The Hige Lab | Drosophila Neurophysiology

The

Hige Lab

From synaptic plasticity to behavior

UNC-Chapel Hill

Research

How do animals make appropriate action selections based on their past experience and the current situation?

We use the small, simple brains of fruit flies to draw out general circuit principles that underlie this process. We combine multiple physiological techniques to study synapses, circuits and behavior.

Our mission

Animals show different behavioral responses to the same sensory input depending on their past experience or current context. How does the brain enable such flexibility? Our goal is to understand the mechanisms of this process at the levels of synaptic plasticity, neural circuit and behavior. Our lab uses the fruit fly, Drosophila melanogaster, as a model organism. We employ multiple physiological techniques including in vivo whole-cell patch-clamp recording, two-photon calcium imaging and behavior assays. Previously, we demonstrated the long-term synaptic plasticity that underlies associative olfactory learning in this system (Hige et al., 2015, Neuron). We ask how these synaptic changes are integrated by the circuit and ultimately alter the animal’s action selection. We also address molecular basis of synaptic plasticity by using genetic tools.

Why flies?

The Drosophila’s brain consists of 100,000 neurons, 1000 times less than the mouse’s. Nonetheless, some of the important circuit motifs are conserved between these animals both in sensory circuits and higher-order brain areas. With this small brain, flies indeed exhibit a range of sophisticated adaptive behaviors. Furthermore, genetic tools that label a specific cell type of neurons are becoming available in nearly every brain area. This allows us to record from a particular neuron reproducibly in different animals as well as to manipulate the activity of as small as a single pair of neurons in behaving animals. Finally, the whole-brain connectome data is becoming available. Overall, the compact architecture of the brain together with the enormous community effort in the field collectively makes Drosophila an extremely attractive model system for systems neuroscience. We believe that our goal of linking synaptic plasticity to behavior by understanding circuit logic at each relay would be a finite, rather than infinite, endeavor in this system.

People

Toshihide Hige, Ph.D

hige@email.unc.edu

Principal Investigator

Toshi received his Ph.D. from Kyoto University in Japan, where he studied synaptic physiology using rat brain slices. He switched to the Drosophila system when he started his postdoc in Glenn Turner's lab at Cold Spring Harbor Laboratory (and later at Janelia Research Campus). While in the lab, Toshi enjoys one-to-one conversations with a neuron through a glass pipette. When outside the lab, he is constantly looking for an opportunity to eat good food.

Visiting Scientist

People

Toshihide Hige, Ph.D

Principal Investigator

hige@email.unc.edu

Chad Heer, Ph.D

Postdoctoral Fellow

Chad completed his PhD at The University of Chicago in the lab of Dr. Mark Sheffield, where he used in-vivo imaging techniques to characterize the activity of dopaminergic inputs to the hippocampus during spatial navigation and learning. As a part of the Hige lab, he is excited to use imaging techniques, genetic approaches, and behavioral assays to dissect the neural circuits underlying behavior in Drosophila. Chad enjoys spending his time outside of the lab baking pizza, playing videogames, and hiking with his girlfriend and their dog.

Debapriya Ghosh, MS

Graduate Student (QBio)

Debapriya completed her Master's in Chemical and Molecular Biology from Indian Institute of technology Kharagpur. She previously studied the cerebellar circuit in zebrafish larvae in National Centre for Biological Sciences, Bangalore. Her broad research interests are to understand the physiological basis underlying the emergence of behavior in an animal. Outside lab, Debapriya engages in the art of Bharatanatyam dance and loves listening to Indian classical music.

Thomas Moonjeli, BA

Research Technician

Thomas received his bachelor's in biology from Berea College, a liberal arts college in Kentucky. His research interests align with the lab's focus on studying the biological mechanisms behind behavioral learning and adaptation. He has previous experience studying the development of digenetic trematodes in largemouth bass and is passionate about integrating his knowledge in biology, chemistry, and math to contribute to the understanding of the brain. Outside the lab, Thomas is an avid photographer with expertise in light painting and B&W photography. He also enjoys cooking new cuisines and playing badminton.

Hannah-Marie Santos

Undergraduate Student

Hannah-Marie is an undergraduate at the University of North Carolina at Chapel Hill, studying Neuroscience & Women's and Gender Studies. Previously, Hannah-Marie was at the Garcia Lab where she used immunohistochemistry and flow cytometry to characterize next-generation mouse models. She also spent time in the Reiser Lab at Janelia Research Campus, exploring visual pathways in Drosophila melanogaster using optogenetic control of neuron activity and virtual reality. After graduation, Hannah-Marie hopes to pursue a PhD in neuroscience. Outside the lab, Hannah-Marie enjoys crocheting and playing video games with her friends and family.

