Control of Axon Branch Dynamics by Correlated Activity in Vivo

Ruthazer, Edward S.; Akerman, Colin J.; Cline, Hollis T.

doi:10.1126/science.1082545

Cited by 231 publications

(243 citation statements)

References 35 publications

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“…Indeed, elaborate axon arbors are observed in the cat visual cortex when both pre-and postsynaptic cells are silent (12,25). This is also true in the remodeling of axon arbors in the retinotectal projection (26,27). In contrast, TC axons did not form elaborate branches in TTX-treated cocultures and in cocultures of the thalamus and Kir2.1-expressing cortex, in which both pre-and postsynaptic activity was suppressed.…”

Section: Discussionmentioning

confidence: 81%

Role of pre- and postsynaptic activity in thalamocortical axon branching

Yamada

Uesaka

Hayano

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Axonal branching is thought to be regulated not only by genetically defined programs but also by neural activity in the developing nervous system. Here we investigated the role of pre-and postsynaptic activity in axon branching in the thalamocortical (TC) projection using organotypic coculture preparations of the thalamus and cortex. Individual TC axons were labeled with enhanced yellow fluorescent protein by transfection into thalamic neurons. To manipulate firing activity, a vector encoding an inward rectifying potassium channel (Kir2.1) was introduced into either thalamic or cortical cells. Firing activity was monitored with multielectrode dishes during culturing. We found that axon branching was markedly suppressed in Kir2.1-overexpressing thalamic cells, in which neural activity was silenced. Similar suppression of TC axon branching was also found when cortical cell activity was reduced by expressing Kir2.1. These results indicate that both preand postsynaptic activity is required for TC axon branching during development.D uring development, axons navigate to their target regions and form elaborate branches when they make synaptic connections with multiple target cells. It has been demonstrated that axon guidance to the target region is regulated by attractive and repulsive molecular cues that are expressed in particular spatiotemporal patterns (1). Similar molecular mechanisms are thought to influence axon branching (2). In addition, neural activity such as firing and synaptic activity can also affect branch formation (3-5). An intriguing and unanswered problem is how neural activity regulates axonal branching.The thalamocortical (TC) projection in the mammalian cortex is a well-characterized system in which to investigate activity-dependent axon branching. In the developing sensory cortices, TC axons form elaborate terminal arbors, whose size and complexity are altered by neural activity. In the primary visual cortex of higher mammals such as cats, ferrets, and monkeys, TC axons serving left and right eyes are segregated into eye-specific stripes (6). This segregation is established during development (7), but is disrupted by blockade of retinal activity (8, 9). Regarding individual axon arbors, it is known that after monocular deprivation, TC axons serving the deprived and nondeprived eyes shrink and expand their arbors, respectively (10, 11). A recent study in which monocular deprivation was combined with silencing cortical activity has further suggested that correlations between pre-and postsynaptic activity play a dominant role in segregation of axon arbors (12). In accordance with this view, molecular machinery in pre-and postsynaptic sites has also been shown to affect arbor formation of TC axons in the somatosensory cortex (13-15). However, the relative role of pre-and postsynaptic activity in TC axon branching remains unclear.To address this issue, we investigated TC axon branching in cocultures of the thalamus and cortex by manipulating the firing activity of thalamic (presynaptic) and cortical (...

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Section: Discussionmentioning

confidence: 81%

Role of pre- and postsynaptic activity in thalamocortical axon branching

Yamada

Uesaka

Hayano

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Recent in vivo imaging of zebrafish and tadpole retinotectal axons reveals that synapse formation and maturation are tightly correlated with branch dynamics and may play an instructive role in arbor remodeling during map formation (Meyer and Smith, 2006;Ruthazer et al, 2006). Indeed, correlated activity is known to regulate RGC axon branch dynamics during development (Ruthazer et al, 2003;Hua et al, 2005), offering additional evidence that the refinement of retinotopic projections proceeds through activitydependent instruction and synaptic competition.…”

