The goal of the Research Support Core is to develop and provide genetic tools, disease models and behavioral analysis to dissect PV neuron development and function as well as their dysfunction in ASD. These unique resources will be available not only to the investigators at this Conte Center but also to the whole neuroscience community.
For the Research Core of the Conte grant, he will generate and provide both mouse and marmoset ASD models as well as cell type-specific genetic tools for studying neurobiological mechanisms of ASD. He will also facilitate the neurophysiological and behavioral characterization of these models.
In the past 10 years, my laboratory has developed many cell type-specific transgenic mouse tools. These include transgenic mice for Single-neuron Labeling with Inducible cre-mediated Knockout (SLICK), cell type-specific optogenetic mice for manipulating neuronal activity, Thy1-GCaMP3 mice for monitoring neuronal activity, and PV-Tdtomato mice with fluorescently-labeled PV neurons. In addition, we have developed several animal models of neurodevelopmental and psychiatric disorders including SAPAP3 model for repetitive behavior, Shank3 models of ASD and schizophrenia, and Ptchd1 model for neurodevelopmental disorders. Some of these genetic tools and models will become an integral part of Conte Center projects.
Although the ability to genetically modify the mouse genome has revolutionized biomedical research, rodent models for brain disorders have their limitations due to the inherent differences in the structure and physiology of the brain between rodents and humans. In particular, the prefrontal cortex is one of the largest and most developed portions of the human brain, and it is a top candidate for pathological processes in psychiatric disease. Yet, rodents have only a rudimentary prefrontal cortex and do not exhibit some of the complex cognitive functions that are mediated by this region in humans. Thus, expanding studies of cortical PV neuron function and dysfunction to primate models and human cellular models will be an important step towards better understanding of the neurobiological mechanisms of these disorders.
Striatopallidal dysfunction underlies repetitive behavior in Shank3-deficient model of autism
Wang W, Li C, Chen Q, van der Goes MS, Hawrot J, Yao AY, Gao X, Lu C, Zang Y, Zhang Q, Lyman K, Wang D, Guo B, Wu S, Gerfen CR, Fu Z and Feng G.
The Journal of clinical investigation. May 2017, 127(5):1978-1990, doi: 10.1172/JCI87997.
SHANK proteins: roles at the synapse and in autism spectrum disorder
Monteiro P and Feng G.
Nature Reviews Neuroscience. Mar 2017, 18(3):147-157, doi: 10.1038/nrn.2016.183.
Chd8 mutation leads to autistic-like behaviors and impaired striatal circuits
Platt RJ, Zhou Y, Slaymaker IM, Shetty AS, Weisbach NR, Kim JA, Sharma J, Desai M, Sood S, Kempton HR, Crabtree GR, Feng G and Zhang F.
Cell Reports. Apr 2017, 19(2):335-350, doi: 10.1016/j.celrep.2017.03.052.
Animal models for neuropsychiatric disorders: prospects for circuit intervention
Kaiser T, Zhou Y and Feng G.
Current Opinion in Neurobiology. Apr 2017, 45:59-65, doi: 10.1016/j.conb.2017.03.010.
A viral strategy for targeting and manipulating interneurons across vertebrate species
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Nature Neuroscience. Dec 2016, 19(12):1743-1749, doi: 10.1038/nn.4430
Decreased Anxiety-Related Behaviour but Apparently Unperturbed NUMB Function in Ligand of NUMB Protein-X (LNX) 1/2 Double Knockout Mice
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Molecular Neurobiology. Nov 2016, doi: 10.1007/s12035-016-0261-0.
Direct modulation of GFAP-expressing glia in the arcuate nucleus bi-directionally regulates feeding
Chen N, Sugihara H, Kim J, Fu Z, Barak B, Sur M, Feng G and Han W.
Molecular Neurobiology. Oct 2016;5. pii: e18716, doi: 10.7554/eLife.18716.
Opportunities and challenges in modeling human brain disorders in transgenic primates
Jennings CG, Landman R, Zhou Y, Sharma J, Hyman J, Movshon JA, Qiu Z, Roberts AC, Roe AW, Wang X, Zhou H, Wang L, Zhang F, Desimone R and Feng G.
Nature Neuroscience. Aug 2016, 19(9):1123-30, doi: 10.1038/nn.4362.
