Bio


My work is focused on how visual neurons form accurate connections in the brain during development. In particular, I am interested in the parallel visual circuits in midbrain pretectum, which mediate different reflexive behaviors. I am currently exploring the role of axon-axon competition during RGC axon-target matching using mutant mice and cell deletion approaches.

Honors & Awards


  • Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship, NIH/NEI (2015-2017)
  • Institutional National Research Service Award (T32) - Neural Circuits Postdoctoral Training Program, NIH/NINDS (2014-2015)

Professional Education


  • Bachelor of Science, Virginia Commonwealth University, Forensic Science (2005)
  • Bachelor of Science, Virginia Commonwealth University, Biology with Minor in Chemistry (2005)
  • Doctor of Philosophy, Virginia Commonwealth University, Neuroscience (2012)

Stanford Advisors


Lab Affiliations


All Publications


  • Architecture, Function, and Assembly of the Mouse Visual System. Annual review of neuroscience Seabrook, T. A., Burbridge, T. J., Crair, M. C., Huberman, A. D. 2017; 40: 499–538

    Abstract

    Vision is the sense humans rely on most to navigate the world, make decisions, and perform complex tasks. Understanding how humans see thus represents one of the most fundamental and important goals of neuroscience. The use of the mouse as a model for parsing how vision works at a fundamental level started approximately a decade ago, ushered in by the mouse's convenient size, relatively low cost, and, above all, amenability to genetic perturbations. In the course of that effort, a large cadre of new and powerful tools for in vivo labeling, monitoring, and manipulation of neurons were applied to this species. As a consequence, a significant body of work now exists on the architecture, function, and development of mouse central visual pathways. Excitingly, much of that work includes causal testing of the role of specific cell types and circuits in visual perception and behavior-something rare to find in studies of the visual system of other species. Indeed, one could argue that more information is now available about the mouse visual system than any other sensory system, in any species, including humans. As such, the mouse visual system has become a platform for multilevel analysis of the mammalian central nervous system generally. Here we review the mouse visual system structure, function, and development literature and comment on the similarities and differences between the visual system of this and other model species. We also make it a point to highlight the aspects of mouse visual circuitry that remain opaque and that are in need of additional experimentation to enrich our understanding of how vision works on a broad scale.

    View details for DOI 10.1146/annurev-neuro-071714-033842

    View details for PubMedID 28772103

  • Cortical Cliques: A Few Plastic Neurons Get All the Action NEURON Seabrook, T. A., Huberman, A. D. 2015; 86 (5): 1113-1116

    Abstract

    Adjustments in neural activity can drive cortical plasticity, but the underlying circuit components remain unclear. In this issue of Neuron, Barnes et al. (2015) show that visual deprivation-induced homeostatic plasticity invokes specific changes among select categories of V1 neurons.

    View details for DOI 10.1016/j.neuron.2015.05.039

    View details for Web of Science ID 000355666400002

    View details for PubMedID 26050030

  • Absence of Plateau Potentials in dLGN Cells Leads to a Breakdown in Retinogeniculate Refinement JOURNAL OF NEUROSCIENCE Dilger, E. K., Krahe, T. E., Morhardt, D. R., Seabrook, T. A., Shin, H., Guido, W. 2015; 35 (8): 3652-3662

    Abstract

    The link between neural activity and the refinement of projections from retina to the dorsal lateral geniculate nucleus (dLGN) of thalamus is based largely on studies that disrupt presynaptic retinogeniculate activity. Postsynaptic mechanisms responsible for implementing the activity-dependent remodeling in dLGN remain unknown. We tested whether L-type Ca(2+) channel activity in the form of synaptically evoked plateau potentials in dLGN cells is needed for remodeling by using a mutant mouse that lacks the ancillary β3 subunit and, as a consequence, has highly reduced L-type channel expression and attenuated L-type Ca(2+) currents. In the dLGNs of β3-null mice, glutamatergic postsynaptic activity evoked by optic tract stimulation was normal, but plateau potentials were rarely observed. The few plateaus that were evoked required high rates of retinal stimulation, but were still greatly attenuated compared with those recorded in age-matched wild-type mice. While β3-null mice exhibit normal stage II and III retinal waves, their retinogeniculate projections fail to segregate properly and dLGN cells show a high degree of retinal convergence even at late postnatal ages. These structural and functional defects were also accompanied by a reduction in CREB phosphorylation, a signaling event that has been shown to be essential for retinogeniculate axon segregation. Thus, postsynaptic L-type Ca(2+) activity plays an important role in mediating the refinement of the retinogeniculate pathway.

    View details for DOI 10.1523/JNEUROSCI.2343-14.2015

    View details for Web of Science ID 000350738800035

    View details for PubMedID 25716863

  • Interneurons in the mouse visual thalamus maintain a high degree of retinal convergence throughout postnatal development NEURAL DEVELOPMENT Seabrook, T. A., Krahe, T. E., Govindaiah, G., Guido, W. 2013; 8

