Andrew Plested
@andrewplested
Glutamate ORCID: 0000-0001-6062-0832
Great! I’m very jealous. Complete disaster here (northern Italy)- the relatively young tree (2 year old) grew fruits but lost all its leaves in the recent heatwave. The head of the family council thinks it is dead/dying. I’m irrigating daily in the hope of saving it.
We don’t yet know all that slow AMPA can do. It might unlock NMDA, maybe synaptic plasticity. It's slowness could be important for cognitive processes. The craphical abstract from 2021 shows key ideas: STP, diversity and detonation. But now we do know: CNIH3 is a main actor for slow AMPA! 20/n
CNIH3 is not just a marker, it's a great candidate for slow AMPA. Jenn Noonan did tough experiments in HEK cells (everything dies...) to show CNIH3 makes AMPARs very slow, at least 100 ms decay and a big reduction of desensitisation (confirming results from Bowie, Nakagawa and Cull-Candy labs). 17/n
We were amazed to see that two different shRNAs against CNIH3 (which should spare CNIH2, AMPA nerds) completely removed all trace of slow AMPA. Not reduced - GONE! A scrambled control shRNA did not affect slow AMPA. 15/n
Marin did the bioinformatics and one stunning candidate appeared: CNIH3, an understudied auxiliary protein. Marin confirmed that the functional dorsal ventral gradient was indeed rather strong, and then the critical experiment. 14/n
One clue, if you have a slow current that is not blocked by APV and NBQX/DNQX/CNQX, but is blocked by GYKI, this could well be slow AMPA. In the 2021 paper, we called the slow AMPA current "the Pedestal". 10/n
We found a molecular mechanism in heterologous expression, and then started hunting for slow currents at synapses. To our surprise and delight, slow AMPA currents were hiding in plain sight in the well-studied CA1 pyramidal cells. This is still my favourite figure ever *thanks Nico*! 7/n
On my way back from the Synaptic Transmission GRC. Possibly the best scientific meeting that I have ever attended. Great spirit, unbelievable quality. Trainees on fire, revelations and maybe the best GRC location. Many thanks to the chairs, Sam Young and Inna Slutsky! See you again in 2 years!
What’s frustrating is, having left Trent (Real Madrid RB for pity’s sake!) at home ostensibly because he’s not a good enough defender, England end up playing a centre back at right back, and a barely-fit right back plays inverted at the base of midfield. Neither does anything creative. But Trent..
I found it quite hard to do the Martin Parr homage. @christlet.bsky.social
Very interesting. A new axis of hippocampal diversity. If I got it right, St18+/+ pyramids are basically non-thorny deep local excitatory “interneurons” barely projecting out of CA3. In mouse and human! Beautiful work from @jakefwatson.bsky.social and colleagues in the Jonas lab!
Incredible. Not sure if you can read- underneath the statue of Confucius at Clare College. “Goose itself is not golden. 1% of papers are golden” At least, that’s what Gemini told Claude.
I tried out the new S15 S-Bahn from gesundbrunnen to Hauptbahnhof. Very smooth. I tried to live Skeet, but well, Berlin internet…you might as well be on Mars sometimes.
Striking improvement with the laser phase plate to boost contrast, and in exactly the range that's needed for modelling the details of protein structures. Still lots of headroom in Cryo-EM. www.science.org/doi/10.1126/... #biophysics