Joel Geerling

Ten3–Lphn2-mediated target selection across the extended hippocampal network demonstrates a repeated strategy for circuit assembly How do a limited number of wiring molecules specify trillions of connections in developing brains? We previously found that inverse expression of a ligand–receptor pair, Teneurin-3 (Ten3) and Latrophi...

See also the accompanying bioRxiv paper on the Ten3/Lphn2 gradient in the developing hippocampus:
www.biorxiv.org/content/10.1...

Very cool paper — Ten1/Lphn2 expression gradients in the developing brain may be responsible for polysynaptic wiring topography across multiple brain systems (cerebellum, basal ganglia, visual and auditory brainstem).

www.biorxiv.org/content/10.1...

Follow this link to advocate for research, especially on model organisms. www.fda.gov/news-events/...

Whole-brain tracing of axonal projections from prefrontal cortex in monkey (via fMOST serial confocal imaging). AI template followed by manual, touch-up tracing by “more than 100…annotators,” working a few microns at a time. Unsettlingly impressive.

t.co/cowyQJbujt

Here is a chat with Bosilijka Tasic and myself about the enhancer-mediated AAVs that we were both centrally involved in publishing. I truly believe these approaches are fundamentally important for both basic and clinical approaches! braininitiative.nih.gov/news-events/...

Thank you to all who served and sacrificed for our freedom.

(Iowa City VA this morning)

An MSL for a famous drug company just sent me an email with the line “You know the drill…” Yes, I do know the drill. It’s called rebranding sales reps to bypass University and hospital ethics restrictions while pretending otherwise.

Longitudinal analysis of a dominantly inherited Alzheimer disease mutation carrier protected from dementia - Nature Medicine A rare case of asymptomatic dominantly inherited Alzheimer’s reveals confined tau pathology and unique proteomic features, highlighting potential resilience mechanisms decades beyond expected onset.

Delayed neurodegenerative symptoms in a PSEN2 carrier (dominantly inherited Alzheimer’s “escapee”). Despite tons of amyloid plaque, tau pathology delayed >10y. Analogous to PSEN1 patients with APOE3-Christchurch homozygosity (2019) & RELN-COLBOS (2023).

www.nature.com/articles/s41...

High-Precision Optical Fiber-Based Lickometer Visit the post for more.

Researchers from the Champalimaud Foundation have shared an open-source lickometer that uses optical fibers for precise lick detection and includes an integrated nosepoke detector and LEDs for visual cue. Read about it in this week's post on OpenBehavior:

edspace.american.edu/openbehavior...

But Brawndo’s what plants crave! It’s got electrolytes!

RNAscope of GHS-R (yellow) with GFAP and NEUN immunoreactivity in the mouse dorsal vagal complex

Fluorescence Friday - combined RNAscope for GHS-R and immunoreactivity for GFAP and NEUN in the dorsal vagal complex. We are RNAscope newbies and very proud of Katherine Pye for setting this up from scratch in the lab. Apologies for wonky orientation - just run out of steam on Friday!

Dear professional and scientific associations: please stop sending emails explaining that you don’t know what is happening or what will happen next.

Notable Articles of 2024 Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction S.D. Solomon et al. (published September 1, 2024) Illustration of a heart and a bottle of finerenone The New England Journal of Medicine

𝐍𝐨𝐭𝐚𝐛𝐥𝐞 𝐀𝐫𝐭𝐢𝐜𝐥𝐞𝐬 𝐨𝐟 𝟐𝟎𝟐𝟒

In the FINEARTS-HF trial, finerenone resulted in a lower rate of total worsening heart failure events and death from cardiovascular causes than placebo, marking a notable benefit with respect to its primary end point.

Full trial results: nej.md/470x4ix

#MedSky

How Your Brain Chooses What to Remember YouTube video by Artem Kirsanov

Lovely video about recent work from the Buzsáki lab at NYU. Accessible explanation of manifold concept (transforming 100s of recordings into a low-dimensional manifold), which reveals the replay of salient spatial patterns (w/ripples) during sleep.

youtu.be/ceFFEmkxTLg?...

What is the home test you referenced? (empowerdx maybe?)

What lab runs your APOE tests? Is it in the USA, CLIA certified?

Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study - Nature Communications APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia ris...

70% by 80y (clinical-stage dementia symptoms) undersells the disease risk (see Fig 1 of www.nature.com/articles/s41...).
Lifetime penetrance of Alzheimer’s-type neuropathologic change is closer to 100% (www.nature.com/articles/s41...).

In vivo hyperphosphorylation of tau is associated with synaptic loss and behavioral abnormalities in the absence of tau seeds - Nature Neuroscience Mice expressing humanized mutant tau exhibit synaptic loss and behavioral abnormalities in the absence of abnormal tau conformers, suggesting that hyperphosphorylated tau can be pathological, at least...

Cool paper. Hyperphosphorylated tau causes issues at the synapse & w/ behavior in new mouse model. No tangles necessary.

www.nature.com/articles/s41...

Interesting read. Also the first example I’ve seen of authors picking a fight with @elonmusk in a high-profile Neuroscience journal:

“The unbearable slowness of being: Why do we live at 10 bits/s?”

t.co/1EfDKbXjFU

A Woman With a Rare Gene Mutation Fights to Avoid Her Mother’s Fate A mutant gene is coming to steal Linde Jacobs’s mind. Can she find a way to stop it?

Heartbreaking and inspiring. Best news article I’ve ever read about FTLD (MAPT, familial):
www.nytimes.com/2024/12/22/h...

Paper figure showing Allen Inst snRNAseq UMAPs of genes marking dopamine neuron clusters, relevant channels, and receptors

Nothing says cozy reading by the fireplace like our new review, “Molecular heterogeneity and development of the VTA”
Thanks @bensaunders.bsky.social and @bellonec.bsky.social for the invitation to contribute to this special issue on #Dopamine!
authors.elsevier.com/a/1kIwj8MqMi...

It was lovely to have everyone in the Resch and Geerling labs together for a holiday dinner.

Hello, Bluesky!