Jeanne Paz, PhD
Associate Professor
Neurology
School of Medicine

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.

• Mapping general anesthesia states based on electro-encephalogram transition phases.
  NeuroImage 2023 Loison V, Voskobiynyk Y, Lindquist B, Necula D, Longrois D, Paz J, Holcman D
• Alzheimer risk-increasing TREM2 variant causes aberrant cortical synapse density and promotes network hyperexcitability in mouse models.
  Neurobiology of disease 2023 Das M, Mao W, Voskobiynyk Y, Necula D, Lew I, Petersen C, Zahn A, Yu GQ, Yu X, Smith N, Sayed FA, Gan L, Paz JT, Mucke L
• Patient-derived SLC6A1 variant S295L results in an epileptic phenotype similar to haploinsufficient mice.
  Epilepsia 2023 Lindquist BE, Voskobiynyk Y, Goodspeed K, Paz JT
• AI-nalyzing Mouse Behavior to Combat Epilepsy.
  Epilepsy currents 2023 Voskobiynyk Y, Paz JT
• Thalamocortical circuits in generalized epilepsy: Pathophysiologic mechanisms and therapeutic targets.
  Neurobiology of disease 2023 Lindquist BE, Timbie C, Voskobiynyk Y, Paz JT
• Complement: The Road Less Traveled.
  Journal of immunology (Baltimore, Md. : 1950) 2023 Kemper C, Ferreira VP, Paz JT, Holers VM, Lionakis MS, Alexander JJ
• Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice.
  The Journal of experimental medicine 2022 Han RT, Vainchtein ID, Schlachetzki JCM, Cho FS, Dorman LC, Ahn E, Kim DK, Barron JJ, Nakao-Inoue H, Molofsky AB, Glass CK, Paz JT, Molofsky AV
• International Post Stroke Epilepsy Research Consortium (IPSERC): A consortium to accelerate discoveries in preventing epileptogenesis after stroke.
  Epilepsy & behavior : E&B 2021 Mishra NK, Engel J, Liebeskind DS, Sharma VK, Hirsch LJ, Kasner SE, French JA, Devinsky O, Friedman A, Dawson J, Quinn TJ, Selim M, de Havenon A, Yasuda CL, Cendes F, Benninger F, Zaveri HP, Burneo JG…
• Behavioral and neural network abnormalities in human APP transgenic mice resemble those of App knock-in mice and are modulated by familial Alzheimer's disease mutations but not by inhibition of BACE1.
  Molecular neurodegeneration 2020 Johnson ECB, Ho K, Yu GQ, Das M, Sanchez PE, Djukic B, Lopez I, Yu X, Gill M, Zhang W, Paz JT, Palop JJ, Mucke L
• Maf and Mafb control mouse pallial interneuron fate and maturation through neuropsychiatric disease gene regulation.
  eLife 2020 Pai EL, Chen J, Fazel Darbandi S, Cho FS, Chen J, Lindtner S, Chu JS, Paz JT, Vogt D, Paredes MF, Rubenstein JL
• Mafb and c-Maf Have Prenatal Compensatory and Postnatal Antagonistic Roles in Cortical Interneuron Fate and Function.
  Cell reports 2019 Pai EL, Vogt D, Clemente-Perez A, McKinsey GL, Cho FS, Hu JS, Wimer M, Paul A, Fazel Darbandi S, Pla R, Nowakowski TJ, Goodrich LV, Paz JT, Rubenstein JLR
• Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome.
  Cell reports 2019 Ritter-Makinson S, Clemente-Perez A, Higashikubo B, Cho FS, Holden SS, Bennett E, Chkhaidze A, Eelkman Rooda OHJ, Cornet MC, Hoebeek FE, Yamakawa K, Cilio MR, Delord B, Paz JT
• Conditional Bistability, a Generic Cellular Mnemonic Mechanism for Robust and Flexible Working Memory Computations.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2018 Rodriguez G, Sarazin M, Clemente A, Holden S, Paz JT, Delord B
• Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms.
  Cell reports 2017 Clemente-Perez A, Makinson SR, Higashikubo B, Brovarney S, Cho FS, Urry A, Holden SS, Wimer M, Dávid C, Fenno LE, Acsády L, Deisseroth K, Paz JT
• Absence seizure susceptibility correlates with pre-ictal β oscillations.
  Journal of physiology, Paris 2017 Sorokin JM, Paz JT, Huguenard JR
• Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation.
  Cell 2016 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…
• Voices of biotech.
  Nature biotechnology 2016 Amit I, Baker D, Barker R, Berger B, Bertozzi C, Bhatia S, Biffi A, Demichelis F, Doudna J, Dowdy SF, Endy D, Helmstaedter M, Junca H, June C, Kamb S, Khvorova A, Kim DH, Kim JS, Krishnan Y, …
• Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target.
  Brain : a journal of neurology 2015 Hiu T, Farzampour Z, Paz JT, Wang EH, Badgely C, Olson A, Micheva KD, Wang G, Lemmens R, Tran KV, Nishiyama Y, Liang X, Hamilton SA, O'Rourke N, Smith SJ, Huguenard JR, Bliss TM, Steinberg GK
• Microcircuits and their interactions in epilepsy: is the focus out of focus?
  Nature neuroscience 2015 Paz JT, Huguenard JR
• Optogenetics and epilepsy: past, present and future.
  Epilepsy currents 2015 Paz JT, Huguenard JR
• R U OK? The Novel Therapeutic Potential of R Channels in Epilepsy.
  Epilepsy currents 2012 Paz JT, Huguenard JR
• A theory of rate coding control by intrinsic plasticity effects.
  PLoS computational biology 2012 Naudé J, Paz JT, Berry H, Delord B
• Focal cortical infarcts alter intrinsic excitability and synaptic excitation in the reticular thalamic nucleus.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2010 Paz JT, Christian CA, Parada I, Prince DA, Huguenard JR
• Activity of ventral medial thalamic neurons during absence seizures and modulation of cortical paroxysms by the nigrothalamic pathway.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2007 Paz JT, Chavez M, Saillet S, Deniau JM, Charpier S
• Rhythmic bursting in the cortico-subthalamo-pallidal network during spontaneous genetically determined spike and wave discharges.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2005 Paz JT, Deniau JM, Charpier S
• On the activity of the corticostriatal networks during spike-and-wave discharges in a genetic model of absence epilepsy.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2004 Slaght SJ, Paz T, Chavez M, Deniau JM, Mahon S, Charpier S