Bart Borghuis, PhD

Bart Borghuis, PhD

Bart Borghuis, Ph.D.

Bart Borghuis, PhD

Assistant Professor
Office: MDR425
Phone: 502-852-4968
Lab website
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Research Focus

A ubiquitous feature of the brain is the division of sensory information into parallel signaling pathways. Parallel processing makes the brain more efficient, because each pathway can be optimized for encoding a specific class of information. While functional differences between parallel pathways are well established, many of the underlying cell-intrinsic and circuit mechanisms remain unclear. Our research concentrates on the synaptic and circuit mechanisms for parallel processing in the mouse visual system. Parallel processing starts at the first visual synapse in the retina, where a cone photoreceptor connects to each of approximately twelve bipolar cell types, each with distinct response properties at the level of its synaptic output. This functional diversity is critical for the formation of ~20 distinct visual representations at the level of the retinal ganglion cells, which selectively encode contrast polarity, size, and color, the presence of edges, and visual motion and transmit this information through the optic nerve to retinorecipient areas in the brain. We combine cutting-edge imaging methods with whole-cell electrophysiology to study these emergent properties at the level of synapses and circuits in the intact retina, in vitro.


Current Projects

1. At the first synaptic stage, a cone photoreceptor makes synapses with 10 - 12 cone bipolar cell types, each with distinct visual responses. For example, a cell may respond to either light increments (‘ON’) or decrements (‘OFF’), either briefly (‘transient’) or continuously (‘sustained’). This functional diversity is critical for the formation of about twenty distinct visual representations at the level of the retinal ganglion cells, which selectively encode contrast polarity, size, and color, the presence of edges, and visual motion. While the response properties of bipolar cells depend in part on the glutamate receptors expressed on their dendrites (for example, ON bipolar cells express mGluR6 receptors, whereas OFF bipolar cells express kainate receptors), increasing evidence suggests that bipolar cell properties strongly depend on interactions at the other end of the cell – the axon terminal - where bipolar cells receive inhibitory inputs from amacrine cells. Our goal is to determine which bipolar cell properties are generated at the level of the dendrites in the outer retina, and which at the axon terminal in the inner retina. We use advanced imaging with genetically targeted fluorescent biosensors during visual stimulation of the retina addresses this question. An important new insight from these imaging studies is that parallel pathways are not strictly parallel: ON-type bipolar cells, through cross-over inhibition, strongly influence the OFF-type bipolar cells. The goal of the current experiments is to understand the extend of this cross-over signaling, and the properties that it bestows on OFF bipolar cell pathways.

2. More than fifty years ago, Horace Barlow and colleagues discovered that the mammalian retina contains ganglion cells that respond selectively to visual motion in a particular direction. Solving the neural mechanisms underlying this direction selectivity has been the focus of intense study, not only as a key example of retinal signal processing, but also more generally, as an example of detection of spatio-temporal patterns - a task solved in neural circuits throughout the brain. The origin of direction selectivity has been located unambiguously to the dendrites of a particular amacrine cell, the starburst amacrine cell (SAC). SACs come in two types ('ON', activated by light increments, and 'OFF', activated by light decrements) and are directly presynaptic to the direction selective ganglion cells. The next question is what makes SACs directionally selective? While a dendrite-dependent mechanism has been proposed for the ON SACs, a recent study based on EM reconstruction predicts a dendrite-independent mechanism for the OFF SACs. We use two-photon fluorescece imaging and targeted electrophysiology to explore the spatial organization of synaptic inputs onto ON and OFF SACs and their selective responses to visual motion under a variety of conditiona, to distinguish between these two alternative models for direction selectivity at the level of the SAC dendrites, and to explain how a specific computation is performed within a defined retinal neural circuit. 


Key Publications

Tuthill JC, Borghuis BG. Four to Foxtrot: How Visual Motion Is Computed in the Fly Brain. Neuron. 2016 Feb 17;89(4):677-80

Borghuis BG
, Leonardo A. The Role of Motion Extrapolation in Amphibian Prey Capture. J Neurosci. 2015 Nov 18;35(46):15430-41. featured article, cover article

Park SJ, Borghuis BG, Rahmani P, Zeng Q, Kim IJ, Demb JB. Function and Circuitry of VIP+ Interneurons in the Mouse Retina. J Neurosci. 2015 Jul 29;35(30):10685-700.

Borghuis BG, Looger LL, Tomita S, Demb JB. Kainate receptors mediate signaling in both transient and sustained OFF bipolar cell pathways in mouse retina. J Neurosci. 2014 Apr 30;34(18):6128-39*. featured article

Park SJ, Kim IJ, Looger LL, Demb JB, Borghuis BG. Excitatory synaptic inputs to mouse on-off direction-selective retinal ganglion cells lack direction tuning. J Neurosci. 2014 Mar 12;34(11):3976-81.

Borghuis BG, Marvin JS, Looger LL, Demb JB. Two-photon imaging of nonlinear glutamate release dynamics at bipolar cell synapses in the mouse retina. J Neurosci. 2013 Jul 3;33(27):10972-85.

Marvin JS, Borghuis BG, Tian L, Cichon J, Harnett MT, Akerboom J, Gordus A, Renninger SL, Chen TW, Bargmann CI, Orger MB, Schreiter ER, Demb JB, Gan WB, Hires SA, Looger LL. An optimized fluorescent probe for visualizing glutamate neurotransmission. Nat Methods. 2013 Feb;10(2):162-70.

Borghuis BG, Tian L, Xu Y, Nikonov SS, Vardi N, Zemelman BV, Looger LL. Imaging light responses of targeted neuron populations in the rodent retina. J Neurosci. 2011 Feb 23;31(8):2855-67.

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