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Dive into the research topics where Andrew D. Huberman is active.

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Featured researches published by Andrew D. Huberman.


Cell | 2007

The Classical Complement Cascade Mediates CNS Synapse Elimination

Beth Stevens; Nicola J. Allen; Luis E. Vazquez; Gareth R. Howell; Karen S. Christopherson; Navid Nouri; Kristina D. Micheva; Adrienne K. Mehalow; Andrew D. Huberman; Benjamin K. Stafford; Alexander Sher; Alan Litke; John D. Lambris; Stephen J. Smith; Simon W. M. John; Ben A. Barres

During development, the formation of mature neural circuits requires the selective elimination of inappropriate synaptic connections. Here we show that C1q, the initiating protein in the classical complement cascade, is expressed by postnatal neurons in response to immature astrocytes and is localized to synapses throughout the postnatal CNS and retina. Mice deficient in complement protein C1q or the downstream complement protein C3 exhibit large sustained defects in CNS synapse elimination, as shown by the failure of anatomical refinement of retinogeniculate connections and the retention of excess retinal innervation by lateral geniculate neurons. Neuronal C1q is normally downregulated in the adult CNS; however, in a mouse model of glaucoma, C1q becomes upregulated and synaptically relocalized in the adult retina early in the disease. These findings support a model in which unwanted synapses are tagged by complement for elimination and suggest that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative disease.


Nature | 2000

Finger-length ratios and sexual orientation

Terrance J. Williams; Michelle E. Pepitone; Scott E. Christensen; Bradley M. Cooke; Andrew D. Huberman; Nicholas J. Breedlove; Tessa J. Breedlove; Cynthia L. Jordan; S. Marc Breedlove

Animal models have indicated that androgenic steroids acting before birth might influence the sexual orientation of adult humans. Here we examine the androgen-sensitive pattern of finger lengths, and find evidence that homosexual women are exposed to more prenatal androgen than heterosexual women are; also, men with more than one older brother, who are more likely than first-born males to be homosexual in adulthood, are exposed to more prenatal androgen than eldest sons. Prenatal androgens may therefore influence adult human sexual orientation in both sexes, and a mothers body appears to ‘remember’ previously carried sons, altering the fetal development of subsequent sons and increasing the likelihood of homosexuality in adulthood.


Cell | 2009

Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis

Cagla Eroglu; Nicola J. Allen; Michael W. Susman; Nancy A. O'Rourke; Chan Young Park; Engin Özkan; Chandrani Chakraborty; Sara B. Mulinyawe; Douglas S. Annis; Andrew D. Huberman; Eric M. Green; Jack Lawler; Ricardo E. Dolmetsch; K. Christopher Garcia; Stephen J. Smith; Z. David Luo; Arnon Rosenthal; Deane F. Mosher; Ben A. Barres

Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS synapse formation as alpha2delta-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of alpha2delta-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. alpha2delta-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to alpha2delta-1 and powerfully inhibits excitatory synapse formation in vitro and in vivo. These findings identify alpha2delta-1 as a receptor involved in excitatory synapse formation and suggest that gabapentin may function therapeutically by blocking new synapse formation.


Annual Review of Neuroscience | 2008

Mechanisms underlying development of visual maps and receptive fields.

Andrew D. Huberman; Marla B. Feller; Barbara Chapman

Patterns of synaptic connections in the visual system are remarkably precise. These connections dictate the receptive field properties of individual visual neurons and ultimately determine the quality of visual perception. Spontaneous neural activity is necessary for the development of various receptive field properties and visual feature maps. In recent years, attention has shifted to understanding the mechanisms by which spontaneous activity in the developing retina, lateral geniculate nucleus, and visual cortex instruct the axonal and dendritic refinements that give rise to orderly connections in the visual system. Axon guidance cues and a growing list of other molecules, including immune system factors, have also recently been implicated in visual circuit wiring. A major goal now is to determine how these molecules cooperate with spontaneous and visually evoked activity to give rise to the circuits underlying precise receptive field tuning and orderly visual maps.


