Stephen Zhang Profile
Stephen Zhang

@StephenXZhang

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Incoming PI. Neuroscientist. Dopamine devotee. FLIM fanatic. Audiobook addict.

Boston
Joined June 2011
Don't wanna be here? Send us removal request.
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@StephenXZhang
Stephen Zhang
1 year
I am excited to share our preprint on how hypothalamic hunger- and satiety-promoting neuropeptides compete at the level of cAMP to regulate feeding. We imaged endogenous peptide signals in subcellular compartments during behavior. Below are the findings:
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@StephenXZhang
Stephen Zhang
3 years
I am excited to share our new paper on mating drive! We found dopamine neurons in the hypothalamus that control the motivation to mate in male mice, and these dopamine neurons signal through persistent cAMP elevations in the downstream circuitry.
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@StephenXZhang
Stephen Zhang
3 months
I will start my group in @NYU_CNS in January 2025 to study how the brain tracks and predicts physiological needs using intracellular signals. Please keep an eye out for updates!
@aa_fenton
Andre Fenton
3 months
Been years since my last post - here’s big news… Excited to announce that @StephenXZhang will join the community of our CNS faculty @NYU_CNS to launch his independent research program! Ready to support and collaborate to help Stephen discover rules of biomolecular computation!
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@StephenXZhang
Stephen Zhang
19 days
My lab at @NYU_CNS is recruiting trainees at all levels starting in Jan 2025! Our goal is to understand how behavioral variables such as calorie intake and time estimates are computed using molecules inside individual neurons.
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@StephenXZhang
Stephen Zhang
2 years
Very, very honored to be able to share my science at this meeting!
@OptoGRC
Optogenetics Gordon Research Conference
2 years
#OptoGRC2022 Session update! ✨ 🧠💕🧠 Bring your social brain and join us for this session on the neural circuits underlying sociality led by @bjmarlin & featuring @DulacLab , @moccalin , @IshmailSaboor , #GulDolen , @gstuber & @StephenXZhang .
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@StephenXZhang
Stephen Zhang
1 year
Yes, our goal is to make it a great opportunity for trainees to engage in one-to-few conversations with speakers, panelists, and each other!
@OptoGRC
Optogenetics Gordon Research Conference
1 year
Introducing your #OptoGRS2024 co-chairs: @StephenXZhang & @brains_with_deb ! This GRS will provide an exciting opportunity for trainees to connect and delve into discussions about their work! Look out for more info soon 🧠🔦
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@StephenXZhang
Stephen Zhang
4 months
⏰Last few spots remain for #optogrs ! This is a trainee-focused prelude to the @OptoGRC . Apply now to be considered as a speaker and help us decide whether we want to expand this GRS. Keynote talk by the great Haruo Kasai!
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@StephenXZhang
Stephen Zhang
2 years
Very honored and grateful for the fellowship!
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@StephenXZhang
Stephen Zhang
3 years
I am excited and grateful to be selected to present our work @Vidaconference ! The talk is about a persistent mode of dopamine signal transduction and how it may relate to an innate motivational state. New tools to come as well. #ViDA2021
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@StephenXZhang
Stephen Zhang
3 years
My talk at @VidaConference is now available online. Please check it out if you are interested in dopamine transduction and motivation! Many thanks to the wonderful organizers for making the event happen.
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@StephenXZhang
Stephen Zhang
4 months
Both GRC and GRS are set to take place in Lucca, Italy, July 20-21 (GRS) + July 21-26 (GRC). See the link above for details. If you applied already, please make sure your abstracts and speaker/discussion leader preferences are up to date!
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@StephenXZhang
Stephen Zhang
2 years
At GRC, I waited my turn to ask Ian to nerd out and walk me through his holography rig. I walked away really impressed. Ian is very knowledgeable and patient in explaining his setup. Great for trainees!
@ianOldenburg
Ian Antón Oldenburg
2 years
Oldenburg lab is hiring (postdoc, techs, other). If you think that population codes are a thing, and want to test the idea come talk to me. We use multiphoton optogenetics to write to whole populations of cells to test what different patterns do
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@StephenXZhang
Stephen Zhang
1 year
This paper is insanely well done and cool!
@NiraoShah
Nirao Shah
1 year
Thrilled to share that our study is now online @CellCellPress , outlining a neural circuit for male sexual behavior, drive, and reward.
