Action Potentials for September
1: New study on the neurobiology behind the evolution of vocal cords between two species of mice. First, the authors show that there is a clear vocal mode seen in the singing mouse that is not seen in the lab mouse:
Next, they report that this behavioral difference between species cannot be explained by differences in the size of the brain regions. Phrenology: still wrong.
Instead, they used a technique called MAPseq and found that there was a difference in the proportion of neurons projecting from the orofacial motor cortex to two specific regions: (a) the auditory region (AudR): ~14% in singing mice vs ~5% in lab mice, and (b) the periaqueductal gray (PAG): ~40% in singing mice vs ~12% in lab mice.
Now, could one argue that this is just another form of phrenology. That instead of pointing at bumps on the skull, we’re now pointing at spikes on an adjacency matrix. It’s arguable how much closer this gets us to “understanding”, whatever that means. But if this is simply a modern type of phrenology, at least it has the virtue of actually being accurate.
2: New study finds that dopamine is primarily released from varicosities that form synapse-like structures with target neurons that express dopamine receptors. This more precise and efficient model of dopamine signaling suggests a higher degree of control in neuromodulation than was previously thought.
As one piece of evidence for this, they show that in dopamine projections to the prefrontal cortex (labeled red with tdTom), varicosities in contact with neuronal cell bodies (pericellular) have much higher levels of BSN, a protein important for neurotransmitter release, compared to varicosities not in contact with cell bodies (neuropil).
3: New study finds that within dendrites, ribosomes and mitochondria are very close to one another. It turns out this is because co-transport with mitochondria is necessary and sufficient for ribosome positioning in dendrites. A nice example of how sub-cellular molecular information content comes to be correlated.
4: A new microscopy technique allows for highly multiplexed molecular labeling with correlative light and electron microscopy. For example, they visualize CGRP (typically stored in large dense-core vesicles) and VGluT2 (associated with small synaptic vesicles) signals in axon terminals forming synapses onto neuronal cell bodies, with distinct pools of both vesicle types clearly visible at the ultrastructural level.
5: In hydrocephalus ex vacuo, brain atrophy creates the illusion of increased CSF on neuroimaging. A new study proposes a similar concept, amyloid-removal related pseudo-atrophy (ARPA), where the brain appears to shrink after amyloid plaques are cleared. However, this reduction in volume is attributed to the removal of plaques, dystrophic cells, and immune cells, rather than actual neuron loss. In clinical trials of amyloid immunotherapy, volume loss actually correlates with better cognitive outcomes. This reminds me of data in schizophrenia showing that antipsychotics can be associated with loss of brain volume but improved clinical outcomes.
6: There are many trade-offs to testosterone. It has some general anti-inflammatory effects, which might be why it promotes muscle growth and repair. However, it also suppresses certain immune responses, particularly interferon signaling, which is associated with an increased susceptibility to infectious diseases in men. A new study shows that androgen therapy in trans men rapidly shifts their immune profiles to match those of cis men, including a functional decline in interferon responses in immune cells.
7: New study finds that semaglutide decreases all-cause mortality in an n = 17,604 RCT of people >= 45 yo with BMI >= 27 who had cardiovascular disease but not diabetes. People treated had significantly lower risk of dying from sudden cardiac death or infection, including death from Covid in particular. As these positive results continue to accumulate, it seems that we really might need Universal Basic GLP1A (UBG) for those who fit the indications.
8: Weaponized red tape is one reason that many mental health clinicians leave insurance networks. Former Cigna manager Anneliese Hanson says: “The idea is if you make it so frustrating for providers to follow up on claim denials, they’re just going to give up and the insurance company is not going to have to pay out.”
9: A case report describes a 31 year old man with comorbid depression and alcohol use disorder who relapsed after discontinuing the SSRI (escitalopram 10 mg daily) for a psilocybin “ceremony.”
10: In a prospective cohort study, perinatal OCD onset was much more common in the postpartum period (83%), compared to in pregnancy (17%).
11: An n=6 placebo-controlled crossover trial of high-dose propranolol (a beta blocker) finds that it is effective for aggression in patients age 12-19 yo with autism spectrum disorder.
12: I missed it but this March there was an update to the largest GWAS of OCD to date (still unpublished). They found that OCD genetic risk is positively correlated with genetic risk of all psychiatric disorders tested except for cannabis use disorder:
OCD genetic risk is associated positively with memory function and negatively with adult IQ. Among personality traits, it is strongly associated with the worry sub-cluster of neuroticism, less so the depressive sub-cluster.
13: Study finds that heritable aspects of non-cognitive “skills”, such as motivation and behavioral/emotional self-regulation, seem to become increasingly important for predicting academic success over the course of childhood development. However, I’m not sure motivation is a skill! That seems like kind of a key point.
14: Ancient DNA finds that people in Rapa Nui (European name Easter Island) had about 6.5–12.4% Native American admixture, consistent with them having contact with Native Americans prior to Columbus, in around 1250-1430.
15: Interview with Angela Thornton about her research on people’s interest in mind uploading. She found that more people said yes than no when asked about their willingness to do mind uploading if their body was physically dying. The proportion making this decision increased from 2020 to 2023, although it is unclear why. The most common reason that people wanted it is that people wanted to continue to be connected with and have relationships with loved ones. She found that telling stories about the topic seemed to help people be more open minded to it and think more deeply about it.
16: Our biostasis research roadmap is now published at Brain Sciences. To me this is an example of where the published version is a clear improvement over the preprint.
17: Our article on structural brain preservation is now published in Frontiers in Medical Technology. We discuss whether contemporary methods for preserving the brain could potentially one day allow for revival. Here are some personal reflections from me about the topic on Less Wrong.
A loose outline of the kind of system we need to build to make MAPseq data deterministic. Is a standard model of cell biology on the horizon? http://arxiv.org/abs/2409.11654
Interesting, testosterone seems to shift resources towards functions better suited for intra-male competition. We could expect that from models of optimal behaviour in contests.