Conference Agenda

Symposium Chair

Chair Name:
Denise Ferkey

Co-Chair Name (Optional):

Email:
Preferred
dmferkey@buffalo.edu

Email:

Organization:

Department:

Position:
Associate Professor

Species:
C. elegans

Description

Title:
C. elegans neurogenetics: Behavior, Learning, Stress and Disease

Abstract (500 word limit):
All animals rely on their ability to sense and respond to their environment to survive. However, the suitability of a behavioral response is context-dependent, and must reflect an animal’s genetic sex, life-history and present internal state. Based on the integration of these variables, an animal’s needs can be prioritized to optimize survival strategies. The four talks in this symposium will highlight the power of C. elegans genetics to dissect the underlying mechanisms that regulate neuronal signaling across the continuum ranging from behavior to the disease state. The first two speakers will focus on the regulation of olfactory behavior, and the second two talks will focus on the nervous system’s response to stress and neurodegenerative disease models. The chair is Denise Ferkey, who will introduce the speakers and moderate the discussion. Each of the proposed speakers has confirmed their willingness to attend in-person and present. Dr. Doug Portman’s work focuses on the genetic control of sex differences in behavior and disease susceptibility. In this symposium he will give an overview of the lab’s work on C. elegans male chemosensory behavior. In particular, he will highlight recent work describing how males optimize mate-choice decisions via sex-specific responses to multimodal sensory cues, as well has how males prioritize food- versus mate-seeking behaviors. The lab has developed powerful genetic tools to sex-reverse individual neurons, giving cell-specific resolution to the signaling mechanisms involved. Dr. Rashmi Chandra is a Postdoctoral Fellow in the laboratory of Dr. Noelle L’Etoile. Rashmi is first author on their recent Cell paper, and the opportunity to present at the IBANGS Genes, Brain and Behavior meeting would be a particularly valuable experience for her as she transitions to an independent research career. Rashmi’s work uses C. elegans olfactory learning as a model to understand the role sleep plays in memory consolidation. She will present their recent finding that spaced odor-training and post-training sleep induce long-term olfactory memory consolidation and synaptic remodeling. (If the committee prefers, Dr. Noelle L’Etoile, Full Professor, is also willing to attend and present this work.) Dr. Veena Prahlad’s work focuses on the role of the C. elegans nervous system in regulating stress response pathways. Numerous diseases, including Huntington’s disease and Alzheimer’s disease result from protein misfolding leading to cellular dysfunction. Veena’s lab has shown that upregulation of the stress-responsive heat shock proteins (HSPs) that help to refold and/or degrade damaged proteins happens in a non-cell autonomous manner, and is regulated by signals from the organism’s nervous system – sometimes also signaling to non-neural tissues. She will present an overview of the involved neurons and pathways. Dr. Anne Hart has a long-standing interest in understanding the genetic underpinnings of neurodegeneration. She has developed C. elegans models for neurodegenerative diseases – including poly-Q expansion diseases and amyotrophic lateral sclerosis (ALS). She will present an overview of this work, which includes identification of genetic modifiers of disease susceptibility and severity, as well as “humanized” C. elegans strains that have been engineered to express human disease variants of causal genes.

Speaker 1

Name:
Douglas Portman

Email:
Preferred
douglas.portman@rochester.edu

Email:

Organization:
University of Rochester

Department:
Department of Biomedical Genetics

Position:
Professor

Species:
C. elegans

Speaker 2

Name:
Rashmi Chandra

Email:
Preferred
rrpchandra@gmail.com

Email:

Organization:
University of California, San Francisco

Department:
Department of Cell and Tissue Biology

Position:
Postdoctoral Associate

Species:
C. elegans

Speaker 3

Name:
Veena Prahlad

Email:
Preferred
Veena.Prahlad@roswellpark.org

Email:

Organization:
Roswell Park Cancer Center

Department:
Department of Cell Stress Biology

Position:
Professor

Species:
C. elegans

Speaker 4

Name:
Anne Hart

Email:
Preferred
anne_hart@brown.edu

Email:

Organization:
Brown University

Department:
Department of Neuroscience

Position:
Professor and Chair

Species:
C. elegans

Rashmi Chandra, Angel Garcia, Fatima Farah, Fernando Muñoz-Lobato, Anirudh Bokka, Kelli L. Benedetti, Chantal Brueggemann, Fatema Saifuddin, Sarah K. Nordquist, Evangeline Chien, Joy Li, Eric Chang, Aruna Varshney, Vanessa Jimenez, Anjana Baradwaj, Kristine Andersen, Julia M. Miller, Raymond L. Dunn, Kevin Diagle, Bryan Tsujimoto, Alan Tran, Alex Duong, Rebekka Paisner, Sara Alladin, Cibelle Nassif, Carlos E. Zuazo, Matthew A. Churgin, Chris Fang-Yen, Martina Bremer, Saul Kato, Miri K. VanHoven, and Noëlle D. L’Étoile

