The first part of my grad work @CSHL is finally out! To celebrate, here's a GIF summary of what I labored over for a few years
"A central amygdala-globus pallidus circuit conveys unconditioned stimulus-related information and controls fear learning https://www.jneurosci.org/content/early/2020/10/15/JNEUROSCI.2090-20.2020.long

The central amygdala is a hub for stress and fear-related behaviors (among other stuff). The Li Lab is particularly fond of this region. So the twitter-less Kai Yu, (my neuro Obi-Wan) did some anterograde tracing from the central amygdala to map all of its targets.

He found the CeA sends strong projections to the globus pallidus externa (GPe), part of the basal ganglia and directly downstream of the striatal indirect pathway. We were like huh, interesting. This isn't one of the canonical targets of the CeA. So what does this pathway do?

So given i'm particularly interested in how limbic regions convey info about stress and fear to the basal ganglia, I said, let's find out! Because the CeA is a hub for fear, I decided, First stop: Fear Conditioning Land.

We used an intersectional strategy to constitutively inhibit only these projections prior to training animals on a discrimination fear conditioning task. We found that animals with the pathway inhibited couldn't learn fear associations. We were all "What the what???"

We were surprised b/c like I said, the GPe isn't a canonical target of CeA, isn't thought to be involved in fear (and us fear conditioning-folk thought we had it all figured out). So next we labeled CeA-GPe cells with GcAMP and used fiber photometry to image during fear learning.

We found that unlike most CeA neurons, these cells are only active in response to the shock (US). Again, what the what?? No tone (CS) response ? Apparently, not. Turns out these cells also show higher activity to higher intensity shocks.

So we figured, if these cells are encoding info about the US, we should attenuate fear conditioning by inhibiting these cells only during the US. Indeed that was the case. Opto inhibition with GtACR during US presentations decreases fear conditioning.

Oppositely, we reasoned we should be able to boost fear conditioning by exciting these cells during the US. Boom, opto activation with ChR2 during the US increases fear conditioning to a lower shock intensity.

But interestingly, activation or inhibition of these cells alone in a Real Time Place Preference assay doesn't show any effect. Meaning these neurons are not conveying ALL the info about the US alone and are not inherently aversive, but can control the level of fear conditioning

So what are these neurons doing? My guess is conveying info (like salience) about aversive stimuli to direct the degree of learning/response. Interesting in context of stress-related disorders like anxiety/PTSD where people (like me!) attribute high threat to innocuous stimuli.

Stay tuned for the rest of my grad work in the coming months, showing how this pathway is hyperactive in a mouse model of autism that also shows increased stress sensitivity! P.S. it's only in females. What the what??

Big thanks to my mentor Bo Li and my co-authors, Kai Yu, @A__Furlan, Shree Sharma, and our collaborators at @StanfordBrain, Xiaoke Chen and Greg Nachtrab!