relative to the VIE. These findings advance our understanding of the molecular profiles unique to PER and LEC regions, and may support the generation of novel hypotheses regarding functional roles of these cortical populations that may be explored in future research.

molecular biology↗

bioRxiv2023

Meta-learning in head fixed mice navigating in virtual reality: A Behavioral Analysis

Animals can learn general task structures and use them to solve new problems with novel sensory specifics. This capacity of learning to learn, or meta-learning, is difficult to achieve in artificial systems, and the mechanisms by which it is achieved in animals are unknown. As a step toward enabling mechanistic studies, we developed a behavioral paradigm that demonstrates meta-learning in head-fixed mice. We trained mice to perform a two-alternative forced-choice task in virtual reality (VR), and successively changed the visual cues that signaled reward location. Mice showed increased learning speed in both cue generalization and serial reversal tasks. During reversal learning, behavior exhibited sharp transitions, with the transition occurring earlier in each successive reversal. Analysis of motor patterns revealed that animals utilized similar motor programs to execute the same actions in response to different cues but modified the motor programs during reversal learning. Our study demonstrates that mice can perform meta-learning tasks in VR, thus opening up opportunities for future mechanistic studies.

neuroscience↗

bioRxiv2019

A sparse, spatially biased subtype of mature granule cell is preferentially recruited in hippocampal-associated behaviors

Animals can store information about experiences by activating specific neuronal populations, and subsequent reactivation of these neural ensembles can lead to recall of salient experiences. In the hippocampus, granule cells of the dentate gyrus participate in such memory engrams; however, whether there is an underlying logic to granule cell participation has not been examined. Here, we found that a broad range of novel experiences preferentially activates granule cells of the suprapyramidal blade relative to the infrapyramidal blade. Motivated by this, we identified a suprapyramidal-blade-enriched population of granule cells with distinct spatial, morphological, physiological, and developmental properties. Via transcriptomics, we mapped these traits onto a sparse and discrete granule cell subtype that was recruited at a ten-fold greater frequency than expected by subtype prevalence, constituting the majority of all recruited granule cells. Thus, a rare and spatially localized granule cell subtype is intrinsically predisposed to activation during hippocampal memory formation.

neuroscience↗