Seeds, Andrew, PhD

Neural circuits and Behavior

Our research addresses how the nervous system is organized to drive sequences of different movements. We study the grooming behavior of fruit flies because it consists of a stereotyped sequence of leg movements that clean the different body parts. The predictability of the movements provides a great behavioral readout for determining how manipulations to different parts of the nervous system change the behavior. Grooming is of general interest because the neural mechanisms that control sequential behavior are implicated in disorders whereby movements become overrepresented (e.g. obsessive-compulsive disorder). Therefore, we also examine how mutations in specific genes can impact grooming circuitry to understand the etiology of grooming-related disorders.

HOW IS THE GROOMING SEQUENCE ORGANIZED IN THE NERVOUS SYSTEM?

We use fruit flies for our research because of the cutting edge genetic tools that enable us to identify and manipulate the activity of neural circuitry that controls grooming. Using these tools, we test hypotheses about how the sequence is formed. The image below shows our current model that features independently evoked grooming movements that are activated in parallel by dust and selected serially through a hierarchical suppression mechanism.

WHAT NEURAL CIRCUITS DRIVE GROOMING BEHAVIOR?

We use a number of cutting-edge circuit mapping techniques to determine the neural implementations of the grooming sequence. Grooming movements feature highly stereotyped, and often repetitive movements that sweep across the body surface, yet the execution of these movements must be flexible to fulfill particular needs. For example, the grooming duration over which a particular movement is performed can vary in response to particular stimuli such as displacement of the body part, debris, or parasites. Therefore, we also examine grooming neural circuitry as a model for understanding how movements are selected and flexibly controlled.

HOW DO GENETIC DEFECTS CAUSE ABNORMALLY REPETITIVE BEHAVIORS?

Nervous systems produce produce complex sequential behaviors by sequentially selecting specific movements. Importantly, brain regions controlling this selection are implicated in disorders in which movements become abnormally repetitive, such as in obsessive-compulsive disorder (OCD). Because abnormally high levels of grooming occur in animals with mutations in specific genes, grooming may serve as a model of repetitive movement disorders. We combine our tools for studying grooming neural circuitry with the genetic amenability of fruit flies to study how mutations in specific genes can lead to abnormally repetitive grooming.

NIH R01, Puerto Rico Research and Science Trust, NSF CREST

• Eichler K, Hampel S, Alejandro-García A, Calle-Schuler SA, Santana-Cruz A, Kmecova L, Blagburn JM, Hoopfer ED, Seeds AM (2023) Somatotopic organization among parallel sensory pathways that promote a grooming sequence in Drosophila. bioRxiv [Preprint]. 2023 Feb 16:2023.02.11.528119. doi: 10.1101/2023.02.11.528119. PMID: 36798384; PMCID: PMC9934617.
• Court R, Namiki S, Armstrong JD, Börner J, Card G, Costa M, Dickinson M, Duch C, Korff W, Mann R, Merritt D, Murphey RK, Seeds AM, Shirangi T, Simpson JH, Truman JW, Tuthill JC, Williams DW, Shepherd D (2020) A Systematic Nomenclature for the Drosophila Ventral Nerve Cord. Neuron. 2020 Sep 23;107(6):1071-1079.e2. doi: 10.1016/j.neuron.2020.08.005. Epub 2020 Sep 14. PMID: 32931755
• Hampel S, Eichler K, Yamada D, Bock DD, Kamikouchi A, Seeds AM (2020) Distinct subpopulations of mechanosensory chordotonal organ neurons elicit grooming of the fruit fly antennae. Elife. 2020 Oct 26;9:e59976. doi: 10.7554/eLife.59976. PMID: 33103999
• Hampel S, Seeds AM. Decoding neural circuit’s structure and function (2017) Springer. Also in PeerJPreprints, 4:e2354v1.
• Hampel S, McKellar CE, Simpson JH, Seeds AM (2017) Simultaneous activation of parallel sensory pathways promotes a grooming sequence in Drosophila. eLife 6:e28804.
• *Corresponding author. Also in bioRxiv https://doi.org/10.1101/139956.
• Neukomm LJ, Burdett TC, Seeds AM, Hampel S, Coutinho-Budd JC, Farley JE, Wong J, Karadeniz YB, Osterloh JM, AE, Freeman MR. (2017) Axon death pathways converge on Axundead to promote functional and structural axon disassembly. Neuron, 95, 78–91, July 5.
• Seeds AM, Tsui MM, Sunu C, Spana EP, York JD. (2015) Inositol phosphate kinase 2 is required for imaginal disc development in Drosophila. Proc. Natl. Acad. Sci. pii: 201514684. †Equal contributions
• Hampel S, Franconville R, Simpson JH, Seeds AM. (2015) A neural command circuit for grooming movement control. eLife, 10.7554/eLife.08758.
• *Corresponding author
• Seeds AM, Ravbar P, Chung P, Hampel S, Midgley FM, Mensh BD, Simpson JH*. (2014) A suppression hierarchy among competing motor programs drives sequential grooming
• in Drosophila. eLife, 3:e02951.
• Peng H, Chung P, Long F, Qu L, Jenett A, Seeds AM, Myers EW, Simpson JH. (2011) BrainAligner: 3D registration atlases of Drosophila brains. Nature Methods, 8:493-500.
• Seeds AM, Bastidas RJ, York JD. (2005) Molecular definition of a novel inositol polyphosphate metabolic pathway initiated by inositol 1,4,5-trisphosphate 3-kinase activity in Saccharomyces cerevisiae. J. Biol. Chem., 280(30):27654-61.
• Seeds AM, Sandquist JC, Spana EP, York JD. (2004) A molecular basis for inositol polyphosphate synthesis in Drosophila melanogaster. J. Biol. Chem., 5;279 (45): 47222-32.
• Mondal MS, Wang Z, Seeds AM, Rando RR. (2000) The specific binding of small molecule isoprenoids to rhoGDP dissociation inhibitor (rhoGDI). Biochemistry, 18;39(2):406-12.
• Seeds AM, Frederick JP, Tsui MM, York JD. (2007) Roles for inositol polyphosphate kinases in the regulation of nuclear processes and developmental biology. Advances in Enzyme Regulation, 47:10- 25.
• Seeds AM, York JD. (2007) Inositol polyphosphate kinases: Regulators of nuclear function. Biochem.
• Soc. Symp., 74:183-197.
• Stevenson-Paulik, J, Chiou, ST, Frederick, JP, dela Cruz, J, Seeds AM, Otto, JC, York JD. (2006) Inositol phosphate metabolomics: Merging genetic perturbation with modernized radiolabeling methods. Methods, 39: 112-121.