Biology subjects

Schohl, A.

Publications and source records attributed to Schohl, A..

5 recordsLinked to original sources

bioRxiv2021

BDNF signaling in Hebbian and Stentian structural plasticity in the developing visual system

During development, patterned neural activity instructs topographic map refinement. Axons with similar patterns of neural activity, converge onto target neurons and stabilize their synapses with these postsynaptic partners, restricting exploratory branch elaboration (Hebbian structural plasticity). On the other hand, non-correlated firing in inputs leads to synapse weakening and increased exploratory growth of axons (Stentian structural plasticity). We used visual stimulation to control the correlation structure of neural activity in a few ipsilaterally projecting (ipsi) retinal ganglion cell (RGC) axons with respect to the majority contralateral eye inputs in the optic tectum of albino Xenopus laevis tadpoles. Multiphoton live imaging of ipsi axons, combined with specific targeted disruptions of brain-derived neurotrophic factor (BDNF) signaling, revealed that both presynaptic p75NTR and TrkB are required for Stentian axonal branch addition, whereas presumptive postsynaptic BDNF signaling is necessary for Hebbian axon stabilization. Additionally, we found that BDNF signaling mediates local suppression of branch elimination in response to correlated firing of inputs. Daily In vivo imaging of contralateral RGC axons demonstrated that p75NTR knockdown reduces axon branch elongation and arbor spanning field volume.

neuroscience↗

bioRxiv2021

The effects of the NMDAR co-agonist D-serine on the structure and function of the optic tectum

The N-methyl-D-aspartate type glutamate receptor (NMDAR) is a molecular coincidence detector which converts correlated patterns of neuronal activity into cues for the structural and functional refinement of developing circuits in the brain. D-serine is an endogenous co-agonist of the NMDAR. In this study, we investigated the effects of potent enhancement of NMDAR-mediated currents by chronic administration of saturating levels of D-serine on the developing Xenopus retinotectal circuit. Chronic exposure to the NMDAR co-agonist D-serine resulted in structural and functional changes to the optic tectum. D-serine administration affected synaptogenesis and dendritic morphology in recently differentiated tectal neurons, resulting in increased arbor compaction, reduced branch dynamics, and higher synapse density. These effects were not observed in more mature neurons. Calcium imaging to examine retinotopic map organization revealed that tectal neurons of animals raised in D-serine had sharper visual receptive fields. These findings suggest that the availability of endogenous NMDAR co-agonists like D-serine at glutamatergic synapses may regulate the refinement of circuits in the developing brain. Significance statementN-methyl-D-aspartate receptors (NMDAR) are implicated in activity-dependent circuit plasticity. We used administration of the NMDAR co-agonist D-serine to further examine the role of the NMDAR in circuit development in vivo. D-serine stabilised dendritic arbors specifically of recently differentiated neurons, promoted synaptogenesis, and led to sharper retinotopic receptive fields in the optic tectum. Together, these results support the idea that signaling in response to synaptic current through NMDARs promotes the maturation of developing brain circuits.

neuroscience↗

bioRxiv2021

Activity-dependent alteration of early myelin ensheathment in a developing sensory circuit

Adaptive myelination has been reported in response to experimental manipulations of neuronal activity, but the links between sensory experience, corresponding neuronal activity, and resultant alterations in myelination require investigation. To study this, we used the Xenopus laevis tadpole, which is a classic model for studies of visual system development and function because it is translucent and visually responsive throughout the formation of this retinotectal system. Here, we report the timecourse of early myelin ensheathment in the Xenopus retinotectal system using immunohistochemistry of myelin basic protein (MBP) along with third-harmonic generation (THG) microscopy, a label-free structural imaging technique. Characterization of the myelination progression revealed an appropriate developmental window to address the effects of early patterned visual experience on myelin ensheathment. To alter patterned activity, we showed tadpoles stroboscopic stimuli and measured the calcium responses of retinal ganglion cell axon terminals. We identified strobe frequencies that elicited robust versus dampened calcium responses, reared animals in these strobe conditions for 7 d, and subsequently observed differences in the amount of early myelin ensheathment at the optic chiasm. This study provides evidence that it is not just the presence but also to the specific temporal properties of sensory stimuli that are important for myelin plasticity.

neuroscience↗

bioRxiv2020

Sodium-Calcium Exchanger Mediates Sensory-Evoked Glial Calcium Transients in the Developing Retinotectal System

Various types of sensory stimuli have been shown to induce calcium elevations in glia. However, a mechanistic understanding of the signalling pathways mediating sensory-evoked activity in glia in intact animals is still emerging. Here we demonstrate that during early development of the Xenopus laevis visual system, radial astrocytes in the optic tectum are highly responsive to sensory stimulation. Calcium transients occur spontaneously in radial astrocytes at rest and are abolished by silencing neuronal activity with tetrodotoxin. Visual stimulation drives temporally correlated increases in the activity patterns of neighbouring radial astrocytes. Following blockade of all glutamate receptors, visually-evoked calcium activity in radial astrocytes is enhanced, rather than suppressed, while the additional blockade of either glutamate transporters or sodium-calcium exchangers (NCX) fully prevents visually-evoked responses. Additionally, we demonstrate that blockade of NCX alone is sufficient to prevent visually-evoked responses in radial astrocytes, highlighting a pivotal role for NCX in glia during development.

neuroscience↗

bioRxiv2020

Improved genetically encoded near-infrared fluorescent calcium ion indicators for in vivo imaging

Near-infrared (NIR) genetically-encoded calcium ion (Ca2+) indicators (GECIs) can provide advantages over visible wavelength fluorescent GECIs in terms of reduced phototoxicity, minimal spectral cross-talk with visible-light excitable optogenetic tools and fluorescent probes, and decreased scattering and absorption in mammalian tissues. Our previously reported NIR GECI, NIR-GECO1, has these advantages but also has several disadvantages including lower brightness and limited fluorescence response compared to state-of-the-art visible wavelength GECIs, when used for imaging of neuronal activity. Here, we report two improved NIR GECI variants, designated NIR-GECO2 and NIR-GECO2G, derived from NIR-GECO1. We characterized the performance of the new NIR GECIs in cultured cells, acute mouse brain slices, and C. elegans and Xenopus laevis in vivo. Our results demonstrate that NIR-GECO2 and NIR-GECO2G provide substantial improvements over NIR-GECO1 for imaging of neuronal Ca2+ dynamics.

molecular biology↗