Angela Liu

Undergraduate Student

Angela is an undergraduate student majoring in Neuroscience and Psychology at UNC-Chapel Hill. She previously used EEG techniques to study the neuroendocrine factors that mood across the female reproductive lifespan at the NERD/SHAARP Lab. Angela is also involved in epidemiology research, studying cancer prevention, incidence, and survival. Currently, she is most interested in delving into neuroscience at the microscale in the Hige Lab, specifically the interplay between behavior and synaptic plasticity. Outside the lab, Angela enjoys playing piano, reading books, and watching animated films.

This could be you!

Postdoctoral fellow or Ph.D. student

We are looking for enthusiastic people to join our lab! Please see the detail here.

Former Members

Audra Hawley (Kenan Fellow)
Drew Davidson (Postdoctoral Fellow)
Daichi Yamada (Postdoctoral Fellow)
Christine Sudzina Schut (Kenan Fellow)
Will Silander (Research Technician)
Emily Simpson (Kenan Fellow)
Shivam Kaushik (Graduate Student/QBio)
Robyn Stanek-Dembisky (Kenan Fellow)
Aneesh Purohit (Undergraduate Student)
Samantha Chery (Rotation Student)
Carlotta Martelli (Visiting Scientist)

Publications

*(co-)corresponding author

Genetic and circuit mechanisms underlying natural variation in value-based decision making
Motevalli, D., Alfredson, R., Fogleman, S., Medrano, E., Silander, W.I., Hige, T., Dickson, B., Stern, U. and Yang, C-H.
bioRxiv. (2025) – preprint –

A lightweight data-driven spiking neural network model of Drosophila olfactory nervous system with dedicated hardware support
Nanami, T., Yamada, D., Someya, M., Hige, T., Kazama, H., and Kohno, T.
Front. Neurosci. 18, 1384336 (2024)
– preprint published in bioRxiv on 10/13/2023

Roles of feedback and feed-forward networks of dopamine subsystems: insights from Drosophila studies
Davidson, A.M. and Hige, T.*
Learn. Mem. 31, a053807 (2024)

Cyclic nucleotide-induced bidirectional long-term synaptic plasticity in Drosophila mushroom body
Yamada, D., Davidson, A.M., and Hige, T.*
J. Physiol. 602, 2019-2045. (2024)

– preprint published in bioRxiv on 9/29/2023

Dopamine-dependent plasticity is heterogeneously expressed by presynaptic calcium activity across individual boutons of the Drosophila mushroom body

Davidson, A.M., Kaushik, S., and Hige, T.*

eNeuro ENEURO.0275-23.2023 (2023)

Neural circuit mechanisms for transforming learned olfactory valences into wind-oriented movement

Aso, Y.*, Yamada, D., Bushey, D., Hibbard, K., Sammons M., Otsuna H., Shuai, Y., and Hige, T.*

Elife e85756. (2023)

– preprint published in bioRxiv on 12/22/2022

Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila

Yamada, D., Bushey, D., Li, F., Hibbard, K., Sammons, M., Funke, J., Litwin-Kumar, A., Hige, T.*, and Aso, Y.*

Elife e79042. (2023)

– preprint published in bioRxiv on 3/31/2022

Lateral axonal modulation is required for stimulus-specific olfactory conditioning in Drosophila

Manoim, J.E., Davidson, A.M., Weiss, S., Hige, T.*, and Parnas, M.*

Curr. Biol. 32, 4438-4450.e5. (2022)

– preprint published in bioRxiv on 6/3/2022

What can tiny mushrooms in fruit flies tell us about learning and memory?

Hige, T.*

Neurosci. Res. 129, 8-16. (2018)

A connectome of a learning and memory center in the adult Drosophila brain.

Takemura, S-Y., Aso, Y., Hige, T., Wong, A., Lu, Z., Xu, C.S., Rivlin, P.K., Hess, H.F., Zhao, T., Parag, T., Berg, S., Huang, G., Katz, W., Olbris, D.J., Plaza, S., Umayam, L., Aniceto, R., Chang, L-A., Lauchie, S., Ogundeyi, O., Ordish, C., Shinomiya, A., Sigmund, C., Takemura, S., Tran, J., Turner, G.C., Rubin, G.M., and Scheffer, L.K.

Elife e26975. (2017)

Direct neural pathways convey distinct visual information to Drosophila mushroom bodies.

Vogt, K., Aso, Y., Hige, T., Knapek, S., Ichinose, T., Friedrich A.B., Turner, G.C., Rubin, G.M., and Tanimoto H.

Elife e14009. (2016)

Heterosynaptic plasticity underlies aversive olfactory learning in Drosophila.

Hige, T.*, Aso, Y., Modi, M.N., Rubin, G.M., and Turner, G.C*.

Neuron 88, 985-998. (2015)

Plasticity-driven individualization of olfactory coding in mushroom body output neurons.

Hige, T., Aso, Y., Rubin, G.M., and Turner, G.C.

Nature 526, 258-262. (2015)

Learning: The good, the bad, and the fly.

Hige, T., and Turner, G.C.