Neuron | 2009

Genetic Identification of an On-Off Direction- Selective Retinal Ganglion Cell Subtype Reveals a Layer-Specific Subcortical Map of Posterior Motion

Andrew D. Huberman; Wei Wei; Justin Elstrott; Ben K. Stafford; Marla B. Feller; Ben A. Barres

Motion detection is an essential component of visual processing. On-Off direction-selective retinal ganglion cells (On-Off DSGCs) detect objects moving along specific axes of the visual field due to their precise retinal circuitry. The brain circuitry of On-Off DSGCs, however, is largely unknown. We report a mouse with GFP expressed selectively by the On-Off DSGCs that detect posterior motion (On-Off pDSGCs), allowing two-photon targeted recordings of their light responses and delineation of their complete map of central connections. On-Off pDSGCs project exclusively to the dorsal lateral geniculate nucleus and superior colliculus and in both targets form synaptic lamina that are separate from a lamina corresponding to non-DSGCs. Thus, individual On-Off DSGC subtypes are molecularly distinct and establish circuits that map specific qualities of directional motion to dedicated subcortical areas. This suggests that each RGC subtype represents a unique parallel pathway whose synaptic specificity in the retina is recapitulated in central targets.


Neuron | 2008

Architecture and Activity-Mediated Refinement of Axonal Projections from a Mosaic of Genetically Identified Retinal Ganglion Cells

Andrew D. Huberman; Mihai Manu; Selina M. Koch; Michael W. Susman; Amanda Brosius Lutz; Erik M. Ullian; Stephen A. Baccus; Ben A. Barres

Our understanding of how mammalian sensory circuits are organized and develop has long been hindered by the lack of genetic markers of neurons with discrete functions. Here, we report a transgenic mouse selectively expressing GFP in a complete mosaic of transient OFF-alpha retinal ganglion cells (tOFF-alphaRGCs). This enabled us to relate the mosaic spacing, dendritic anatomy, and electrophysiology of these RGCs to their complete map of projections in the brain. We find that tOFF-alphaRGCs project exclusively to the superior colliculus (SC) and dorsal lateral geniculate nucleus and are restricted to a specific laminar depth within each of these targets. The axons of tOFF-alphaRGC are also organized into columns in the SC. Both laminar and columnar specificity develop through axon refinement. Disruption of cholinergic retinal waves prevents the emergence of columnar- but not laminar-specific tOFF-alphaRGC connections. Our findings reveal that in a genetically identified sensory map, spontaneous activity promotes synaptic specificity by segregating axons arising from RGCs of the same subtype.


The Journal of Neuroscience | 2013

Diverse visual features encoded in mouse lateral geniculate nucleus

Denise M. Piscopo; Rana N. El-Danaf; Andrew D. Huberman; Cristopher M. Niell

The thalamus is crucial in determining the sensory information conveyed to cortex. In the visual system, the thalamic lateral geniculate nucleus (LGN) is generally thought to encode simple center-surround receptive fields, which are combined into more sophisticated features in cortex, such as orientation and direction selectivity. However, recent evidence suggests that a more diverse set of retinal ganglion cells projects to the LGN. We therefore used multisite extracellular recordings to define the repertoire of visual features represented in the LGN of mouse, an emerging model for visual processing. In addition to center-surround cells, we discovered a substantial population with more selective coding properties, including direction and orientation selectivity, as well as neurons that signal absence of contrast in a visual scene. The direction and orientation selective neurons were enriched in regions that match the termination zones of direction selective ganglion cells from the retina, suggesting a source for their tuning. Together, these data demonstrate that the mouse LGN contains a far more elaborate representation of the visual scene than current models posit. These findings should therefore have a significant impact on our understanding of the computations performed in mouse visual cortex.


