April 19, 2024

MIT Reveals: How Nervous Systems Integrate Environment and State To Control Behavior

By David Orenstein, MIT Picower Institute for Learning and Memory
November 27, 2022

The neuron AWA extends from a worms brain to its nose. In one experiment McLachlan and Flavells team showed that while both fed and hungry worms would wriggle toward the receptors preferred smells if they were strong enough, just fasted worms (which express more of the receptor) could spot fainter concentrations. In another experiment, they discovered that while starving worms will slow down to consume upon reaching a food source even as well-fed worms cruise on by, they might make well-fed worms act like fasted ones by synthetically overexpressing STR-44. They found that when they included a chemical that stresses the worms, that ratcheted down STR-44 expression even in fasted worms. Hints about whether the worm is actively eating come to AWA from nerve cells in the intestine that use a molecular nutrient sensor called TORC2.

To get deep insight, the research team based at The Picower Institute for Learning and Memory turned to the C. elegans worm, whose distinct behavioral states and 302-cell worried system make the complex issue at least tractable. They emerged with a case research study of how, in a crucial olfactory nerve cell called AWA, many sources of state and sensory information converge to individually throttle the expression of an essential odor receptor.
The neuron AWA stretches from a worms brain to its nose. A brand-new study reveals that the brain routes lots of internal states and sensory cues to this neuron, impacting expression of a smell receptor.
” In this research study, we dissected the mechanisms that control the levels of a single olfactory receptor in a single olfactory nerve cell, based upon the ongoing state and stimuli the animal experiences,” says senior author Steven Flavell, Lister Brothers Associate Professor in MITs Department of Brain and Cognitive Sciences. “Understanding how the integration takes place in one cell will point the way for how it may take place in basic, in other worm nerve cells and in other animals.”
MIT postdoc Ian McLachlan led the study, which was just recently released in the journal eLife. He said the group didnt always know what they d discover when they started.
” We were amazed to discover that the animals internal states might have such an impact on gene expression at the level of sensory nerve cells– essentially, cravings and stress caused changes in how the animal senses the outdoors world by changing what sensory neurons react to,” he says. “We were also thrilled to see that the chemoreceptor expression wasnt simply depending on one input, but depended on the amount overall of external environment, dietary status, and levels of stress. This is a brand-new method to think of how animals encode competing states and stimuli in their brains.”
Instead, those targets emerged from the unbiased information they collected when they looked at what genes altered in expression the most when worms were kept from food for 3 hours compared to when they were well-fed. AWA proved to be a neuron with a big number of these up-regulated genes and two receptors, STR-44 and SRD-28, appeared particularly popular amongst those.
McLachlan and his co-authors were then able to show that STR-44 expression likewise independently changed based on the presence of a stressful chemical, based on a range of food smells, and on whether the worm had received the metabolic advantages of consuming food. Additional tests led by co-second author Talya Kramer, a graduate student, exposed which smells trigger STR-44, enabling the researchers to then demonstrate how modifications in STR-44 expression within AWA directly impacted food-seeking habits.
In one experiment McLachlan and Flavells group showed that while both fed and starving worms would wriggle toward the receptors favorite smells if they were strong enough, only fasted worms (which express more of the receptor) might identify fainter concentrations. In another experiment, they discovered that while hungry worms will decrease to eat upon reaching a food source even as well-fed worms cruise on by, they might make well-fed worms act like fasted ones by artificially overexpressing STR-44. Such experiments demonstrated that STR-44 expression modifications have a direct result on food-seeking.
Other experiments demonstrated how several elements push and pull on STR-44. For instance, they found that when they included a chemical that worries the worms, that ratcheted down STR-44 expression even in fasted worms. And later they showed that the exact same stress factor suppressed the worms desire to twitch toward the odor that STR-44 reacts to. So much like you may avoid following your nose to the pastry shop, even when starving, if you see your ex there, worms weigh sources of stress against their hunger when choosing whether to approach food. They do so, the study reveals, based upon how these various hints and states push and pull on STR-44 expression in AWA.
Numerous other experiments took a look at the pathways of the worms nerve system that bring sensory, appetite, and active consuming hints to AWA. Technical assistant Malvika Dua helped to expose how other food-sensing nerve cells affect STR-44 expression in AWA by means of insulin signaling and synaptic connections. Cues about whether the worm is actively eating pertained to AWA from neurons in the intestine that use a molecular nutrient sensing unit called TORC2. These, and the stress-detecting path, all acted upon FOXO, which is a regulator of gene expression. In other words, all the inputs that impact STR-44 expression in AWA were doing so by independently pressing and pulling on the same molecular lever.
Flavell and McLachlan note that paths such as insulin and TORC2 exist in not just other worm sensory nerve cells however also many other animals, including people. Sensory receptors were up-regulated by fasting in more neurons than just AWA. These overlaps suggest that the system they found in AWA for integrating details is likely at play in other neurons and maybe in other animals, Flavell states.
And, McLachlan includes, standard insights from this research study could assist notify research on how gut-brain signaling by means of TORC2 works in people.
” This is becoming a major pathway for gut-to-brain signaling in C. elegans, and I hope it will ultimately have translational value for human health,” McLachlan says.
Recommendation: “Diverse states and stimuli tune olfactory receptor expression levels to regulate food-seeking habits” by Ian G McLachlan, Talya S Kramer, Malvika Dua, Elizabeth M DiLoreto, Matthew A Gomes, Ugur Dag, Jagan Srinivasan and Steven W Flavell, 31 August 2022, eLife.DOI: 10.7554/ eLife.79557.
In addition to McLachlan, Flavell, Kramer, and Dua, the papers other authors are Matthew Gomes and Ugur Dag of MIT and Elizabeth DiLoreto and Jagan Srinivasan of Worcester Polytechnic Institute.
The JPB Foundation, the National Institutes of Health, the National Science Foundation, the McKnight Foundation, and the Alfred P. Sloan Foundation provided funding for the study.

New research by MIT reveals how environment and state are incorporated to manage habits. They looked, in detail, at the systems that manage the levels of a single olfactory receptor in a single olfactory neuron of the C. elegans worm based upon the ongoing state and stimuli experienced.
An easy animal design reveals how states and stimuli such as smells, stress factors, and satiety assemble in an olfactory neuron to assist food-seeking behavior.
In some cases you are starving and for that reason tempted when aromas waft through your window. Your brain balances many impacts in determining what youll do.
An example of this operating in a much simpler animal is detailed in a brand-new MIT study. It highlights a possibly fundamental principle of how nerve systems incorporate several factors to guide food-seeking behavior.