While sleep's importance in optimizing brain function is undeniable, the physiological outcomes that sleep precisely benefits remain unclear. Using experience-dependent olfactory plasticity as our behavioral readout, we provide the first evidence that sleep after spaced odor training is necessary and sufficient to produce long-lasting olfactory memory in Caenorhabditis elegans. Taking advantage of the optically accessible in vivo system, we showed that sleep-dependent olfactory memory is stored between specific synapses within the olfactory circuit, which decreases when memory is retained. When sleep after training is disrupted, the synaptic communication between the AWC sensory neuron and AIY interneurons remains unchanged; these animals do not retain memory. Thus, we demonstrated that sleep sculpts the olfactory circuit to consolidate memory in a living organism at a single synapse resolution. However, how sleep downscales AWC-AIY synaptic pairs that drive memory consolidation remains unknown. While exploring the olfactory circuit, we found astrocytes in C. elegans, CEPsh glia, are required during sleep to consolidate memory; this makes astrocytes-like CEPsh glia the newest member of the olfactory circuit. Simultaneously, evidence suggests that mutants with defective ced-10 (racGTPase), essential for phagocytosis, exhibit a lack of sleep after training and an inability to retain memory. This defect is rectified by overexpressing the ced-10 cDNA under its native promoter, given the high expression of ced-10 in glial cells, particularly CEPsh glia, ongoing cell-specific rescue experiments and advanced imaging aim to elucidate how astrocytes in C. elegans phagocytose synapses during sleep, contributing to the consolidation of olfactory memory.

University of California San Francisco

Veena Prahlad

Cells possess natural defense mechanisms to counteract protein misfolding. One such mechanism is the activation of a conserved gene expression program, the so-called heat-shock response that increases the cellular protein quality control (QC) capacity to help refold and/or degrade misfolded proteins. Experimentally activating this response ameliorates disease pathology, making it a prime target for medical intervention. Yet, in neurodegenerative diseases, cells accumulate misfolded and aggregated proteins but fail to naturally activate this response. As in human disease, we have shown that cells of the metazoan C. elegans also do not naturally activate their protein QC machinery upon protein misfolding: neuronal activity inhibits the cells’ natural defense against misfolding. However, upon a sensed threat in the environment, the nervous system activates the cellular defense response against protein damage. Specifically, we showed that C. elegans can be trained to initiate HSF-1-dependent chaperone gene expression prior to, and in anticipation of, a proteotoxic encounter, through olfactory exposure to specific smells that signify threat. This occurs through the release of the neuromodulator serotonin. We will present the mechanisms, epigenetic sequalae that underlie serotonergic activation of HSF1, and the significance of cell non-autonomous control over a fundamental stress-survival mechanism of cells.

Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14221

AC Hart¹

Despite the remarkable diversity of animal species on our planet, there is profound conservation of protein function, biochemical processes, cellular pathways, and cell-cell interactions across the animal kingdom. In many cases, we can take advantage of this conservation to create non-human animal models of human disease, which can be used to provide insight into what processes go awry in disease, leading to pathological changes. Strategies for human disease model development and examples of useful C. elegans disease models will be discussed.

¹ Department of Neuroscience and the Robert J. And Nancy D Carney Institute for Brain Science, Brown University, Providence RI, 02912 USA.

Funding Support: Carney Institute Innovation Award, NIH NINDS R21 NS116254, Alternating Hemiplegia of Childhood Foundation, Cure AHC, and HOPE for Annabel.

DS Portman^1,2,3,4, C Bainbridge¹, J Luo^1,5, GR Reilly^3,4, ZC Ward¹, J Zhang²

Biological sex provides a unique opportunity to understand how a single genetic cue gives rise to naturally occurring, adaptive variation in behavior. Because of its precisely defined neuroanatomy and powerful genetic tractability, the nematode C. elegans is an ideal model for using biological sex as an entry point for understanding the relationships between genes, circuits, and behavior. In C. elegans, adult males and hermaphrodites (the female equivalent in this species) show marked behavioral differences. A central theme of these differences is their contribution to behavioral prioritization: while hermaphrodites prioritize feeding behavior, males favor exploration and mate-searching. We have found that a key source of this behavioral variation is sex-specific modulation of the properties of sex-shared neurons and circuits, brought about cell-autonomously by the genetic sex-determination hierarchy. Differential tuning of shared chemosensory neurons refocuses the male’s “attention” away from food and towards sex pheromones, while sex differences in neuromodulatory state allow males to generate increased exploratory behavior. Interestingly, the effects of biological sex on these properties is not fixed; rather, internal and external cues interact with biological sex to dynamically sculpt sex differences in behavior. These studies have shed light on the genetic mechanisms by which sex tunes neuronal properties; further, they have identified key neurogenetic nodes whose modulation can adaptively alter patterns of behavior.

¹Department of Biomedical Genetics, ²Department of Biology, ³Department of Neuroscience, and ⁴Ernest J. DelMonte Institute for Neuroscience, University of Rochester, Rochester, NY, USA

⁵School of Life Sciences, Xiamen University, Xiamen, Fujian, Chin

Funding support: NIGMS R35 GM148439