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@StephenXZhang
Stephen Zhang
5 months
Slow-timescale plasticity over days. Lauren's thesis work shows dopamine desensitization as a natural mechanism of behavioral flexibility.
@biorxiv_neursci
bioRxiv Neuroscience
6 months
Local desensitization to dopamine devalues recurring behavior #biorxiv_neursci
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@StephenXZhang
Stephen Zhang
2 years
This is a very cool paper. GPCRs have a life after endocytosis that is not just being taken out of commission. The activated beta2 receptor is here shown to activate ERK, in a process that requires arrestin mediated endocytosis, a long Gs variant, and mek & raf recruitment.
@jinzhanglab
Jin Zhang Lab
2 years
Excited to share our new paper out in @Nature , led by our postdoc @Dr_Yonghoon . We report the discovery of spatially organized GPCR-mediated ERK signaling using biosensors. #GPCR #ERK #biosensor #imaging #CellSignaling 1/6
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@StephenXZhang
Stephen Zhang
3 years
I was very lucky to be able to join @boron110 et al in the podcast. The topic is how a motivational state emerges over time. I had a blast talking about the dew lovers with Sarah!
@boron110
SarCrespi
3 years
New @ScienceMagazine podcast: Does Botox combat depression w/ @cathleenogrady , the fruit fly sex drive w/Steven Zhang @andermann_mark lab, and a series on race and science w/ @angeladsaini Keith Wailoo @princeton
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@StephenXZhang
Stephen Zhang
3 years
1/n We first characterized the basic properties of male mating drive. We found that a single successful mating greatly diminishes male mating drive, which then gradually recovers over ~1 week (!). We call this phenomenon long-term satiety.
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@StephenXZhang
Stephen Zhang
1 year
10/n This project benefits from stimulating collaborations with Brad Lowell and Lin Tian labs. In particular, I want to thank Angela Kim, who contributed equally to this study, @LinTianPhD for sharing a new NPY sensor, and @andermann_mark for continued guidance. TY for reading!
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@StephenXZhang
Stephen Zhang
3 years
16/n The new molecular tools biPAC and PDE4D3-Cat are being deposited to Addgene! For Arduino, Trinket, and Teensy gadgets that we used to do photometry and optogenetics experiments, please see: Thank you for reading!
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@StephenXZhang
Stephen Zhang
3 years
3/n To study these phenomena, we followed a key lesson from previous studies in rats, humans, and flies: dopamine. In particular, studies by Elaine Hull showed that dopamine-agonist infusion in the MPOA (a critical area for mating) is very effective in promoting mating.
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@StephenXZhang
Stephen Zhang
3 months
@aa_fenton @NYU_CNS Thank you so much, André! I am really, really exited to share a new chapter of my career with new colleagues, new trainees, and new friends!
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@StephenXZhang
Stephen Zhang
2 years
Interesting development. Two Qs: 1) Are editors the only shot callers? 2) How does this affect reviewer motivation?
@eLife
eLife - the journal
2 years
Today, we’re introducing a new model that eliminates accept/reject decisions. By publishing every paper with eLife reviews as a Reviewed Preprint, we plan to restore autonomy to authors, ensuring that they will be judged by what, not where, they publish.
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@StephenXZhang
Stephen Zhang
3 years
@boron110 The paper is here: Much of the credit goes to twitterless coauthors: Ethan Glantz, Lauren Miner, Dragana Rogulja, and Mike Crickmore
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@StephenXZhang
Stephen Zhang
3 years
5/n We determined the source of dopamine to be the neighboring AVPV and PVpo dopamine cells. Silencing these neurons mimics sexual satiety but does not demotivate feeding or drinking. After natural satiation, stimulating these dopamine neurons reinvigorates male mating behaviors.
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@StephenXZhang
Stephen Zhang
3 years
2/n On the other hand, social interactions with females without the transfer of reproductive fluids result in sustained elevations in mating drive for ~30 min, which gradually declined back to baseline over ~2 hours. We call this short-term priming.
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@StephenXZhang
Stephen Zhang
19 days
We turn problems of behavior into problems of molecules, and ultimately problems of in vivo two-photon microscopy and optogenetics. Come work with us in a vibrant scientific environment at the heart of NYC!
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@StephenXZhang
Stephen Zhang
3 years
Another important optogenetic AC by @Gao_SQ and colleagues, with significant improvements on dark activity. Looks like flies are made and ready to use too!
