Biology subjects

Tiriac, A.

Publications and source records attributed to Tiriac, A..

6 recordsLinked to original sources

bioRxiv2026

Microvascular architecture and dynamics of the choroid plexus brain barrier

The choroid plexus is a specialized blood-cerebrospinal fluid barrier that supports cerebrospinal fluid production, immune surveillance, and molecular exchange between the circulation and the central nervous system, yet its vascular bed remains poorly understood. Here, we combine whole-tissue clearing and light-sheet imaging, single-nucleus transcriptomic reanalysis, and live calcium imaging of intact murine explants to define the structural and functional organization of choroid plexus endothelial networks across development. Three-dimensional imaging and reconstruction highlights a dense, epithelial-ensheathed vascular plexus that is continuous with the broader cerebrovasculature and organized into anatomically distinct inflow and ventricular margin regions. Transcriptomic analysis identified developmentally stratified endothelial subtypes, with embryonic populations enriched for proliferative, motor, and membrane remodeling programs and adult and aged populations enriched for adhesion, extracellular matrix, transport, and mechanosensory pathways. Endothelial subsets across stages expressed genes linked to flow sensing and calcium-dependent mechanotransduction, including Piezo1, Piezo2, and Trpv4. Consistent with these signatures, intact explants exhibited spontaneous, spatially graded calcium oscillations, and pharmacologic activation by Piezo1, triggered robust network-wide calcium responses in embryonic and adult tissue with distinct temporal dynamics. Piezo1 activation also promoted stabilization of PECAM1-associated endothelial adhesion under ex vivo flow conditions. Together, these findings establish the choroid plexus endothelium as a structurally specialized, developmentally dynamic, and mechanosensitive vascular network and provide a framework for investigating endothelial contributions to blood-cerebrospinal fluid barrier function in health and disease.

neuroscience↗

bioRxiv2025

A toolbox for navigating and analyzing the spatiotemporal properties of retinal waves

The precise development of the visual system is driven by retinal waves, which are bursts of spontaneous activity that propagate across retinal neurons in a wave-like fashion. In mice, retinal waves begin embryonically and continue until eye opening at the end of the second postnatal week. During this time, the mechanisms for generating and propagating retinal waves are changing, thus causing retinal waves to exhibit highly dynamic spatiotemporal properties from one day to the next. Critically, the spatiotemporal properties of retinal waves have been shown to instruct the development of the visual system, including eye-specific segregation, retinotopic mapping, direction selectivity, and potentially retinal vascularization. Currently, there is no method for the automatic detection and high-throughput quantitative analysis of the spatiotemporal properties of retinal waves. To overcome this barrier, we developed WaveMiner, an automated, high-throughput toolbox for detecting, segregating, and quantifying retinal waves from microelectrode-array (MEA) and calcium-imaging recordings. After first validating our toolbox, we use it to uncover novel dynamic spatiotemporal properties of retinal waves in the first two postnatal weeks. We also use this toolbox to analyze ultra long physiological recordings, revealing that waves exhibit both stable and dynamic spatiotemporal properties on an hourly basis. Finally, we demonstrate that this toolbox can detect waves in the presence of pharmacological agents that increase the baseline firing of neurons, enabling the discovery of novel factors that perturb the spatiotemporal properties of retinal waves and visual development. In summary, WaveMiner is a platform to standardize the detection and quantification of retinal waves across recording modalities and experimental conditions, enabling novel discoveries about their dynamic spatiotemporal properties and the factors that govern them.

neuroscience↗

bioRxiv2024

Development and Organization of the Retinal Orientation Selectivity Map

Orientation or axial selectivity, the property of neurons in the visual system to respond preferentially to certain angles of a visual stimuli, plays a pivotal role in our understanding of visual perception and information processing. This computation is performed as early as the retina, and although much work has established the cellular mechanisms of retinal orientation selectivity, how this computation is organized across the retina is unknown. Using a large dataset collected across the mouse retina, we demonstrate functional organization rules of retinal orientation selectivity. First, we identify three major functional classes of retinal cells that are orientation selective and match previous descriptions. Second, we show that one orientation is predominantly represented in the retina and that this predominant orientation changes as a function of retinal location. Third, we demonstrate that neural activity plays little role on the organization of retinal orientation selectivity. Lastly, we use in silico modeling followed by validation experiments to demonstrate that the overrepresented orientation aligns along concentric axes. These results demonstrate that, similar to direction selectivity, orientation selectivity is organized in a functional map as early as the retina. One Sentence SummaryDevelopment and organization of retinal orientation selectivity

