Increasing Spontaneous Retinal Activity before Eye Opening Accelerates the Development of Geniculate Receptive Fields

Abstract

Visually evoked activity is necessary for the normal development of the visual system. However, little is known about the capacity for patterned spontaneous activity to drive the maturation of receptive fields before visual experience. Retinal waves provide instructive retinotopic information for the anatomical organization of the visual thalamus. To determine whether retinal waves also drive the maturation of functional responses, we increased the frequency of retinal waves pharmacologically in the ferret (Mustela putorius furo) during a period of retinogeniculate development before eye opening. The development of geniculate receptive fields after receiving these increased neural activities was measured using single-unit electrophysiology. We found that increased retinal waves accelerate the developmental reduction of geniculate receptive field sizes. This reduction is due to a decrease in receptive field center size rather than an increase in inhibitory surround strength. This work reveals an instructive role for patterned spontaneous activity in guiding the functional development of neural circuits.

An excitatory cortical feedback loop gates retinal wave transmission in rodent thalamus

“…The prominent role of corticothalamic feedback in patterning LGN responses to glutamatergic waves suggests it is particularly critical for synaptic refinement driven by these waves. The role of glutamatergic waves remains controversial ( Kerschensteiner, 2016 ), but their perturbation reduces segregation of C-lamina and maintenance of A-lamina segregation in LGN ( Davis et al, 2015a , 2015b ) as well as orientation selectivity in VC ( Huberman et al, 2008 ).…”

Activity-dependent development of visual receptive fields

“…Pharmacological rescue of wave frequency improved this phenotype, but without the proper spatiotemporal character of the waves, retinotopic refinement remained abnormal, indicating the importance of different features of spontaneous activity on circuit development 32** . Furthermore, in ferrets, increasing the frequency of waves accelerates the development of relay neuron receptive fields 41 . This effect is driven by a sharpening of the RF center (Figure 2d) rather than changes in the inhibitory surround, but recent work in mice also demonstrated a role for retinal activity in the initial recruitment of inhibitory interneurons into visual thalamic circuits 42 .…”

Spatiotemporal Features of Retinal Waves Instruct the Wiring of the Visual Circuitry

“…The role of waves in the retinotopic refinement of retinogeniculate projections in ferrets has also seen recent advancements. Intraocular blockade of inhibition to enhance glutamatergic stage 3 retinal waves led to abnormally early retinotopic refinement of retinogeniculate projections, as measured anatomically and functionally (Davis et al, 2015 ). Based on in vitro experiments, blockade of inhibition increases the frequency of glutamatergic waves while maintaining local correlations (Kerschensteiner and Wong, 2008 ; Firl et al, 2013 ).…”