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.)
Nagaraj V., Lee S., Krook-Magnuson, E.,Soltesz I., Benquet P., Irazoqui P., Netoff T. Future of seizure prediction and intervention: Closing the loop. Journal of Clinical Neurophysiology. 2015 Jun;32(3):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 Apr 15;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 Dec;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 Mar;60(3):610-24.
Miranda-Domínguez Ó, Netoff TI. Parameterized phase response curves for characterizing neuronal behaviors under transient conditions. J Neurophysiol. 2013 May;109(9):2306-16.
Holt AB, Netoff TI. Computational modeling of epilepsy for an experimental neurologist. Exp Neurol. 2013 Jun;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 Aug;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 Jun;7(6):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 Oct 15;58(4):984-92. Epub 2011 Jul 12.
Miranda-Domínguez O, Gonia J, Netoff TI. Firing rate control of a neuron using a linear proportional-integral controller. J Neural Eng. 2010 Dec;7(6):066004. Epub 2010 Oct 26.
Verhagen JV, Wesson DW, Netoff TI, White JA, Wachowiak M. Sniffing controls an adaptive filter of sensory input to the olfactory bulb. Nat Neurosci. 2007 May;10(5):631-9.
Pervouchine DD, Netoff TI, Rotstein HG, White JA, Cunningham MO, Whittington MA, Kopell NJ. Low-dimensional maps encoding dynamics in entorhinal cortex and hippocampus. Neural Comput. 2006 Nov;18(11):2617-50. Erratum in: Neural Comput. 2007 Jan;19(1):302.
Netoff, T.I., Acker, C.D., Bettencourt, J.C., White, J.A.. Beyond two-cell networks: experimental measurement of neuronal responses to multiple synaptic inputs. J Comput Neurosci. 2005 May-Jun;18(3):287-95 (2005).
Netoff, T.I., Banks, M.I., Dorval , A.D., Acker, C.D., Haas, J.S., Kopell, N., White, J.A., Synchronization in Hybrid Neuronal Networks of the Hippocampal Formation. J Neurophysiol. 2005 Mar;93(3):1197-208. Epub 2004 Nov 3 (2005).
Netoff, T.I., Clewley, R., Arno , S., Keck, T., White, J.A.. Epilepsy in Small-World Networks. J Neurosci. Sep 15; 24(37):8075-83 (2004).
Netoff, T.I., Pecora, L.M., Schiff, S.J.. Analyitical coupling detection in the presence of noise and nonlinearity, Phys. Rev. E 69(017201) (2004).
Netoff, T.I., Schiff, S.J.. Decreased Neuronal Synchronization During Experimental Seizures. J Neurosci. Aug 15;22(16):7297-307. (2002).
Current Graduate Students:
Abbey Holt (Neuroscience, University of Minnesota).