| Popis: |
Neuromodulation in sensory circuits is critical because it allows an organism to respond appropriately to a given stimulus. Sensory systems are modulated by monoamine neurotransmitters as well as neuropeptides, which act in concert to regulate sensory circuits to give rise to complex behavioral states. One common technique for studying sensory circuits is brain activity mapping, where circuits are probed with fluorescent indicators whose readouts are related directly to neuronal activity. In the present work, we focus on the modulation of a pair of sensory neurons, the ASHs, in the nematode Caenorhabditis elegans. ASHs are polymodal, nociceptive neurons that are extensively modulated by monoamines and neuropeptides. Using a combination of genetics, Ca2+ imaging, electrophysiology, and behavioral assays, we have identified a complex instance where the monoamine serotonin (5-HT) stimulates aversive behaviors and neuronal depolarization, but decreases sensory-evoked Ca2+ signals, indicating that the recorded Ca2+ levels do not positively correlate with neuronal activity. Mechanistically, 5-HT is likely acting through the SER-5 receptor and Gαq signaling in ASHs to downregulate Ca2+ directly by initiating a Ca2+-driven negative feedback loop targeting the L-type Ca2+ channel EGL-19. Together, these studies reveal a complex inhibitory feedback mechanism for sensory modulation, and have broad implications for activity mapping of complex neural circuits. |
