Neural dynamics and plasticity in Epilepsy and associated cognitive dysfunction
Our lab studies how neural synchronization and circuit plasticity relate to adaptive and maladaptive behavior. Our interests span many levels of analysis, from the cell to the circuit to animal behavior. The current major focus of our lab is epileptogenesis, the process by which a normal brain develops epilepsy. Our ultimate goal is to identify epilepsy control points in the brain and to develop strategies to prevent epileptogenesis.
Epilepsy occurs in a number of neurological diseases. However, the underlying mechanisms of the condition are not well understood. While many antiepileptic drugs exist, they often have side effects and are unable to fully suppress the highly disruptive and potentially fatal symptoms seen in patients with epilepsy. We seek to improve this situation by investigating the cellular, circuit, and molecular mechanisms by which brain injuries, cerebrovascular disease, and genetic mutations cause epilepsy. In addition, we are exploring new strategies that predict seizures and block the pathogenic loops that can emerge between the cortical and subcortical brain regions in animal models of epilepsy. We combine bioengineering, engineering, neurophysiology and signal processing to achieve these goals. In particular, we are using optogenetic tools, which allow the control of specific elements of intact biological systems using light, to interrogate cells and synaptic components involved in adaptive and maladaptive neural circuit oscillations (i.e. epileptic seizure). We then couple these results with our in vitro findings to determine the cellular and microcircuit mechanisms that relate to these oscillations. After we identify the neural circuit that alleviates symptoms, we then target these circuits in the behaving animal at the onset of abnormal brain activity in real-time.
Our work (Paz et al., Nature Neuroscience 2012) was the first to reveal that seizures can be instantaneously aborted in real-time with closed-loop optogenetic control of a specific cell type. This work led us to identify thalamocortical neurons as novel targets that control post-stroke seizures in real-time without side effects. We are currently adapting this approach to reveal control points in the brain—regions, cells, and circuits—in other forms of epilepsy and cognitive disorders.
Current Projects
- Online seizure prediction and closed-loop optogenetic control of seizures in real-time
- Neural circuit remapping after cerebral stroke
- Mechanisms underlying epilepsy after brain injuries and prevention of epileptogenesis
- Neuron-glia interactions in stroke and epilepsy
- Co-morbidities of neural circuit dysfunction in epilepsy and psychiatric and cognitive disorders
- Subcellular, cellular and circuit organization in the thalamus
- Basal ganglia – thalamic interactions and relevance for epilepsy
Lab Members
Jeanne Paz
Associate Investigator
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Agnieszka Ciesielska
Postdoctoral Scholar
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Jeremy Ford
Postdoctoral Scholar
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Yuliya Voskobiynyk
Postdoctoral Scholar
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Clare Timbie
Clinical Fellow
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Britta Lindquist
Clinical Fellow
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Isaac Chang
Graduate Student
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Morgane Leroux
Graduate Student
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Audrey Magsig
Graduate Student
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Deanna Necula
Graduate Student
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Olive Tambou Nzoutchoum
Graduate Student
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Charlotte Taylor
Graduate Student
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Drew Willoughby
Graduate Student
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Vivianna DeNittis
Research Associate [email protected]
Laura Craciun
Visiting Scientist [email protected]
Annie Dalton
Administrative Assistant
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Lab Website
Academic community service and committee membership:
NS Admissions committee, NS Formal Seminar committee co-chair, NS Student Advisors/Student Progress committee, BMS program faculty; qualifying exam and/or thesis committees for the for five graduate programs including Neuroscience (UCSF), Biomedical Science “BMS” (UCSF), Development and Stem Cell Biology “DSCB” (UCSF), Bioengineering (UC Berkeley/UCSF), and Pharmaceutical Sciences Pharmacogenomics “PSPG” (UCSF) graduate programs; Hosted and Mentored students for the SRTP (Summer Research Training Program) and PUMAS (Program for Underrepresented Minority Students); Gladstone Mentoring Task Committee; Mentor for two R25-recipient physician-scientists; Women's Initiative Gladstone; Gladstone All Investigators Committee; Associate Editor for the journal Progress in Neurobiology; Professional Advisory Board for the Lennox Gastaut Syndrome Foundation; Served on the Diversity committee for the Neurology Department, and the Faculty promotions committees.