Li Zhang, PhD

Professor of Physiology & Neuroscience

Director of the Center for Neural Circuits and Sensory Processing Disorders

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Overview

As a systems neuroscientist, our ultimate research goal is to decipher the brain circuits, and to understand how perception and behaviors are generated and controlled, how the brain’s cortex adapts in response to changes in the dynamic external environment, and how specific changes in cortical functions result in neurological and psychiatric disorders. To address these highly challenging questions, our approach is to resolve the neural circuitry (how neurons are wired in the brain), i.e. the structural basis underlying the brain functions.

Technical innovation is the key for exploring the dauntingly complex brain circuits. In the past years, we have committed substantial efforts in developing molecular/genetic and electrophysiological/imaging techniques for elucidating the neural circuits for both local neuronal computation and for controlling animal behavior. To this end, we have pioneered in applying in vivo whole-cell voltage-clamp recording, to reveal at the synaptic connection level, how the excitatory and inhibitory synaptic interplay determines the sensory response/processing properties. We have now integrated a broad spectrum of state-of-the-art approaches, including in vivo and in vitro electrophysiology, two-photon Ca2+ imaging, neural modeling, anatomical tracing and optogentics, to build an understanding of neural circuits composed of different cell types.

Awards

  • White House: Presidential Early Career Award for Scientists and Engineers, 2008
  • David and Lucile Packard Foundation: Packard Fellowship for Science and Engineering, 2006
  • Searle Scholar Program, Kinship Foundation: Searle Scholar Award, 2005
  • The Esther A. & and Joseph Klingenstein Fund: Klingenstein Fellowship Award in Neuroscience, 2005

