Honors & Awards
Postdoctoral Fellow, Ruth L Kirschstein NRSA, National Institute of Mental Health; BRAIN initiative (F32-MH118707) (9/30/2018 -)
Predoctoral Fellow, Ruth L. Kirschstein NRSA, National Eye Institute (F31-EY026288) (12/16/2015 - 6/15/2017)
PhD, University of Washington, Neuroscience (2017)
BS, University of Iowa, Biology, Mathematics (2011)
Receptive field center-surround interactions mediate context-dependent spatial contrast encoding in the retina
Antagonistic receptive field surrounds are a near-universal property of early sensory processing. A key assumption in many models for retinal ganglion cell encoding is that receptive field surrounds are added only to the fully formed center signal. But anatomical and functional observations indicate that surrounds are added before the summation of signals across receptive field subunits that creates the center. Here, we show that this receptive field architecture has an important consequence for spatial contrast encoding in the macaque monkey retina: the surround can control sensitivity to fine spatial structure by changing the way the center integrates visual information over space. The impact of the surround is particularly prominent when center and surround signals are correlated, as they are in natural stimuli. This effect of the surround differs substantially from classic center-surround models and raises the possibility that the surround plays unappreciated roles in shaping ganglion cell sensitivity to natural inputs.
View details for DOI 10.7554/eLife.38841
View details for Web of Science ID 000447118900001
View details for PubMedID 30188320
View details for PubMedCentralID PMC6185113
Synaptic Rectification Controls Nonlinear Spatial Integration of Natural Visual Inputs
2016; 90 (6): 1257–71
A central goal in the study of any sensory system is to predict neural responses to complex inputs, especially those encountered during natural stimulation. Nowhere is the transformation from stimulus to response better understood than the vertebrate retina. Nevertheless, descriptions of retinal computation are largely based on stimulation using artificial visual stimuli, and it is unclear how these descriptions map onto the encoding of natural stimuli. We demonstrate that nonlinear spatial integration, a common feature of retinal ganglion cell (RGC) processing, shapes neural responses to natural visual stimuli in primate Off parasol RGCs, whereas On parasol RGCs exhibit surprisingly linear spatial integration. Despite this asymmetry, both cell types show strong nonlinear integration when presented with artificial stimuli. We show that nonlinear integration of natural stimuli is a consequence of rectified excitatory synaptic input and that accounting for nonlinear spatial integration substantially improves models that predict RGC responses to natural images.
View details for DOI 10.1016/j.neuron.2016.05.006
View details for Web of Science ID 000378527600014
View details for PubMedID 27263968
View details for PubMedCentralID PMC4917290
Direction-Selective Circuits Shape Noise to Ensure a Precise Population Code
2016; 89 (2): 369–83
Neural responses are noisy, and circuit structure can correlate this noise across neurons. Theoretical studies show that noise correlations can have diverse effects on population coding, but these studies rarely explore stimulus dependence of noise correlations. Here, we show that noise correlations in responses of ON-OFF direction-selective retinal ganglion cells are strongly stimulus dependent, and we uncover the circuit mechanisms producing this stimulus dependence. A population model based on these mechanistic studies shows that stimulus-dependent noise correlations improve the encoding of motion direction 2-fold compared to independent noise. This work demonstrates a mechanism by which a neural circuit effectively shapes its signal and noise in concert, minimizing corruption of signal by noise. Finally, we generalize our findings beyond direction coding in the retina and show that stimulus-dependent correlations will generally enhance information coding in populations of diversely tuned neurons.
View details for DOI 10.1016/j.neuron.2015.11.019
View details for Web of Science ID 000373564700014
View details for PubMedID 26796691
View details for PubMedCentralID PMC4724064
Type I intrinsically photosensitive retinal ganglion cells of early post-natal development correspond to the M4 subtype
2015; 10: 17
Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate circadian light entrainment and the pupillary light response in adult mice. In early development these cells mediate different processes, including negative phototaxis and the timing of retinal vascular development. To determine if ipRGC physiologic properties also change with development, we measured ipRGC cell density and light responses in wild-type mouse retinas at post-natal days 8, 15 and 30.Melanopsin-positive cell density decreases by 17% between post-natal days 8 and 15 and by 25% between days 8 and 30. This decrease is due specifically to a decrease in cells co-labeled with a SMI-32, a marker for alpha-on ganglion cells (corresponding to adult morphologic type M4 ipRGCs). On multi-electrode array recordings, post-natal day 8 (P8) ipRGC light responses show more robust firing, reduced adaptation and more rapid recovery from short and extended light pulses than do the light responses of P15 and P30 ipRGCs. Three ipRGC subtypes - Types I-III - have been defined in early development based on sensitivity and latency on multielectrode array recordings. We find that Type I cells largely account for the unique physiologic properties of P8 ipRGCs. Type I cells have previously been shown to have relatively short latencies and high sensitivity. We now show that Type I cells show have rapid and robust recovery from long and short bright light exposures compared with Type II and III cells, suggesting differential light adaptation mechanisms between cell types. By P15, Type I ipRGCs are no longer detectable. Loose patch recordings of P8 M4 ipRGCs demonstrate Type I physiology.Type I ipRGCs are found only in early development. In addition to their previously described high sensitivity and rapid kinetics, these cells are uniquely resistant to adaptation and recover quickly and fully to short and prolonged light exposure. Type I ipRGCs correspond to the SMI-32 positive, M4 subtype and largely lose melanopsin expression in development. These cells constitute a unique morphologic and physiologic class of ipRGCs functioning early in postnatal development.
