Regulation of Radial Glial Motility by Visual Experience

Abstract

Radial glia in the developing optic tectum express the key guidance molecules responsible for topographic targeting of retinal axons. However, the extent to which the radial glia are themselves influenced by retinal inputs and visual experience remains unknown. Using multiphoton live imaging of radial glia in the optic tectum of intact Xenopus laevis tadpoles in conjunction with manipulations of neural activity and sensory stimuli, radial glia were observed to exhibit spontaneous calcium transients that were modulated by visual stimulation. Structurally, radial glia extended and retracted many filopodial processes within the tectal neuropil over minutes. These processes interacted with retinotectal synapses and their motility was modulated by nitric oxide (NO) signaling downstream of neuronal NMDA receptor (NMDAR) activation and visual stimulation. These findings provide the first in vivo demonstration that radial glia actively respond both structurally and functionally to neural activity, via NMDAR-dependent NO release during the period of retinal axon ingrowth.

Rules for Shaping Neural Connections in the Developing Brain

“…This creates a need for ongoing structural dynamism and plasticity at least until metamorphosis in order to optimize the map. The dendritic arbors of tectal neurons and even the filopodial processes extended by radial glial cells are similarly labile during this period, consistent with the notion that dynamic process remodeling can combinatorially increase the potential set of connections available for the network to sample and also reduce the steric interference that may result when multiple cells are actively rewiring within the same volume (Rajan et al, 1999; Chklovskii et al, 2004; Tremblay et al, 2009). Thus even in relatively mature tadpoles, in which most RGC axons have attained their mature size and complexity, time lapse imaging still reveals ongoing remodeling and exploratory probing at branch tips, albeit at considerably slower rates than are observed during the initial establishment of the retinotectal projection.…”

Visual Activity Regulates Neural Progenitor Cells in Developing Xenopus CNS through Musashi1

“…Retinal ganglion cells first innervate and transmit visual information to the optic tectum at stage 39 (Holt and Harris, 1983) when the majority of cells in the tectum have radial glial morphology and neurons have very simple dendritic arbors (Wu et al, 1999). An initial topographic retinotectal map is established by stage 45 (O'Rourke and Fraser, 1990) and between stages 46 and 49 visual experience drives many aspects of visual circuit development pertaining to the detection and processing of visual inputs (Bestman and Cline, 2008; Chiu et al, 2008; Cline and Haas, 2008; Engert et al, 2002; Pratt and Aizenman, 2007, 2009; Pratt et al, 2008; Tao and Poo, 2005) even as ventricular layer cells with radial glial morphology persist in the tectum (Tremblay et al, 2009). Although it is well known that tectal ventricular layer cells proliferate throughout tadpole stages of development and generate neurons within the tectum (Peunova et al, 2001; Straznicky and Gaze, 1972), a potential relation between development of the functional visual circuit and cell proliferation has not been explored.…”

“…To further characterize the musashi1-immunoreactive cells, we labeled radial glial cells in stage 47 tadpoles by bulk electroporation of a CMV::eGFP expression plasmid into ventricular layer cells (Haas et al, 2002). The day after electroporation, eGFP is expressed in cells with radial glial morphology lining the ventricle (Haas et al, 2002; Tremblay et al, 2009). The majority of eGFP-expressing radial glial cells in stage 47 optic tectum are musashi1-immunoreactive (Fig 3D,E).…”

Modeling human neurodevelopmental disorders in theXenopustadpole: from mechanisms to therapeutic targets

“…Because of their transparency, and the extreme dorsal location of the brain, the axons and dendrites of single living neurons can be imaged in vivo (Harris et al, 1987; Ruthazer et al, 2003; Cohen-Cory, 2007; Li et al, 2011; Dong and Aizenman, 2012) and, better yet, in awake animals (Chen et al, 2012; Hossain et al, 2012). Time-lapse imaging of radial glia in the tectum has provided the first in vivo description of how neural activity affects the structure and function of these cells (Tremblay et al, 2009), and advances in morphometric software (Liu et al, 2009; Chen et al, 2012) have allowed for an improved ability to track and measure all processes in 3D across short intervals over long periods of time (Hossain et al, 2012). Furthermore, calcium imaging in tadpoles can be carried out readily (Tao et al, 2001; Junek et al, 2010; Xu et al, 2011), including in vivo recordings from intact awake animals (Chen et al, 2012; Podgorski et al, 2012; Imaizumi et al, 2013).…”