Adam Douglass, PhD
Languages spoken: English
Departments: Neurobiology - Associate Professor
Academic Office Information
- Neuronal Circuits
Despite their relatively small numbers, modulatory neurons contribute to an overwhelming number of essential behaviors. My lab exploits the relative simplicity of the larval zebrafish brain to understand how neurons that produce the neuromodulators dopamine and oxytocin shape locomotion, pain processing, learning, and social behavior, and in the process derive general principles for the operation of modulatory circuits. There are currently three, specific projects in the lab.
Dopaminergic control of locomotion
Normal dopamine function is essential for locomotion in all vertebrates. We have discovered that a population of dopamine neurons in the fish hypothalamus, defined by expression of tyrosine hydroxylase 2, is strongly activated during all forms of swimming behavior and promotes movement by sensitizing locomotor networks to sensory input. We are using a combination of molecular, microscopic, and optogenetic techniques to identify the targets of these neurons and describe how dopamine signaling shapes their activity to control locomotor output.
Oxytocin and pain processing
Although better known for its social functions, the modulatory neuropeptide oxytocin is central to many aspects of pain-related behavior. In collaboration with Caroline Wee and Florian Engert (Harvard University), we have discovered that acute activation of oxytocin neurons by painful stimuli promotes defensive swimming. We now seek to understand how coordinated oxytocin and glutamate release from these neurons affects downstream locomotor targets to elicit such specific behavior.
Danionella translucida: A new fish model for systems neuroscience
The zebrafish has become a popular experimental model owing largely to its transparency during larval stages of development, which enables optical interrogation of every neuron in the brain. However, larval fish are behaviorally immature, making social behavior, reward learning, and other important phenomena impossible to study. To investigate these behaviors using the full repertoire of imaging and optogenetic techniques, we are developing the zebrafish relative Danionella translucida as an experimental model. These fish are pedomorphic, remaining small (~10 mm long) and optically transparent into adulthood. The establishment of molecular, behavioral, and optical techniques in this species will allow us to understand how oxytocin and other modulators shape a variety of sophisicated behaviors.
University of California, San Francisco, Tetrad Graduate Program
- Wee CL, Nikitchenko M, Wang WC, Luks-Morgan SJ, Song E, Gagnon JA, Randlett O, Bianco IH, Lacoste AMB, Glushenkova E, Barrios JP, Schier AF, Kunes S, Engert F, Douglass AD (2019). Zebrafish oxytocin neurons drive nocifensive behavior via brainstem premotor targets. Nat Neurosci, 22(9), 1477-1492.
- Julien DP, Chan AW, Barrios J, Mathiaparanam J, Douglass A, Wolman MA, Sagasti A (2018). Zebrafish expression reporters and mutants reveal that the IgSF cell adhesion molecule Dscamb is required for feeding and survival. J Neurogenet, 32(4), 336-352.
- Gao J, Stevenson TJ, Douglass AD, Barrios JP, Bonkowsky JL (2018). The Midline Axon Crossing Decision Is Regulated through an Activity-Dependent Mechanism by the NMDA Receptor. eNeuro, 5(2).
- Schoppik D, Bianco IH, Prober DA, Douglass AD, Robson DN, Li JMB, Greenwood JSF, Soucy E, Engert F, Schier AF (2017). Gaze-Stabilizing Central Vestibular Neurons Project Asymmetrically to Extraocular Motoneuron Pools. J Neurosci, 37(47), 11353-11365.
- Cohen AE, Douglass AD, Kralj JM (2015). Optogenetic Probes for Measuring Membrane Potential. U.S. Patent No. US 9,057,734 B2. Washington, D.C.:U.S. Patent and Trademark Office.
- Kralj JM, Douglass AD, Hochbaum DR, Maclaurin D, Cohen AE (2012). Optical recording of action potentials in mammalian neurons using a microbial rhodopsin. Nat Methods, 9(1), 90-5.
- Kralj JM, Hochbaum DR, Douglass AD, Cohen AE (2011). Electrical spiking in Escherichia coli probed with a fluorescent voltage-indicating protein. Science, 333(6040), 345-8.
- Kaizuka Y, Douglass AD, Vardhana S, Dustin ML, Vale RD (2009). The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells. J Cell Biol, 185(3), 521-34.
- Douglass AD, Kraves S, Deisseroth K, Schier AF, Engert F (2008). Escape behavior elicited by single, channelrhodopsin-2-evoked spikes in zebrafish somatosensory neurons. Curr Biol, 18(15), 1133-7.
- Douglass AD, Vale RD (2008). Single-molecule imaging of fluorescent proteins. Methods Cell Biol, 85, 113-25.
- Kaizuka Y, Douglass AD, Varma R, Dustin ML, Vale RD (2007). Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cells. Proc Natl Acad Sci U S A, 104(51), 20296-301.
- Dustin ML, Starr T, Coombs D, Majeau GR, Meier W, Hochman PS, Douglass A, Vale R, Goldstein B, Whitty A (2007). Quantification and modeling of tripartite CD2-, CD58FC chimera (alefacept)-, and CD16-mediated cell adhesion. J Biol Chem, 282(48), 34748-57.
- Mahoney NM, Goshima G, Douglass AD, Vale RD (2006). Making microtubules and mitotic spindles in cells without functional centrosomes. Curr Biol, 16(6), 564-9.
- Finn DA, Douglass AD, Beadles-Bohling AS, Tanchuck MA, Long SL, Crabbe JC (2006). Selected line difference in sensitivity to a GABAergic neurosteroid during ethanol withdrawal. Genes Brain Behav, 5(1), 53-63.
- Douglass AD, Vale RD (2005). Single-molecule microscopy reveals plasma membrane microdomains created by protein-protein networks that exclude or trap signaling molecules in T cells. Cell, 121(6), 937-50.
- Tooley AJ, Jacobelli J, Moldovan MC, Douglas A, Krummel MF (2005). T cell synapse assembly: proteins, motors and the underlying cell biology. [Review]. Semin Immunol, 17(1), 65-75.
- Douglass AD, Vale RD (2005). Single molecule imaging in living cells by total internal reflection fluorescence microscopy. In Cell Biology: A Laboratory Handbook (3rd, pp. 129-136). London: Elsevier Science.
- Collins SR, Douglass A, Vale RD, Weissman JS (2004). Mechanism of prion propagation: amyloid growth occurs by monomer addition. PLoS Biol, 2(10), e321.