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Phase response curves of subthalamic neurons: experimental measurement and theoretical prediction

Phase response curves of subthalamic neurons: experimental measurement and theoretical prediction Farries and Wilson BMC Neuroscience 2011, 12(Suppl 1):P370 http://www.biomedcentral.com/1471-2202/12/S1/P370 POSTER PRESENTATION Open Access Phase response curves of subthalamic neurons: experimental measurement and theoretical prediction Michael A Farries , Charles J Wilson From Twentieth Annual Computational Neuroscience Meeting: CNS*2011 Stockholm, Sweden. 23-28 July 2011 The subthalamic nucleus (STN) is an autonomously dependent currents and AHP currents that can be treated active population of glutamatergic neurons that occupies as a function of time since the last spike, we explored the a pivotal location within the basal ganglia, receiving iPRCs of cells whose conductances are direct functions of direct cortical input and innervating the globus pallidus voltage. Ignoring the spike itself by assuming that it is trig- and substantia nigra. As intrinsically oscillating neurons, gered at a certain threshold potential followed by return STN cells maybesuitablecandidates for reduction to (2 ms later) to resetting potential, we found that the iPRC phase models, where the state of each neuron is repre- of such cells is a simple function of their IV curves and sented by a single number (phase) and their response to that their iPRC is valid for arbitrarily large currents. The synaptic input is given by infinitesimal phase response contribution of AHP currents could therefore be covered curves (iPRCs). Phase models are analytically tractable by treating them as applied currents acting through this and assist the study of large neural populations, but IV curve-based iPRC. Following this approach, we devel- whether they can describe the behavior of STN cells with oped a method for deriving the iPRC of any cell well sufficient accuracy is an open question. We addressed described by a combination of fast voltage-dependent cur- this issue by measuring the iPRCs of STN cells in brain rents and time-dependent AHP currents, covering a wide slices, using both glutamatergic synaptic input and brief range of cell types. We were also able to estimate experi- current injection. We found that iPRCs measured synap- mentally the IV curves and AHP currents of STN cells in tically were relatively insensitive to the size of the EPSP which we had empirically determined the synaptic and used to measure them, and that iPRCs measured with current pulse iPRCs, allowing us to compare theoretically current pulses were the same regardless of the polarity of predicted iPRCs to experimentally measured iPRCs. We the current, at least during the first 60% of the oscillation found that the theoretically predicted PRC approximated cycle; both observations suggest that iPRCs might accu- the synaptic–but not the current pulse–iPRC. We rately describe the response of STN cells to finite inputs. hypothesize that somatically injected charge slowly trickles However, we also found that iPRCs measured synapti- into distal dendrites, reducing its effectiveness at advan- cally and by current injection were dramatically different, cing the phase, whereas synaptically delivered charge with current pulse iPRCs giving much less phase shift for comes from precharged dendrites. We conclude that cur- a given stimulus amplitude. rent injection is not an effective method for measuring We developed and analyzed a biophysical model of STN iPRCs in dendritic neurons. cells, to better understand the nature of subthalamic iPRCs. This model produced an iPRC that closely Published: 18 July 2011 resembled those we measured experimentally. Observing that this model consisted mainly of kinetically fast voltage- doi:10.1186/1471-2202-12-S1-P370 * Correspondence: michael.farries@utsa.edu Cite this article as: Farries and Wilson: Phase response curves of Department of Biology, University of Texas San Antonio, San Antonio, TX subthalamic neurons: experimental measurement and theoretical 78249, USA prediction. BMC Neuroscience 2011 12(Suppl 1):P370. © 2011 Farries and Wilson; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png BMC Neuroscience Springer Journals

Phase response curves of subthalamic neurons: experimental measurement and theoretical prediction

Farries, Michael; Wilson, Charles
BMC Neuroscience , Volume 12 (1) – Jul 18, 2011
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Springer Journals
Copyright
Copyright © 2011 by Farries and Wilson; licensee BioMed Central Ltd.
Subject
Biomedicine; Neurosciences; Neurobiology; Animal Models
eISSN
1471-2202
DOI
10.1186/1471-2202-12-S1-P370
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Abstract

Farries and Wilson BMC Neuroscience 2011, 12(Suppl 1):P370 http://www.biomedcentral.com/1471-2202/12/S1/P370 POSTER PRESENTATION Open Access Phase response curves of subthalamic neurons: experimental measurement and theoretical prediction Michael A Farries , Charles J Wilson From Twentieth Annual Computational Neuroscience Meeting: CNS*2011 Stockholm, Sweden. 23-28 July 2011 The subthalamic nucleus (STN) is an autonomously dependent currents and AHP currents that can be treated active population of glutamatergic neurons that occupies as a function of time since the last spike, we explored the a pivotal location within the basal ganglia, receiving iPRCs of cells whose conductances are direct functions of direct cortical input and innervating the globus pallidus voltage. Ignoring the spike itself by assuming that it is trig- and substantia nigra. As intrinsically oscillating neurons, gered at a certain threshold potential followed by return STN cells maybesuitablecandidates for reduction to (2 ms later) to resetting potential, we found that the iPRC phase models, where the state of each neuron is repre- of such cells is a simple function of their IV curves and sented by a single number (phase) and their response to that their iPRC is valid for arbitrarily large currents. The synaptic input is given by infinitesimal phase response contribution of AHP currents could therefore be covered curves (iPRCs). Phase models are analytically tractable by treating them as applied currents acting through this and assist the study of large neural populations, but IV curve-based iPRC. Following this approach, we devel- whether they can describe the behavior of STN cells with oped a method for deriving the iPRC of any cell well sufficient accuracy is an open question. We addressed described by a combination of fast voltage-dependent cur- this issue by measuring the iPRCs of STN cells in brain rents and time-dependent AHP currents, covering a wide slices, using both glutamatergic synaptic input and brief range of cell types. We were also able to estimate experi- current injection. We found that iPRCs measured synap- mentally the IV curves and AHP currents of STN cells in tically were relatively insensitive to the size of the EPSP which we had empirically determined the synaptic and used to measure them, and that iPRCs measured with current pulse iPRCs, allowing us to compare theoretically current pulses were the same regardless of the polarity of predicted iPRCs to experimentally measured iPRCs. We the current, at least during the first 60% of the oscillation found that the theoretically predicted PRC approximated cycle; both observations suggest that iPRCs might accu- the synaptic–but not the current pulse–iPRC. We rately describe the response of STN cells to finite inputs. hypothesize that somatically injected charge slowly trickles However, we also found that iPRCs measured synapti- into distal dendrites, reducing its effectiveness at advan- cally and by current injection were dramatically different, cing the phase, whereas synaptically delivered charge with current pulse iPRCs giving much less phase shift for comes from precharged dendrites. We conclude that cur- a given stimulus amplitude. rent injection is not an effective method for measuring We developed and analyzed a biophysical model of STN iPRCs in dendritic neurons. cells, to better understand the nature of subthalamic iPRCs. This model produced an iPRC that closely Published: 18 July 2011 resembled those we measured experimentally. Observing that this model consisted mainly of kinetically fast voltage- doi:10.1186/1471-2202-12-S1-P370 * Correspondence: michael.farries@utsa.edu Cite this article as: Farries and Wilson: Phase response curves of Department of Biology, University of Texas San Antonio, San Antonio, TX subthalamic neurons: experimental measurement and theoretical 78249, USA prediction. BMC Neuroscience 2011 12(Suppl 1):P370. © 2011 Farries and Wilson; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Journal

BMC Neuroscience – Springer Journals

Published: Jul 18, 2011

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