Biology subjects

Sansone, G.

Publications and source records attributed to Sansone, G..

3 recordsLinked to original sources

bioRxiv2025

Context-dependent presynaptic inhibition of somatostatin interneuron inputs to Layer 1 of the visual cortex

Layer 1 of the cortex is a critical site for integrating top-down inputs onto the distal dendrites of pyramidal neurons, where inhibitory neurons modulate these inputs to enable context-dependent sensory processing. Yet, it remains unclear how behavioral context dynamically regulates inhibition in Layer 1. We discover a circuit motif in which NDNF cortical interneurons (cINs) presynaptically inhibit the axonal outputs of somatostatin (SST) cINs in Layer 1 of the visual cortex. Using combinatorial genetics, monosynaptic retrograde tracing, super-resolution imaging, optogenetics, slice electrophysiology, and in vivo calcium imaging, we show that NDNF cINs form direct contacts onto SST axons and suppress their output, thereby modulating inhibitory responses in L2/3 pyramidal neurons. This presynaptic inhibitory circuit is preferentially engaged during locomotion and low-contrast visual conditions. By dynamically modulating Layer 1-mediated inhibitory output onto pyramidal neurons, this circuit motif enables context-dependent modulation of visual processing.

neuroscience↗

bioRxiv2025

Charting the single cell transcriptional landscape governing visual imprinting.

Memory-related transcriptional events in brain remain poorly understood. Visual imprinting is a form of learning in which young animals develop preferences through early exposure to specific stimuli. In chicks, visual imprinting memory is stored in the intermediate medial mesopallium (IMM) of the forebrain. To investigate learning-associated molecular changes, we performed single-nucleus RNA sequencing of the left IMM in strongly imprinted chicks and untrained controls. This analysis generated the first classification of cells composing the IMM, identifying as a result over 30 cell clusters with distinct transcriptional differences putatively linked to memory formation, nearly half of them in long non-coding RNAs (lncRNAs). Follow-up analysis on selected genes, confirmed that the gene expression levels of two lncRNAs and protein levels of FOXP2, RORA (transcription factors), LUC7L (splicing factor), and ROBO1 (axon guidance molecule) correlate with memory strength, reflecting either innate learning potential or imprinting experience. Additionally, among the confirmed lncRNAs, the brain- and avian-specific lncRNA ENSGALG00010007489 is enriched in the nuclei of specific glutamatergic clusters and its association with imprinting was further confirmed through quantitative multi-probe in situ hybridization. These findings offer the first single-cell resolution map of transcriptional changes underlying memory formation in the avian brain.

neuroscience↗

bioRxiv2022

Poor sensitivity of iPSC-derived neural progenitors and glutamatergic neurons to SARS-CoV-2

COVID-19 is a respiratory disease affecting multiple organs including the central nervous system (CNS), with a characteristic loss of smell and taste. Although frequently reported, the neurological symptoms remain enigmatic. There is no consensus on the extent of CNS infection. Here, we derived human induced pluripotent stem cells (hiPSC) into neural progenitor cells (NPCs) and cortical excitatory neurons to study their permissiveness to SARS-CoV-2 infection. Flow cytometry and western blot analysis indicated that NPCs and neurons do not express detectable levels of the SARS-CoV-2 receptor ACE2. We thus generated cells expressing ACE2 by lentiviral transduction to analyze in a controlled manner the properties of SARS-CoV-2 infection relative to ACE2 expression. Sensitivity of parental and ACE2 expressing cells was assessed with GFP- or luciferase-carrying pseudoviruses and with authentic SARS-CoV-2 Wuhan, D614G, Alpha or Delta variants. SARS-CoV-2 replication was assessed by microscopy, RT-qPCR and infectivity assays. Pseudoviruses infected only cells overexpressing ACE2. Neurons and NPCs were unable to efficiently replicate SARS-CoV-2, whereas ACE2 overexpressing neurons were highly sensitive to productive infection. Altogether, our results indicate that primary NPCs and cortical neurons remain poorly permissive to SARS-CoV-2 across the variants spectrum, in the absence of ACE2 expression.

neuroscience↗