Abstract
Many neuronal groups such as dopamine-releasing (dopaminergic) neurons are functionally divergent, although the details of such divergence are not well understood. Dopamine in the nematode Caenorhabditis elegans modulates various neural functions and is released from four left-right pairs of neurons. The terminal identities of these dopaminergic neurons are regulated by the same genetic program, and previous studies have suggested that they are functionally redundant. In this study, however, we show functional divergence within the dopaminergic neurons of C. elegans. Because dopaminergic neurons of the animals were supposedly activated by mechanical stimulus upon entry into a lawn of their food bacteria, we developed a novel integrated microscope system that can auto-track a freely-moving (in actio) C. elegans to individually monitor and stimulate the neuronal activities of multiple neurons. We found that only head-dorsal pair of dopaminergic neurons (CEPD), but not head-ventral or posterior pairs, were preferentially activated upon food entry. In addition, the optogenetic activation of CEPD neurons alone exhibited effects similar to those observed upon food entry. Thus, our results demonstrated functional divergence in the genetically similar dopaminergic neurons, which may provide a new entry point toward understanding functional diversity of neurons beyond genetic terminal identification.
Highlights
Neural functions have been studied at the cellular and molecular levels
Auto-tracking microscope systems for in vivo calcium imaging or optogenetic stimulation of freely-moving C. elegans recently became available[27,28,29,30,31,32], separately analysing the activities of individual DAergic neurons remains challenging because 3 pairs of DAergic neurons (CEPD, CEPV, and ADE) are all located in the head ganglia (Fig. 1a), and the machine-vision discrimination of these neurons has been difficult, especially during tracking
While the terminal identities of all of the DAergic neurons are tightly regulated by the same genetic program[19,20] and these neurons are considered functionally redundant[8], we found functional diversification among DAergic neuron pairs in the slowing response upon food entry
Summary
Neural functions have been studied at the cellular and molecular levels. In hermaphrodites (the major sexual form of the animals), four left-right pairs of neurons are DAergic: CEPD (cephalic sensilla-dorsal), CEPV (cephalic sensilla-ventral), ADE (anterior deirids), and PDE (posterior deirids)[18] (Fig. 1a; note that the animals’ left-right axis is vertical and their dorsal-ventral axis is horizontal when they move in the standard laboratory condition). The animal’s locomotor speed is slowed upon entry into a bacterial lawn, which is mimicked by a mechanical stimulus from Sephadex beads[8] This slowing response is mediated by DA signalling, and laser ablation of all four pairs DAergic neurons was necessary to fully suppress the slowing, suggesting that the neurons function redundantly[8]. Auto-tracking microscope systems for in vivo calcium imaging or optogenetic stimulation of freely-moving C. elegans recently became available[27,28,29,30,31,32], separately analysing the activities of individual DAergic neurons remains challenging because 3 pairs of DAergic neurons (CEPD, CEPV, and ADE) are all located in the head ganglia (Fig. 1a), and the machine-vision discrimination of these neurons has been difficult, especially during tracking. Our results demonstrate the functional diversification of genetically and even anatomically similar DAergic neurons
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