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Pacheco, C. M.

Publications and source records attributed to Pacheco, C. M..

4 recordsLinked to original sources

Basolateral amygdala dopamine signals behavioural salience across exploration and learning

Animals must balance exploration with threat avoidance, yet how neuromodulatory signals shape information-seeking states remains unclear. Using fibre photometry recordings in the basolateral amygdala in freely moving mice, we show that dopamine release is selectively elevated during self-initiated exploratory actions, adapts with repeated exposure, and tracks the behavioural relevance of predictive cues in associative learning and extinction. Our results advance current models of amygdala dopamine function by suggesting that it conveys a state-dependent salience signal that highlights behaviourally relevant moments arising from both environmental cues and self-generated exploration, thereby priming amygdala circuits for plasticity.

neuroscience↗

Heterogeneous plasticity of amygdala interneurons in associative learning and extinction

Neural circuits undergo experience-dependent plasticity to form long-lasting memories. Excitatory projection neurons are considered to be the primary neuronal substrate for memory acquisition and storage. However, inhibitory interneurons control the activity of projection neurons in a in a spatially and temporally precise manner, yet their contribution to memory acquisition, storage and expression remains poorly understood. Here, we employ a miniature microscope imaging approach to monitor the activity of large amygdala interneuron populations in freely moving mice during fear learning and extinction at the single cell level. We find that amygdala interneurons display mixed-selectivity and show complex plastic responses at both the ensemble and single neuron level across the acquisition, expression and extinction of aversive memories. In contrast to bidirectional single cell plasticity across distinct fear states, learning-induced changes at the population level occur transiently during conditioning and do not consolidate across days. Examining molecular interneuron subpopulations revealed that disinhibitory vasoactive intestinal peptide (VIP) expressing cells are predominantly activated by high fear states. In contrast, somatostatin (SST) interneurons display a preference for safety cues and thereby suppress excitatory neuron responsiveness. However, responses of individual neurons within the SST and VIP populations are non-uniform, indicating the presence of functional subtypes within classical molecularly-defined interneuron populations. Taken together, we identify complex neuronal plasticity within amygdala interneuron ensembles that goes beyond a passive processing function, suggesting a critical role of inhibitory microcircuit elements for memory selectivity and stability.

neuroscience↗

Moonlight synchronous flights across three western palearctic swifts mirror size dependent prey preferences

Recent studies have suggested the presence of moonlight mediated behaviour in avian aerial insectivores, such as swifts. At the same time swift species also show differences in prey (size) preferences. Here, we use the combined analysis of state-of-the-art activity logger data across three swift species, the Common, Pallid and Alpine swifts, to quantify flight height and activity responses to crepuscular and nocturnal light conditions. Our results show a significant response in flight heights to moonlight illuminance for Common and Pallid swifts, while a moonlight driven response is absent in Alpine swifts. Swift flight responses followed the size dependent altitude gradient of their insect prey. We show a weak relationship between night-time illuminance driven responses and twilight ascending behaviour, suggesting a decoupling of both crepuscular and night-time behaviour. We suggest that swifts optimise their flight behaviour to adapt to favourable night-time light conditions, driven by light responsive and size-dependent vertical insect stratification and weather conditions.

animal behavior and cognition↗

A simple, scalable approach to building a cross-platform transcriptome atlas

Gene expression atlases have transformed our understanding of the development, composition and function of human tissues. New technologies promise improved cellular or molecular resolution, and have led to the identification of new cell types, or better defined cell states. But as new technologies emerge, information derived on old platforms becomes obsolete. We demonstrate that it is possible to combine a large number of different profiling experiments summarised from dozens of laboratories and representing hundreds of donors, to create an integrated molecular map of human tissue. As an example, we combine 850 samples from 38 platforms to build an integrated atlas of human blood cells. We achieve robust and unbiased cell type clustering using a variance partitioning method, selecting genes with low platform bias relative to biological variation. Other than an initial rescaling, no other transformation to the primary data is applied through batch correction or renormalisation. Additional data, including single-cell datasets, can be projected for comparison, classification and annotation. The resulting atlas provides a multi-scaled approach to visualise and analyse the relationships between sets of genes and blood cell lineages, including the maturation and activation of leukocytes in vivo and in vitro. In allowing for data integration across hundreds of studies, we address a key reproduciblity challenge which is faced by any new technology. This allows us to draw on the deep phenotypes and functional annotations that accompany traditional profiling methods, and provide important context to the high cellular resolution of single cell profiling. Here, we have implemented the blood atlas in the open access Stemformatics.org platform, drawing on its extensive collection of curated transcriptome data. The method is simple, scalable and amenable for rapid deployment in other biological systems or computational workflows. Graphical abstractRecursive approach to generating a multi-scaled atlas. Top panel: The method integrates data from all cell types in the Stemformatics database, and shows clear division of samples into global categories of stromal, pluripotent or blood (inset) cell types. Bottom panel: Integration of only the blood cell subsets provides a blood atlas. Projection of external samples (green) onto the blood atlas. Samples are coloured by curated annotations derived from the original studies, and can be viewed at Stemformatics.org O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/984468v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@2de08dorg.highwire.dtl.DTLVardef@1f18284org.highwire.dtl.DTLVardef@afd32aorg.highwire.dtl.DTLVardef@1507502_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