Biology subjects

Quattrocolo, G.

Publications and source records attributed to Quattrocolo, G..

6 recordsLinked to original sources

bioRxiv2026

The ontogeny of hippocampal spatial memory is supported by postnatal Cajal-Retzius cells

The functional capabilities of the adult hippocampus depend on specialized circuits that are established during development. Cajal-Retzius (CR) cells persist in the hippocampus long after their disappearance from the neocortex and contribute to the postnatal maturation of hippocampal circuits, but how this developmental role shapes adult hippocampal function remains unknown. Here, we selectively ablated CR cells from the postnatal hippocampus and examined the consequences for spatial learning, navigation, and CA1 spatial representations. CR-cell ablated animals learned reward locations and adapted to changing task conditions, but learned more slowly and made more errors. Reinforcement-learning models suggest that these behavioral differences reflect less stable internal representations guiding behavior. Consistent with this, CA1 spatial representations remained present but were more unstable and showed reduced differentiation of reward locations, particularly when task conditions changed. Our findings identify postnatal CR cells as key developmental contributors to the stability of hippocampal spatial representations and the adaptive behavior they support.

neuroscience↗

bioRxiv2026

Long-Range Glutamatergic Projections Target Hippocampal Cajal-Retzius Cells Through Atypical Receptor Signaling

Cajal-Retzius (CR) cells are a population of early-born, transient neurons that serve an indispensable role during embryonic brain development. Postnatally, most CR cells undergo programmed cell-death, except in a few areas, including the hippocampus, where they persist until adulthood. The hippocampal population of CR (hCR) cells have previously been implicated in receiving and facilitating ingrowth of entorhinal afferents and the establishment of the hippocampal circuit. Nevertheless, only local GABAergic synaptic input has been demonstrated onto hCR cells before. Through transsynaptic rabies tracing we show that hCR cells receive input for at least seven extrahippocampal areas, all putative glutamatergic populations, even though CR cell spontaneous activity is speculated to be exclusively mediated through GABAergic action. Here, we show that a portion of CR cell spontaneous activity is strychnine-sensitive, and that glutamatergic fibers from entorhinal cortex layer II apposition themselves in physiological distance (<300 nm) to glycinergic receptors on hCR cells. We propose that hCR cells guide several, if not all, afferents terminating in stratum lacunosum moleculare and the outer molecular layer in the hippocampus. These findings shine new light on how hCR cells might facilitate hippocampal maturation.

neuroscience↗

bioRxiv2026

Spatial representation in CA1 superficial pyramidal cells is impaired after postnatal ablation of hippocampal Cajal Retzius cells

Cajal-Retzius neurons (CRs) are a transient cell type that populates the postnatal hippocampus. To test how the persistence of CRs shapes the maturation of hippocampal function, we used a CRs-specific transgenic mouse line combined with targeted viral delivery to selectively ablate CRs in the postnatal hippocampus. Single cell sequencing revealed that gene networks in superficial CA1 pyramidal cells were more strongly perturbed compared to deep CA1 pyramidal cells. To test if these two subpopulations were also distinctly affected in their function, we performed in vivo recordings from spatially modulated cells in CA1. Our analysis showed an impaired spatial representation specifically in superficial CA1 pyramidal cells. Additionally, we observed an increased CA3 to CA1 excitatory drive, as indicated by increased gamma oscillations, and alterations of intrinsic firing properties in superficial CA1 pyramidal neurons confirmed by in vitro electrophysiological recordings. Together, these results indicate a crucial role for CRs in the maturation of hippocampal subcircuits.

neuroscience↗

bioRxiv2025

Proteomic profile of hippocampal growth cones through early postnatal development

1.The early postnatal period represents a critical window for neural circuit assembly in the developing hippocampus. Growth cones (GCs) play essential roles in establishing connectivity patterns, yet their proteomic composition during this dynamic developmental phase remains poorly characterized. Here, we performed comprehensive proteomic profiling of GCs isolated from the whole hippocampus (HP-GCs) and dentate gyrus (DG-GCs) across the first five postnatal days (P1, P3, P5) in mice. Mass spectrometry and proteomic analysis revealed that GCs from both regions are highly similar at P1, subsequently diverging. This earliest timepoint seems to be characterized by a high metabolic demand. Developmental trajectories of the GCs from the two subregions then start to differ, with P3 being a very dynamic period for HP-GCs, with GO terms related to RNA splicing, and a transition towards synapse formation by P5. On the contrary, DG-GCs seem to still be in an exploratory phase by P5, suggesting a delayed maturation and reflecting the later time course of the invasion of EC layer 2 Reelin-positive axons into this region. We identified over 5,000 proteins, with each timepoint characterized by distinct protein subsets. Temporal trajectory analysis revealed key GC markers including DCC, DPSYL2, and FABP7, which showed dynamic regulation across development. Notably, we identified multiple proteins containing nuclear localization sequences, suggesting bidirectional communication between GCs and the nucleus during critical developmental periods. Furthermore, our dataset contains over 400 proteins associated with neurological and neurodegenerative diseases, with twenty showing temporal regulation, highlighting the potential relevance of early developmental disruptions to disease pathogenesis. These findings provide a comprehensive proteomic resource for understanding GC function during hippocampal circuit formation and offer insights into the molecular mechanisms underlying region-specific developmental timelines in the brain.

neuroscience↗

bioRxiv2025

Differences in Cajal-Retzius cell density and postnatal persistence across cortical areas revealed by a novel intersectional genetic labeling approach

Cajal-Retzius (CR) cells are glutamatergic neurons that transiently populate the most superficial layer of the isocortex and allocortex during development, serving an essential role during both prenatal and early postnatal brain development. Notably, these cells disappear from most cortical areas by postnatal day 14, but persist for much longer in the hippocampus. We developed a novel intersectional genetic labeling approach for CR cells that captures almost all of the TRP73-positive CR cells throughout the isocortex and allocortex. This intersectional strategy offers several advantages over previous methods commonly used for CR cell targeting. Here, we applied this new CR cell labeling strategy to investigate the distribution and persistence of CR cells throughout the whole mouse brain, at four different postnatal ages. We observed that the initial CR cell density and the rate of their disappearance varies substantially across different brain areas during development. Strikingly, we observed variation in cell death rate even between adjacent cortical subregions: comparing the medial and the lateral entorhinal cortex, the former retains a high density of CR cells for several months in contrast to the latter. Our results present a necessary revision of the phenomenon of CR cell persistence, showing that, in addition to hippocampus, several other cortical areas maintain a high density of these cells beyond the first two postnatal weeks.

neuroscience↗

bioRxiv2022

Persistence of Cajal-Retzius cells in the postnatal hippocampus is required for development of dendritic spines of CA1 pyramidal cells

Cajal-Retzius (CR) cells are a transient type of neuron that populate the postnatal hippocampus. The role of transient cell types and circuits have been vastly addressed in neocortical regions, but poorly studied in the hippocampus. To understand how CR cells persistence influences the maturation of hippocampal circuits, we specifically ablated CR cells from the postnatal hippocampus. Our results highlighted layer-specific effects on dendritic spines and synaptic-related genes and revealed a critical role of CR cells in the establishment of the hippocampal network.

neuroscience↗