By: solteszlab

Darian Hadjiabadi, Matthew Lovett-Barron, Ivan Georgiev Raikov, Fraser T. Sparks, Zhenrui Liao, Scott C. Baraban, Jure Leskovec, Attila Losonczy, Karl Deisseroth, Ivan Soltesz. Neuron, 2021 Jun 30. doi: 10.1016/j.neuron.2021.06.007. Online ahead of print.

Neurological and psychiatric disorders are associated with pathological neural dynamics. The fundamental connectivity patterns of cell-cell communication networks that enable pathological dynamics to emerge remain unknown. Here, we studied epileptic circuits using a newly developed computational pipeline that leveraged single-cell calcium imaging of larval zebrafish and chronically epileptic mice, biologically constrained effective connectivity modeling, and higher-order motif-focused network analysis. We uncovered a novel functional cell type that preferentially emerged in the preseizure state, the superhub, that was unusually richly connected to the rest of the network through feedforward motifs, critically enhancing downstream excitation. Perturbation simulations indicated that disconnecting superhubs was significantly more effective in stabilizing epileptic circuits than disconnecting hub cells that were defined traditionally by connection count. In the dentate gyrus of chronically epileptic mice, superhubs were predominately modeled adult-born granule cells. Collectively, these results predict a new maximally selective and minimally invasive cellular target for seizure control.

Jordan S Farrell, Roberto Colangeli, Ao Dong, Antis G George, Kwaku Addo-Osafo, Philip J Kingsley, Maria Morena, Marshal D Wolff, Barna Dudok, Kaikai He, Toni A Patrick, Keith A Sharkey, Sachin Patel, Lawrence J Marnett, Matthew N Hill, Yulong Li, G Campbell Teskey, Ivan Soltesz. Neuron. 2021 Aug 4. doi: 10.1016/j.neuron.2021.05.026.

The brain’s endocannabinoid system is a powerful controller of neurotransmitter release, shaping synaptic communication under physiological and pathological conditions. However, our understanding of endocannabinoid signaling in vivo is limited by the inability to measure their changes at timescales commensurate with the high lability of lipid signals, leaving fundamental questions of whether, how, and which endocannabinoids fluctuate with neural activity unresolved. Using novel imaging approaches in awake behaving mice, we now demonstrate that the endocannabinoid 2-arachidonoylglycerol, not anandamide, is dynamically coupled to hippocampal neural activity with high spatiotemporal specificity. Furthermore, we show that seizures amplify the physiological endocannabinoid increase by orders of magnitude and drive the downstream synthesis of vasoactive prostaglandins that culminate in a prolonged stroke-like event. These results shed new light on normal and pathological endocannabinoid signaling in vivo.

We are excited to announce that our graduate student Darian Hadjiabadi was awarded by the American Epilepsy Society with the AES Early Career Fellowship. Darian will be investigating the cellular pathways underlying pathological high-frequency oscillations during his pre-doctoral research fellowship.

Quynh Anh Nguyen received a K99/R00 Career Development Award, entitled “Neural circuit mechanisms controlling seizures”. Quynh Anh will utilize recently developed molecular and optogenetic tools to identify and study neuronal circuits active during seizures in mouse models of temporal lobe epilepsy.

We are pleased to announce that Dr. Ernie Hwaun has been awarded with the 2021 Interdisciplinary Scholar Award from the Wu Tsai Neurosciences Institute. The promising young postdoctoral researchers of this Interdisciplinary Scholar Award come from the schools of Medicine, Engineering, Education and Humanities & Sciences, and stand out for their drive to challenge themselves and the traditional boundaries of their field. The postdoctoral Interdisciplinary Scholar Awards include a two-year fellowship, career development and funds for experiments or travel. The newest scholars join thirty previous fellowship recipients including alumni who have made important advances in the neurosciences and gone on to careers in academia, industry, nonprofit and government organizations.

Ernie Hwaun is currently a postdoctoral fellow in Dr. Soltesz Lab. Ernie received his Bachelor of Science in Physiology & Neuroscience and Master of Science in Biology from the University of California, San Diego. He then moved to the University of Texas at Austin to pursue PhD in Neuroscience. In his doctoral studies, Ernie investigated how rodents acquire memory of new locations during awake behaviors and subsequent sleep. As a postdoctoral researcher in the Soltesz lab at Stanford, he has been investigating the distinct roles of key inhibitory cell types in normal and abnormal circuit functions in mice. To explore whether neural mechanisms that support spatial memory in mammals also exist in invertebrates, Ernie has turned to octopuses, which possess the most advanced nervous system among invertebrates, with the ability to learn and navigate in open water. In collaboration with Prof. Zhenan Bao’s laboratory in the Department of Chemical Engineering, Ernie plans to employ new soft-material probes suitable to collect neural signals from behaving octopuses. With these new tools, he aims to gain insights into common fundamental neuronal mechanisms underlying spatial navigation in evolutionarily distant species living in markedly different natural environments.