Publications

  • Dcc Mediates Functional Assembly of Peripheral Auditory Circuits Sci Rep. 2016 Apr 04; 6:23799. . View in PubMed
  • EphA7 regulates spiral ganglion innervation of cochlear hair cells Dev Neurobiol. 2016 Apr; 76(4):452-69. . View in PubMed
  • Cross-Modality Sharpening of Visual Cortical Processing through Layer-1-Mediated Inhibition and Disinhibition Neuron. 2016 Mar 02; 89(5):1031-45. . View in PubMed
  • Thalamocortical Innervation Pattern in Mouse Auditory and Visual Cortex: Laminar and Cell-Type Specificity Cereb Cortex. 2016 06; 26(6):2612-25. . View in PubMed
  • Strengthening of Direction Selectivity by Broadly Tuned and Spatiotemporally Slightly Offset Inhibition in Mouse Visual Cortex Cereb Cortex. 2015 Sep; 25(9):2466-77. . View in PubMed
  • Synaptic Basis for Differential Orientation Selectivity between Complex and Simple Cells in Mouse Visual Cortex J Neurosci. 2015 Aug 05; 35(31):11081-93. . View in PubMed
  • Differential Receptive Field Properties of Parvalbumin and Somatostatin Inhibitory Neurons in Mouse Auditory Cortex Cereb Cortex. 2015 Jul; 25(7):1782-91. . View in PubMed
  • Auditory cortex controls sound-driven innate defense behaviour through corticofugal projections to inferior colliculus Nat Commun. 2015 Jun 11; 6:7224. . View in PubMed
  • Sensory Cortical Control of a Visually Induced Arrest Behavior via Corticotectal Projections Neuron. 2015 May 06; 86(3):755-67. . View in PubMed
  • Synaptic mechanisms for generating temporal diversity of auditory representation in the dorsal cochlear nucleus J Neurophysiol. 2015 Mar 01; 113(5):1358-68. . View in PubMed
  • At the interface of sensory and motor dysfunctions and Alzheimer’s disease Alzheimers Dement. 2015 Jan; 11(1):70-98. . View in PubMed
  • Functional response properties of VIP-expressing inhibitory neurons in mouse visual and auditory cortex Front Neural Circuits. 2015; 9:22. . View in PubMed
  • A feedforward inhibitory circuit mediates lateral refinement of sensory representation in upper layer 2/3 of mouse primary auditory cortex J Neurosci. 2014 Oct 08; 34(41):13670-83. . View in PubMed
  • Formation of excitation-inhibition balance: inhibition listens and changes its tune Trends Neurosci. 2014 Oct; 37(10):528-30. . View in PubMed
  • Scaling down of balanced excitation and inhibition by active behavioral states in auditory cortex Nat Neurosci. 2014 Jun; 17(6):841-50. . View in PubMed
  • Thresholding of auditory cortical representation by background noise Front Neural Circuits. 2014; 8:133. . View in PubMed
  • Enhancing gene delivery of adeno-associated viruses by cell-permeable peptides Mol Ther Methods Clin Dev. 2014; 1:12. . View in PubMed
  • Intracortical multiplication of thalamocortical signals in mouse auditory cortex Nat Neurosci. 2013 Sep; 16(9):1179-81. . View in PubMed
  • Linear transformation of thalamocortical input by intracortical excitation Nat Neurosci. 2013 Sep; 16(9):1324-30. . View in PubMed
  • Interaural level difference-dependent gain control and synaptic scaling underlying binaural computation Neuron. 2013 Aug 21; 79(4):738-53. . View in PubMed
  • Slit/Robo signaling mediates spatial positioning of spiral ganglion neurons during development of cochlear innervation J Neurosci. 2013 Jul 24; 33(30):12242-54. . View in PubMed
  • Synaptic mechanisms underlying functional dichotomy between intrinsic-bursting and regular-spiking neurons in auditory cortical layer 5 J Neurosci. 2013 Mar 20; 33(12):5326-39. . View in PubMed
  • Generation of intensity selectivity by differential synaptic tuning: fast-saturating excitation but slow-saturating inhibition J Neurosci. 2012 Dec 12; 32(50):18068-78. . View in PubMed
  • Generation of spike latency tuning by thalamocortical circuits in auditory cortex J Neurosci. 2012 Jul 18; 32(29):9969-80. . View in PubMed
  • Broadening of cortical inhibition mediates developmental sharpening of orientation selectivity J Neurosci. 2012 Mar 21; 32(12):3981-91. . View in PubMed
  • Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination Proc Natl Acad Sci U S A. 2012 Jan 24; 109(4):1299-304. . View in PubMed
  • From elementary synaptic circuits to information processing in primary auditory cortex Neurosci Biobehav Rev. 2011 Nov; 35(10):2094-104. . View in PubMed
  • Perspectives on: information and coding in mammalian sensory physiology: inhibitory synaptic mechanisms underlying functional diversity in auditory cortex J Gen Physiol. 2011 Sep; 138(3):311-20. . View in PubMed
  • Broad inhibition sharpens orientation selectivity by expanding input dynamic range in mouse simple cells Neuron. 2011 Aug 11; 71(3):542-54. . View in PubMed
  • Visual representations by cortical somatostatin inhibitory neurons–selective but with weak and delayed responses J Neurosci. 2010 Oct 27; 30(43):14371-9. . View in PubMed
  • Fine-tuning of pre-balanced excitation and inhibition during auditory cortical development Nature. 2010 Jun 17; 465(7300):927-31. . View in PubMed
  • Preceding inhibition silences layer 6 neurons in auditory cortex Neuron. 2010 Mar 11; 65(5):706-17. . View in PubMed
  • Intervening inhibition underlies simple-cell receptive field structure in visual cortex Nat Neurosci. 2010 Jan; 13(1):89-96. . View in PubMed
  • Visual receptive field structure of cortical inhibitory neurons revealed by two-photon imaging guided recording J Neurosci. 2009 Aug 26; 29(34):10520-32. . View in PubMed
  • A genetic strategy for stochastic gene activation with regulated sparseness (STARS) PLoS One. 2009; 4(1):e4200. . View in PubMed
  • Lateral sharpening of cortical frequency tuning by approximately balanced inhibition Neuron. 2008 Apr 10; 58(1):132-43. . View in PubMed
  • Defining cortical frequency tuning with recurrent excitatory circuitry Nat Neurosci. 2007 Dec; 10(12):1594-600. . View in PubMed
  • Heterosynaptic scaling of developing GABAergic synapses: dependence on glutamatergic input and developmental stage J Neurosci. 2007 May 16; 27(20):5301-12. . View in PubMed
  • Nonmonotonic synaptic excitation and imbalanced inhibition underlying cortical intensity tuning Neuron. 2006 Nov 22; 52(4):705-15. . View in PubMed
  • Tone-evoked excitatory and inhibitory synaptic conductances of primary auditory cortex neurons J Neurophysiol. 2004 Jul; 92(1):630-43. . View in PubMed
  • Specialization of primary auditory cortex processing by sound exposure in the “critical period” Proc Natl Acad Sci U S A. 2004 May 04; 101(18):7170-4. . View in PubMed
  • Topography and synaptic shaping of direction selectivity in primary auditory cortex Nature. 2003 Jul 10; 424(6945):201-5. . View in PubMed
  • Suppression of cortical representation through backward conditioning Proc Natl Acad Sci U S A. 2003 Feb 04; 100(3):1405-8. . View in PubMed
  • Moving visual stimuli rapidly induce direction sensitivity of developing tectal neurons Nature. 2002 Oct 03; 419(6906):470-5. . View in PubMed
  • Disruption of primary auditory cortex by synchronous auditory inputs during a critical period Proc Natl Acad Sci U S A. 2002 Feb 19; 99(4):2309-14. . View in PubMed
  • Persistent and specific influences of early acoustic environments on primary auditory cortex Nat Neurosci. 2001 Nov; 4(11):1123-30. . View in PubMed
  • Electrical activity and development of neural circuits Nat Neurosci. 2001 Nov; 4 Suppl:1207-14. . View in PubMed
  • Emergence of input specificity of ltp during development of retinotectal connections in vivo Neuron. 2001 Aug 30; 31(4):569-80. . View in PubMed
  • Visual input induces long-term potentiation of developing retinotectal synapses Nat Neurosci. 2000 Jul; 3(7):708-15. . View in PubMed
  • Selective presynaptic propagation of long-term potentiation in defined neural networks J Neurosci. 2000 May 01; 20(9):3233-43. . View in PubMed
  • A critical window for cooperation and competition among developing retinotectal synapses Nature. 1998 Sep 03; 395(6697):37-44. . View in PubMed