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Abstract:
The vertebrate retina, with its exquisitely regular organisation and its planar, near transparent structure
offers a powerful playground for the detailed exploration of principles in sensory information processing in general. Moreover, detailed knowledge the anatomy of the mouse retina is paralleled by few other model systems in neuroscience today. Here, we present a systematic approach to add a physiological dimension to this description, by optically imaging light-evoked activity to visual stimuli that systematically survey key transformations during retinal signal decomposition, including contrast and frequency response functions and responses to Gaussian noise. By following such ”elementary visual responses” at
key sites within the retinal circuitry, including a clear link to anatomy, that we believe will prove instrumental in exploring a computational description of retinal signal decomposition as whole. We recorded from synapses, dendrites and somata of all excitatory neurons of the mouse cone-pathway. In addition, we recorded from a subset of inhibitory neurons. In the outer retina, we imaged (i) calcium responses from S- and M-cone photoreceptor pedicles in retinal slice of the HR2.1:TN-XL mouse line (Wei et al. 2012, Baden, Schubert et al. 2013). In addition, we monitored (ii) calcium responses in both somata and individual varicosities of horizontal cells using GCaMP3 and GCaMP6 expressed in the Cx57cre/+ line (Ströh et al., 2013) using cross-breeding and AAV, respectively. In the inner retina, we recorded (iii) calcium responses in individual presynaptic terminals of bipolar cells (Baden et al. 2013) and (iv) dendritic tips of retinal ganglion cells labelled with the synthetic calcium indicator OGB-1 or
GCaMP6 introduced using AAV. We also surveyed (v) glutamate release based on iGluSnFR responses (Marvin et al., 2013, Borghuis et al., 2013), expressed either ubiquitously or in specific Cre lines (PV:Cre, Feng et al. 2000; Farrow et al. 2013; Pcp2:Cre, Lewis et al. 2004; Ivanova et al., 2013; ChAT:Cre, Lowell et al., 2006). We also recorded calcium responses in the somata of (vi) all RGCs and (vii) displaced
amacrine cells in the ganglion cell layer after electroporation with OGB-1 (Briggmann and Euler 2011).
These recordings were complemented with (viii) single-unit spike recordings and subsequent intracellularfillings, as well as the use of reporter lines PV:Ai9tdTomato, PcP2:Ai9tdTomato or subsequent immunohistochemistry (GAD67, ChAT) to aid genetic/anatomical classification. Reference to this database will benefit the development of computational models aiming to describe retinal function. In addition, it will form the foundation for a more systematic approach towards understanding the changes in processing during degeneration.
