Professor, Parsons Endowed Chair
-
whatshotResearch Description
Since the first description of ‘critical periods’ in the 1930’s, neuroscientists have sought methods to manipulate them for therapeutic benefit. In parallel, early interest in psychedelics has been reinvigorated by recent clinical successes with these compounds, although to date the mechanisms underlying their therapeutic effects remain largely unknown. My lab has made a series of discoveries (Dölen, et al Nature, 2013; Edsinger and Dölen, Current Biology, 2018; Nardou et al, Nature2019; Nardou et al., Nature, 2023) which indicate that psychedelics may be the long sought “master key” for unlocking critical periods; furthermore, this property may explain the wide diversity of psychiatric applications for which psychedelics show therapeutic promise. Building on these insights, we are currently working to delineate the mechanisms underlying the shared ability of psychedelics to reopen critical periods and expand the repertoire of clinical conditions they can be used to treat. Specifically, we are examining how psychedelics induce degradation of the extracellular matrix and how context supervises the selection of the appropriate critical period for reopening. In a parallel set of studies, we have made significant progress towards developing Octopus chierchiae for use in laboratory research. Specifically, we have closed the life cycle, enabling us to breed and raise octopuses in a laboratory setting for the first time (Grearson, et al., 2021). We have also completed whole genome sequencing, assembly, and annotation in this species, enabling modern molecular manipulations and the discovery of novel genetic mechanisms (Albertin, et al., in preparation). Together these resources will enable us to understand why critical periods exist, why they close, and why they can be reopened, by comparing solutions across human, mouse, and octopus nervous systems.
-
placeSelected Publications
Nardou R., Sawyer E., Song Y.J., Wilkinson M., Padovan-Hernandez Y., de Deus J.L., Wright N., Lama C., Faltin S., Goff L.A., Stein-O’Brien G.L., and Dölen G. Psychedelics reopen the critical period for social reward learning. Nature 2023. DOI: 10.1038/s41586-023-06204-3
Hayes LN, An K, Carloni E, Li F, Vincent E, Trippaers C, Paranjpe M, Dölen G, Goff LA, Ramos A, Kano S, Sawa A. Prenatal immune stress blunts microglia reactivity, impairing neurocircuitry. Nature 2022. DOI: https://doi.org/10.1038/s41586-022-05274-z.
Grearson A, Dugan A, Sakmar T, Sivitilli, DM, Gire DH, Caldwell RL, Niell CM, Dölen G, Wang ZY, Grasse B. The lesser Pacific striped octopus, Octopus chierchiae: an emerging laboratory model for the study of octopuses. Frontiers in Marine Science 2021. DOI: 10.3389/fmars.2021.753483
Lewis E.M, Stein-O'Brien G.L., Patino A.V., Nardou R., Grossman C.D., Brown M., Bangamwabo B., Ndiaye N., Giovinazzo D., Dardani I., Jiang C., Goff L.A., & Dölen G. Parallel Social Information Processing Circuits Are Differentially Impacted in Autism.Neuron. 2020 (in press). doi: 10.1016/j.neuron.2020.10.002. Epub 2020 Oct 27,2020. PMID: 33113347
Nardou R, Lewis EM, Rothhaas R, Xu R, Yang A, Boyden E, & Dölen G. Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Nature. 2019 May;569(7754):116-120. doi: 10.1038/s41586-019-1075-9. Epub 2019 Apr 3.PMID: 30944474
Edsinger, E and Dölen G. A conserved role for serotonergic neurotransmission in mediating social behavior in octopus.Current Biology. 2018 October 8; 28: 1–7. PMID: 30245101
Dölen G. Mindreading emerged at least twice in the course of evolution. In Linden, D.J., ed. Think Tank: Forty Curious Neuroscientists Explain the Biological Roots of Human Experience. Yale University Press (April 2018). ISBN: 9780300225549. Library (Worldcat.org)
Hung LW, Neuner S, Polepalli JS, Beier K, Wright M, Walsh J, Lewis E, Luo L, Deisseroth K , Dölen G, Malenka, RC. Gating of social reward by oxytocin in the ventral tegmental area. Science. 2017 Sep 29;357(6358):1406-1411. PMID: 28963257
Dölen G, Setting the mood for love. Nature Neuroscience. 2017 Feb 23;20(3):379-380. PMID: 28230842
Dölen G, and Sahin M Editorial: Essential Pathways and Circuits of Autism Pathogenesis.2016 Apr 26;10:182. Frontiers in Neuroscience. PMCID: PMC4844597
Lammel S,Dölen G,and Malenka RC. Optogenetic Approaches to Neural Circuit Analysis in the Mammalian Brain. In Lehner T, Miller BL, and State MW, eds. Genomics, Circuits, and Pathways in Clinical Neuropsychiatry. Elsevier, Inc. 2016. ISBN: 9780128001059
Dölen G, Autism: oxytocin, serotonin, and social reward.Social Neuroscience. 2015 Aug 28. PMID: 26317636
Dölen G, Malenka RC, Perlumutter JS, Brose N, Frackowiak R, Cuthbert BN, Diester I, Mansuy I, Kroker, KS, Boekers TM, Pascual-Leone A, Feng G. Pathophysiological Toolkit: Genes to Circuits. In Nikolich, K. and S. E. Hyman, eds. Translational Neuroscience: Toward New Therapies. Strüngmann Forum Reports, vol. 17, J. Lupp, series editor. Cambridge, MA: MIT Press, 2015. ISBN: 9780262029865.
