A Burst-Based “Hebbian” Learning Rule at Retinogeniculate Synapses Links Retinal Waves to Activity-Dependent Refinement

Butts, Daniel A.; Kanold, Patrick O.; Shatz, Carla J.

doi:10.1371/journal.pbio.0050061

Cited by 189 publications

(240 citation statements)

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“…Our previous study using the same coculture preparations showed that synchronized firing activity between thalamic and cortical cells develops during the second week in vitro, when axonal branches are added in great numbers (18). Thus, precise synchrony rather than the overall amounts of pre-and postsynaptic activity for a given period may play an important role in the promotion of axon branching (18,(31)(32)(33)(34), although our investigations did not distinguish between these two possibilities. The NMDA receptor, a coincidence detector of pre-and postsynaptic activity, is likely to be involved in this process (13,35,36).…”

Section: Discussionmentioning

confidence: 59%

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: 59%

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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“…After the pairing, the cell is returned to voltage clamp, and the amplitude of the AMPA current is monitored for any change. A similar protocol was recently demonstrated to induce plasticity at the developing retinogeniculate synapse (Butts et al, 2007).…”

Section: Prevalence Of Silent Synapses Over Developmentmentioning

confidence: 86%

“…These results were seen during a period of significant refinement and maturation of retinogeniculate synapses, including increases in AMPA/ NMDA ratios and decreases in the presence of silent synapses (Chen and Regehr, 2000). By varying the timings of presynaptic and postsynaptic burst onsets, Butts et al (2007) also demonstrated that LTP did not depend on burst order, and that longterm depression (LTD) could be induced by separating burst onsets by hundreds to thousands of milliseconds. This supports a model in which the refinement of retinofugal projections not Using a Mann-Whitney U test, we find that the control P3-P4 distribution is different from the control P6 -P7 distribution ( p Ͻ 0.05), whereas the ␤2 Ϫ/Ϫ distributions at P3-P4 and P6 -P7 are not significantly different ( p ϭ 0.6).…”

Section: Model Of Retinal-wave-dependent Synaptic Plasticitymentioning

confidence: 89%

“…A recent study at the developing retinogeniculate synapse demonstrated that a burst-timing-dependent plasticity rule can lead to synaptic enhancement and, interestingly, that the underlying spike timings on the millisecond timescale cannot fully account for the observed plasticity (Butts et al, 2007). These results were seen during a period of significant refinement and maturation of retinogeniculate synapses, including increases in AMPA/ NMDA ratios and decreases in the presence of silent synapses (Chen and Regehr, 2000).…”

Section: Model Of Retinal-wave-dependent Synaptic Plasticitymentioning

confidence: 99%

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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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“…This question was first addressed by using information-theoretic approaches (Butts and Rokhsar, 2001) suggesting that information content was mostly preserved when using broad time scales (on the order of seconds, rather than milliseconds). This led to the proposal that information was transmitted at the level of bursts of action potentials, rather than individual action potentials (Butts and Rokhsar, 2001;Butts et al, 2007). To use this information, burst time-dependent plasticity (BTDP) has been proposed, based upon recordings in developing retinogeniculate pathway, mirroring that of spike time-dependent plasticity (STDP) (Butts et al, 2007).…”

Section: Spike-based or Burst-based Rules?mentioning

confidence: 99%