Section: Model Of Synaptic-competition-based Retinotopic Map Refinementmentioning

confidence: 99%

Retinocollicular Synapse Maturation and Plasticity Are Regulated by Correlated Retinal Waves

Shah¹,

Crair²

2008

J. Neurosci.

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During development, spontaneous retinal waves are thought to provide an instructive signal for retinotopic map formation in the superior colliculus. In mice lacking the ␤2 subunit of nicotinic ACh receptors (␤2 Ϫ/Ϫ ), correlated retinal waves are absent during the first postnatal week, but return during the second postnatal week. In control retinocollicular synapses, in vitro analysis reveals that AMPA/ NMDA ratios and AMPA quantal amplitudes increase during the first postnatal week while the prevalence of silent synapses decreases. In age-matched ␤2 Ϫ/Ϫ mice, however, these parameters remain unchanged through the first postnatal week in the absence of retinal waves, but quickly mature to control levels by the end of the second week, suggesting that the delayed onset of correlated waves is able to drive synapse maturation. To examine whether such a mechanistic relationship exists, we applied a "burst-based" plasticity protocol that mimics coincident activity during retinal waves. We find that this pattern of activation is indeed capable of inducing synaptic strengthening [long-term potentiation (LTP)] on average across genotypes early in the first postnatal week [postnatal day 3 (P3) to P4] and, interestingly, that the capacity for LTP at the end of the first week (P6 -P7) is significantly greater in immature ␤2 Ϫ/Ϫ synapses than in mature control synapses. Together, our results suggest that retinal waves drive retinocollicular synapse maturation through a learning rule that is physiologically relevant to natural wave statistics and that these synaptic changes may serve an instructive role during retinotopic map refinement.

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“…Activity-dependent competition between axons converging on common targets has been shown to modify patterns of synaptic connectivity in the visual cortex (Wiesel, 1982), olfactory system (Yu et al, 2004), neuromuscular junction (Buffelli et al, 2003), and the retinotectal projection of fish and frogs (Ruthazer et al, 2003;Hua et al, 2005). We therefore asked whether any of the features of TeNT-Lc:EGFP-expressing axons we had observed so far were a consequence of silencing just a single cell in a field of active ones.…”

Section: Activity-dependent Competition Regulates Arbor Sizementioning

confidence: 99%

Synaptic Activity and Activity-Dependent Competition Regulates Axon Arbor Maturation, Growth Arrest, and Territory in the Retinotectal Projection

Fredj¹,

Hammond²,

Otsuna³

et al. 2010

J. Neurosci.

116

130

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In the retinotectal projection, synapses guide retinal ganglion cell (RGC) axon arbor growth by promoting branch formation and by selectively stabilizing branches. To ask whether presynaptic function is required for this dual role of synapses, we have suppressed presynaptic function in single RGCs using targeted expression of tetanus toxin light-chain fused to enhanced green fluorescent protein (TeNT-Lc:EGFP). Time-lapse imaging of singly silenced axons as they arborize in the tectum of zebrafish larvae shows that presynaptic function is not required for stabilizing branches or for generating an arbor of appropriate complexity. However, synaptic activity does regulate two distinct aspects of arbor development. Although expansion of arbor territory is prevented when neighbors are silent, formation of transient filopodia is not. These results suggest that synaptic activity by itself regulates filopodia formation regardless of activity in neighboring cells but that the ability to arrest growth and focusing of axonal arbors in the target is an activity-dependent, competitive process.

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Control of Axon Branch Dynamics by Correlated Activity in Vivo

Cited by 231 publications

References 35 publications

Role of pre- and postsynaptic activity in thalamocortical axon branching

Role of pre- and postsynaptic activity in thalamocortical axon branching

Retinocollicular Synapse Maturation and Plasticity Are Regulated by Correlated Retinal Waves

Synaptic Activity and Activity-Dependent Competition Regulates Axon Arbor Maturation, Growth Arrest, and Territory in the Retinotectal Projection

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