Primate Models

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.

Recent Publications

Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research.
Feng G, Jensen FE, Greely HT, Okano H, Treue S, Roberts AC, Fox JG, Caddick S, Poo MM, Newsome WT, Morrison JH. 2020
Proc Natl Acad Sci U S A. 29;117:24022-24031

The dawn of non-human primate models for neurodevelopmental disorders.
Aida T, Feng G. 2020
Curr Opin Genet Dev. 65:160-168.

Close-range vocal interaction in the common marmoset (Callithrix jacchus).
Landman R, Sharma J, Hyman JB, Fanucci-Kiss A, Meisner O, Parmar S, Feng G, Desimone R. 2020
PLoS One. 16;15:e0227392

Innovations present in the primate interneuron repertoire.
Krienen FM, Goldman M, Zhang Q, C H Del Rosario R, Florio M, Machold R, Saunders A, Levandowski K, Zaniewski H, Schuman B, Wu C, Lutservitz A, Mullally CD, Reed N, Bien E, Bortolin L, Fernandez-Otero M, Lin JD, Wysoker A, Nemesh J, Kulp D, Burns M, Tkachev V, Smith R, Walsh CA, Dimidschstein J, Rudy B, S Kean L, Berretta S, Fishell G, Feng G, McCarroll SA. 2020
Nature. Oct;586:262-269

Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans.
Vormstein-Schneider D, Lin JD, Pelkey KA, Chittajallu R, Guo B, Arias-Garcia MA, Allaway K, Sakopoulos S, Schneider G, Stevenson O, Vergara J, Sharma J, Zhang Q, Franken TP, Smith J, Ibrahim LA, M Astro KJ, Sabri E, Huang S, Favuzzi E, Burbridge T, Xu Q, Guo L, Vogel I, Sanchez V, Saldi GA, Gorissen BL, Yuan X, Zaghloul KA, Devinsky O, Sabatini BL, Batista-Brito R, Reynolds J, Feng G, Fu Z, McBain CJ, Fishell G, Dimidschstein 2020
J. Nat Neurosci. 23:1629-1636

Distinct subnetworks of the thalamic reticular nucleus.
Li Y, Lopez-Huerta VG, Adiconis X, Levandowski K, Choi S, Simmons SK, Arias-Garcia MA, Guo B, Yao AY, Blosser TR, Wimmer RD, Aida T, Atamian A, Naik T, Sun X, Bi D, Malhotra D, Hession CC, Shema R, Gomes M, Li T, Hwang E, Krol A, Kowalczyk M, Peça J, Pan G, Halassa MM, Levin JZ, Fu Z, Feng G. 2020
Nature, 583:819-824.

An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques.
Gong X, Mendoza-Halliday D, Ting JT, Kaiser T, Sun X, Bastos AM, Wimmer RD, Guo B, Chen Q, Zhou Y, Pruner M, Wu C W.-H, Park D, Deisseroth K, Barak B, Boyden ES, Miller EK, Halassa MM, Fu Z, Bi G, Desimone R, Feng G. 2020
Neuron, 8;107:197

Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD.
Chen Q, Deister CA, Gao X, Guo B, Lynn-Jones T, Chen N, Wells MF, Liu R, Goard MJ, Dimidschstein J, Feng S, Shi Y, Liao W, Lu Z, Fishell G, Moore CI, Feng G. 2020
Nat Neurosci. 23:520-532.

Combinatorial Targeting of Distributed Forebrain Networks Reverses Noise Hypersensitivity in a Model of Autism Spectrum Disorder.
Nakajima M, Schmitt LI, Feng G, Halassa MM. 2019
Neuron. 104:488-500.

Remotely controlled chemomagnetic modulation of targeted neural circuits.
Rao S, Chen R, LaRocca AA, Christiansen MG, Senko AW, Shi CH, Chiang PH, Varnavides G, Xue J, Zhou Y, Park S, Ding R, Moon J, Feng G, Anikeeva P. 2019
Nat Nanotechnol. 14:967-973.

Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models.
Orefice LL, Mosko JR, Morency DT, Wells MF, Tasnim A, Mozeika SM, Ye M, Chirila AM, Emanuel AJ, Rankin G, Fame RM, Lehtinen MK, Feng G, Ginty DD. 2019
Cell 178:867-886.e24.

Tmem119-EGFP and Tmem119-CreERT2 transgenic mice for labeling and manipulating microglia.
Kaiser T, Feng G. 2019
eNeuro. 26;6(4). pii: ENEURO.0448-18.2019.

Atypical behaviour and connectivity in SHANK3-mutant macaques.
Zhou Y, Sharma J, Ke Q, Landman R, Yuan J, Chen H, Hayden DS, Fisher JW 3rd, Jiang M, Menegas W, Aida T, Yan T, Zou Y, Xu D, Parmar S, Hyman JB, Fanucci-Kiss A, Meisner O, Wang D, Huang Y, Li Y, Bai Y, Ji W, Lai X, Li W, Huang L, Lu Z, Wang L, Anteraper SA, Sur M, Zhou H, Xiang AP, Desimone R, Feng G, Yang S. 2019
Nature. 570:326-331. 

A VTA GABAergic Neural Circuit Mediates Visually Evoked Innate Defensive Responses.
Zhou Z, Liu X, Chen S, Zhang Z, Liu Y, Montardy Q, Tang Y, Wei P, Liu N, Li L, Song R, Lai J, He X, Chen C, Bi G, Feng G, Xu F, Wang L. 2019
Neuron 103:473-488.e6.

Anterior cingulate cortex dysfunction underlies social deficits in Shank3 mutant mice.
Guo B, Chen J, Chen Q, Ren K, Feng D, Mao H, Yao H, Yang J, Liu H, Liu Y, Jia F, Qi C, Lynn-Jones T, Hu H, Fu Z, Feng G, Wang W, Wu S. 2019
Nat Neurosci. 22(8):1223-1234

Neuronal deletion of Gtf2i, a gene in the Williams syndrome critical region, leads to myelination defects that can be rescued by clemastine.
Barak B, Zhang Z, Liu Y, Nir A, Trangle SS, Ennis M, Levandowski KM, Wang D, Quast K, Boulting GL, Li Y, Bayarsaihan D, He Z* and Feng G 2019
Nat Neurosci. 22:700-708.

Two eARCHT3.0 lines for optogenetic silencing of dopaminergic and serotonergic neuron function.
Krol A, Lopez-Huerta VG, Corey TE, Deisseroth K, Ting J, Feng G 2019
Frontiers In Neural Circuits. 13:4

Shank3 mutation in a mouse model of autism leads to changes in the S-nitroso-proteome and affects key proteins involved in vesicle release and synaptic function.
Amal H, Barak B, Bhat V, Gong G, Joughin BA, Wishnok JS, Feng G, Tannenbaum SR. 2018
Mol Psychiatry. doi: 10.1038/s41380-018-0113-6

Dichotomous parvalbumin interneuron populations in dorsolateral and dorsomedial striatum.
Monteiro P, Barak B, Zhou Y, McRae R, Rodrigues D, Wickersham IR, Feng G. 2018
J Physiol. 596:3695-3707.

Combining NGN2 Programming with Developmental Patterning Generates Human Excitatory Neurons with NMDAR-Mediated Synaptic Transmission.
Nehme R, Zuccaro E, Ghosh SD, Li C, Sherwood JL, Pietilainen O, Barrett LE, Limone F, Worringer KA, Kommineni S, Zang Y, Cacchiarelli D, Meissner A, Adolfsson R, Haggarty S, Madison J, Muller M, Arlotta P, Fu Z, Feng G, Eggan K. 2018
Cell Rep. 23(8):2509-2523.

Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice.
Cao W, Lin S, Xia QQ, Du YL, Yang Q, Zhang MY, Lu YQ, Xu J, Duan SM, Xia J, Feng G, Xu J, Luo JH. 2018
Neuron. 97(6) pp. 1394

Thalamic Reticular Dysfunction as a Circuit Endophenotype in Neurodevelopmental Disorders
Krol A, Wimmer RD, Halassa MM, Feng G. 2018
Neuron. 98:282-295.

