Biology subjects

Pacary, E.

Publications and source records attributed to Pacary, E..

5 recordsLinked to original sources

bioRxiv2026

Blade-dependent molecular identity and neurogenic potential in the adult dentate gyrus

The dentate gyrus (DG) is a key hippocampal gateway for cognition and emotion and a major site of adult neurogenesis, yet its organization along the transverse (suprapyramidal- infrapyramidal) axis remains poorly understood. Here, by integrating bulk RNA sequencing of microdissected mouse DG blades with spatial transcriptomics and single-nucleus RNA sequencing, we define the suprapyramidal and infrapyramidal blades (SB and IB) as distinct molecular compartments characterized by anterior-posterior-dependent gene expression programs. Functionally, the SB exhibits enhanced neurogenic activity, particularly in the anterior DG, including increased progenitor proliferation and neuronal differentiation, whereas the IB contains a larger pool of quiescent neural stem cells. Together, these findings reveal molecular and functional specialization along both transverse and longitudinal axes of the DG and provide a framework for interrogating hippocampal subregional organization in health and disease.

neuroscience↗

bioRxiv2026

Neocortical astrocyte diversity stems from distinct developmental origins

Key regulators of neural network activity in multiple advanced cognitive processes and essential components of the blood-brain barrier, astrocytes constitute a highly heterogeneous population at the morphological, molecular, and functional levels. However, how this diversity arises during mammalian brain development remains poorly investigated. Here, using a combination of multicolour genetic fate mapping, single-cell transcriptomic analyses, multichannel large-volume imaging and detailed 3D cell morphology reconstructions, we uncover a discrete subpopulation of neocortical astrocytes generated from an early restricted embryonic domain located outside of the dorsal pallium. Besides their separate lineage from pyramidal neurons, these astrocytes exhibit a developmental trajectory that differs from astrocytes produced by dorsal cortical progenitors, including different migratory pathways, spatial distributions and morphology. Overall, our results reveal the diversity of embryonic sources responsible for neocortical astrocyte genesis and provide key insights into the unsuspected complex developmental processes that underlie cortical astrocyte heterogeneity.

neuroscience↗

bioRxiv2024

Long-lived adult-born hippocampal neurons promote successful cognitive aging

Aging is commonly associated with a decline in memory abilities, yet some individuals remain resilient with preserved memory abilities. Memory processing is critically dependent on adult neurogenesis, a unique form of plasticity in the hippocampus. However, it remains unknown if cognitive aging influences the integration and role of adult-born hippocampal neurons (ABNs) generated early in adult life. Here, we investigated the role of long-lived ABNs in rats characterized as either resilient or vulnerable to cognitive aging using a peudo-longitudinal approach. Our findings reveal that long-lived ABNs support successful cognitive aging by preserving their synaptic inputs onto the proximal segments of their dendrites, and that these proximal synaptic sites also demonstrate a maintenance of their mitochondrial homeostasis. Furthermore, by-passing the reduced inputs of ABNs in vulnerable rats through direct optogenetic stimulation successfully improved their memory abilities. Overall, our data indicate that the maintenance of long-lived ABNs integration within the neuronal network is essential for successful cognitive aging, highlighting their potential as a therapeutic target for restoring cognitive functions in old age. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/604332v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@524afforg.highwire.dtl.DTLVardef@b9b2b1org.highwire.dtl.DTLVardef@182a19corg.highwire.dtl.DTLVardef@1402b64_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Genetic labeling of embryonically-born dentate granule neurons in young mice using the PenkCre mouse line

The dentate gyrus (DG) of the hippocampus is a mosaic of dentate granule neurons (DGNs) accumulated throughout life. While many studies focused on the morpho-functional properties of adult-born DGNs, much less is known about DGNs generated during development, and in particular those born during embryogenesis. One of the main reasons for this gap is the lack of methods available to specifically label and manipulate embryonically-born DGNs. Here, we have assessed the relevance of the PenkCre mouse line as a genetic model to target this embryonically-born population. In young animals, PenkCre expression allows to tag neurons in the DG with positional, morphological and electrophysiological properties characteristic of DGNs born during the embryonic period. In addition, PenkCre+ cells in the DG are distributed in both blades along the entire septo-temporal axis. This model thus offers new possibilities to explore the functions of this underexplored population of embryonically-born DGNs.

neuroscience↗

bioRxiv2020

The atypical Rho GTPase Rnd2 is critical for dentate granule neuron development and anxiety-like behavior during adult but not neonatal neurogenesis

Despite the central role of Rho GTPases in neuronal development, their functions in adult hippocampal neurogenesis remain poorly explored. Here, by using a retrovirus-based loss-of-function approach in vivo, we show that the atypical Rho GTPase Rnd2 is crucial for the survival, positioning, somatodendritic morphogenesis and functional maturation of adult-born dentate granule neurons. Interestingly, most of these functions are specific to granule neurons generated during adulthood since the deletion of Rnd2 in neonatally-born granule neurons only affects dendritogenesis. In addition, suppression of Rnd2 in adult-born dentate granule neurons increases anxiety-like behaviour whereas its deletion in pups has no such effect, a finding supporting the adult neurogenesis hypothesis of anxiety disorders. Thus, our results provide mechanistic insight into the differential regulation of hippocampal neurogenesis during development and adulthood, and establishes a causal relationship between Rnd2 expression and anxiety.

neuroscience↗