Central Mechanisms Mediating Thrombospondin-4-induced Pain StatesAdult restoration of Shank3 expression rescues selective autistic-like phenotypes
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The Journal of Biological Chemistry. Jun 2016, 291(25):13335-48, doi: 10.1074/jbc.M116.723478.
Optogenetic visualization of presynaptic tonic inhibition of cerebellar parallel fibers
Berglund K, Wen L, Dunbar RL, Feng G and Augustine GJ.
The Journal of Neuroscience. May 2016, 36(21):5709-23, doi: 10.1523/JNEUROSCI.4366-15.2016.
Efficient production of cynomolgus monkeys with a toolbox of enhanced assisted reproductive technologies
Ma Y, Li J, Wang G, Ke Q, Qiu S, Gao L, Wan H, Zhou Y, Xiang AP, Huang Q, Feng G, Zhou Q and Yang S.
Scientific Reports. May 2016, 6:25888, doi: 10.1038/srep25888
Neurobiology of social behavior abnormalities in autism and Williams syndrome
Barak B and Feng G.
Nature Neuroscience. Apr 2016, 19(6):647-55, doi: 10.1038/nn.4276.
Thalamic reticular impairment underlies attention deficit in Ptchd1(Y/-) mice
Wells MF, Wimmer RD, Schmitt LI, Feng G and Halassa MM.
Nature. Apr 2016; 532(7597):58-63, doi: 10.1038/nature17427
Optogenetic dissection of ictal propagation in the hippocampal-entorhinal cortex structures
Lu Y, Zhong C, Wang L, Wei P, He W, Huang K, Zhang Y, Zhan Y, Feng G and Wang L.
Nature Communications. Mar 2016, 7:10962. doi: 10.1038/ncomms10962.
Adult restoration of Shank3 expression rescues selective autistic-like phenotypes
Mei Y, Monteiro P, Zhou Y, Kim JA, Gao X, Fu Z and Feng G.
Nature. Feb 2016, 530(7591):481-4, doi: 10.1038/nature16971.
Impaired dendritic development and memory in Sorbs2 knock-out mice
Zhang Q, Gao X, Li C, Feliciano C, Wang D, Zhou D, Mei Y, Monteiro P, Anand M, Itohara S, Dong X, Fu Z and Feng G.
The Journal of Neuroscience. Feb 2016, 36(7):2247-60, doi: 10.1523/JNEUROSCI.2528-15.2016.
Mice with Shank3 mutations associated with ASD and schizophrenia display both shared and distinct defects
Zhou Y, Kaiser T, Monteiro P, Zhang X, Van der Goes MS, Wang D, Barak B, Zeng M, Li C, Lu C, Wells M, Amaya A, Nguyen S, Lewis M, Sanjana N, Zhou Y, Zhang M, Zhang F, Fu Z and Feng G.
Neuron. Jan 2016, 89(1):147-62, doi: 10.1016/j.neuron.2015.11.023.
Striatal magnetic resonance spectroscopy abnormalities in young adult SAPAP3 knockout mice
Mintzopoulos D, Gillis TE, Robertson HR, Dalia T, Feng G, Rauch SL and Kaufman MJ.
Biological Psychiatry Cognitive Neuroscience and Neuroimaging. Jan 2016, 1(1):39-48, doi: 10.1016/j.bpsc.2015.10.001.
Learning from animal models of obsessive-compulsive disorder
Monteiro P and Feng G.
Biological Psychiatry. Jan 2016, 79(1):7-16, doi: 10.1016/j.biopsych.2015.04.020
Modeling psychiatric disorders for developing effective treatments
Kaiser T and Feng G.
Nature Medicine. Sep 2015, 21(9):979-88, doi: 10.1038/nm.3935.
CRISPR germline engineering–the community speaks
Bosley KS, Botchan M, Bredenoord AL, Carroll D, Charo RA, Charpentier E, Cohen R, Corn J, Doudna J, Feng G, Greely HT, Isasi R, Ji W, Kim JS, Knoppers B, Lanphier E, Li J, Lovell-Badge R, Martin GS, Moreno J, Naldini L, Pera M, Perry AC, Venter JC, Zhang F and Zhou Q.
Nature Biotechnology. May 2015, 33(5):478-86, doi: 10.1038/nbt.3227.
Striatal circuits, habits, and implications for obsessive-compulsive disorder
Burguière E, Monteiro P, Mallet L, Feng G and Graybiel AM.
Current Opinion in Neurobiology. Feb 2015, 30:59-65, doi: 10.1016/j.conb.2014.08.008.