    Abstract

    The dorsal lateral geniculate nucleus (dLGN) of the mouse thalamus has emerged as a powerful experimental system for understanding the refinement of developing sensory connections. Interestingly, many of the basic tenets for such developmental remodeling (for example, pruning of connections to form precise sensory maps) fail to take into account a fundamental aspect of sensory organization, cell-type specific wiring. To date, studies have focused on thalamocortical relay neurons and little is known about the development of retinal connections onto the other principal cell type of dLGN, intrinsic interneurons. Here, we used a transgenic mouse line in which green fluorescent protein (GFP) is expressed within dLGN interneurons (GAD67-GFP), making it possible to visualize them in acutely prepared thalamic slices in order to examine their morphology and functional patterns of connectivity throughout postnatal life.GFP-expressing interneurons were evenly distributed throughout dLGN and had highly complex and widespread dendritic processes that often crossed eye-specific borders. Estimates of retinal convergence derived from excitatory postsynaptic potential (EPSP) amplitude by stimulus intensity plots revealed that unlike relay cells, interneurons recorded throughout the first 5 weeks of life, maintain a large number (approximately eight to ten) of retinal inputs.The lack of pruning onto interneurons suggests that the activity-dependent refinement of retinal connections in dLGN is cell-type specific. The high degree of retinal convergence onto interneurons may be necessary for these cells to provide both widespread and local forms of inhibition in dLGN.

    View details for DOI 10.1186/1749-8104-8-24

    View details for Web of Science ID 000329832100001

    View details for PubMedID 24359973

  • A Molecular Mechanism Regulating the Timing of Corticogeniculate Innervation CELL REPORTS Brooks, J. M., Su, J., Levy, C., Wang, J. S., Seabrook, T. A., Guido, W., Fox, M. A. 2013; 5 (3): 573-581

    Abstract

    Neural circuit formation demands precise timing of innervation by different classes of axons. However, the mechanisms underlying such activity remain largely unknown. In the dorsal lateral geniculate nucleus (dLGN), axons from the retina and visual cortex innervate thalamic relay neurons in a highly coordinated manner, with those from the cortex arriving well after those from retina. The differential timing of retino- and corticogeniculate innervation is not a coincidence but is orchestrated by retinal inputs. Here, we identified a chondroitin sulfate proteoglycan (CSPG) that regulates the timing of corticogeniculate innervation. Aggrecan, a repulsive CSPG, is enriched in neonatal dLGN and inhibits cortical axons from prematurely entering the dLGN. Postnatal loss of aggrecan from dLGN coincides with upregulation of aggrecanase expression in the dLGN and corticogeniculate innervation and, it is important to note, is regulated by retinal inputs. Taken together, these studies reveal a molecular mechanism through which one class of axons coordinates the temporal targeting of another class of axons.

    View details for DOI 10.1016/j.celrep.2013.09.041

    View details for Web of Science ID 000328263400003

    View details for PubMedID 24183669

  • Retinal Input Regulates the Timing of Corticogeniculate Innervation JOURNAL OF NEUROSCIENCE Seabrook, T. A., El-Danaf, R. N., Krahe, T. E., Fox, M. A., Guido, W. 2013; 33 (24): 10085-10097

    Abstract

    Neurons in layer VI of visual cortex represent one of the largest sources of nonretinal input to the dorsal lateral geniculate nucleus (dLGN) and play a major role in modulating the gain of thalamic signal transmission. However, little is known about how and when these descending projections arrive and make functional connections with dLGN cells. Here we used a transgenic mouse to visualize corticogeniculate projections to examine the timing of cortical innervation in dLGN. Corticogeniculate innervation occurred at postnatal ages and was delayed compared with the arrival of retinal afferents. Cortical fibers began to enter dLGN at postnatal day 3 (P3) to P4, a time when retinogeniculate innervation is complete. However, cortical projections did not fully innervate dLGN until eye opening (P12), well after the time when retinal inputs from the two eyes segregate to form nonoverlapping eye-specific domains. In vitro thalamic slice recordings revealed that newly arriving cortical axons form functional connections with dLGN cells. However, adult-like responses that exhibited paired pulse facilitation did not fully emerge until 2 weeks of age. Finally, surgical or genetic elimination of retinal input greatly accelerated the rate of corticogeniculate innervation, with axons invading between P2 and P3 and fully innervating dLGN by P8 to P10. However, recordings in genetically deafferented mice showed that corticogeniculate synapses continued to mature at the same rate as controls. These studies suggest that retinal and cortical innervation of dLGN is highly coordinated and that input from retina plays an important role in regulating the rate of corticogeniculate innervation.

    View details for DOI 10.1523/JNEUROSCI.5271-12.2013

    View details for Web of Science ID 000320235300024

    View details for PubMedID 23761904

  • Modulation of CREB in the Dorsal Lateral Geniculate Nucleus of Dark-Reared Mice NEURAL PLASTICITY Krahe, T. E., Seabrook, T. A., Chen, C. J., Fox, M. A., Guido, W. 2012

    Abstract

    The cAMP-response element-binding protein (CREB) plays an important role in visual cortical plasticity that follows the disruption of sensory activity, as induced by dark rearing (DR). Recent findings indicate that the dorsal lateral geniculate nucleus (dLGN) of thalamus is also sensitive to altered sensory activity. DR disrupts retinogeniculate synaptic strength and pruning in mice, but only when DR starts one week after eye opening (delayed DR, DDR) and not after chronic DR (CDR) from birth. While DR upregulates CREB in visual cortex, whether it also modulates this pathway in dLGN remains unknown. Here we investigate the role of CREB in the dLGN of mice that were CDR or DDR using western blot and immunofluorescence. Similar to findings in visual cortex, CREB is upregulated in dLGN after CDR and DDR. These findings are consistent with the proposal that DR up-regulates the CREB pathway in response to decreased visual drive.

    View details for DOI 10.1155/2012/426437

    View details for Web of Science ID 000299529600001

    View details for PubMedID 22292123