@Gao_SQ
Shiqiang Gao
3 years
Not PACman, but PACmn, after a series of bPAC modification, for improved optogenetic control of cAMP @BMCBiology . A fruitful collaboration with Christine E. Gee group, @Kittellab group, @OertnerLab , @Kozjak_Lab and @TobbeKunz . Tool development supported by @TR_240 . @Uni_WUE .
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@StephenXZhang
Stephen Zhang
2 years
Also, the feeling of being able to be included in a panel with the greats of the field is still sinking in. So far, super pumped!
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@StephenXZhang
Stephen Zhang
3 years
10/n Meanwhile, our collaborators in the Nagel lab developed tools to directly manipulate cAMP signaling. Using biPAC, a new optogenetic adenylyl cyclase that makes cAMP on demand, we showed that cAMP elevation in dopamine-receiving neurons is sufficient for priming.
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@StephenXZhang
Stephen Zhang
2 years
This science issue's cover paper has adorable figures. Let's do more putting dog pictures in pie chart please, relevant or not.
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@StephenXZhang
Stephen Zhang
3 years
9/n Dopamine receptors can alter intracellular cAMP levels and PKA activity. Using 2p fluorescence lifetime imaging, we found persistent elevations in both cAMP concentration and PKA activity in the MPOA that last for ~30 min after dopamine stimulation or female pairing!
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@StephenXZhang
Stephen Zhang
3 years
7/n Sure enough, 30-sec dopamine stimulation was sufficient to prime mating drive for ~30 min. When we combined both dopamine stimulation and natural priming, we could shorten the male’s latency to mate from ~5 min to ~6 seconds!
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@StephenXZhang
Stephen Zhang
3 years
11/n In contrast, when we used PDE4D3-Cat – a constitutively active phosphodiesterase – to erase cAMP, natural priming is blocked. These results show that persistent cAMP sustains mating drive over tens of minutes.
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@StephenXZhang
Stephen Zhang
2 years
Big fan of Cellpose 1 and now 2. It is versatile and user friendly. The resource cost for 2D segmentation is minimal. Nice job!
@computingnature
Carsen Stringer @[email protected]
2 years
Cellpose 2 paper 🦠🤖 is out now: Train your own models in <1h in the GUI. For an overview, see the research briefing: @naturemethods , with @marius10p , #notthecover by @ChrisCzaja #cellpose
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@StephenXZhang
Stephen Zhang
3 years
15/n We also had a wonderful time collaborating with the Nagel lab. @Gao_SQ , Shang Yang, and Georg Nagel were incredible in protein engineering and made new tools from zero to fully functional in a couple of months.
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@StephenXZhang
Stephen Zhang
3 years
4/n We found that endogenous dopamine release in the MPOA ramps up as a male mouse approaches a female and drops back to baseline when the male sniffs the female. After satiation, dopamine release is largely gone!
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@StephenXZhang
Stephen Zhang
3 years
14/n Many, many thanks to my PI @andermann_mark for his patience and guidance throughout the process. This work was massively accelerated by the technical foundations built by @andrewlutas . Other twitterless authors are Adriana Diaz are Hugo Fluhr.
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@StephenXZhang
Stephen Zhang
3 years
Great new paper from Andrew, on dopamine and cAMP transients, timescales, and plasticity in BA.
@andrewlutas
Andrew Lutas
3 years
History-dependent dopamine release increases cAMP levels in most basal amygdala glutamatergic neurons to control learning
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@StephenXZhang
Stephen Zhang
2 years
@sarah_stern @brains_with_deb You set the bar high Sarah. We will do our best!
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@StephenXZhang
Stephen Zhang
2 years
Case in point.
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@StephenXZhang
Stephen Zhang
3 years
6/n These results show that satiety is at least partially controlled at the level of AVPV/PVpo dopamine neurons’ activity. We next asked if the same dopamine release in the MPOA can also prime mating drive. If so, how does the 30-min persistence work?
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@StephenXZhang
Stephen Zhang
2 years
Oh cool, one highlight for me is the overriding of "diestrus unreceptiveness" in figure 4. This is a pretty rare effect to get as far as I understand.
@moccalin
Dayu Lin
2 years
In the midst of our first #HypoGRC , I am happy to share our new works that is out today in Neuron, led by an extremely talented postdoc fellow @yinluping662 . Luping will present a poster this Thursday on the story. So check it out! | Home
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@StephenXZhang
Stephen Zhang
3 years
12/n We think our results explain the side effects of cAMP-altering drugs on libido (e.g., SSRIs, opioids). Many of these drugs prevent cAMP elevation, therefore diminishing the motivating effects of dopamine.
