Lab News

Congrats to Helen, Caroline, and Jess

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.

 

May 16th, 2013 by bsabatini

Congrats to Kevin and Jun!

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.

February 20th, 2013 by bsabatini

Finally – Congrats to Hyungbae Kwon and others…

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.

November 15th, 2012 by bsabatini

Podcast…

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…

October 31st, 2012 by bsabatini

Congrats to Nic and Jun

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!

October 5th, 2012 by bsabatini

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Howard Hughes Medical Institute
Harvard Medical School