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
Senior Investigator
[email protected]
Yuliya Voskobiynyk
NOMIS-Gladstone Postdoctoral Fellow
[email protected]
Agnieszka Ciesielska
Postdoctoral Scholar
[email protected]
Clare Timbie
Clinical Fellow
[email protected]
Britta Lindquist
Assistant Professor of Neurology
[email protected]
Isaac Chang
Graduate Student (Neuroscience Program)
[email protected]
Audrey Magsig
Graduate Student (Neuroscience Program)
[email protected]
Olive Tambou Nzoutchoum
Graduate Student (Neuroscience Program)
[email protected]
Drew Willoughby
Graduate Student (Neuroscience Program)
[email protected]
Bret Holt
Research Associate
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Jeremy Guiman
Administrative Associate
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Lab Website
Academic Community Service and Committee Membership:
Neuroscience Graduate Program
● Executive Committee
● Admissions Committee
● Co-Chair, Neuroscience Seminar Committee
● Student Advisors / Student Progress Committee
● Qualifying exam and PhD thesis committees
● Vice-Chair, Annual Program Retreat
● PhD thesis mentor for 10 graduate students since 2015 (9 in the Neuroscience Graduate Program)
Other Graduate Programs
● Faculty member, Biomedical Sciences (BMS) Graduate Program
● Qualifying exam and PhD thesis committees for:
○ Biomedical Sciences (BMS), UCSF
○ Developmental and Stem Cell Biology (DSCB), UCSF
○ Bioengineering, UC Berkeley / UCSF
○ Pharmaceutical Sciences and Pharmacogenomics (PSPG), UCSF
Other UCSF and Gladstone Service
● Admissions and student placement committee, UCSF-wide Summer Research Training Program (SRTP)
● Mentor, UCSF Science and Health Education Program (SEP) for high school students
● Mentor, PUMAS undergraduate summer interns, Gladstone Institutes
● Council Committee member, Physician-Scientist Career Development Program (PSCDP) (mentorship of two physician-scientists)
● Member, Gladstone-wide Mentoring Task Committee
● Faculty search committees