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@StephenXZhang
Stephen Zhang
1 year
@DanielBayless @0chungha @YRenzhi @NiraoShah Congratulations Daniel. This is phenomenal work overall!
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@StephenXZhang
Stephen Zhang
3 years
13/n Questions remain regarding the utility of persistent cAMP in other systems, sexual dimorphic roles of AVPV/PVpo dopamine neurons, the orchestration of the 1-week recovery timeline, and how cAMP/PKA is used to gate the activity of the mating circuitry.
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@StephenXZhang
Stephen Zhang
3 months
@alexbchen Thanks so much, Alex!
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@StephenXZhang
Stephen Zhang
10 months
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@StephenXZhang
Stephen Zhang
3 years
@BrainsExplained Congrats on the new jobs! You guys make it happen!
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@StephenXZhang
Stephen Zhang
1 year
9/n Unlike in other brain regions where elevations in cAMP drive spiking, here cAMP calibrates the rate of satiation by gradually potentiating feeding-related excitatory inputs to the satiety-promoting neurons, ultimately stopping meal consumption.
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@StephenXZhang
Stephen Zhang
3 years
8/n We next searched for the biological basis of motivational persistence. We were unable to detect persistence at the level of dopamine release, so we looked one step further into the transduction of dopamine signals in downstream neurons.
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@StephenXZhang
Stephen Zhang
3 years
For brief summaries please see the thread here or this blurb
@scthornquist
Stephen Thornquist
3 years
Animals exhibit most behaviors in the juvenile state. But a few (e.g. sex drive, parenting) develop later in life. Is the capacity for those behaviors only built in adulthood, or does the appropriate circuitry lie latent? Stephen Zhang and others answer this for flies:
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@StephenXZhang
Stephen Zhang
1 year
8/n When we mimicked the simultaneous increase in satiety peptides and decrease in hunger peptides, we saw a stronger satiety-promoting effect than either manipulation alone. We thank Jens Brüning and @FenselauHenning for providing reagents for this experiment.
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@StephenXZhang
Stephen Zhang
3 months
@Albert_T_Liu Thank you friend!
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@StephenXZhang
Stephen Zhang
3 years
Continues here:
@StephenXZhang
Stephen Zhang
3 years
9/n Dopamine receptors can alter intracellular cAMP levels and PKA activity. Using 2p fluorescence lifetime imaging, we found persistent elevations in both cAMP concentration and PKA activity in the MPOA that last for ~30 min after dopamine stimulation or female pairing!
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@StephenXZhang
Stephen Zhang
1 year
@michael_krashes Thanks Mike for the kind words!
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@StephenXZhang
Stephen Zhang
2 years
@scthornquist I don't mean motivation to strike down but to point out weaknesses and mistakes that the authors are compelled to address. Knowing that it's a one-way glass may affect how invested the reviewers are.
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@StephenXZhang
Stephen Zhang
3 months
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@StephenXZhang
Stephen Zhang
1 year
6/n Peptide signals can be made more persistent by a) elevating peptide tone or b) reducing competition. Supporting a), extended axon stimulation led to hunger-peptide signaling that lasted >10 min, possibly explaining its previously reported persistent behavioral impact.
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@StephenXZhang
Stephen Zhang
4 years
Congratulations man!
@HHMIJanelia
HHMI | Janelia
4 years
Welcome to our newest Mechanistic Cognitive Neuroscience group leader, Rob Johnson! Rob ( @blobology ) recently completed his PhD at Harvard and will start his lab at Janelia in January, studying how rodents make predictions and plan future actions.
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@StephenXZhang
Stephen Zhang
3 years
@Yoav_Livneh Chuckled at the scare quotes on "diabetes". 😂
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@StephenXZhang
Stephen Zhang
4 years
@casa_tuthill @matthewcobb @CurrentBiology Great book! I listened to the audio version of it and it's wonderful.
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@StephenXZhang
Stephen Zhang
1 year
7/n Peptide competition also means that cAMP levels and food intake are most effectively controlled if hunger and satiety peptides are regulated in opposite directions, which is precisely what is achieved by feeding, exercise, and hormones such as leptin and ghrelin.
