Retinal Waves
retinal waves
Alexandre Tiriac
The laboratory of Dr. Alexandre Tiriac is seeking an ambitious candidate for a postdoctoral research position. The Tiriac lab studies how various factors promote or impair the development of the nervous system with the goal of understanding the neural basis of cognitive disorders. Specifically, we are interested in recruiting a postdoctoral researcher interested in taking the lead on a project studying the role of brain states on the development of the nervous system. We study these questions in the mouse visual system, but opportunities exist to branch out to other sensory and motor systems. More information about our current research projects can be found here (https://www.tiriaclab.org/research). With mentorship from Dr. Tiriac, the postdoctoral researcher is expected to independently design and conduct experiments. Example research techniques include dissections, surgeries, calcium imaging using two-photon microscopy, electrophysiological recording using multielectrode arrays, processing brain tissue for histology, and computational techniques. The postdoctoral researcher is expected to perform data analyses, generate figures, and draft research manuscripts that will be submitted to neuroscience journals. Support will be provided for the postdoctoral researcher to attend at least one scientific conference a year to network and present data. If desired by the candidate, the postdoctoral researcher would be supported in the submission of competitive grant applications (e.g.: F32, K99/R00, LSRF, T32). A curated mentorship plan will be designed depending on the candidate’s career goal (industry vs tenure track position). The Tiriac lab strives to provide a supportive and inclusive research environment that fosters interdisciplinary training and collaborative exchange. The lab is based in Vanderbilt’s Department of Biological Sciences. We are also affiliated with the Vanderbilt Brain Institute and the Vanderbilt Vision Research Center. As part of so these programs, the Tiriac lab has access to numerous cores that enhance and speed up our research (currently used example cores: automated genotyping, microscopy core, histology core, and behavior core).
Interplay between circuits that mediate spontaneous retinal waves and early light responses during retinal development
When spontaneous waves meet angiogenesis: a case study from the neonatal retina
By continuously producing electrical signals, neurones are amongst the most energy-demanding cells in the organism. Resting ionic levels are restored via metabolic pumps that receive the necessary energy from oxygen supplied by blood vessels. Intense spontaneous neural activity is omnipresent in the developing CNS. It occurs during short, well-defined periods that coincide precisely with the timing of angiogenesis. Such coincidence cannot be random; there must be a universal mechanism triggering spontaneous activity concurrently with blood vessels invading neural territories for the first time. However, surprisingly little is known about the role of neural activity per se in guiding angiogenesis. Part of the reason is that it is challenging to study developing neurovascular networks in tri-dimensional space in the brain. We investigate these questions in the neonatal mouse retina, where blood vessels are much easier to visualise because they initially grow in a plane, while waves of spontaneous neural activity (spreading via cholinergic starburst amacrine cells) sweep across the retinal ganglion cell layer, in close juxtaposition with the growing vasculature. Blood vessels reach the periphery by postnatal day (P) 7-8, shortly before the cholinergic waves disappear (at P10). We discovered transient clusters of auto-fluorescent cells that form an annulus around the optic disc, gradually expanding to the periphery, which they reach at the same time as the growing blood vessels. Remarkably, these cells appear locked to the frontline of the growing vasculature. Moreover, by recording waves with a large-scale multielectrode array that enables us to visualise them at pan-retinal level, we found that their initiation points are not random; they follow a developmental centre-to-periphery pattern similar to the clusters and blood vessels. The density of growing blood vessels is higher in cluster areas than in-between clusters at matching eccentricity. The cluster cells appear to be phagocytosed by microglia. Blocking Pannexin1 (PANX1) hemichannels activity with probenecid completely blocks the spontaneous waves and results in the disappearance of the fluorescent cell clusters. We suggest that these transient cells are specialised, hyperactive neurones that form spontaneous activity hotspots, thereby triggering retinal waves through the release of ATP via PANX1 hemichannels. These activity hotspots attract new blood vessels to enhance local oxygen supply. Signalling through PANX1 attracts microglia that establish contact with these cells, eventually eliminating them once blood vessels have reached their vicinity. The auto-fluorescence that characterises the cell clusters may develop only once the process of microglial phagocytosis is initiated.
Wiring up direction selective circuits in the retina
The development of neural circuits is profoundly impacted by both spontaneous and sensory experience. This is perhaps most well studied in the visual system, where disruption of early spontaneous activity called retinal waves prior to eye opening and visual deprivation after eye opening leads to alterations in the response properties and connectivity in several visual centers in the brain. We address this question in the retina, which comprises multiple circuits that encode different features of the visual scene, culminating in over 40 different types of retinal ganglion cells. Direction-selective ganglion cells respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite, or null, direction. Moreover, as recently described (Sabbah et al, 2017) the preferred directions of direction selective ganglion cells cluster along four directions that align along two optic flow axes, causing variation of the relative orientation of preferred directions along the retinal surface. I will provide recent progress in the lab that addresses the role of visual experience and spontaneous retinal waves in the establishment of direction selective tuning and direction selectivity maps in the retina.
Emergence of an orientation map in the mouse superior colliculus from stage III retinal waves
COSYNE 2022
The early light experience alters Stage II retinal waves via dopamine-modulated pathway in the developing mouse retina
FENS Forum 2024