Bernardo Sabatini Lab Website

Congrats to Helen, Caroline, and Jess

bsabatini — Thu, 16 May 2013 15:05:09 +0000

Our paper on the mechanisms of network hyper-excitability caused by loss of Tsc1 was just published and featured in Neuron (link) and with nice discussions here (Simons Foundation) and here (Harvard). Mutations in Tsc1 or Tsc2 cause the autism spectrum disorder Tuberous Sclerosis Complex. The function of these negative regulators of mTOR in neurons in still unclear. We demonstrated that in hippocampal CA1 pyramidal neurons the pathway both responds to activity and promotes activity, forming a positive feedback loop that acts in opposition to the ERK/ARC synaptic homeostatic pathway. These results likely explain the pathological engagement of mTOR that occurs following seizures.

There is lots of supplemental information include Affymetrix analysis of transcriptional changes 1, 6, and 24 hours post up or down regulation of activity in control neurons and Tsc1 lacking neurons. This dataset makes it clear that Tsc1 null neurons look like high-activity state neurons with chronic engagement of homeostatic pathways. However, these changes are secondary to the network hyper-excitability and not a primary result of mTOR over-activation. The primary defect is a mTOR dependent loss of GABAergic inhibition.

Helen Bateup is starting her own lab at Berkeley.

Congrats to Kevin and Jun!

bsabatini — Wed, 20 Feb 2013 14:44:40 +0000

Our paper using pulsed stimulated emission depletion (STED) to achieve super-resolution 2-photon laser scanning microscopy has come out in Biophysical Journal. We are able to reach about ~50 nm resolution imaging of living neurons in acute brain slices using ~800 nm excitation light, an approximately 6-8 fold improvement beyond the classical diffraction limit. It was paired with a beautiful companion paper from the Nagerl group and featured in a nice commentary by Stefan Hell and Leslie Loew. Jun Ding is now at Stanford leading his own lab.

Finally – Congrats to Hyungbae Kwon and others…

bsabatini — Thu, 15 Nov 2012 20:36:44 +0000

After ~1.5 years in review, our paper on the competitive nature of cortical synaptogenesis and the function of Neuroligin-1 in this process is finally out. This paper demonstrates a true cell-to-cell competition for the formation of new synapses in developing cortex.

Hyungbae Kwon is now leading his own group at the Max Planck Florida.

See also the paper by one of our new postdocs Rui Peixoto on activity dependent cleavage of the extracellular domain of Neuroligin-1, a phenomenon that may be related the competition described in Kwon et al.

Podcast…

bsabatini — Wed, 31 Oct 2012 01:01:37 +0000

Check out the laser 5 minutes of the Nature Neuropod podcast for October. Not bad interview with me about Nic and Jun’s dopamine/GABA co-release story…

Manipulating circuits and synapses

David Bozzi — Wed, 17 Oct 2012 13:09:52 +0000

Studying synapses and circuits in situ requires methods to probe cells and subcellular elements within complex brain tissue. These techniques include: 2-photon microscopy laser scanning microscopy to monitor cell structure and the activation of signaling cascades; photoactivation of biologically relevant molecules to turn signaling cascades on and off; and optogenetics to manipulate the activity of genetically-defined cell populations.

Congrats to Nic and Jun

bsabatini — Fri, 05 Oct 2012 18:11:20 +0000

Their paper showing that dopaminergic neurons that innervate the striatum release GABA has been published online in Nature. Not only do these neurons inhibit striatum projection neurons, they do it without the vesicular GABA transporter VGAT. It turns out that the monoamine transporter VMAT2 is necessary and sufficient for GABA packaging in vesicles, suggesting that many monoamiergic neurons likely to the same thing. Furthermore, their work indicates that loss of GABA may contribute to the symptoms of Parkinson’s.

Jun is now leading his own lab at Stanford.

Coincidently, the review that Nic and I just wrote on dopaminergic regulation in the striatum and prefrontal cortex came out in Neuron. They didn’t let us cite our own article in Nature because it had technically not been published!

Congrats Arpy and Caroline

bsabatini — Sun, 29 Jul 2012 01:17:28 +0000

Congratulations once again to Arpy and Caroline. Their paper described a new set of virus for independent expression of proteins in Cre positive and negative neurons was published in Frontiers and is now available. The viral backbones, including many for expression of optogenetic proteins, are available here at Addgene.
More information is present at Arpy’s website

Congrats Genia and Arpy!

bsabatini — Mon, 14 May 2012 23:32:50 +0000

Their new paper showing that recurrent activity reverberating through the cortex-basal ganglia-thalamus circuit drives the formation of corticostriatal synapses is available online at the Nature site. This was a monster study that could only be accomplished through their teamwork. Thanks too to Caroline for graciously keeping things moving.
See accompanying blog by Nature editor Noah Gray on the review process

New Chairlift video

bsabatini — Sat, 03 Mar 2012 01:09:04 +0000

Check out the new interactive video “met before” by chairlift filmed in the Sabatini lab. Great way to get to know our machinery and even some of our people. Enjoy!

Photoactivatable peptides

bsabatini — Fri, 27 Jan 2012 01:38:34 +0000

Matt Banghart’s paper describing the synthesis, validation, and use of photoactivatable opioids just came out in Neuron. Stay tuned for much more work on photoactivatable molecules….