Congrats to Margaret Cunniff for, IMHO, leading the Hurricanes to the Stanley Cup! Margaret received her PhD in Neurosci from UCSF, doing awesome work with @vikaassohal.bsky.social. She's one of the first to "moneyball" hockey; looks like it worked! www.sloansportsconference.com/event/of-mic...

Decent EPSC, but they really need to fix their amplifier gain.

How I feel teaching first year grad students every fall… (you have to watch it to understand).

Mayor Zohran Kwame Mamdani@mayor.nyc.gov · 2mo ago

Today, I signed an Executive Order temporarily repealing bedtimes in the City of New York so that kids of all ages can watch our team in the NBA Finals. As Mayor, you’re forced to make many difficult decisions. This was not one of them. Go Knicks.

New work from @danfeldman.bsky.social's lab, exploring sensory representations in Scn2a loss of function mice. Whisker representations are blurred, akin to cortical visual impairment often seen in SCN2A kiddos. Rescuable w/ @nadavahituv.bsky.social's CRISPRa @P30! www.biorxiv.org/content/10.6...

Degraded sensory coding in a mouse model of Scn2a-related disorder and its rescue by CRISPRa gene activation

Heterozygous loss-of-function mutations in SCN2A, a sodium channel gene expressed in cortical pyramidal (PYR) cells, lead to a neurodevelopmental disorder characterized by autism, intellectual disabil...

biorxiv.org

Fresh off the press! @selinsch.bsky.social discovered some really cool features of mouse frontal cortex pyramidal cells that co-vary with dopamine receptor expression. D3R+ cells appear very responsive to AP bursts, producing Ca transients across dendritic arbors. www.jneurosci.org/content/earl...

Intrinsic dendritic integration features of prefrontal layer 5 pyramidal cell subclasses

Prefrontal cortex (PFC) is an associative center in the brain and integrates various inputs to support cognition. Layer 5 pyramidal cells are themselves associative centers, as their dendrites span al...

jneurosci.org

SCN2A loss is strongly linked to neurodevelopmental delays and, at times, seizure. In an amazing collaboration with @nadavahituv.bsky.social, led by Serena Tamura, Andrew Nelson, and Perry Spratt, we leveraged CRISPR activator approaches to rescue this loss. rdcu.be/eGU0W

CRISPR activation for SCN2A-related neurodevelopmental disorders

Nature - Using SCN2A haploinsufficiency as a proof-of-concept, upregulation of the existing functional gene copy through CRISPR activation was able to rescue neurological-associated phenotypes in...

rdcu.be

Patch clampers: we got an error 52 on our Leica vibracheck and the normal "blow on it like a nintendo in the 80s" fix didn't work. Nor did a cleaning of the LED and diode. LED does shine. Has anyone else had such an issue and managed to resurrect this very simple but stupidly expensive thing?

Not posting that much lately, because... well, yeah. But i have to share this text i got from my daughter. I totally see it.

New work from Josh Garcia in our lab! This is a collaboration with David Hackos (formerly Genentech) Roy Ben-Shalom (UC Davis) and Al George (Northwestern) where we use fancy knockin mice to allow for selective block of different sodium channels, revealing their unique roles in excitability.

bioRxiv Neuroscience@biorxiv-neursci.bsky.social · 2y ago

Differential roles of NaV1.2 and NaV1.6 in neocortical pyramidal cell excitability https://www.biorxiv.org/content/10.1101/2024.12.17.629038v1

@pjenkinslab.bsky.social and I wrote a review on the axon initial segment. We tried our best to discuss the state of the field and provide our perspective (and resolution for) some current sticking points. Hope it's useful! doi.org/10.1152/phys...

Axon Initial Segment Structure and Function in Health and Disease | Physiological Reviews

At the simplest level, neurons are structured to integrate synaptic input and perform computational transforms on that input, converting it into an action potential (AP) code. This process-converting synaptic input into AP output-typically occurs in a specialized region of axon termed the axon initial segment (AIS). The AIS, as its name implies, is often contained to the first section of axon abutted to the soma and is home to a dizzying array of ion channels, attendant scaffolding proteins, intracellular organelles, extracellular proteins, and, in some cases, synapses. The AIS serves multiple roles as the final arbiter for determining if inputs are sufficient to evoke APs, as a gatekeeper that physically separates the somatodendritic domain from the axon proper, and as a regulator of overall neuronal excitability, dynamically tuning its size to best suit the needs of parent neurons. These complex roles have received considerable attention from experimentalists and theoreticians alike. Here, we review recent advances in our understanding of the AIS and its role in neuronal integration and polarity in health and disease.

doi.org

Can cerebellar reflexive learning shine a little light on ASD related dysfunction? For SCN2A, it sure looks like it. New paper from Chenyu Wang, in collaboration with Guy Bouvier and FamilieSCN2A: urldefense.com/v3/__https:/...

Amazing collaborative project with @pjenkinslab.bsky.social on the interactions between two major ASD associated genes: SCN2A and ANK2. All led by the incomparable Andrew Nelson. doi.org/10.1016/j.ne...

New paper from @selinsch.bsky.social in collaboration with @alexkwan.bsky.social doi.org/10.1523/ENEU... Scn2a loss is a major ASD/ID risk, and it brings along comorbidities like epilepsy. Selin found that mouse models do just fine in foraging tasks, but the associated water restriction ⬆️ seizure

Dynamic Foraging Behavior Performance Is Not Affected by Scn2a Haploinsufficiency

Dysfunction in the gene SCN2A , which encodes the voltage-gated sodium channel Nav1.2, is strongly associated with neurodevelopmental disorders including autism spectrum disorder and intellectual disa...

doi.org

Congrats to Dr Schamiloglou for her amazing thesis defense today. Third student to defend this year from the lab! She’s off to bigger and better things in the DiGregorio lab (now at Colorado)… but not before we sort out two final papers!

Too much strontium.

If I get this and ride all the way in instead of taking the ferry it'll pay for itself in ~300 commutes. Those are surprisingly reasonable numbers... right? velo.outsideonline.com/ebike/santa-...

I’m on here now. Here’s a photo of one of my cats judging me from atop our hutch. I hope this brings blue skies to your feed.