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

Daniel A Butts,Patrick O Kanold,Carla J Shatz,Charles F Stevens

doi:10.1371/journal.pbio.0050061

Daniel A Butts, Patrick O Kanold + Show 2 more

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https://doi.org/10.1371/journal.pbio.0050061

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Journal: PLoS Biology	Publication Date: Mar 1, 2007
Citations: 211	License type: CC BY 4.0

Affiliation: Harvard University

Abstract

Patterned spontaneous activity in the developing retina is necessary to drive synaptic refinement in the lateral geniculate nucleus (LGN). Using perforated patch recordings from neurons in LGN slices during the period of eye segregation, we examine how such burst-based activity can instruct this refinement. Retinogeniculate synapses have a novel learning rule that depends on the latencies between pre- and postsynaptic bursts on the order of one second: coincident bursts produce long-lasting synaptic enhancement, whereas non-overlapping bursts produce mild synaptic weakening. It is consistent with “Hebbian” development thought to exist at this synapse, and we demonstrate computationally that such a rule can robustly use retinal waves to drive eye segregation and retinotopic refinement. Thus, by measuring plasticity induced by natural activity patterns, synaptic learning rules can be linked directly to their larger role in instructing the patterning of neural connectivity.

Highlights

Though synaptic plasticity is a feature of most excitatory synapses in the brain, how it functions in realistic contexts is largely unclear because its effects usually only manifest on the system level
We study connections in the visual pathway between the retina and lateral geniculate nucleus (LGN), which—to develop correctly— require spontaneous ‘‘retinal waves’’ before the eye is responsive to light
By replaying the retinal wave activity as it appears at single LGN synapses, we observe a novel learning rule that describes a relatively simple computation for the developing synapse in the context of retinal wave activity

Summary

Introduction

Though synaptic plasticity is a feature of most excitatory synapses in the brain, how it functions in realistic contexts is largely unclear because its effects usually only manifest on the system level. This synaptic refinement results in segregation into eye-specific regions and establishment of fine retinotopy, with neighboring RGCs projecting to neighboring LGN neurons [6] This synaptic refinement—as well as similar refinement in the developing visual cortex [7,8] and superior colliculus [9]— is known to require spontaneously generated activity in the developing retina [10,11]. This activity consists of correlated bursts of action potentials that spread across large regions of the retinal ganglion cell layer [12]. These retinal waves have distinct spatiotemporal properties that have been studied in detail through a variety of multi-electrode [13,14] and calcium imaging studies [12,15,16]

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