Insights into activity‐dependent map formation from the retinotectal system: A middle‐of‐the‐brain perspective

Ruthazer, Edward S.; Cline, Hollis T.

doi:10.1002/neu.10344

Cited by 157 publications

(156 citation statements)

References 111 publications

(118 reference statements)

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“…Consequently, type II SGNs probably undergo axon competition and adapt by forming incomplete projections. This observation is consistent with the fact that competition for target territory refines the map by suppressing or eliminating branches 44 . Neuronal immunolabelings therefore reveal opposite shifts: a partial displacement of type I innervation from IHCs to OHCs and a subsequent withdrawal of type II projections from OHCs.…”

Section: Discussionsupporting

confidence: 88%

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

et al. 2013

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Hearing requires an optimal afferent innervation of sensory hair cells by spiral ganglion neurons in the cochlea. Here we report that complementary expression of ephrin-A5 in hair cells and EphA4 receptor among spiral ganglion neuron populations controls the targeting of type I and type II afferent fibres to inner and outer hair cells, respectively. In the absence of ephrin-A5 or EphA4 forward signalling, a subset of type I projections aberrantly overshoot the inner hair cell layer and invade the outer hair cell area. Lack of type I afferent synapses impairs neurotransmission from inner hair cells to the auditory nerve. By contrast, radial shift of type I projections coincides with a gain of presynaptic ribbons that could enhance the afferent signalling from outer hair cells. Ephexin-1, cofilin and myosin light chain kinase act downstream of EphA4 to induce type I spiral ganglion neuron growth cone collapse. Our findings constitute the first identification of an Eph/ephrin-mediated mutual repulsion mechanism responsible for specific sorting of auditory projections in the cochlea.

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Section: Discussionsupporting

confidence: 88%

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

et al. 2013

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“…Mapping along the N-T axis of these connections has been proposed to use a combination of EphA/ephrin-A signaling (Feldheim et al, 1998(Feldheim et al, , 2000(Feldheim et al, , 2004Frisén et al, 1998;Rashid et al, 2005), patterned retinal activity-dependent axonal refinement (Ruthazer and Cline, 2004;Torborg and Feller, 2005), and axonaxon competition to ensure innervation of the entire target (Walsh et al, 1983;Garraghty, 1995); however, the relative roles of each are not known. Here, using anterograde labeling of RGCs from four retinal poles, we provided the first thorough characterization of the topographic retinogeniculate projection in wildtype mice.…”

Section: Discussionmentioning

confidence: 99%

Ephrin-As and Patterned Retinal Activity Act Together in the Development of Topographic Maps in the Primary Visual System

Pfeiffenberger

Yamada²,

Feldheim³

2006

J. Neurosci.

147

185

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The development of topographic maps in the primary visual system is thought to rely on a combination of EphA/ephrin-A interactions and patterned neural activity. Here, we characterize the retinogeniculate and retinocollicular maps of mice mutant for ephrins-A2, -A3, and -A5 (the three ephrin-As expressed in the mouse visual system), mice mutant for the ␤2 subunit of the nicotinic acetylcholine receptor (that lack early patterned retinal activity), and mice mutant for both ephrin-As and ␤2. We also provide the first comprehensive anatomical description of the topographic connections between the retina and the dorsal lateral geniculate nucleus. We find that, although ephrin-A2/A3/A5 triple knock-out mice have severe mapping defects in both projections, they do not completely lack topography. Mice lacking ␤2-dependent retinal activity have nearly normal topography but fail to refine axonal arbors. Mice mutant for both ephrin-As and ␤2 have synergistic mapping defects that result in a near absence of map in the retinocollicular projection; however, the retinogeniculate projection is not as severely disrupted as the retinocollicular projection is in these mutants. These results show that ephrin-As and patterned retinal activity act together to establish topographic maps, and demonstrate that midbrain and forebrain connections have a differential requirement for ephrin-As and patterned retinal activity in topographic map development.

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“…During development and in adulthood, NMDA glutamate receptor activity is involved in synapse elimination or stabilization, and inhibition or promotion of axonal sprouting (Li et al, 1994;Katz and Shatz, 1996;Constantine-Paton and Cline, 1998;Ruthazer and Cline, 2004;Colonnese et al, 2005;Lee et al, 2005). The roles of axonal presynaptic versus somatodendritic postsynaptic NMDA receptors in these processes are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Glycine Transporter-1 Inhibition Promotes Striatal Axon Sprouting via NMDA Receptors in Dopamine Neurons

Schmitz¹,

Castagna²,

Mrejeru³

et al. 2013

J. Neurosci.

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NMDA receptor activity is involved in shaping synaptic connections throughout development and adulthood. We recently reported that brief activation of NMDA receptors on cultured ventral midbrain dopamine neurons enhanced their axon growth rate and induced axonal branching. To test whether this mechanism was relevant to axon regrowth in adult animals, we examined the reinnervation of dorsal striatum following nigral dopamine neuron loss induced by unilateral intrastriatal injections of the toxin 6-hydroxydopamine. We used a pharmacological approach to enhance NMDA receptor-dependent signaling by treatment with an inhibitor of glycine transporter-1 that elevates levels of extracellular glycine, a coagonist required for NMDA receptor activation. All mice displayed sprouting of dopaminergic axons from spared fibers in the ventral striatum to the denervated dorsal striatum at 7 weeks post-lesion, but the reinnervation in mice treated for 4 weeks with glycine uptake inhibitor was approximately twice as dense as in untreated mice. The treated mice also displayed higher levels of striatal dopamine and a complete recovery from lateralization in a test of sensorimotor behavior. We confirmed that the actions of glycine uptake inhibition on reinnervation and behavioral recovery required NMDA receptors in dopamine neurons using targeted deletion of the NR1 NMDA receptor subunit in dopamine neurons. Glycine transport inhibitors promote functionally relevant sprouting of surviving dopamine axons and could provide clinical treatment for disorders such as Parkinson's disease.

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Insights into activity‐dependent map formation from the retinotectal system: A middle‐of‐the‐brain perspective

Cited by 157 publications

References 111 publications

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

Ephrin-As and Patterned Retinal Activity Act Together in the Development of Topographic Maps in the Primary Visual System

Glycine Transporter-1 Inhibition Promotes Striatal Axon Sprouting via NMDA Receptors in Dopamine Neurons

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