Research
Learning & 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.
Collaborators: Miri VanHoven (SJSU), Saul Kato (UCSF), Martina Bremer (SJSU), and Chriss Fang-Yen (OSU)
SYNAPTIC PLASTICITY
How are synapses affected by prolonged signaling and do these changes result in memory formation? Where is the engram for memory?
AWC olfactory neuron with GRASP puncta
Image by Torsten Wittmann
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. 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: Miri VanHoven (SJSU)
TOOLS TO MEASURE DYNAMIC MOLECULAR CHANGES IN NEURONS
What molecular changes occur in neurons as an organism is learning and forming memories? Can we watch those changes in real time in live animals?
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 and are interested in developing tools to probe this process.
Collaborators: Saul Kato (UCSF), Torsten Wittmann (UCSF), Bo Huang (UCSF), Miri VanHoven (SJSU), Denise Ferkey (SUNY Buffalo), Bi-Tzen Juang (National Chiao Tsung University).
SMALL RNA IN NUERONAL FUNCTION
AND BEYOND...
Are small RNAs formed in neurons in response to certain stimuli? Could they act as neuronal signals to regulate the organism's behavior and physiology?
DAPI and HTP-3 staining of the wild type C.elegans germ line
Images by Aarati Asundi in collaboration with Gina Caldas (Dernburg lab)
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. 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
OPEN POSITIONS
We are actively recruiting a post-doc to pursue some of our several interesting open projects that will likely result in high-impact publications.
SLEEP ANALYSIS
Whole brain dynamical analysis of sleep with the beginnings of replay during sleep - collaboration with Dr Brendon Watson U. Michigan.
AGING & MEMORY
Evidence that as worms age, they lose the ability to form memory (in just 24 hours!)- we have funding to look at the cellular and molecular processes that drive these changes in aging.
SLEEP DYNAMICS
We have funds to discover the dynamic molecular processes that shape synapses and how specific synapses are sculpted in sleep.
...IN THE FUTURE
We are deeply interested in analyzing how the simple worm brain commits an experience to memory and then collaborating with physicists and computer scientists to model this and use for inspiration for new artificial neural network geometries.
Interested in joining our lab?
Email noelle.letoile@ucsf.edu with your CV, letter of inquiry and 3 references.
I'll set up an interview!