Professor, Department of Biology
Ph.D. University of California, San Diego
Research Interests: Neuronal basis of behavior
Overview: We study how the nervous system controls behavior by analyzing the neural networks for decision making, focusing on spatial exploration behaviors, and food choice involving trade-offs that mimic human economic decisions. We investigate how these networks function using a combination of experimental and theoretical approaches. We track the movements of worms at high spatiotemporal resolution in complex naturalistic environments to determine the underlying behavioral strategies. Neuronal function is assessed by investigating changes in behavior caused by genetic mutations, neuronal ablations, and optogenetic manipulations. We also make optical recordings in freely moving animals to correlate neuronal activity patterns and behavior; these experiments are facilitated by microfluidic devices to control the worm's local sensory environment. Patch-clamp electrophysiological recordings are made from normal and mutant animals to determine how the electrical properties of neurons influence network function. Experimental data are synthesized in predictive theoretical models. Predictions are tested experimentally and the results are used to improve our theoretical understanding of the function of biological networks. These results provide new insights into the cellular and molecular mechanisms of information processing underlying animal behavior.
Microfluidic platform for electrophysiological recordings from host-stage hookworm and Ascaris suum larvae: A new tool for anthelmintic research.
Int J Parasitol Drugs Drug Resist. 2016 Sep 15;:
Authors: Weeks JC, Roberts WM, Robinson KJ, Keaney M, Vermeire JJ, Urban JF, Lockery SR, Hawdon JM
The screening of candidate compounds and natural products for anthelmintic activity is important for discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device ('chip') that records non-invasively the tiny electrophysiological signals generated by rhythmic contraction (pumping) of the worm's pharynx. These electropharyngeograms (EPGs) are recorded simultaneously from multiple worms per chip, providing a medium-throughput readout of muscular and neural activity that is especially useful for compounds targeting neurotransmitter receptors and ion channels. Microfluidic technologies have transformed C. elegans research and the goal of the current study was to validate hookworm and Ascaris suum host-stage larvae in the microfluidic EPG platform. Ancylostoma ceylanicum and A. caninum infective L3s (iL3s) that had been activated in vitro generally produced erratic EPG activity under the conditions tested. In contrast, A. ceylanicum L4s recovered from hamsters exhibited robust, sustained EPG activity, consisting of three waveforms: (1) conventional pumps as seen in other nematodes; (2) rapid voltage deflections, associated with irregular contractions of the esophagus and openings of the esophogeal-intestinal valve (termed a 'flutter'); and (3) hybrid waveforms, which we classified as pumps. For data analysis, pumps and flutters were combined and termed EPG 'events.' EPG waveform identification and analysis were performed semi-automatically using custom-designed software. The neuromodulator serotonin (5-hydroxytryptamine; 5HT) increased EPG event frequency in A. ceylanicum L4s at an optimal concentration of 0.5 mM. The anthelmintic drug ivermectin (IVM) inhibited EPG activity in a concentration-dependent manner. EPGs from A. suum L3s recovered from pig lungs exhibited robust pharyngeal pumping in 1 mM 5HT, which was inhibited by IVM. These experiments validate the use of A. ceylanicum L4s and A. suum L3s with the microfluidic EPG platform, providing a new tool for screening anthelmintic candidates or investigating parasitic nematode feeding behavior.
PMID: 27751868 [PubMed - as supplied by publisher]