We are interested in understanding the mechanisms of sensory perception and behavior. Our studies focus on how animals sense and respond to climatic variables, particularly temperature, and our goal is to understand the mechanisms underlying thermosensory behaviors from the molecular to the systems level. In addition to addressing fundamental issues in neuroscience, the study of thermosensory behavior is also of practical importance. The molecules controlling thermosensation are important for pain and inflammation in humans, so that molecular insights into temperature processing will be relevant to the treatment of diseases ranging from asthma and arthritis to chronic pain. Thermosensory behavior is also of ecological importance, as thermal preference and tolerance are important for an animal’s adaptability to different ecological niches. A molecular to systems level understanding of thermosensory behavior will help uncover the mechanisms that determine animal distributions on Earth and how animals adapt to climate variation and climate change.
Using the fruit fly Drosophila melanogaster as our primary model system, we study how animals avoid extreme temperatures and seek out preferred temperatures. We are also studying how these behavioral responses vary among populations and species. To achieve an understanding of thermosensory behavior and its evolution that extends from the molecular to systems levels, we use a combination of experimental approaches that includes Drosophila molecular genetics, comparative genomics, in vivo monitoring of neuronal activity, and ion channel electrophysiology.
Projects in the lab address three main topics:
1) The molecular mechanisms of temperature perception and thermosensory behavior. We are using molecular genetics and physiology in the fruit fly Drosophila melanogaster to study the molecular mechanisms through which thermosensory neurons sense temperature with precision. A significant focus of this work involves evolutionarily conserved TRP family cation channels, such as dTRPA1, the Drosophila ortholog of the human TRPA1 protein. Temperature activated TRP channels like dTRPA1 have the remarkable ability to
function as molecular thermometers, opening at specific threshold temperatures to depolarize the neurons that express them and mediate behavioral responses to temperature. We are investigating the molecular mechanisms that underlie the temperature-sensing ability of these channels. We are also using fly genetics to identify molecules that regulate the activity of these channels and molecules that function downstream of these thermal sensors in the transmission of thermosensory information. Work in our lab indicates that the molecules regulating thermosensory behavior in fruit flies are closely related to the molecules that control pain and inflammation in humans. Thus, we anticipate that these molecular investigations will not only be important for understanding how animals respond to their terrestrial environments, they will yield insights of direct relevance to the treatment of human pain and inflammation. A spin-off from this work has been the development of dTRPA1 as a tool for the remote-control manipulation of neuronal activity. dTRPA1 expression is sufficient to convert cells into warmth activated thermosensors; thus ectopic expression of dTRPA1 in selected sets of neurons provides a simple molecular genetic approach for cell-specific activation of neurons in intact, behaving animals.
2) Thermosensory circuit function. Using a combination of molecular genetics, physiology and behavior, we are investigating how the neural circuits responsible for thermosensory behavior process subtly graded thermosensory information to produce robust thermotactic responses. We have identified small populations of neurons that act as fly thermosensory neurons and are pursuing the neural circuits through which these thermosensors trigger avoidance of excessive warmth and cold. In addition, in collaborative work with physicist Aravi Samuel’s lab at Harvard, the quantitative approaches previously used to describe phenomena like bacterial chemotaxis are applied to de-construct the fly’s thermotactic behavior into its core strategic elements. This work provides a mechanistic depiction of thermotactic behavior and a precise quantitative framework for dissecting the neural circuits controlling thermosensory behavior.
3) Natural variation and evolution of thermosensory behavior. Using molecular and genetic studies combined with physiology and behavior, we are investigating the nature of intra- and inter-species variation in temperature sensing. We are investigating how thermal sensors have been altered over the course of animal evolution, studying the molecular and physiological properties of temperature sensors in species from across the biosphere, from malaria mosquitoes to cactus-dwelling fruit flies to marine invertebrates. We are also interested in natural variation in thermosensory behavior among Drosophila melanogaster populationsfrom different climates. Together these studies probe the molecular basis of the adaptation of behavior in response to differences in climate.
