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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
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What causes 'individual' behavior?

Born at the same time, in the same place, with the same genes - yet not the same...

Put 50 newborn worms in 50 separate containers, and they'll all start looking for food at roughly the same time. Like members of every other species, 'baby' C. elegans worms tend to act like others their own age.

However, the in-born "rules" that control age-appropriate behavior in a developing worm are not really stable. Despite sharing identical genes and growing up in an identical environment, petri dishes, individual worms march to the beat of their own drum.

New research from Rockefeller University suggests how variations in certain neuromodulators in a c elegans worm's developing nervous system can lead to variations in its behavior. The study, led by Cori Bargmann, is made possible by a newly engineered system that allows scientists to record behavior of individual worms over their entire lifecycle about 50 hours total and is published in the journal Cell.
"There are patterns at every stage of life different from other stages, and with the system we created we can see that really clearly in ways that are surprisingly complex and robust. We can also observe something as complex as individuality and start to break down the biology behind it."

Cori I. Bargmann PhD, Torsten I. Wiesel Professor, Head of the Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY, USA; and funded under the Chan Zuckerberg Initiative, Palo Alto, CA, USA.

Born this way?

Our understanding of how genes govern behavior comes largely from experiments that involve altering a subject's normal state with external stimuli over a short period of time, such as giving a mouse some cheese as a reward for completing a maze. We know less about how genes affect behavior as animals go about their normal routines.

Shay Stern, a postdoctoral associate in Bargmann's laboratory, engineered a system to capture spontaneous, internally-generated behavior in worms over the span of their entire 50 hours of development. They focused on foraging behavior the worms' roaming movements in search for food and found incredibly similar patterns of activity between individuals.
"Even though the worms were separated and not receiving external cues, they were actively searching for food at the same time point in development as other worms. And we saw very precise differences in foraging behavior at each stage of development."

By creating genetic mutations in some worms, researchers were also able to identify specific neuromodulators (chemical messengers in the brain) that normally keep the animals on schedule.
A mutation that disrupted the chemical messenger dopamine, affected the worms' roaming speed during late development. Mutations also affected behavioral patterns within each stage of development, suggesting neuromodulators influence behavior at different times.

While the majority of worms conformed to the same behavioral patterns, a number of individual worms stood out for their atypical foraging. Variation between individuals is typically attributed to genetic differences or exposure to different environments, but researchers designed this study to account for these differences, using genetically identical worms raised in identical petri dishes. One explanation for this variation could be small differences in how neurons connect to each other which is not controlled by genetics.
There was also added support for contribution by neuromodulators as removing the chemical messenger serotonin from a population of worms drastically reduced the number of worms displaying unique roaming - or individuality.

Indeed, without serotonin, all of the worms exhibited the same foraging behavior at the same time which suggests how important individuality is to survival. "From an evolutionary point of view, we can't have everyone going off the cliff all at once like lemmings someone's got to be doing something different for a species to survive," explains Bargmann.

Long-term tracking reveals stereotyped behavioral trajectories in C. elegans
Spontaneous behavior is patterned within and between developmental stages
Some individuals have consistent, non-genetic behavioral biases
Neuromodulation regulates stage-specific behaviors and levels of individuality

Animals generate complex patterns of behavior across development that may be shared or unique to individuals. Here, we examine the contributions of developmental programs and individual variation to behavior by monitoring single Caenorhabditis elegans nematodes over their complete developmental trajectories and quantifying their behavior at high spatiotemporal resolution. These measurements reveal reproducible trajectories of spontaneous foraging behaviors that are stereotyped within and between developmental stages. Dopamine, serotonin, the neuropeptide receptor NPR-1, and the TGF-? peptide DAF-7 each have stage-specific effects on behavioral trajectories, implying the existence of a modular temporal program controlled by neuromodulators. In addition, a fraction of individuals within isogenic populations raised in controlled environments have consistent, non-genetic behavioral biases that persist across development. Several neuromodulatory systems increase or decrease the degree of non-genetic individuality to shape sustained patterns of behavior across the population.

Authors: Shay Stern, Christoph Kirst, Cornelia I. Bargmann.

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Feb 19, 2018   Fetal Timeline   Maternal Timeline   News   News Archive

Activity patterns of individual worms were similar (RED outlined petri dish) throughout development - except when dopamine or serotonin neuromodulators were disrupted (BLUE outlined petri dish). Image credit: Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, Rockefeller University

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