neuroscience↗

bioRxiv2022

Cellular Mechanisms Underlying Embryonic Retinal Waves

Spontaneous activity is a hallmark of developing neural systems. In the retina, spontaneous activity comes in the form of retinal waves, comprised of three stages persisting from embryonic day 16 (E16) to eye opening at postnatal day 14 (P14). Though postnatal retinal waves have been well characterized, little is known about the spatiotemporal properties or the mechanisms mediating embryonic retinal waves, designated Stage 1 waves. Using a custom-built macroscope to record spontaneous calcium transients from whole embryonic retinas, we show that Stage 1 waves are initiated at several locations across the retina and propagate across finite regions of a broad range of areas. A gap junction antagonist, meclofenamic acid, reduced the frequency and size of Stage 1 waves but did not abolish them. The general nAChR antagonist, hexamethonium blocked Stage 1 waves, while they persisted in the presence of 4{beta}2 nAChR antagonist dihydro-{beta}-erythroidine, indicating that the spatiotemporal properties of Stage 1 waves are mediated by a complex circuitry involving subtypes of nAChRs and gap junctions. Stage 1 waves in mice lacking the {beta}2 subunit of the nAChRs ({beta}2-nAChR-KO) were reduced, but in contrast to WT mice, they persisted in the hexamethonium and were completely blocked by meclofenamic acid. To assay the impact of Stage 1 waves on retinal development, we compared the spatial distribution of a subtype of retinal ganglion cells, intrinsically photosensitive retinal ganglion cells (ipRGCs) in WT and {beta}2-nAChR-KO mice. We found that the developmental decrease of ipRGC density is preserved between WT and {beta}2-nAChR-KO mice, indicating that processes regulating ipRGC distribution are not influenced by spontaneous activity.

neuroscience↗

bioRxiv2022

The Retinal Basis of Photoaversion in Neonatal Mice

Aversive responses to bright light (photoaversion) require signaling from the eye to the brain. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) encode absolute light intensity and are thought to provide the light signals for photoaversion. Consistent with this, neonatal mice exhibit photoaversion prior to the developmental onset of image vision, and melanopsin deletion abolishes photoaversion in neonates. It is not well understood how the population of ipRGCs, which constitutes multiple physiologically distinct types (denoted M1-M6 in mouse) encodes light stimuli to produce an aversive response. Here, we provide several lines of evidence that M1 ipRGCs that lack the Brn3b transcription factor drive photoaversion in neonatal mice. First, neonatal mice lacking TRPC6 and TRPC7 ion channels failed to turn away from bright light, while two photon Ca2+ imaging of their acutely isolated retinas revealed reduced photosensitivity in M1 ipRGCs, but not other ipRGC types. Second, mice in which all ipRGC types except for Brn3b-negative M1 ipRGCs are ablated, exhibited normal photoaversion. Third, pharmacological blockade or genetic knockout of gap junction channels expressed by ipRGCs, which reduces the light sensitivity of M2-M6 ipRGCs in the neonatal retina, had small effects on photoaversion only at the brightest light intensities. Finally, M1s were not strongly depolarized by spontaneous retinal waves, a robust source of activity in the developing retina that depolarizes all other ipRGC types. M1s therefore constitute a separate information channel between the neonatal retina and brain that could ensure behavioral responses to light but not spontaneous retinal waves.

neuroscience↗

bioRxiv2021

Retinal waves but not visual experience are required for development of retinal direction selectivity maps

Retinal waves and visual experience have been implicated in the formation of retinotopic and eye-specific maps throughout the visual system, but whether either play a role in the development of the maps within the retina itself is unknown. We explore this question using direction-selective retinal ganglion cells, which are organized into a map that aligns to the body and gravitational axes of optic flow. Using two-photon population calcium imaging, we find that the direction selectivity map is present at eye opening and is unaltered by dark-rearing. Remarkably, the horizontal component of the direction selectivity map is absent in mice lacking normal retinal waves, whereas the vertical component remains normal. These results indicate that intrinsic patterns of activity, rather than extrinsic motion signals are critical for the establishment of direction selectivity maps in the retina. One Sentence SummaryHorizontal direction selectivity in the retina is absent in mice lacking normal retinal waves.

neuroscience↗