View details for DOI 10.1186/s13064-015-0042-x
View details for Web of Science ID 000356923900001
View details for PubMedID 26091805
View details for PubMedCentralID PMC4480886
Nonlinear dendritic integration of electrical and chemical synaptic inputs drives fine-scale correlations
2014; 17 (12): 1759–66
Throughout the CNS, gap junction-mediated electrical signals synchronize neural activity on millisecond timescales via cooperative interactions with chemical synapses. However, gap junction-mediated synchrony has rarely been studied in the context of varying spatiotemporal patterns of electrical and chemical synaptic activity. Thus, the mechanism underlying fine-scale synchrony and its relationship to neural coding remain unclear. We examined spike synchrony in pairs of genetically identified, electrically coupled ganglion cells in mouse retina. We found that coincident electrical and chemical synaptic inputs, but not electrical inputs alone, elicited synchronized dendritic spikes in subregions of coupled dendritic trees. The resulting nonlinear integration produced fine-scale synchrony in the cells' spike output, specifically for light stimuli driving input to the regions of dendritic overlap. In addition, the strength of synchrony varied inversely with spike rate. Together, these features may allow synchronized activity to encode information about the spatial distribution of light that is ambiguous on the basis of spike rate alone.
View details for DOI 10.1038/nn.3851
View details for Web of Science ID 000345484000024
View details for PubMedID 25344631
View details for PubMedCentralID PMC4265022
Visual Space Is Represented by Nonmatching Topographies of Distinct Mouse Retinal Ganglion Cell Types
2014; 24 (3): 310–15
The distributions of neurons in sensory circuits display ordered spatial patterns arranged to enhance or encode specific regions or features of the external environment. Indeed, visual space is not sampled uniformly across the vertebrate retina. Retinal ganglion cell (RGC) density increases and dendritic arbor size decreases toward retinal locations with higher sampling frequency, such as the fovea in primates and area centralis in carnivores . In these locations, higher acuity at the level of individual cells is obtained because the receptive field center of a RGC corresponds approximately to the spatial extent of its dendritic arbor [2, 3]. For most species, structurally and functionally distinct RGC types appear to have similar topographies, collectively scaling their cell densities and arbor sizes toward the same retinal location . Thus, visual space is represented across the retina in parallel by multiple distinct circuits . In contrast, we find a population of mouse RGCs, known as alpha or alpha-like , that displays a nasal-to-temporal gradient in cell density, size, and receptive fields, which facilitates enhanced visual sampling in frontal visual fields. The distribution of alpha-like RGCs contrasts with other known mouse RGC types and suggests that, unlike most mammals, RGC topographies in mice are arranged to sample space differentially.
View details for DOI 10.1016/j.cub.2013.12.020
View details for Web of Science ID 000330918900026
View details for PubMedID 24440397
View details for PubMedCentralID PMC3990865
A method for detecting molecular transport within the cerebral ventricles of live zebrafish (Danio rerio) larvae
JOURNAL OF PHYSIOLOGY-LONDON
2012; 590 (10): 2233–40
The production and flow of cerebrospinal fluid performs an important role in the development and homeostasis of the central nervous system.However, these processes are difficult to study in the mammalian brain because the ventricles are situated deep within the parenchyma.In this communication we introduce the zebrafish larva as an in vivo model for studying cerebral ventricle and blood–brain barrier function. Using confocal microscopy we show that zebrafish ventricles are topologically similar to those of the mammalian brain.We describe a new method for measuring the dynamics of molecular transport within the ventricles of live zebrafish by means of the uncaging of a fluorescein derivative. Furthermore, we determine that in 5–6 days post-fertilization zebrafish, the dispersal of molecules in the ventricles is driven by a combination of ciliary motion and diffusion. The zebrafish presents a tractable system with the advantage of genetics, size and transparency for exploring ventricular physiology and for mounting large-scale high throughput experiments.
View details for DOI 10.1113/jphysiol.2011.225896
View details for Web of Science ID 000304090000011
View details for PubMedID 22371478
View details for PubMedCentralID PMC3424749