Nature | 2014

A dedicated circuit links direction-selective retinal ganglion cells to the primary visual cortex

Alberto Cruz-Martín; Rana N. El-Danaf; Fumitaka Osakada; Balaji Sriram; Onkar S. Dhande; Phong L. Nguyen; Edward M. Callaway; Anirvan Ghosh; Andrew D. Huberman

How specific features in the environment are represented within the brain is an important unanswered question in neuroscience. A subset of retinal neurons, called direction-selective ganglion cells (DSGCs), are specialized for detecting motion along specific axes of the visual field. Despite extensive study of the retinal circuitry that endows DSGCs with their unique tuning properties, their downstream circuitry in the brain and thus their contribution to visual processing has remained unclear. In mice, several different types of DSGCs connect to the dorsal lateral geniculate nucleus (dLGN), the visual thalamic structure that harbours cortical relay neurons. Whether direction-selective information computed at the level of the retina is routed to cortical circuits and integrated with other visual channels, however, is unknown. Here we show that there is a di-synaptic circuit linking DSGCs with the superficial layers of the primary visual cortex (V1) by using viral trans-synaptic circuit mapping and functional imaging of visually driven calcium signals in thalamocortical axons. This circuit pools information from several types of DSGCs, converges in a specialized subdivision of the dLGN, and delivers direction-tuned and orientation-tuned signals to superficial V1. Notably, this circuit is anatomically segregated from the retino-geniculo-cortical pathway carrying non-direction-tuned visual information to deeper layers of V1, such as layer 4. Thus, the mouse harbours several functionally specialized, parallel retino-geniculo-cortical pathways, one of which originates with retinal DSGCs and delivers direction- and orientation-tuned information specifically to the superficial layers of the primary visual cortex. These data provide evidence that direction and orientation selectivity of some V1 neurons may be influenced by the activation of DSGCs.


The Journal of Neuroscience | 2006

Neuronal Pentraxins Mediate Synaptic Refinement in the Developing Visual System

Lisa Bjartmar; Andrew D. Huberman; Erik M. Ullian; René C. Rentería; Xiaoquin Liu; Weifeng Xu; Jennifer Prezioso; Michael W. Susman; David Stellwagen; C. Stokes; Richard W. Cho; Paul F. Worley; Robert C. Malenka; Sherry L. Ball; Neal S. Peachey; David R. Copenhagen; Barbara Chapman; Masaru Nakamoto; Ben A. Barres; Mark S. Perin

Neuronal pentraxins (NPs) define a family of proteins that are homologous to C-reactive and acute-phase proteins in the immune system and have been hypothesized to be involved in activity-dependent synaptic plasticity. To investigate the role of NPs in vivo, we generated mice that lack one, two, or all three NPs. NP1/2 knock-out mice exhibited defects in the segregation of eye-specific retinal ganglion cell (RGC) projections to the dorsal lateral geniculate nucleus, a process that involves activity-dependent synapse formation and elimination. Retinas from mice lacking NP1 and NP2 had cholinergically driven waves of activity that occurred at a frequency similar to that of wild-type mice, but several other parameters of retinal activity were altered. RGCs cultured from these mice exhibited a significant delay in functional maturation of glutamatergic synapses. Other developmental processes, such as pathfinding of RGCs at the optic chiasm and hippocampal long-term potentiation and long-term depression, appeared normal in NP-deficient mice. These data indicate that NPs are necessary for early synaptic refinements in the mammalian retina and dorsal lateral geniculate nucleus. We speculate that NPs exert their effects through mechanisms that parallel the known role of short pentraxins outside the CNS.


Trends in Neurosciences | 2011

What can mice tell us about how vision works

Andrew D. Huberman; Cristopher M. Niell

Understanding the neural basis of visual perception is a long-standing fundamental goal of neuroscience. Historically, most vision studies were carried out on humans, macaques and cats. Over the past 5 years, however, a growing number of researchers have begun using mice to parse the mechanisms underlying visual processing; the rationale is that, despite having relatively poor acuity, mice are unmatched in terms of the variety and sophistication of tools available to label, monitor and manipulate specific cell types and circuits. In this review, we discuss recent advances in understanding the mouse visual system at the anatomical, receptive field and perceptual level, focusing on the opportunities and constraints those features provide toward the goal of understanding how vision works.

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