The development of intrinsic excitability in mouse retinal ganglion cells

Abstract

Activity-dependent refinement of synaptic connections occurs throughout the developing nervous system, including the visual system. Retinal ganglion cells (RGCs) overproduce synapses then refine them in an activity-dependent manner that segregates RGC connections into multicellular patterns, such as eye-specific regions and retinotopic maps. Ferrets additionally segregate ON and OFF retinogeniculate pathways in an activity-dependent manner. It was unknown whether differences in ON versus OFF intrinsic and spontaneous activity occur in postnatal mouse. The work reported here measured the intrinsic properties and spontaneous activity of morphologically identified postnatal mouse RGCs, and tested the hypothesis that mouse ON and OFF RGCs develop differences in spontaneous activity. We found developmental changes in resting potential, action potential threshold, depolarization to threshold, action potential width, action potential patterns, and maximal firing rates. These results are consistent with the maturation of the intrinsic properties of RGCs extending through the first three postnatal weeks. However, there were no differences among mouse ON, OFF, and multistratified RGCs in intrinsic excitability, spontaneous synaptic drive or spontaneous action potential patterns. The absence of differences between ON and OFF activity patterns is unlike the differences that arise in ferrets. In contrast to the ferret, the ON and OFF target neurons in the mouse are organized in a random pattern, not layers. This supports the hypothesis that the absence of systematic differences in activity results in the nonlayered distribution of retinogeniculate connections.

Receptive Field Mosaics of Retinal Ganglion Cells Are Established Without Visual Experience

“…4). These findings are consistent with several other studies that have shown that both excitatory and inhibitory synaptic inputs (Tian et al 1998), as well as RGC firing properties (Myhr et al 2001;Qu and Myhr 2008;Wang et al 1997), do not mature until 2-4 wk after eye opening. A similar observation has been made in a recent study of mice that lack transcription factors critical for the development of particular bipolar cell types: despite significantly altered temporal RFs and contrast adaptation, the organization of spatial receptive fields was unaltered .…”

“…However, previous studies indicate that, at this stage of development, several aspects of retinal circuits remain immature, including the intrinsic firing properties of RGCs (Myhr et al 2001;Qu and Myhr 2008;Wang et al 1997), synaptic inputs to RGCs (Tian et al 1998), and RF structure (Bowe-Anders et al 1975;Masland 1977;Rusoff and Dubin 1977;Tootle 1993 observed at eye opening were accompanied by mature light responses, we compared the RGC light response properties with those observed in adult retinas.…”

Receptive field center size decreases and firing properties mature in ON and OFF retinal ganglion cells after eye opening in the mouse

“…In mouse RGCs, both the resting potential and firing threshold hyperpolarize during development, and the cells become capable of firing at higher rates (Qu and Myhr 2008;Rothe et al 1999aRothe et al , 1999b. At the same time, the strength of light-evoked inputs to RGCs, both excitatory and inhibitory, decrease from eye opening through ϳP30 (He et al 2011).…”

“…The characteristics of an RGC's spike train generated in response to center stimulation are defined by a mix of parameters both intrinsic and extrinsic to the RGC, including resting potential, threshold, spiking patterns, peak spike rates, and inhibition. Each of these parameters undergoes maturation during development (Qu and Myhr 2008;Tian and Copenhagen 2001). To determine if the firing properties revealed by RGCs during white noise checkerboard stimulation were immature at eye opening, we further examined their white noise spike trains and linear filters.…”

“…Indeed, spontaneous synaptic events recorded from mouse RGCs during this period increase markedly before tapering down to the adult level (Tian and Copenhagen 2001), while light-evoked excitatory and inhibitory currents decrease (He et al 2011). At the same time, RGC intrinsic properties are also maturing, and together these changes result in more robust light-evoked spiking from RGCs (He et al 2011;Qu and Myhr 2008). Thus, changes to the functional receptive field-the area of the retina that, when stimulated with either increments or decrements of light relative to background, affects the firing rate of that RGC-may be occurring during this period.…”