Dunkel, E. | Search bioRxiv

bioRxiv2024

Neurons and molecules involved in noxious light sensation in Caenorhabditis elegans

Ultraviolet (UV) light is a danger to unpigmented organisms, inducing photodamage of cells and DNA. The transparent nematode Caenorhabditis elegans, despite having no eyes, detects light and exhibits negative phototaxis in order to evade sunlight. UV absorption is detected by the photosensor protein LITE-1, that also responds to reactive oxygen species. We investigated which neurons express LITE-1 and act as noxious photosensors and how they transmit this sensation to the nervous system to evoke escape behavior. We identified the interneuron AVG as a main focus of LITE-1 function in mediating the noxious light evoked escape behavior, with minor roles of the interneuron PVT, the sensory ASK neurons and touch receptor neurons. AVG is activated by blue light, and also its optogenetic stimulation causes escape behavior. Signaling from AVG involves chemical neurotransmission, likely directly to premotor interneurons, and to other cells, by extrasynaptic signaling through the neuropeptide NLP-10. NLP-10 signaling is not required for the acute response, but for maintaining responsiveness to repeated noxious stimuli. The source of NLP-10 in this context is largely AVG, however, also other cells contribute, possibly PVT. This work uncovers entry points of sensory information to the neuronal circuits mediating behavioral responses to noxious UV/blue light. Article SummaryC. elegans senses noxious light and induces escape behavior to avoid damage. The photosensor protein LITE-1 mediates this sensation but understanding responsible neural circuits is incomplete. We identified neurons expressing LITE-1 and identify AVG as the main site of action. The neurotransmitter GABA plays a role in acuteness of the response. AVG, and other cells, need to release the neuropeptide NLP-10 to maintain responsiveness to repeated noxious stimuli. These findings help understanding the C. elegans photophobic response and will guide future work delineating the precise circuit pathways, as an example of how similar photosensation can evoke protective behavior in invertebrates.

neuroscience↗

bioRxiv2023

Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair

Neuronal communication involves small-molecule transmitters, gap junctions, and neuropeptides. While neurons often express multiple neuropeptides, our understanding of the coordination of their action and their mutual interactions remains limited. Here, we demonstrate that two neuropeptides, NLP-10 and FLP-1, released from the same interneuron pair, AVKL/R, exert antagonistic effects on locomotion speed in Caenorhabditis elegans. NLP-10 accelerates locomotion by activating the G protein-coupled receptor NPR- 35 on premotor interneurons that promote forward movement. Notably, we establish that NLP-10 is crucial for the aversive response to mechanical and noxious light stimuli. Conversely, AVK-derived FLP-1 slows down locomotion by suppressing the secretion of NLP-10 from AVK, through autocrine feedback via activation of its receptor DMSR-7 in AVK neurons. Our findings suggest that peptidergic autocrine motifs, exemplified by the interaction between NLP-10 and FLP-1, might represent a widespread mechanism in nervous systems across species. These mutual functional interactions among peptidergic co-transmitters could fine-tune brain activity. Highlights* A pair of neurons elicits opposing behaviors via two distinct neuropeptides * The neuropeptide NLP-10 accelerates locomotion by activating premotor interneurons * Release of the neuropeptide FLP-1 reduces NLP-10 release via autocrine feedback * NLP-10 is crucial for escaping aversive mechanical stimuli and noxious blue light eTOC blurbNeuropeptidergic communication is complex due to the hundreds of proteinaceous transmitters and receptors involved. Aoki and colleagues demonstrate a further layer of regulation, where one neuropeptide negatively influences release of an antagonistic neuropeptide by autocrine feedback, in a single neuron pair. This may represent a general principle in neuropeptidergic signaling.

neuroscience↗