Tim Vogels Profile picture
Oct 18 11 tweets 6 min read
Dear #neurotwitter, we dropped this onto @biorxiv_neursci for your perusal. It's an unusual piece from my lab & I really, really enjoyed working on it with @chc1987. Here it is: Metabolically spikes serve neuronal energy homeostasis (and protect neurons). doi.org/10.1101/2022.1…
"Metabolic Spikes" is a modelling study on the origins of "spontaneous" activity in neural systems. That sort of baseline activity is ubiquitous! As a field, we accept it's there & include it in models, but why do neurons do that? Fire in the absence of input? Seems kinda weird.
More formally speaking, non-causal spiking contradicts the notion that spikes should be used for coding, and what's more, such "null spikes" seem like a waste of energy. Sort of like opening a window in an NYC apartment in the middle of winter....
We argue, YASS, they are a waste of energy, but not insensibly so. To grok this, we need to take a dive into undergrad biochemistry, so hold on tight ( actually don't worry, it's easy:) Welcome to the wonderful world of #mitochondria, the power house of the cell.
Mitos make ATP & it's rather fascinating, but for us it came down to one thing: When mitochondria make ATP, they also make #free_radicals. That's bad bad bad! Worse, this relationship is non-monotonic! More ATP, more reactive oxygens (ROS). Less ATP, more ROS, too! Seems #toxic!
Especially given that it's not easy for a neuron to guess how much ATP it's gonna need. Some neurons can use more than 50% of their energy budget on input and output processing, and both can fluctuate wildly! And because thinking is sorta important, neurons can't just chill.
They must be ready for action, but we think that when they don't use up their ATP budget, they will quickly start poisoning themselves! Wouldn't it be nice if the cell could just, I dunno, waste a bunch of ATP? Enter the #metabolic_spike!
Here, we propose that a neuron senses its metabolic state (+toxic byproducts) & adjusts its activity accordingly. When it's low on ATP, it hits the brakes, when it's high, it spikes; all by way of your friendly neighbourhood metabolically-sensitive #ion_channels. That's the story
But that's not all folks! We have a bunch of quirky & interesting consequences of metabolic spikes, knock-on effects, what-ifs, experimental predictions & we take a look at where spontaneous activity is super important, the dopamine system. What if metabolic spikes broke😱?
Read the paper, doi.org/10.1101/2022.1… or stay tuned for more, later right here on this thread in #technicolor.

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More from @TPVogels

Oct 19
Good morning. Thanks for coming back. Yesterday we discussed how neurons may benefit from spiking even in absence of inputs, maintaining a base level of ADP production, from ATP that would otherwise clog its production line & thus create free radicals.
But there is quite a lot more to unpack still, and some of you may not have read the paper (yet ;) so let's see where we can go with this. Would you like to hear about
Oh, right, we also got these: What do you wanna read about?
Read 10 tweets
Dec 8, 2020
OK, finally our tweeprint for the NeurIPS paper. Here we go. Synaptic plasticity, it's the holy grail of learning and memory. This is work by @basile_cfx, @hisspikeness, @ejagnes, @countzerozz & myself, on how to find the grail, maybe biorxiv.org/content/10.110…
Common dogma dictates that we remember, learn, and develop to sense, see, hear, etc. in early devo by way of activity-dependent rules that determine how we wire up, how we maintain and how we adjust our synapses.
Slice physiology points towards distinct and precise rules that determine synaptic strength. The most famous one is the Gerstner / Markram / Bi & Poo / Nelson Abbott STDP curve, for excitatory plasticity, read all about it e.g. here Magee & Grienberg annualreviews.org/doi/abs/10.114…
Read 16 tweets
Jul 4, 2019
So, the deadline for the IBRO SIMONS #imbizo is approaching quickly. It's quite possibly the best computational neuroscience summer school south of the equator, so do apply at imbizo.africa @SCglobalbrain @isiCNI @ibroSecretariat @alfairhall @JosephRaimondo @adantro
While you're here, we have some tips and tricks for a successful application to the imbizo, but more generally to anything you will ever want to apply for:
(added pics for added value)
0) Ignore the odds & competition. Deliver the best you got. Inquire if you got questions. Don’t take rejection personally. Request feedback, apply again. You want in? You'll make it eventually. These typically empty catchphrases, esp. 4 POC, are true for imbizo.africa
Read 10 tweets
Oct 15, 2018
@markdhumphries @cian_neuro @marius10p @ulisespereirao @neurograce @computingnature @bitking69 @CousinAmygdala @michael_okun Thanks Mark! A few answers on E/I balance. Re: Experimental influence, yeah, I'd say the early E/I papers by @HSompolinsky et al. were definitely an inspiration for the field & I'd say it's the constant T&E interplay that makes the EI balance example great ncbi.nlm.nih.gov/pubmed/8939866
@markdhumphries @cian_neuro @marius10p @ulisespereirao @neurograce @computingnature @bitking69 @CousinAmygdala @michael_okun @HSompolinsky @shadlen & Newsome had been thinking about the origins of irregular firing for a long time, & theory provided an explanation for what they saw. I think the first people to actually record EI balance were Moore & @SachaNelsonLab physiology.org/doi/abs/10.115… in parallel w/ the theory.
@markdhumphries @cian_neuro @marius10p @ulisespereirao @neurograce @computingnature @bitking69 @CousinAmygdala @michael_okun @HSompolinsky @shadlen @SachaNelsonLab The follow up experimental papers by Wehr & Zador & Shu et al, both 2003, then drove the story home, and pointing towards more interesting questions. ncbi.nlm.nih.gov/pubmed/14647382 & ncbi.nlm.nih.gov/pubmed/12748642
Read 8 tweets

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