Neurotrophic regulation of retinal ganglion cell synaptic connectivity: from axons and dendrites to synapses

Abstract

This review highlights important events during the morphological development of retinal ganglion cells (RGCs), focusing on mechanisms that control axon and dendritic arborization as a means to understand synaptic connectivity with special emphasis on the role of neurotrophins during structural and functional development of RGCs. Neurotrophins and their receptors participate in the development of visual connectivity at multiple levels. In the visual system, neurotrophins have been shown to exert various developmental influences, from guiding the morphological differentiation of neurons to controlling the functional plasticity of visual circuits. This review article examines the role of neurotrophins, and in particular of BDNF, during the morphological development of RGCs, and discusses potential interactions between activity and neurotrophins during development of neuronal connectivity. Retinal ganglion cells (RGCs), the sole projection neurons from the retina, integrate, process, and convey all visual information transmitted to the brain (Dowling, 1987). Within the retina, RGCs attain their fates and differentiate early, preceding other types of retinal neurons (Fig. 1). RGCs reside near the lens in the ganglion cell layer (GCL) and exhibit distinctive, characteristic morphologies. Different morphological subtypes of mature RGCs are characterized by soma size and dendritic arborization patterns. To receive synaptic inputs from amacrine and bipolar neurons, each RGC elaborates several branched dendrites into the retina's inner plexiform layer (IPL) and to provide synaptic input to the central targets, each RGC extends a single axon that exits the retina via the optic nerve to synapse on neurons in the brain (the optic tectum in lower vertebrates or superior colliculus, pretectum, and lateral geniculate nucleus in higher vertebrates). When the RGC growth cone has reached and recognized its target region, the growth cone transforms into an actively branching axon terminal, extending and retracting branches it forms synapses with target neurons in the brain. The events of RGC axon extension, growth cone pathfinding, and target recognition all coincide with RGC dendritic arborization in the retina. RGCs begin to extend primary dendrites as their axons course towards their targets, and continue to elaborate complex dendritic arbors as their axon terminals innervate and branch within the target (Holt, 1989). KEY WORDS: retina, optic tectum, arborization, BDNF, visual systemThis review highlights important events during the morphological development of RGC that influence both the presynaptic (dendritic) and postsynaptic (axon) connectivity of RGC projection neurons. The elucidation of the events that guide development and differentiation of RGCs is due in part to recent advances in in vivo imaging techniques that have permitted visualization of cellular events that underlie the establishment of RGC synaptic connectivity (Cohen-Cory, 2002;Debski and Cline, 2002). The frog and fish retinotectal projections have p...

Effects of Monocular Deprivation on the Dendritic Features of Retinal Ganglion Cells

“…The morphology of ganglion cell dendrites continues to be modified by pruning mechanisms that persist long after initial synaptic contacts are formed in the visual system (Coombs et al; Huberman). The extent and form of the dendritic arbor is modulated within the retina by afferent input mediated through neurotransmitters produced by bipolar and amacrine cells (Cohen-Cory & Lom, 2004). As was observed in the present study, the cell densities of the inner nuclear layer that contains bipolar and amacrine cells, had significantly increased in the non-deprived eye with increasing duration of deprivation.…”

Growth dynamics and morphology of regenerating optic fibers in tectum are altered by injury conditions: An in vivo imaging study in goldfish

“…Optic axons in lower vertebrates express the cognate BDNF receptor, trkB, and tectum produces limited BDNF (4). Exogenous application of BDNF directly to axons during development promotes branching (3,4) and similar results have been obtained for regenerating fibers (Dawson and Meyer, unpublished).…”

Cell-Autonomous TrkB Signaling in Presynaptic Retinal Ganglion Cells Mediates Axon Arbor Growth and Synapse Maturation during the Establishment of Retinotectal Synaptic Connectivity

“…In the developing visual system, neurotrophins have been shown to exert various influences, from guiding the morphological differentiation of neurons to controlling the functional plasticity of visual circuits. BDNF contributes to the establishment and refinement of visual connectivity by acting at multiple levels in the visual pathway, from the retina to the visual cortex (von Bartheld, 1998;Hanover et al, 1999;Huang et al, 1999;Berardi et al, 2003;Cohen-Cory and Lom, 2004;Mandolesi et al, 2005). The spatial and temporal patterns of expression of BDNF and its high-affinity receptor TrkB are consistent with a role for BDNF in modulating visual circuit development.…”

“…Work in Xenopus has demonstrated that BDNF shapes the morphological differentiation of RGCs and their synaptic connectivity (Lom and Cohen-Cory, 1999;Alsina et al, 2001; Cohen-Cory and Lom, 2004;Du and Poo, 2004;Hu et al, 2005) and to a lesser extent affects the morphological and synaptic differentiation of postsyn-aptic tectal cells (Du and Poo, 2004;Sanchez et al, 2006). It remained to be determined, however, whether BDNF acts directly on RGCs or whether it influences both presynaptic and postsynaptic neurons to shape their synaptic connectivity.…”