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@StephenXZhang
Stephen Zhang
1 year
4/n This observation is consistent with recent recordings of oxytocin release in brain slices by Yulong Li’s group, and supports the local-diffusion model proposed by the late neuroscientist Tony van den Pol.
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@StephenXZhang
Stephen Zhang
3 months
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@StephenXZhang
Stephen Zhang
3 years
@ColumboAhmed Thank you, Sama!
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@StephenXZhang
Stephen Zhang
1 year
@iaahmed123 Too kind and thanks Ismail!
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@StephenXZhang
Stephen Zhang
3 months
@s_k_inoue Thank you Sayaka!
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@StephenXZhang
Stephen Zhang
3 years
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@StephenXZhang
Stephen Zhang
1 year
1/n Neuropeptide signals are stochastic. Either optogenetic axon stimulation or feeding can trigger cAMP transients in downstream neurons, but only on a random subset of trials. We traced this randomness to the stochastic release of neuropeptides.
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@StephenXZhang
Stephen Zhang
3 years
@Jonna_Singh_ Congratulations doctor
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@StephenXZhang
Stephen Zhang
3 years
@scthornquist Thanks! Appreciate the write up. Nicely done!
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@StephenXZhang
Stephen Zhang
3 years
@scthornquist And yes last paper!
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@StephenXZhang
Stephen Zhang
3 months
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@StephenXZhang
Stephen Zhang
1 month
@iaahmed123 @UUtah Congratulations!!
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@StephenXZhang
Stephen Zhang
2 months
@Kat_Evans_Neuro Thank you Kathryn 😊
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@StephenXZhang
Stephen Zhang
1 year
2/n This phenomenon is very different from cAMP signaling mediated by neuromodulators such as dopamine, for which the same postsynaptic neuron will show at least some cAMP responses on every trial.
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@StephenXZhang
Stephen Zhang
3 months
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@StephenXZhang
Stephen Zhang
1 year
5/n Hunger and satiety peptides push cAMP levels in opposite directions, and their signals compete intracellularly. This competition causes state-dependent cAMP signaling: hunger peptide has more influence in the fasted state, satiety peptide in the fed state.
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@StephenXZhang
Stephen Zhang
1 year
3/n Neuropeptide signals are effectively restricted to a ~100 µm region. Peptide-receiving subcellular domains that are closer than 100 µm are likely to sense the same neuropeptide plume, even if those domains belong to different neurons.
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@StephenXZhang
Stephen Zhang
3 months
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@StephenXZhang
Stephen Zhang
4 years
Whoa! "... waves of Erk activity travel across the osteoblast population as expanding concentric rings that are broadcast from a central source"
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@StephenXZhang
Stephen Zhang
4 months
@brains_with_deb and I are happy to answer questions! 😀
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@StephenXZhang
Stephen Zhang
1 year
@Lchantran @BU_Biology Congratulations Lynne!
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@StephenXZhang
Stephen Zhang
4 years
ICE: Foreign Students Must Leave The U.S. If Their Colleges Go Online-Only This Fall
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@StephenXZhang
Stephen Zhang
17 days
@krishnapri70714 @NYU_CNS Hi, yes please reach out through the website or email.
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@StephenXZhang
Stephen Zhang
18 days
@ihfaragai01 @NYU_CNS Of course! Please reach through the website or send me an email. Thank you!
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@StephenXZhang
Stephen Zhang
2 years
@Agnik85 @scthornquist Yea I'm for changing up the publication landscape, and it will break a few things, naturally. Just curious how things shake out.
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@StephenXZhang
Stephen Zhang
4 years
There is no benefit to this. These students are already in the country, paying tuition, and participating in their communities. This is nothing but a signal of racism.
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@StephenXZhang
Stephen Zhang
3 months
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@StephenXZhang
Stephen Zhang
2 months
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@StephenXZhang
Stephen Zhang
1 year
@pablo_jack Well we know that ultimately cAMP strengthens excitatory inputs these neurons during feeding. cAMP ->PKA -> AMPAR phosphorylation seems to be a reasonable guess on the intermediate step but we didn't test it.
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@StephenXZhang
Stephen Zhang
2 years
@Jingyi_Neuro @JCChildsFund Well deserved and congratulations!
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@StephenXZhang
Stephen Zhang
17 days
@TorresvJoel @NYU_CNS Hi. Yes, please reach out through the website or my email. Thank you
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Stephen Zhang
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Stephen Zhang
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