The Neural Netoff lab is interested in discovering basic mechanisms of epilepsy. We take a dynamical approach to the disease in that we believe you must understand the dynamics of the neurons and their interactions to understand how seizures, a network phenomenon, are generated. We study seizures in brain slices bathed in toxins. By recording from single neurons using patch-clamp recording techniques we can identify changes in the neuron's dynamics as well as changes in the activity a neuron receives. Using a computer interfaced to the neuron through the amplifier, known as a dynamic clamp, we can also simulate changes in neurons that can occur following a seizure. The dynamic clamp can also be used to introduce virtual synapses between real neurons or with virtual neurons simulated on the computer. Patch clamp and dynamic clamp studies are limited to recording the activity of a few neurons at one time. To study the behavior of networks of neurons during a seizure we are turning to optical imaging techniques.
To image the activity, the brain slice is bathed in a dye that indicates the amount of calcium inside neurons, a good indicator of the neuron's activity. This allows us to monitor the activity of hundreds of neurons simultaneously during a seizure.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
- Zeidler Z, Brandt-Fontaine M, Leintz C, Krook-Magnuson C, Netoff T, Krook-Magnuson E.Targeting the mouse ventral hippocampus in the intrahippocampal kainic acid model of temporal lobe epilepsy. eNeuro. 2018 Aug 8;5(4). pii: ENEURO.0158-18.2018.Zick JL, Blackman RK, Crowe DA, Amirikian B, DeNicola AL, Netoff TI, Chafee MV. Blocking NMDAR disrupts spike timing and decouples monkey prefrontal circuits: implications for activity-dependent disconnection in Schizophrenia. Neuron. 2018 Jun 27;98(6):1243-1255.
- Nagaraj V, Lamperski A, Netoff TI. Seizure control in a computational model using a reinforcement learning stimulation paradigm. Int J Neural Syst. 2017 Nov;27(7):1750012.
- Holt AB, Wilson D, Shinn M, Moehlis J, Netoff TI. Phasic burst stimulation: A closed-loop approach to tuning deep brain stimulation parameters for Parkinson's disease. PLoS Comput Biol. 2016 Jul 14;12(7):e1005011.
- MacDonald III AW, Zick JL, Chafee MV, Netoff TI. Integrating insults: Using fault tree analysis to guide schizophrenia research across levels of analysis. Front Hum Neurosci. 2016 Jan 6;9:698
- Snari R, Tinsley MR, Wilson D, Faramarzi S, Netoff TI, Moehlis J, Showalter K. Desynchronization of stochastically synchronized chemical oscillators. Chaos. 2015;25(12):123116
- Nagaraj V, Lee ST, Krook-Magnuson E, Soltesz I, Benquet P, Irazoqui PP, Netoff TI. Future of seizure prediction and intervention: Closing the loop. J Clin Neurophysiol. 2015;32:194-206.
- Bandarabadi M, Rasekhi J, Teixeira CA, Netoff TI, Parhi KK, Dourado A. Early seizure detection using neuronal potential similarity: A generalized low-complexity and robust measure. Int J Neural Syst. 2015 Aug;25(5):1550019.
- Wilson D, Holt AB, Netoff TI, Moehlis Optimal entrainment of heterogeneous noisy neurons. J. Front Neurosci. 2015 May 29;9:192.
- Connolly AT, Jensen AL, Bello EM, Netoff TI, Baker KB, Johnson MD, Vitek JL. Modulations in oscillatory frequency and coupling in globus pallidus with increasing parkinsonian severity. J Neurosci. 2015;35(15):6231-40.
- Holt AB, Netoff TI. Origins and suppression of oscillations in a computational model of Parkinson's disease. J Comput Neurosci. 2014;37(3):505-21.
- Johnson MD, Lim HH, Netoff TI, Connolly AT, Johnson N, Roy A, Holt A, Lim KO, Carey JR, Vitek JL, He B. Neuromodulation for brain disorders: challenges and opportunities. IEEE Trans Biomed Eng. 2013;60(3):610-24.
- Miranda-Domínguez Ó, Netoff TI. Parameterized phase response curves for characterizing neuronal behaviors under transient conditions. J Neurophysiol. 2013;109(9):2306-16.
- Holt AB, Netoff TI. Computational modeling of epilepsy for an experimental neurologist. Exp Neurol. 2013;244:75-86.
- Beverlin B 2nd, Kakalios J, Nykamp D, Netoff TI. Dynamical changes in neurons during seizures determine tonic to clonic shift. J Comput Neurosci. 2012;33(1):41-51.
- Ferguson JE, Boldt C, Puhl JG, Stigen TW, Jackson JC, Crisp KM, Mesce KA, Netoff TI, Redish AD. Nanowires precisely grown on the ends of microwire electrodes permit the recording of intracellular action potentials within deeper neural structures. Nanomedicine (Lond). 2012;7:847-53.
- Wang H, Black AJ, Zhu J, Stigen TW, Al-Qaisi MK, Netoff TI, Abosch A, Akkin T. Reconstructing micrometer-scale fiber pathways in the brain: multi-contrast optical coherence tomography based tractography. Neuroimage. 2011;58:984-92.
Former Graduate Students:
Jennifer Zick (Ph.D. 2018, Neuroscience, University of Minnesota).
Abbey Holt (Ph.D. 2016, Neuroscience, University of Minnesota).