Biology subjects

L'Etoile, N. D.

Publications and source records attributed to L'Etoile, N. D..

3 recordsLinked to original sources

bioRxiv2025

The osm-9 mutant strain is defective in the recovery phase of long-term memory dynamics

Memory by definition is the storage of learned information from experiences where it can be recalled in the future. Memory is essential for organisms of any level, from single celled bacteria to complex mammals like whales in order for them to adapt and survive. The storage of long term memory is known to start in the hippocampus but long-term memory is not simply contained in this one region in the brain but across multiple regions including the cortex, amygdala and nucleus accumbens. This diversity of locations that memory can be located in prompts the question of what molecular components within the nervous system are required to establish and maintain long term memory. To dive into this, we utilize the simple neuroanatomy of C. elegans with only 302 neurons to examine the effects of mutations of specific genes on the success of forming long term memories. Previous work established that C. elegans with defective OSM-9 proteins are unable to sustain an aversion to butanone (an odor that they are innately attracted to) after it is paired once with a negative stimulus. This helped established the importance of OSM-9 proteins for short term memory but how can the OSM-9 protein - a homolog to human TRPV5 and TRPV6 commonly associated with recognising pain and thermoregulation rather than memory - play a part within the dynamics of space training induced long term memory? Here we show that the loss of the OSM-9 protein affects the dynamics of memory consolidation, which is the process by which short term memory is converted to long term memory. Previously, OSM-9 protein was implicated in the formation of short term memory which was termed adaptation. Here, we examine spaced training induced memory that is resistant to re-feeding and depends on sleep. This study indicates that after spaced training, the OSM-9 protein is required for the conversion of short term memory to long term memory and not acquisition. Furthermore, we confirmed that 30 minutes on food after spaced training, Wild type C. elegans seem to lose their memory but gain it back 120 minutes after, emphasizing the dynamics of memory and revealing that it is not a smoothly continuous process. Our results demonstrate that TRPV containing channels plays a role in stabilizing memory for long term use. Analyzing the specific point in which the OSM-9 protein plays a part in reactivating memory may help pave the way to a more detailed understanding of memory dynamics and the processes involved in recovering memory. Future work includes: identifying where the loss of memory goes, whether its masked or truly disappears can further explain what the OSM-9 protein supports when long term memory is formed; understanding if OSM-9 is directly involved with the process of "reviving" the memory or is it involved in the development of the C. elegans circuit which allows for this process to occur.

neuroscience↗

bioRxiv2020

Oncogene Regulated Release of Extracellular Vesicles

Oncogenes can alter cellular structure, function, development and metabolism including changing the balance between anabolic and catabolic processes. However, how oncogenes regulate tumor cell biomass remains poorly understood. Using isogenic mammary breast epithelial cells transformed with a panel of ten oncogenes found commonly mutated, amplified or overexpressed in multiple cancers, we show that specific oncogenes reduce the biomass of cancer cells by promoting extracellular vesicle release. While MYC and AURKB elicited the highest number of EVs, each oncogene tested selectively altered the protein composition of released EVs. Likewise, miRNAs were differentially sorted into EVs in an oncogene-specific manner. MYC overexpressing cells require ceramide, while AURKB require ESCRT to release high levels of EVs. Finally, lysosome-associated genes are broadly downregulated in the context of MYC and AURKB, suggesting that cellular contents instead of being degraded, were released via EVs. Thus, oncogene mediated biomass regulation via differential EV release is a new metabolic phenotype which may have implications for cellular signaling and homeostasis.

cell biology↗

bioRxiv2019

INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans

In order to respond to changing environments and fluctuations in internal states, animals adjust their behavior through diverse neuromodulatory mechanisms. In this study we show that electrical synapses between the ASH primary quinine-detecting sensory neurons and the neighboring ASK neurons are required for modulating the aversive response to the bitter tastant quinine in C. elegans. Mutant worms that lack the electrical synapse proteins INX-18 and INX-19 become hypersensitive to dilute quinine. Cell-specific rescue experiments indicate that inx-18 operates in ASK while inx-19 is required in both ASK and ASH for proper quinine sensitivity. Imaging analyses find that INX-19 in ASK and ASH localizes to the same regions in the nerve ring, suggesting that both sides of ASK-ASH electrical synapses contain INX-19. While inx-18 and inx-19 mutant animals have a similar behavioral phenotype, several lines of evidence suggest the proteins encoded by these genes play different roles in modulating the aversive quinine response. First, INX-18 and INX-19 localize to different regions of the nerve ring, indicating that they are not present in the same synapses. Second, removing inx-18 disrupts the distribution of INX-19, while removing inx-19 does not alter INX-18 localization. Finally, by using a fluorescent cGMP reporter, we find that INX-18 and INX-19 have distinct roles in establishing cGMP levels in ASK and ASH. Together, these results demonstrate that electrical synapses containing INX-18 and INX-19 facilitate modulation of ASH nociceptive signaling. Our findings support the idea that a network of electrical synapses mediates cGMP exchange between neurons, enabling modulation of sensory responses and behavior.\n\nAuthor SummaryAnimals are constantly adjusting their behavior to respond to changes in the environment or to their internal state. This behavior modulation is achieved by altering the activity of neurons and circuits through a variety of neuroplasticity mechanisms. Chemical synapses are known to impact neuroplasticity in several different ways, but the diversity of mechanisms by which electrical synapses contribute is still being investigated. Electrical synapses are specialized sites of connection between neurons where ions and small signaling molecules can pass directly from one cell to the next. By passing small molecules through electrical synapses, neurons may be able to modify the activity of their neighbors. In this study we identify two genes that contribute to electrical synapses between two sensory neurons in C. elegans. We show that these electrical synapses are crucial for proper modulation of sensory responses, as without them animals are overly responsive to an aversive stimulus. In addition to pinpointing their sites of action, we present evidence that they may be contributing to neuromodulation by facilitating passage of the small molecule cGMP between neurons. Our work provides evidence for a role of electrical synapses in regulating animal behavior.

neuroscience↗