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. 2017
The Journal of clinical investigation. 127(5) pp. 1978-1990

SHANK proteins: roles at the synapse and in autism spectrum disorder
Monteiro P and Feng G. 2017
Nature Reviews Neuroscience. 18(3) pp. 147-157

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. 2017
Cell Reports. 19(2) pp. 335-350

Animal models for neuropsychiatric disorders: prospects for circuit intervention
Kaiser T, Zhou Y and Feng G. 2017
Current Opinion in Neurobiology. 45 pp.59-65  

A viral strategy for targeting and manipulating interneurons across vertebrate species
Dimidschstein J, Chen Q, Tremblay R, Rogers SL, Saldi GA, Guo L, Xu Q, Liu R, Lu C, Chu J, Grimley JS, Krostag AR, Kaykas A, Avery MC, Rashid MS, Baek M, Jacob AL, Smith GB, Wilson DE, Kosche G, Kruglikov I, Rusielewicz T, Kotak VC, Mowery TM, Anderson SA, Callaway EM, Dasen JS, Fitzpatrick D, Fossati V, Long MA, Noggle S, Reynolds JH, Sanes DH, Rudy B, Feng G, Fishell G. 2016
Nature Neuroscience. 19(12) pp. 1743-1749

Decreased Anxiety-Related Behaviour but Apparently Unperturbed NUMB Function in Ligand of NUMB Protein-X (LNX) 1/2 Double Knockout Mice
Lenihan JA, Saha O, Heimer-McGinn V, Cryan JF, Feng G and Young PW. 2016
Molecular Neurobiology. Nov 2016, doi: 10.1007

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. 2016
Molecular Neurobiology. 5. pii: e18716

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. 2016
Nature Neuroscience. 19(9) pp. 1123-30

Central Mechanisms Mediating Thrombospondin-4-induced Pain StatesAdult restoration of Shank3 expression rescues selective autistic-like phenotypes
Park J, Yu YP, Zhou CY, Li KW, Wang D, Chang E, Kim DS, Vo B, Zhang X, Gong N, Sharp K, Steward O, Vitko I, Perez-Reyes E, Eroglu C, Barres B, Zaucke F, Feng G and Luo ZD. 2016
The Journal of Biological Chemistry. 291(25) pp.13335-48

Optogenetic visualization of presynaptic tonic inhibition of cerebellar parallel fibers
Berglund K, Wen L, Dunbar RL, Feng G and Augustine GJ. 2016
The Journal of Neuroscience. 36(21) pp. 5709-23

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. 2016
Scientific Reports. 6:25888

Neurobiology of social behavior abnormalities in autism and Williams syndrome
Barak B and Feng G. 2016
Nature Neuroscience. 19(6) pp. 647-55

Thalamic reticular impairment underlies attention deficit in Ptchd1(Y/-) mice
Wells MF, Wimmer RD, Schmitt LI, Feng G and Halassa MM. 2016
Nature. 532(7597) pp. 58-63

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. 2016
Nature Communications. 7: pp.10962

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. 2016
Nature. 530(7591) pp. 481-4

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. 2016
The Journal of Neuroscience. 36(7) pp. 2247-60

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. 2016
Neuron. 89(1) pp. 147-62

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. 2016
Biological Psychiatry Cognitive Neuroscience and Neuroimaging. 1(1) pp. 39-48

Learning from animal models of obsessive-compulsive disorder
Monteiro P and Feng G. 2016
Biological Psychiatry. 79(1) pp. 7-16

Modeling psychiatric disorders for developing effective treatments
Kaiser T and Feng G. 2015
Nature Medicine.  21(9) pp. 979-88

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. 2015
Nature Biotechnology. 33(5) pp. 478-86

Striatal circuits, habits, and implications for obsessive-compulsive disorder
Burguière E, Monteiro P, Mallet L, Feng G and Graybiel AM. 2015
Current Opinion in Neurobiology. 30 pp. 59-65