Chalasani Lab

Prey must balance predator avoidance with feeding, a central dilemma in prey refuge theory. Additionally, prey must assess predatory imminence-how close threats are in space and time. Predatory imminence theory classifies defensive behaviors into three defense modes: pre-encounter, post-encounter, and circa-strike, corresponding to increasing levels of threat–suspecting, detecting, and contacting a predator. Although predatory risk often varies in spatial distribution and imminence, how these factors intersect to influence defensive behaviors is poorly understood. Integrating these factors into a naturalistic environment enables comprehensive analysis of multiple defense modes in consistent conditions. Here, we combine prey refuge and predatory imminence theories to develop a model system of nematode defensive behaviors, with as prey and as predator. In a foraging environment comprised of a food-rich, high-risk patch and a food-poor, low-risk refuge, innately exhibits circa-strike behaviors. With experience, it learns post- and pre-encounter behaviors that proactively anticipate threats. These defense modes intensify with predator lethality, with only life-threatening predators capable of eliciting all three modes. SEB-3 receptors and NLP-49 peptides, key stress regulators, vary in their impact and interdependence across defense modes. Overall, our model system reveals fine-grained insights into how stress-related signaling regulates defensive behaviors.

The brain integrates activity across networks of interconnected neurons to generate behavioral outputs. Several physiological and imaging-based approaches have been previously used to monitor responses of individual neurons. While these techniques can identify cellular responses greater than the neuron’s action potential threshold, less is known about the events that are smaller than this threshold or are localized to subcellular compartments. Here we use NEAs to obtain temporary intracellular access to neurons allowing us to record information-rich data that indicates action potentials, and sub-threshold electrical activity. We demonstrate these recordings from primary hippocampal neurons, induced pluripotent stem cell-derived (iPSC) neurons, and iPSC-derived brain organoids. Moreover, our results show that our arrays can record activity from subcellular compartments of the neuron. We suggest that these data might enable us to correlate activity changes in individual neurons with network behavior, a key goal of systems neuroscience.

Animal foraging is an essential and evolutionarily conserved behavior that occurs in social and solitary contexts, but the underlying molecular pathways are not well defined. We discover that conserved autism-associated genes (NRXN1(nrx-1), NLGN3(nlg-1), GRIA1,2,3(glr-1), GRIA2(glr-2), and GLRA2,GABRA3(avr-15)) regulate aggregate feeding in C. elegans, a simple social behavior. NRX-1 functions in chemosensory neurons (ADL and ASH) independently of its postsynaptic partner NLG-1 to regulate social feeding. Glutamate from these neurons is also crucial for aggregate feeding, acting independently of NRX-1 and NLG-1. Compared to solitary counterparts, social animals show faster presynaptic release and more presynaptic release sites in ASH neurons, with only the latter requiring nrx-1. Disruption of these distinct signaling components additively converts behavior from social to solitary. Collectively, we find that aggregate feeding is tuned by conserved autism-associated genes through complementary synaptic mechanisms, revealing molecular principles driving social feeding.

Animals with small nervous systems have a limited number of sensory neurons that must encode information from a changing environment. This problem is particularly exacerbated in nematodes that populate a wide variety of distinct ecological niches but only have a few sensory neurons available to encode multiple modalities. How does sensory diversity prevail within this neuronal constraint? To identify the genetic basis for patterning different nervous systems, we demonstrate that sensory neurons in the respond to various salt sensory cues in a manner that is partially distinct from that of the distantly related nematode . By visualizing neuronal activity patterns, we show that contrary to previous expectations based on its genome sequence, the salt responses of are encoded in a left/right asymmetric manner in the bilateral ASE neuron pair. Our study illustrates patterns of evolutionary stability and change in the gustatory system of nematodes.

Neurexins and their canonical binding partners, neuroligins, are localized to neuronal pre-, and post-synapses, respectively, but less is known about their role in driving behaviors. Here, we use the nematode C. elegans to show that neurexin, but not neuroligin, is required for avoiding specific chemorepellents. We find that adults with knockouts of the entire neurexin locus exhibit a strong avoidance deficit in response to glycerol and a weaker defect in response to copper. Notably, the C. elegans neurexin (nrx-1) locus, like its mammalian homologs, encodes multiple isoforms, α and γ. Using isoform-specific mutations, we find that the γ isoform is selectively required for glycerol avoidance. Next, we used transgenic rescue experiments to show that this isoform functions at least partially in the nervous system. We also confirm that the transgenes are expressed in the neurons and observe protein accumulation in neurites. Furthermore, we tested whether these mutants affect the behavioral responses of juveniles. We find that juveniles (4th larval stages) of mutants knocking out the entire locus or the α-isoforms, but not γ-isoform, are defective in avoiding glycerol. These results suggest that the different neurexin isoforms affect chemosensory avoidance behavior in juveniles and adults, providing a general principle of how isoforms of this conserved gene affect behavior across species.