第1312回生物科学セミナー

NeuroPAL: A Neuronal Polychromatic Atlas of Landmarks for Whole-Brain Imaging in C. elegans

Dr. Eviatar Yemini(Howard Hughes Medical Institute & Department of Biological Sciences, Columbia University, New York, USA)

2019年11月15日(金)    14:00-15:30  理学部3号館 326号室   

Resolving whole-brain images of neuronal gene expression or neuronal activity
patterns, to the level of single-neuron types with defined identities, represents a
major challenge. In this talk I focus on our development and use of a
multicolor Caenorhabditis elegans transgene, called “NeuroPAL”
(a Neuronal Polychromatic Atlas of Landmarks), to resolve unique neural
identities in whole-brain images. NeuroPAL worms share a stereotypical
multicolor map, permitting complete, unambiguous and automated determination
of individual neuron identities in conjunction with GCaMP-based neuronal
activity reporters and GFP/CFP/YFP/mNeonGreen gene-expression reporters. To
demonstrate the method and its potential, we used NeuroPAL and GFP-based
reporters to map expression of the whole family of metabotropic
acetylcholine, glutamate, and GABA neurotransmitter receptors encoded in the C.
elegans genome, revealing a vast number of potential molecular connections that
go far beyond the anatomically-defined connectome. We then expand the
technique to whole-brain activity, employing NeuroPAL and a panneuronal
neural-activity sensor (GCaMP6s) for functional analysis. We delineate extensive
nervous system activity patterns in response to several stimuli with single,
identified neuron resolution. We find that attractive odors sensed by the same
neuron class exhibit dissimilar activity patterns implying that, despite their shared
valence and stimulus modality, these odors drive distinct neural circuitry.
Our results indicate that the connectome is a poor predictor of observed
functional activity. Lastly, we illustrate NeuroPAL as an unbiased analysis tool
for investigating neuronal cell fate in specific mutant backgrounds. With these
applications in mind, we establish a high-throughput software pipeline for
automated and semi-automated cell identification using NeuroPAL. In conclusion,
this talk will demonstrate the power of NeuroPAL as a tool for decoding
whole-brain gene expression and maps of functional activity.