Many thanks to the hard-working and dedicated members of my lab who did this work (Liz Ramos, Sam Essig, Abby Harr, Nelly Fadil, Griffen Kempskie), and our collaborators in the Gabel lab at Lafayette. Link here: bit.ly/41ZWP0o

No open access, so DM me if you want a copy!

These effects occurred without differences in response latency or anxiety-like behavior. Why? We think it's because Apoe transcription affects different cell types, and therefore network activity, differently in males and females. We found cellular evidence for this by looking at Fos transcription.

Specifically - Apoe overexpression accelerated task learning in female mice, while having no effect on learning in male mice. In contrast, Apoe overexpression decreased performance in well-trained male mice, but had no effect on performance in well-trained female mice. 3/n

They used an expression cassette to induce Apoe transcription in the mouse frontal cortex, and tested these mice on a touchscreen attention task. The big takeaway is that Apoe overexpression affects males and females differently. 2/n

9/ That's my skeetorial(?) Am I saying that right? I'm still new here. Anyway, paper here: bit.ly/3PpbxrU. Thanks also to the Brain and Behavior Research Foundation and the NIMH for supporting our work. Seems timely to point out that this wouldn't have been possible without science funding!

8/ I'm extremely grateful to Genevieve and other lab members, as well as @martinowk.bsky.social and @aejaffe.bsky.social for their support. It was such a boon to have an exciting project to take with me into my new lab. Would highly recommend if you're thinking of starting a lab.

7/ Which types of neurons? Turns out, it's GABAergic neurons, and the subtype is somatostatin-expressing - but only in female mice! Most literature characterizes Apoe as a gene expressed in glia, but its activity-dependent expression seems strongest in inhibitory neurons.

6/ My first thesis student, Genevieve Craig, repeated the original experiment, but this time with male and female mice. She also used RNAscope to look at Apoe expression in specific cell types. She found that LC induced Apoe expression was highest in neurons (compared to astrocytes).

5/ This was an intriguing (and unexpected) finding. Apoe is best known for its role in Alzheimer's disease, but alleles also correlate with attentional performance in humans. But where exactly is Apoe expressed within prelimbic cortex? When I started my lab at Lafayette, I wanted to dig deeper.

4/ To answer this question, we chemogenetically "activated" LC neurons with connections to prelimbic cortex. We did bulk RNA-sequencing on prelimbic cortex tissue, and found that the tissue was enriched for a host of genes. One gene that immediately popped out at us was the "Apoe" gene.

3/ We wondered: Are there molecular signatures of activation in this circuit? Given that the circuit is involved in attention, biomarkers for activity in this circuit would be valuable.

2/ This work started when I was a postdoc in @martinowk.bsky.social's lab. We became interested in connections between the locus coeruleus and frontal cortex because we found that these regions interacted during a touchscreen-based attention task that we ran (published here: bit.ly/4fT9tmJ)

Congratulations Tony!!

How could you turn down having a book sell on eBay?