adrinnenberg.bsky.social

biorxiv.orgLarge-scale cellular-resolution read/write of activity enables discovery of cell types defined by complex circuit propertiesThe complexity of the mammalian brain’s vast population of interconnected neurons poses a formidable challenge to elucidate its underlying mechanisms of coordination and computation. A key step forwar...

✨ New preprint ✨ What if we could watch AND control thousands of individual neurons in behaving mice—with stable access over months? 🧠⚡ Our work introduces transgenic all-optical tools that make this possible - and a resulting surprising discovery! 🔭💡 www.biorxiv.org/content/10.1... 1/13 🧵

Amazing collaboration with @alleninstitute.org team—@hongkuizeng.bsky.social, Bosiljka Tasic, Tanya L. Daigle, La'Akea Siverts—to develop new transgenics for all-optical neuroscience. And deeply grateful to @deisseroth.bsky.social for his support and mentorship. 🙏 12/13

We'll be at @sfn.org #SfN25 #SanDiego✨! 🗓️📍Come visit our late-breaking abstract poster Sunday morning: LBP020.05/LBP041 13/13

This positions them to broadly monitor excitatory activity and potentially gate top-down cortical information. Our approach reveals functional components not discoverable by anatomy/genetics alone! 10/13

Massive thank you to all co-authors, especially @alexattinger.bsky.social (@lgiocomo.bsky.social lab) and Allan Raventos (@suryaganguli.bsky.social lab). 11/13

GER neurons are an SST subtype enriched in deep L2/3. Their broad recruitment pattern contrasts sharply with PV+ interneurons (which were suppressed) and other SST subtypes in L2/3 (lacking broad recruitment). 8/13

How do GER cells achieve broad recruitment 🤔? Computational modeling points to high excitability + long-range spatial integration of excitatory inputs. 9/13

This 'follower-focused' strategy excels at capturing the stimulation-induced effects in the surrounding network. We used this to map single-cell functional architecture of cortical networks in awake mice, confirming 'like-to-like' architecture in visual cortex. 6/13

Then came a surprise: While mapping these circuits, we found neurons robustly recruited by the stimulation of many different, non-overlapping excitatory ensembles. We named them General Ensemble-Response (GER) neurons. 7/13

The transgenics allow for reliable holographic stimulation of large cortical ensembles with minimal power (<10 mW time-averaged power for 60 simultaneous targets). 4/13

In a different strategy, we decouple transgenic opsin expression from dense viral indicator expression, enabling read-write access to >1,000 neurons and read access to 10,000 neurons in a single acquisition volume 🤯 5/13

We're still far from understanding how the brain works, even in the well-studied mouse 🐁. A key step forward will be technologies that both monitor and manipulate large-scale brain activity in behaving animals at cellular resolution. 2/13