Donald Iain MacDonald

ATV catching big air, labelled "neuropeptides."

"The connectome is like a road map."

Really enjoyed this great book telling the story (and experiments) behind our understanding of the hypothalamus, neuron coding, and 'wireless' neurochemical signaling (oxytocin, prolactin etc)... mitpress.mit.edu/978026255193...

Thank you, that makes sense!

This is a great and interesting paper, congrats! I had one question re the heat map in Fig 2C. How should we interpret the channels that are not found in the peripheral terminal, but are present in the other compartments e.g. Scn9a. Is it really absent or just not detected or hidden by the scaling?

Congratulations, this is a phenomenal paper and one to which I referred many times starting out in the field as a phd student!

Some very nice 50 year old immunostaining that showed for the first time that Substance P was in sensory neurons and their central terminals. Only three pictures, published in Science! www.science.org/doi/abs/10.1...

Congratulations to nih scientists Nima and Lars!

"A distributed coding logic for thermosensation and inflammatory pain" Proud to have been involved in this! www.nature.com/articles/s41...

different coloured mice on a white background

Turns out, two of pain’s most famous messengers — Substance P and CGRPα — might not be so essential after all. Mice missing both still felt pain just fine, challenging decades of assumptions about how pain signals travel.
buff.ly/ypISrtx

In science, we don’t give negative data nearly enough love. Showing with genetic precision that CGRP and Substance P aren’t needed for different kinds of acute and chronic pain? That’s huge.

Carriers of SCN9A variants linked to inherited and acquired pain syndromes show no alteration in the prevalence of pain or analgesic usage in the UK Biobank cohort The voltage-gated sodium channel NaV1.7, encoded by the SCN9A gene, is integral to nociceptor excitability and pain sensation. Multiple gain-of-function SCN9A variants have been reported to cause auto...

I'm shook!! www.medrxiv.org/content/10.1...

Its very exciting. I think we still lack fundamental understanding of how these local efferent effects work. What drives release of the peptide? Is it always spike dependent? Can this happen without APs propagating up to DRG and dorsal root to cause sensation/pain? Can the signals go in reverse?

UCL – University College London UCL is consistently ranked as one of the top ten universities in the world (QS World University Rankings 2010-2022) and is No.2 in the UK for research power (Research Excellence Framework 2021).

Come join our lab as Postdoctoral Fellow! The project will investigate the maturation of spinal circuits and their plasticity within chronic widespread pain states.
Apply here: www.ucl.ac.uk/work-at-ucl/... until 11th April.
@ucllifesciences.bsky.social @uclnpp.bsky.social @jobrxiv.bsky.social

I think the amazing thing about patch clamp is it hasn't really ever been superseded as the gold standard to study ion channel function. I think people will still patch 50 years from now !

That's one way to tarnish the Ramon y Cajal name!

Oncostatin M can sensitize sensory neurons in inflammatory pruritus - PubMed Chronic itch is a major symptom of many inflammatory skin diseases. This type of pruritus is thought to be facilitated by cytokines that activate cutaneous nerve fibers; however, the molecular compone...

This is very interesting. These neurons seem highly similar to the SST/NPPB/OSMR neurons whose activation can drive itch pubmed.ncbi.nlm.nih.gov/34757808/

Thank you for sharing our updated preprint, the results surprised me as much as everyone else!

Pain persists in mice lacking both Substance P and CGRPα signaling The neuropeptides Substance P and CGRPα have long been thought important for pain sensation. Both peptides and their receptors are expressed at high levels in pain-responsive neurons from the peripher...

This study challenges traditional views of pain biology by showing that deleting Substance P and CGRPα does not affect acute or chronic pain in mice, underscoring the complexity of finding effective pain targets.
www.biorxiv.org/content/10.1...

What I really admire about LeDoux's books is that he changed his mind about whether his pioneering rat fear conditioning studies were actually studying fear at all! And then criticized the field he basically started to highlight the differences between animal instinctual behaviours and human emotion

The book is great. I was amazed at the crazy hours and single minded dedication at the rig it took to make some of his early discoveries...And I just clocked the forward is by the also remarkable Nancy hopkins, really recommend The Exceptions about her campaign at MIT!

Very excited to read this once it comes out!

Quite a find! Need to order this one!