Jeanne Paz, PhD

Assistant Investigator, Gladstone Institute of Neurological Disease
Assistant Professor
Department of Neurology
jeanne.paz@gladstone.ucsf.edu

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.

Primary Thematic Area: 
Neurobiology
Secondary Thematic Area: 
None
Research Summary: 
Neural dynamics and plasticity in Epilepsy and associated cognitive dysfunction

Websites

Featured Publications: 

Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation.

Cell

Lui H, Zhang J, Makinson SR, Cahill MK, Kelley KW, Huang HY, Shang Y, Oldham MC, Martens LH, Gao F, Coppola G, Sloan SA, Hsieh CL, Kim CC, Bigio EH, Weintraub S, Mesulam MM, Rademakers R, Mackenzie IR, Seeley WW, Karydas A, Miller BL, Borroni B, Ghidoni R, Farese RV, Paz JT, Barres BA, Huang EJ

Optogenetics and epilepsy: past, present and future.

Epilepsy currents / American Epilepsy Society

Paz JT, Huguenard JR

Closed-loop optogenetic control of thalamus as a tool for interrupting seizures after cortical injury.

Nature neuroscience

Paz JT, Davidson TJ, Frechette ES, Delord B, Parada I, Peng K, Deisseroth K, Huguenard JR

A new mode of corticothalamic transmission revealed in the Gria4(-/-) model of absence epilepsy.

Nature neuroscience

Paz JT, Bryant AS, Peng K, Fenno L, Yizhar O, Frankel WN, Deisseroth K, Huguenard JR