The complexity of sensory receptive fields increases from one synaptic stage to the next. In many cases, increased complexity is achieved through spatiotemporal interactions between convergent excitatory and inhibitory inputs. Here, we present evidence that direction selectivity (DS), a complex emergent receptive field property of retinal starburst amacrine cells (SACs), is generated by spatiotemporal interactions between functionally diverse excitatory inputs. Electrophysiological whole-cell recordings from ON and OFF SACs show distinct temporal differences in excitation following proximal compared with distal stimulation of their receptive fields. Distal excitation is both faster and more transient, ruling out passive filtering by the dendrites and indicating a task-specific specialization. Model simulations demonstrate that this specific organization of excitation generates robust DS responses in SACs, consistent with elementary motion detector models. These results indicate that selective integration of spatiotemporally patterned excitation is a computational mechanism for motion detection in the mammalian retina.
Calcium imaging is commonly used to measure the neural activity of large groups of neurons in mice. Genetically encoded calcium indicators (GECIs) can be delivered for this purpose using non-invasive genetic methods. Compared to viral gene transfer, transgenic targeting of GECIs provides stable long-term expression and obviates the need for invasive viral injections. Transgenic mice expressing the green GECI GCaMP6 are already widely used. Here we present the generation and characterization of transgenic mice expressing the sensitive red GECI jRGECO1a, driven by the Thy1 promoter. Four transgenic lines with different expression patterns showed sufficiently high expression for cellular in vivo imaging. We used two-photon microscopy to characterize visual responses of individual neurons in the visual cortex in vivo. The signal-to-noise ratio in transgenic mice was comparable to, or better than, mice transduced with adeno-associated virus. In addition, we show that Thy1-jRGECO1a transgenic mice are useful for transcranial population imaging and functional mapping using widefield fluorescence microscopy. We also demonstrate imaging of visual responses in retinal ganglion cells in vitro. Thy1-jRGECO1a transgenic mice are therefore a useful addition to the toolbox for imaging activity in intact neural networks.
Detailed characterization of neural circuitries furthers our understanding of how nervous systems perform specific functions and enables the use of those systems to test hypotheses. We have characterized the sensory input to the cutaneous trunk muscle (CTM; also cutaneus trunci (rat) or cutaneus maximus (mouse)) reflex (CTMR), which manifests as a puckering of the dorsal thoracolumbar skin and is selectively driven by noxious stimuli. CTM electromyography (EMG) and neurogram recordings in naïve rats revealed that CTMR responses were elicited by natural stimuli and electrical stimulation of all segments from C4 to L6, a much greater extent of segmental drive to the CTMR than previously described. Stimulation of some subcutaneous paraspinal tissue can also elicit this reflex. Using a selective neurotoxin, we also demonstrate differential drive of the CTMR by trkA-expressing and non-expressing small diameter afferents. These observations highlight aspects of the organization of the CTMR system which make it attractive for studies of nociception and anesthesiology and plasticity of primary afferents, motoneurons, and the propriospinal system. We use the CTMR system to qualitatively and quantitatively demonstrate that experimental pharmacological treatments can be compared to controls applied either to the contralateral side or to another segment, with the remaining segments providing controls for systemic or other treatment effects. These data indicate the potential for using the CTMR system as both an invasive and non-invasive quantitative assessment tool providing improved statistical power and reduced animal use.
Lack of early scotopic function in TgP23H swine suggests it as a model of an aggressive form of RP. In this mammalian model of RP, normal cone function develops independent of rod function. Therefore, its retina represents a system in which therapies to rescue cones can be developed to prolong photopic visual function in RP patients.
Objective In clinical trials, retinitis pigmentosa (RP) patients implanted with a retinal prosthetic device show enhanced spatial vision, including the ability to read large text and navigate. New prosthetics aim to increase spatial resolution by decreasing pixel/electrode size and limiting current spread. To examine spatial resolution of a new prosthetic design, we characterized and compared two photovoltaic array (PVA) designs and their interaction with the retina after subretinal implantation in transgenic S334ter line 3 rats (Tg S334ter-3). Approach PVAs were implanted subretinally at two stages of degeneration and assessed in vivo using extracellular recordings in the superior colliculus (SC). Several aspects of this interaction were evaluated by varying duration, irradiance and position of a near infrared (NIR) laser focused on the PVA. These characteristics included: activation threshold, response linearity, SC signal topography and spatial localization. The major design difference between the two PVA designs is the inclusion of local current returns in the newer design. Main Results When tested in vivo, PVA-evoked response thresholds were independent of pixel/electrode size, but differ between the new and old PVA designs. Response thresholds were independent of implantation age and duration (≤ 7.5 months). For both prosthesis designs, threshold intensities were within established safety limits. PVA-evoked responses require inner retina synaptic transmission and do not directly activate retinal ganglion cells (RGCs). The new PVA design evokes local retinal activation, which is not found with the older PVA design that lacks local current returns. Significance Our study provides in vivo evidence that prosthetics make functional contacts with the inner nuclear layer at several stages of degeneration. The new PVA design enhances local activation within the retina and SC. Together these results predict that the new design can potentially harness the inherent processing within the retina and is likely to produce higher spatial resolution in patients.
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