Garrity PA. Weakly acidic, but strongly irritating: TRPA1 and the activation of nociceptors by cytoplasmic acidification. J Gen Physiol. 2011 Jun;137(6):489-91. [abstract]
Glauser DA, Chen WC, Agin R, Macinnis BL, Hellman AB, Garrity PA, Tan MW, Goodman MB. Heat avoidance is regulated by transient receptor potential (TRP) channels and a neuropeptide signaling pathway in Caenorhabditis elegans. Genetics. 2011 May;188(1):91-103. [abstract]
Garrity PA. (2010) Feel the light. Nature, 968, 900-901. [abstract]
Neely CG, Hess A, Costigan M, Keene AC, Belfer I, Dai F, Gupta V, Xia C, Amann S, Kreitz S, Heindl-Erdmann C, Ly CV, Arora S, Sarangi R, Dan D, Novatchkova M, Rosenzweig M, Truong D, Schramek D,. Zoranovic T, Cronin SJF, Angjeli B, Brune K, Dietzl, . Pospisilik JA, Meixner A, Thomas W, Subramaniam S, Garrity PA, Bellen HJ, Woolf CJ, and Penninger JM. (2010) A genome-wide Drosophila pain screen identifies alpha2delta3 as an evolutionarily conserved pain gene. Cell, 143, 628-38. [abstract]
Garrity PA, Goodman MB, Samuel AD, Sengupta P. (2010) Running hot and cold: behavioral strategies, neural circuits and the molecular machinery for thermotaxis in C. elegans and Drosophila. Genes and Development, 24, 2365-2382. [abstract]
Panzano VC, Kang K, and Garrity PA. (2010) Infrared snake eyes: TRPA1 and the thermal sensitivity of the snake pit organ. Science Signaling, 3, pe22. [abstract]
Kang K, Pulver SR, Panzano VC, Chang EC, Griffith LC, Theobald DL and Garrity PA. (2010) Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception. Nature, 464, 597-600. [abstract] (Minireview: L. Macpherson and A. Patapoutian. (2010) "Channels: Flies feel your pain", Nature Chemical Biology, 6, 252-253 [article]; "On the hunt of what makes all of us recoil", Boston Globe [article]).
Luo L, Gershow M, Fang-Yen C, Rosenzweig M, Kang K, Garrity PA*, and Samuel AD*. (2010) Navigational decision-making in
Drosophila thermotaxis. J. Neuroscience, 30, 4261-4272. (*joint corresponding authors) [article]
Pulver SR, Pashkovski S, Hornstein NJ, Garrity PA, and Griffith LC. (2009) Temporal dynamics of neuronal activation by
Channelrhodopsin-2 and TRPA1 determine behavioral output in Drosophila larvae. Journal of Neurophysiology, 101, 3075-3088. [abstract]
Dillon ME, Wang G, Garrity PA, and Huey RB. (2009) Thermal
preference in Drosophila. Journal of Thermal Biology, 2009 Apr 1;34(3):109-119. [abstract]
Parisky KM, Agosto J, Pulver SR, Shang Y, Kuklin E,
Hodge JL, Kang K, Liu X, Garrity PA, Rosbash M and
Griffith LC. (2008) PDF cells are a GABA-responsive wake-promoting
component of the Drosophila sleep circuit. Neuron, 26, 672-681. [abstract]
Rosenzweig M, Kang K, and Garrity PA. (2008) Distinct TRP
channels are required for warm and cool avoidance in Drosophila
melanogaster. PNAS, 105, 14668-14673. [abstract]
Hamada FN, Rosenzweig M, Kang K, Pulver SR, Ghezzi A, Jegla TJ, Garrity PA. An internal thermal sensor controlling temperature preference in Drosophila. Nature. 2008 Jul 10;454(7201):217-20. Epub 2008 Jun 11. [abstract]
Garrity PA. (2007) The role of adaptation in C. elegans thermotaxis. Focus on "Short-term adaptation and temporal processing in the cryophilic response of Caenorabditis elegans". J. Neurophysiology. 2007 Mar;97(3):1874-6. [abstract]
Whited J, Robichaux M, Yang JC, and Garrity PA. (2007)
PTPMEG is required for the proper establishment and maintenance
of axon branches in the Drosophila central brain. Development, 134, 43-53. [full
Khodosh R, Augsburger A, Schwarz TL, Garrity PA. (2006)
Bchs, a BEACH domain protein, antagonizes Rab11 in synapse
morphogenesis and other developmental events. Development,133,4655-65.
Garrity PA (2005). Tinkers to Evers to Chance: Semaphorin
signaling takes teamwork. Nature Neuroscience 8,
Rosenzweig M, Brennan K, Tayler TD, Phelps PO, Patapoutian A, and Garrity PA. (2005) The Drosophila ortholog
of TRPA1 regulates thermotaxis. Genes and Development 19:419-424. [abstract]
Tayler TD, Robichaux M, and Garrity PA. (2004). Compartmentalization
of visual centers in the Drosophila brain requires Slit
and Robo proteins. Development 131:5935-5945. [abstract]
Whited J, Cassell A, Broulliette M, and Garrity PA.
(2004). Dynactin is required to maintain nuclear position
within post-mitotic photoreceptor neurons. Development 131:4677-4686. [abstract]
Garrity PA (2003). How neurons avoid derailment. Nature 422, 570-571.
Sears HC, Kennedy CJ, and Garrity PA. (2003). Macrophage-mediated
corpse engulfment is required for normal Drosophila CNS
morphogenesis. Development 130: 3557-3565. [abstract]
T. Tayler and P.A. Garrity (2003). Axon targeting in the
Drosophila visual system. Curr. Opinion Neurobiology 13, 90-95. [abstract]
Whited J and Garrity PA(2002). Specifying axon identity
with Syd-1. Nature Neuroscience. 5, 1107-1108. [full
Rosenzweig M and Garrity PA (2002). Axon targeting meets
protein trafficking: Comm takes Robo to the cleaners. Dev.
Cell 3, 301-302. [abstract]
Last review: August 8, 2011