Faculty

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Li Zhang, PhD
Professor of Physiology and Biophysics
Zilkha Neurogenetic Institute
ZNI 419 1501 San Pablo Street Health Sciences Campus Los Angeles
+1 323 442 4347

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

The Esther A. & and Joseph Klingenstein Fund: Klingenstein Fellowship Award in Neuroscience, 2005

Searle Scholar Program, Kinship Foundation: Searle Scholar Award, 2005

Publications

Thalamocortical Innervation Pattern in Mouse Auditory and Visual Cortex: Laminar and Cell-Type Specificity. Cereb Cortex. 2016 Jun; 26(6):2612-25. 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 2; 89(5):1031-45. View in: PubMed

Dcc Mediates Functional Assembly of Peripheral Auditory Circuits. Sci Rep. 2016; 6:23799. 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 5; 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

Sensory Cortical Control of a Visually Induced Arrest Behavior via Corticotectal Projections. Neuron. 2015 May 6; 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 1; 113(5):1358-68. View in: PubMed

Auditory cortex controls sound-driven innate defense behaviour through corticofugal projections to inferior colliculus. Nat Commun. 2015; 6:7224. 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 8; 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

Enhancing gene delivery of adeno-associated viruses by cell-permeable peptides. Mol Ther Methods Clin Dev. 2014; 1:12. View in: PubMed

Thresholding of auditory cortical representation by background noise. Front Neural Circuits. 2014; 8:133. View in: PubMed

Linear transformation of thalamocortical input by intracortical excitation. Nat Neurosci. 2013 Sep; 16(9):1324-30. View in: PubMed

Intracortical multiplication of thalamocortical signals in mouse auditory cortex. Nat Neurosci. 2013 Sep; 16(9):1179-81. 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 4; 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 4; 100(3):1405-8. View in: PubMed

Moving visual stimuli rapidly induce direction sensitivity of developing tectal neurons. Nature. 2002 Oct 3; 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

Electrical activity and development of neural circuits. Nat Neurosci. 2001 Nov; 4 Suppl:1207-14. 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

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 1; 20(9):3233-43. View in: PubMed

A critical window for cooperation and competition among developing retinotectal synapses. Nature. 1998 Sep 3; 395(6697):37-44. View in: PubMed

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