Borghuis Lab

About 

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

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.

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. 

Recent Publications

• Microglia are dispensable for experience-dependent refinement of mouse visual circuitry.
• Brown TC, Crouse EC, Attaway CA, Oakes DK, Minton SW, Borghuis BG, McGee AW.Nat Neurosci. 2024 Aug;27(8):1462-1467. doi: 10.1038/s41593-024-01706-3. Epub 2024 Jul 8.PMID: 38977886   

• Microglia are dispensable for experience-dependent refinement of visual circuitry. 

  Brown TC, Crouse EC, Attaway CA, Oakes DK, Minton SW, Borghuis BG, McGee AW.bioRxiv [Preprint]. 2023 Oct 17:2023.10.17.562708. doi: 10.1101/2023.10.17.562708. 

  Update in: Nat Neurosci. 2024 Aug;27(8):1462-1467. doi: 10.1038/s41593-024-01706-3.PMID: 37905138  

• Direct comparison reveals algorithmic similarities in fly and mouse visual motion detection. 

  Chen J, Gish CM, Fransen JW, Salazar-Gatzimas E, Clark DA, Borghuis BG.iScience. 2023 Sep 14;26(10):107928. doi: 10.1016/j.isci.2023.107928. eCollection 2023 Oct 20.PMID: 37810236  

• LRIT3 expression in cone photoreceptors restores post-synaptic bipolar cell signalplex assembly and partial function in Lrit3 -/- mice. 

  Gregg RG, Hasan N, Borghuis BG.iScience. 2023 Mar 24;26(4):106499. doi: 10.1016/j.isci.2023.106499. eCollection 2023 Apr 21.PMID: 37091241  

• Phase advancing is a common property of multiple neuron classes in the mouse retina. 

  DePiero VJ, Borghuis BG.eNeuro. 2022 Aug 22;9(5):ENEURO.0270-22.2022. doi: 10.1523/ENEURO.0270-22.2022. Online ahead of print.PMID: 35995559  

• OFF bipolar cell density varies by subtype, eccentricity, and along the dorsal ventral axis in the mouse retina. 

  Camerino MJ, Engerbretson IJ, Fife PA, Reynolds NB, Berria MH, Doyle JR, Clemons MR, Gencarella MD, Borghuis BG, Fuerst PG.J Comp Neurol. 2021 Jun;529(8):1911-1925. doi: 10.1002/cne.25064. Epub 2020 Nov 9.PMID: 33135176  

Team 

• Bart Borghuis