Biology subjects

Tibi, M.

Publications and source records attributed to Tibi, M..

3 recordsLinked to original sources

bioRxiv2024

Brain-wide monosynaptic connectivity mapping with ROInet-seq

Viral projection tracing strategies help establish regional connectomes of mammalian brains. Monosynaptic connectivity tracing with G-deleted rabies virus (RV) establishes synaptic input connectivity, but cannot distinguish networks at cell resolution. We implemented a barcoded {Delta}G rabies virus to introduce unique molecular tags - and make network tracing amenable to readout by RNA-sequencing. First, we optimized and characterized library complexity and uniformity, such that detection of specific barcodes can reliably distinguish the individual monosynaptic input networks of multiple infected neurons in parallel. To deploy the method at scale; to hundreds of cells and full-brain volume per experiment, we developed regions-of-interest network sequencing (ROInet-seq); an accessible, scalable and low-cost spatial assay. ROInet-seq combines routine fluorescent imaging and processing of fixed tissue sections with a simple molecular biology workflow to capture barcode sequences in relevant regions-of-interest, and ultimately describes single-neuron networks brain-wide. In cortical brain areas the assay revealed preserved regional network motives, including co-inputs to single cortical neurons from distant and local sites. Towards improved spatial resolution and simultaneous detection of transcriptomes and networks we finally sampled barcoded {Delta}G rabies virus-infected hippocampus on commercial spatial transcriptomics assays and reveal details of the regions neurons local network architecture.

neuroscience↗

bioRxiv2023

A telencephalon cell type atlas for goldfish reveals diversity in the evolution of spatial structure and cell types

Teleost fish form the largest group of vertebrates, making them critically important for the study on the mechanisms of brain evolution. In fact, teleosts show a tremendous variety of adaptive behaviors similar to birds and mammals, however, the neural basis mediating these behaviors remains elusive. We performed a systematic comparative survey of the goldfish telencephalon; the seat of plastic behavior, learning and memory in vertebrates. We delineated and mapped goldfish telencephalon cell types using single-cell RNA-seq and spatial transcriptomics, resulting in de novo molecular neuroanatomy parcellation. Glial cells were highly conserved across 450 million years of evolution separating mouse and goldfish, while neurons showed diversity and modularity in gene expression. Specifically, somatostatin (SST) interneurons, famously interspersed in the mammalian isocortex for local inhibitory input, were curiously aggregated in a single goldfish telencephalon nucleus, but molecularly conserved. Cerebral nuclei including the striatum, a hub for motivated behavior in amniotes, had molecularly and spatially conserved goldfish homologues. We further suggest different elements of a hippocampal formation across the goldfish pallium. Together, our atlas provides new insights to organization and evolution of vertebrate forebrains and may serve as a resource for the functional study underlying cognition in teleost fish. TeaserDetailed mapping of goldfish forebrain cells unwraps how 450 million years of evolution may have impacted brain function

neuroscience↗

bioRxiv2022

Cell types in the mouse amygdala and their transcriptional response to fear conditioning

The amygdala is one of the most widely studied regions in behavioral neuroscience. A plethora of classical, and new paradigms have dissected its precise involvement in emotional and social sensing, learning, and memory. Several important insights resulted from the use of genetic markers - yet, in the age of single cell transcriptomics, the amygdala remains molecularly underdescribed. Here, we present a molecular cell type taxonomy of the full mouse amygdala in fear learning and consolidation. We performed single-cell RNA-seq on naive and fear conditioned mice, inferred the 130 neuronal cell types distributions in silico using orthogonal spatial transcriptomic datasets, and describe the cell types transcriptional responses to learning and memory consolidation. Only a fraction of cells, within a subset of all neuronal types, were transcriptionally responsive to fear learning, memory and retrieval. These activated engram cells upregulated activity-response genes, and processes of synaptic signaling, plasticity, development and neurite outgrowth. Our transcriptome-wide data confirm known actors, and describe several new candidate genes. The atlas may help pinpoint the amygdalas circuits in performing emotional sensing and integration, and provide new insights to the global cellular processes involved.

neuroscience↗