Clinical Profile Clinical Profile Clinical Profile ul
UCSF home page UCSF home page About UCSF UCSF Medical Center
UCSF navigation bar

Neuroscience Graduate Program at UCSF

Faculty - Jeanne Paz, Ph.D.

Neural dynamics and plasticity in Epilepsy and associated cognitive dysfunction


Research Description

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.

Back to Top


Current Projects

  1. Online seizure prediction and closed-loop optogenetic control of seizures in real-time
  2. Neural circuit remapping after cerebral stroke
  3. Mechanisms underlying epilepsy after brain injuries and prevention of epileptogenesis
  4. Neuron-glia interactions in stroke and epilepsy
  5. Co-morbidities of neural circuit dysfunction in epilepsy and psychiatric and cognitive disorders
  6. Subcellular, cellular and circuit organization in the thalamus
  7. Basal ganglia – thalamic interactions and relevance for epilepsy

Back to Top


Lab Members

Alexandra Clemente, Graduate Student (UCSF Neuroscience Program)
Stephanie Holden, Graduate Student (UCSF Neuroscience Program)
Frances Cho, Graduate Student (UCSF Neuroscience Program)
Stefanie Makinson, Ph.D., Postdoctoral Fellow
Bryan Higashikubo, Ph.D., Postdoctoral Fellow
Scott Brovarney, Research Associate
Alexander Urry, Research Associate
Matt Wimer, Research Associate
Joni Miyagi, Administrative Assistant

Back to Top


Selected Publications

Lui H, et al., (2016) Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation. Cell 165(4):921-35

Hiu T, Farzampour Z et al., (2015) Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target. Brain. 139(Pt 2):468-80.

Paz JT & Huguenard JR (2015) Microcircuits and their interactions in epilepsy: is the focus out of focus? Nature Neuroscience 18(3):351-9.

Paz JT & Huguenard JR (2015) Optogenetics and epilepsy: past, present and future. Epilepsy Currents 15(1):34-8

Paz JT et al., (2012) Closed-loop optogenetic control of thalamus as a novel tool to interrupt seizures after cortical injury. Nature Neuroscience 16(1):64-70

Paz JT & Huguenard JR (2012) R U OK? The Novel Therapeutic Potential of R Channels in Epilepsy. Epilepsy Currents 12:75–76

Naudé J et al., (2012) A Theory of Rate Coding control by intrinsic plasticity. PloS Computational Biology 8:e1002349

Yizhar O et al., (2011) Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477:171-8

Paz JT et al., (2011) A new mode of corticothalamic transmission revealed in the Gria4-/- model of absence epilepsy. Nature Neuroscience 21:14:1167-73

Paz JT et al., (2010) Focal cortical infarcts alter intrinsic excitability and synaptic excitation in the reticular thalamic nucleus. Journal of Neuroscience 30:5465-79

Paz JT et al., (2009) Multiple forms of activity-dependent intrinsic plasticity in layer V cortical neurones in vivo. Journal of Physiology 587:3189-205

Paz JT et al., (2007) Activity of Ventral Medial Thalamic Neurons during Absence Seizures and Modulation of Cortical Paroxysms by the Nigrothalamic Pathway. Journal of Neuroscience 27:929-41

Paz JT et al., (2005) Rhythmic bursting in the Cortico-Subthalamo-Pallidal pathway during spontaneous Genetically Determined Spike and Wave Discharges. Journal of Neuroscience 25(8):2092-101

Slaght SJ et al., (2004) On the activity of the corticostriatal networks during spike-and-wave discharges in a genetic model of absence epilepsy. Journal of Neuroscience 24:6816-25

Slaght SJ et al., (2002) Functional organization of the circuits connecting the cerebral cortex and the basal ganglia: implications for the role of the basal ganglia in epilepsy. Epileptic Disorders 4 Suppl 3:S9-22
 
BOOK CHAPTERS
Charpier S, Beurrier C, Paz JT (2010) The subthalamic nucleus: from in vitro to in vivo mechanisms. In: Handbook of Basal Ganglia Structure and Function: A Decade of Progress. Eds. Steiner H and Tseng, KY. Elsevier. pp. 259-273

Paz JT et al., (2009) Cortical initiation of absence seizures, propagation to basal ganglia and back to the cortex. Pan-Brain Abnormal Neural Networks in Epilepsy. Eds Feng Ru Tang. Research Signpost. Kerala. India. pp. 41-65

Paz JT et al., (2006) Propagation and dynamic processing of cortical paroxysms in the basal ganglia networks during absence seizures. In: Progress in Epileptic Disorders series. Generalized seizures: from clinical phenomenology to underlying systems and networks. Eds. Hirsch E, Andermann F, Chauvel P, Engels J, Lopes da Silva F, Luders H. pp. 83-99

Paz JT et al., (2005) Propagation of cortical paroxysms in basal ganglia circuits during absence seizures. In: The basal ganglia VIII. Eds. Bolam JP, Ingham CA, Magill PJ. New York: Springer. pp. 55–65

Back to Top

Jeanne Paz, Ph.D.



Email

jeanne.paz@gladstone.ucsf.edu

Phone 415-734-2515

Fax 415-355-0824

Office Address

Gladstone Institute of Neurological Disease
1650 Owens Street, Room 315
San Francisco, CA 94158

Other Websites

Lab Website

Gladstone Institute