- Cutting edge Seminar
Speaker: Masahiko Hibi (Professor, Graduate School of Science, Nagoya University)
Title: Deciphering development and function of the cerebellum using zebrafish
Date&Time: 2 July (wed) 12：00-13：00
Venue: Conference Room(1F), IMEG, Kumamoto University
※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.
https://md.kumamoto-u.ac.jp/course/view.php?id=120331
Abstract:
The cerebellum is essential for smooth motor control and motor learning, and is increasingly recognized for its roles in cognition and emotion. In cerebellar circuits, granule cells and Purkinje cells—the principal neuronal types—receive extracerebellar inputs. These inputs are integrated by Purkinje cells, which send output signals to downstream targets via cerebellar output neurons. GABAergic interneurons further modulate the activity of granule and Purkinje cells. This basic circuit architecture is widely conserved across vertebrates. In this seminar, I will present our recent analyses of cerebellar neurogenesis and function using the zebrafish model.
Cerebellar neurons differentiate from neural progenitor cells expressing proneural genes such as ptf1a, neurog1, and atoh1. While mammalian studies suggest these genes specify distinct lineages, our findings in zebrafish reveal that multiple cerebellar neuron types—including Purkinje cells, GABAergic interneurons, and granule cells—can differentiate from progenitors co-expressing ptf1a and neurog1. We identified transcription regulators from the Foxp and Skor families as key determinants of Purkinje cell specification. I will describe the mechanisms by which diverse cerebellar neurons differentiate from common progenitors.
The cerebellum also contributes to associative learning, including fear conditioning. When animals are repeatedly exposed to a neutral conditioned stimulus (e.g., visual cue) paired with an aversive unconditioned stimulus such as an electric shock, they learn to associate them and eventually show avoidance in response to the conditioned stimulus alone. Using zebrafish in which granule cells or Purkinje cells are selectively inhibited by botulinum toxin, or in which Purkinje cells are ablated, we showed that cerebellar circuits are involved in active avoidance learning. Disruptions in these circuits are increasingly linked to neuropsychiatric conditions such as autism spectrum disorder. Our work also suggests a role for the zebrafish cerebellum in regulating orienting behavior, a model for social responses.
Finally, I will introduce our ongoing efforts to dissect cerebellar circuit dynamics during fear learning, using in vivo Ca²⁺ imaging and optogenetics in a virtual reality setup. I will present our latest findings and discuss their implications for understanding cerebellar contributions to adaptive behavior.
References:
1.Itoh T, Uehara M, Yura S, Wang JC, Fujii Y, Nakanishi A, Shimizu T, and Hibi M. Foxp and Skor family proteins control differentiation of Purkinje cells from Ptf1a- and Neurog1-expressing progenitors in zebrafish. Development 151(7): dev202546 (2024).
2.Hosaka S, Hosokawa M, Hibi M, and Shimizu T. The Zebrafish Cerebellar Neural Circuits Are Involved in Orienting Behavior. eNeuro 11(10): ENEURO.0141-24.2024 (2024).
3.Hagio H, Koyama W, Hosaka S, Song AD, Narantsatsral J, Matsuda K, Shimizu T, Hososhima S, Tsunoda SP, Kandori H, Hibi M. Optogenetic manipulation of neuronal and cardiomyocyte functions in zebrafish using microbial rhodopsins and adenylyl cyclases. eLife 12: e83975 (2023).
4.Hagio H, Koyama W, Hosaka S, Song AD, Narantsatsral J, Matsuda K, Sugihara T, Shimizu T, Koyanagi M, Terakita A, Hibi M. Optogenetic manipulation of Gq- and Gi/o-coupled receptor signaling in neurons and heart muscle cells. eLife 12: e83974 (2023).
5.Koyama W, Hosomi R, Matsuda K, Kawakami K, Hibi M, Shimizu T. Involvement of Cerebellar Neural Circuits in Active Avoidance Conditioning in Zebrafish. eNeuro 8(3): ENEURO.0507-20.2021 (2021).
6.Itoh T, Takeuchi M, Sakagami M, Asakawa K, Sumiyama K, Kawakami K, Shimizu T, Hibi M. Gsx2 is required for specification of neurons in the inferior olivary nuclei from Ptf1a-expressing neural progenitors in zebrafish. Development 147(19): dev190603 (2020).