Diester I, Hefti F, Mansuy I, Pascual-Leone A, Robbins TW, Rubin LL, Sawa A, Wernig M, Dölen G, Hyman SE, Mucke L, Nikolich K, and Sommer B. Bridging the Gap between Patients and Models. In Nikolich, K. and S. E. Hyman, eds. Translational Neuroscience: Toward New Therapies. Strüngmann Forum Reports, vol. 17, J. Lupp, series editor. Cambridge, MA: MIT Press, 2015. ISBN: 9780262029865.
Dölen G.Oxytocin: parallel processing in the social brain?Journal of Neuroendocrinology.2015 Jun;27(6):516-35. PMID: 25912257
Dölen G, Malenka RC. The emerging role of nucleus accumbens oxytocin in social cognition. Biological Psychiatry. 2014 Sep 1;76(5):354-5. PMID: 25103539
Dölen G, Darvishzadeh A, Huang KW, Malenka, RC. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 2013 Sep 12;501(7466):179-84. PMID: 24025838
Portmann T, Yang M, Mao R, Panagiotakos G, Ellegood J, Dölen G, Bader PL, Grueter BA, Goold C, Fisher E, Clifford K, Rengarajan P, Kalikhman D, Loureiro D, Saw NL, Zhengqui Z, Miller MA, Lerch JP, Henkelman RM, Shamloo M, Malenka RC, Crawley JN, and Dolmetsch RE. Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome. Cell Rep. 2014 May 22;7(4):1077-92. PMID: 24794428
Bhakar AL, Dölen G, Bear MF. The pathophysiology of fragile X (and what it teaches us about synapses). Annu Rev Neurosci. 2012;35:417-43. PMID: 22483044
Dölen G, Carpenter RL, Ocain TD, Bear MF. Mechanism-based approaches to trating fragile X. Pharmacol Ther. 2010 Jul;127(1):78-93. PMID: 20303363
Dölen G, Bear MF. Fragile X syndrome and autism: from disease model to therapeutic targets. J Neurodev Disord. 2009 Jun;1(2):133-40 PMID: 21547712
Dölen G, Bear MF. Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome. J Physiol. 2008 Mar 15;586(6):1503-8. PMID: 18202092
Bear MF, Dölen G, Osterweil E, Nagarajan N. Fragile X: translation in action. Neuropsychopharmacology. 2008 Jan;33(1):84-7. PMID: 17940551
Dölen G, Osterweil E, Rao BS, Smith GB, Auerbach BD, Chattarji S, Bear MF. Correction of fragile X syndrome in mice. Neuron. 2007 Dec 20;56(6):955-62. PMID: 18093519
Dölen G, Bear MF. Courting a cure for fragile X. Neuron. 2005 Mar 3;45(5):642-4. PMID: 15748838
Herrera E, Brown L, Aruga J, Rachel RA, Dölen G, Mikoshiba K, Brown S, Mason CA. Zic2 patterns binocular vision by specifying the uncrossed retinal projection. Cell. 2003 Sep 5;114(5):545-57. PMID: 13678579
Rachel RA, Dölen G, Hayes NL, Lu A, Erskine L, Nowakowski RS, Mason CA. Spatiotemporal features of early neuronogenesis differ in wild-type and albino mouse retina. J Neurosci. 2002 Jun 1;22(11):4249-63. PMID: 12040030
-
filter_dramaTeaching