Research
Synaptic Plasticity
The fully mapped out nervous system has allowed us to develop methods to examine synapse plasticity during learning and memory formation with cellular, synaptic and molecular precision. How are synapses affected by prolonged signaling and do these changes result in memory formation? Where is the engram for memory? Our goal is to build tools to watch synapses remodel in sleep. We have on-going projects studying the molecules that may sculpt synapses and are asking how these synapses are marked for pruning and how sleep activates this pruning program. We are keen to understand if exophers are regulated by sleep. This is particularly interesting in the context of the aging animal - we found that animals memory deteriorates in day 2 adults.
Collaborators: VanHoven at SJSU
Tools to Measure Dynamic Molecular Changes in Neurons
We aim to illuminate the secrets of biology by building tools to peer into and manipulate molecular processes of behaving C. elegans in real time. Our current endeavors include developing calcium and cGMP reporters to observe and quantify neuronal activity. We are also interested in probing neuronal chromosome dynamics and their movement within the nucleus and chromatin state using CRISPR- based chromosomal imaging techniques. In addition, we have previously shown that the 3’UTR of egl-4 is important for regulated spatially localized translation (Kaye et al., Neuron 2009) and are interested in developing tools to probe this process.
Collaborators: Kato at UCSF , Wittmann at UCSF, Huang at UCSF, VanHoven at SJSU, Ferkey at SUNY Buffalo, Juang at National Chiao Tsung University
AWC olfactory neuron with GRASP puncta
Image by Torsten Wittmann
GCaMP calcium reporter expressed in the ASER neuron responding to a change in salt concentration
Image by Sarah Woldemariam
Learning and Memory
How do neurons change when an organism learns a new behavior? How do these changes allow organisms to form and keep memories of what they learned? How does this change as animals age? Our lab has projects focused on manipulating and quantitating the learning, memory, and consolidation processes. Ultimately we hope to gain an understanding of whole brain activity as the animals acquire and consolidate memory. We study how behaviors ranging from olfaction to motor plans and how they are encoded. We tend to focus on sleep as Dr Nando Munoz Lobato in our lab was the first to discover that even the 185-neuron C. elegans "brain" requires sleep for long lasting (3 worm-years) memory. Dr Rashmi Chandra proved that sleep is sufficient to strengthen a weak memory and show that a sleep-promoting neuron is required while Fatema Farah showed that sleep sculpts synaptic connections. This was published in a June 2023 issue of Cell (https://www.cell.com/cell/fulltext/S0092-8674(23)00525-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867423005251%3Fshowall%3Dtrue).
Collaborators: Miri VanHoven (SJSU), Saul Kato (UCSF), Martina Bremer (SJSU) and Chris Fang-Yen (OSU).
Chemotaxis plates from Kelli Benedetti
Photos by Kanaga Rajan
Small RNA in Neuronal Function and Beyond...
Neuronal signaling affects physiology as a whole and, in particular, RNA biology. Previous findings from our lab show that the nuclear RNAi pathway is important for odor learning. (Juang et al., Cell 2013) We are investigating the biogenesis of these small RNAs in the neuron upon olfactory stimulation. Once formed, how might such RNA based or elicited signals get out of the neuron? And finally, once in their target tissue, what is the function of small RNAs in maintaining cell populations and tissue integrity?
Collaborators: Goga at UCSF, Floor at UCSF, Dernburg at UC Berkeley
DAPI and HTP-3 staining of the wild type C.elegans germ line
Images by Aarati Asundi in collaboration with Gina Caldas (Dernburg lab)
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Small RNA in Neuronal Function and Beyond...