The UCLA Joint Seminars in Neuroscience Presents - Astra Bryant, Ph.D., and Jiannis Taxidis, Ph.D.

Tuesday, November 3, 2020 - 12:00pm
The Arnold Scheibel Distinguished Postdoctoral Fellow in Neuroscience Lecture

The UCLA Joint Seminars in Neuroscience Presents - Astra Bryant, Ph.D., and Jiannis Taxidis, Ph.D.

"Neural Mechanisms Underlying Temperature-Driven Host Seeking by a Skin-Penetrating Human-Parasitic Nematode"

Astra Bryant, Ph.D.
Postdoctoral Fellow
Laboratory of Dr. Elissa Hallem
Department of Microbiology, Immunology, and Molecular Genetics College of Life Science, University of California, Los Angeles

Abstract: Skin-penetrating parasitic nematodes are a major source of “diseases of disadvantage,” infecting approximately 1 billion people. Their life cycle includes an infective third-larval (iL3) stage that searches for hosts in a poorly understood process involving thermal cues. We measured temperature-driven behaviors in multiple parasitic-nematode species, including the human-parasitic threadworm Strongyloides stercoralis. We found that mammalian-parasitic iL3s are highly sensitive to thermal gradients. At temperatures above their cultivation temperature, iL3s display robust attraction to mammalian body temperatures (37°C). Temperature-driven responses are dominant in multisensory contexts; when below host body temperature, iL3s prioritize temperature-driven behaviors over chemosensory attraction to host odors.

We leveraged the genetic similarities between S. stercoralis and the free-living model nematode Caenorhabditis elegans to investigate mechanisms underlying temperature-driven host seeking. For C. elegans, thermotaxis behaviors within their physiological temperature range (~15-25°C) depend on the Ce-tax-4 gene, which encodes a cyclic nucleotide-gated channel subunit. We showed that targeted mutagenesis of Ss-tax-4 abolishes iL3 heat seeking, suggesting this behavior is generated through adaptations of conserved molecular cascades. In C. elegans, AFD sensory neurons provide the primary thermosensory drive for thermotaxis navigation. We genetically identified the S. stercoralis AFD neurons, and found that inducible silencing of these neurons suppresses iL3 heat seeking. Thus, AFD’s thermosensory role is conserved between S. stercoralis and C. elegans despite species-specific differences in thermal preference, behavior, and AFD dendritic structure. Using genetically encoded calcium sensors, we found that temperature-driven responses in Ss-AFD are distinct from those in Ce-AFD. Furthermore, at least two Ss-AFD-specific receptor guanylate cyclases confer sensitivity to temperature ranges that include mammalian body temperatures, compared to only one in C. elegans. Thus, altered thermal encoding in primary thermosensory neurons likely contributes to parasite-specific behaviors. Together, our results provide insight into the behavioral strategies, neural circuits, and molecular mechanisms that allow skin-penetrating nematodes to target hosts

"Remembering What Happened When: Emergence and Stability of Context-Specific Hippocampal Sequences Encoding Odors and Time"

Jiannis Taxidis, Ph.D.
Associate Project Scientist
Laboratory of Dr. Peyman Golshani
Departments of Neurology and Psychiatry
David Geffen School of Medicine, University of California, Los Angeles

Abstract: How does the brain keep track of events we need to remember as well as the intervals between them? A recent model of hippocampal function posits that spiking sequences in hippocampal networks encode important sensory stimuli (external world) and link them by tiling the place or time between them (internal representations), forming memory maps of spatiotemporally related experiences. But does the hippocampus use one or multiple encoding strategies for external and internal representations? For example, do representations of sensory cues and time share the same stability, adaptability or relationship with learning? I will present our work that addresses this question. We used two-photon calcium imaging in vivo in CA1 of head-fixed mice. We tracked the activity of thousands of cells across days, while mice learned and performed an olfactory delayed non-match-to-sample task requiring working memory. We observed ‘odor-cells’, encoding specific olfactory cues, followed by ‘time-cells’ encoding delay timepoints after a specific odor. Despite forming continuous spiking sequences, the two neuronal groups exhibited strikingly different properties. Odor-cells retained stable fields when the delay or odor presentation was extended as well as across days, whereas time fields were highly unstable and readily remapped in both cases. During learning, the number of odor-cells remained fixed while time-cells increased as performance improved. This increase was learning-related since it did not occur in naïve mice passively exposed to the same task trials. Therefore, the hippocampus can generate and sustain both stable representations of external cues as well as flexible temporal-codes that emerge with learning. This crucial combination of stability and flexibility allows hippocampal circuits to link fixed elements of the external world despite their changing temporal relationships, to construct memory-maps of related experiences.

Host: Dr. Felix Schweizer

Location: Zoom Meeting

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