Biology subjects

Farrugia, F.

Publications and source records attributed to Farrugia, F..

4 recordsLinked to original sources

bioRxiv2026

Adolescent Sugar-Induced Miswiring of Hippocampal Neurons Drives Adult Motivational Dysfunction in rats

Adolescence, a critical period for hippocampal maturation, involves the integration of newly generated neurons into circuits underlying adult behavior. While adolescent, but not adult, sugar overconsumption triggers lasting motivational deficits, the underlying mechanisms remain unclear. Here, we demonstrate that adolescent-born dentate gyrus granule neurons causally mediate adult reward-seeking behavior. Strikingly, sucrose overconsumption during adolescence abolishes this function, inducing selective remodeling of synaptic inputs and disrupting their functional integration.

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↗

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↗

bioRxiv2020

Time-dependent roles of adolescent- and adult-born dentate granule neurons in spatial learning

The dentate gyrus presents the peculiarity to be formed after birth in rodents. Adolescence is a very sensitive period during which cognitive competences are programmed. We investigated and compared the role of dentate neurons born during adolescence or generated during adulthood. We demonstrated that the ontogenetic stage of dentate neurons in relation to when they are generated dictates their participation in memory processes.

neuroscience↗