Refinement of the Retinogeniculate Synapse by Bouton Clustering

Abstract

Mammalian sensory circuits become refined over development in an activity-dependent manner. Retinal ganglion cell (RGC) axons from each eye first map to their target in the geniculate and then segregate into eye-specific layers by the removal and addition of axon branches. Once segregation is complete, robust functional remodeling continues as the number of afferent inputs to each geniculate neuron decreases from many to a few. It is widely assumed that large-scale axon retraction underlies this later phase of circuit refinement. On the contrary, RGC axons remain stable during functional pruning. Instead, presynaptic boutons grow in size and cluster during this process. Moreover, they exhibit dynamic spatial reorganization in response to sensory experience. Surprisingly, axon complexity decreases only after the completion of the thalamic critical period. Therefore, dynamic bouton redistribution along a broad axon backbone represents an unappreciated form of plasticity underlying developmental wiring and rewiring in the central nervous system.

An evolving view of retinogeniculate transmission

“…These findings are consistent with observations in cat and primate studies of the complexity of mature RGC axon morphology (Fig. 1A), with multiple segments that can branch off the primary axon within the optic tract (Sur & Sherman, 1982; Hamos et al, 1987; Sur et al, 1987; Garraghty et al, 1988; Dhande et al, 2011; Hong et al, 2014), although the arbors may be more restricted in the primate dLGN (Glees & Le Gros Clark, 1941; Lachica & Casagrande, 1988; Michael, 1988; Conley & Fitzpatrick, 1989). In cat, one RGC axon arbor spans the territory of far more postsynaptic neurons than it contacts (Hamos et al, 1987).…”

“…1D shows an example of two such close retinogeniculate boutons along one TC neuron dendrite, highlighting that glutamate released from one bouton can diffuse to postsynaptic release sites of the neighboring bouton (Budisantoso et al, 2012). At a developmental phase when boutons are less clustered (Sur et al, 1984; Hong et al, 2014) and glomeruli have not yet formed, retinogeniculate transmission exhibits extensive gluta-mate spillover between neighboring boutons. In fact, glutamate from the bouton of one RGC axon can spill over to the synaptic cleft of a neighboring RGC axon before eye opening (Hauser et al, 2014).…”

“…Surprisingly, there is a disconnect between structure and function—studies in cats, mice, and primates fail to show large-scale pruning of the axon arbor during this later window of development (Sur et al, 1984, 1987; Lachica & Casagrande, 1988; Hong et al, 2014). A recent study that examined individually reconstructed axon arbors of a subtype of mouse RGCs, the BD-RGC (ON–OFF direction-selective RGC, Kim et al, 2010), found that their size and branching complexity remain stable in the 2–3 weeks following eye opening.…”

“…Even in adult mice (p60), the distribution of single RGC input amplitudes ranges from a tens of pA to several nA in strength (Fig. 4D; Hooks & Chen, 2008; Hong et al, 2014; Thompson et al, 2016). The fact that weak convergent inputs persist into adulthood, in both cats and mice, suggest that they have relevance for retinogeniculate function (Alonso et al, 1996; Dan et al, 1998; Usrey et al, 1999).…”

Neural circuit rewiring: insights from DD synapse remodeling

“…Indeed, an example of synapse refinement in the absence of axon growth was described in the mammalian central nervous system, where imaging of individual axonal arbors of retinal ganglion cells showed that retinogeniculate synapse remodeling can occur without axon retraction. 33 Four decades after John White's seminal work, we have learned a great deal about DD remodeling, which has provided a rich platform to study the temporal cues 4,6,7,9,10,14,17 as well as the cellular mechanisms that underlie this complete inversion of synaptic connectivity. [22][23][24] Our findings have also revealed a novel role of dynamic MTs in regulating synaptic vesicle transport in the absence of neurite growth or pruning.…”