Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

T-type calcium channels trigger a hyperpolarization induced afterdepolarization in substantia nigra dopamine neurons

T-type calcium channels trigger a hyperpolarization induced afterdepolarization in substantia... Evans and Khaliq BMC Neuroscience 2015, 16(Suppl 1):P123 http://www.biomedcentral.com/1471-2202/16/S1/P123 POSTER PRESENTATION Open Access T-type calcium channels trigger a hyperpolarization induced afterdepolarization in substantia nigra dopamine neurons Rebekah C Evans , Zayd M Khaliq From 24th Annual Computational Neuroscience Meeting: CNS*2015 Prague, Czech Republic. 18-23 July 2015 Dopamine neuron dendrites integrate synaptic informa- SNc dopamine neuron in Genesis simulation software. tion arriving from a diverse set of cell classes including This model contains a spherical soma with two dendritic excitatory and inhibitory neurons. The majority of trees extending from it, each containing identical primary, synapses formed onto substantia nigra (SNc) dopamine secondary and tertiary branches. Our simulations showed that a high density of dendritic T-type calcium channels is neurons (>70 %) arrive from inhibitory GABAergic neu- rons [1]. Activation of GABA receptors pauses tonic fir- critical to the generation of the HI-ADP. Specifically, we ing and hyperpolarizes cells. Although the pause in found that reducing the T-type channel conductance by dopamine neuron firing has behavioral relevance during half throughout the entire cell completely abolished the reward omission [2], the hyperpolarization may also HI-ADP. On the other hand, removing T-type channels enable burst firing through disinhibition [3] or engage- from only one dendritic tree slightly reduced, but did not ment of voltage-gated ion channels [4]. However, it is eliminate the HI-ADP. These simulations show that a not clear how hyperpolarization influences dendritic high, localized density of T-type channels is more impor- integration. Here we use detailed single-cell computa- tant to the generation of the HI-ADP than the total num- tional modeling, patch-clamp electrophysiology, and ber of T-type channels in the cell. two-photon calcium imaging to investigate the dendritic Further simulations predict that the tightly coupled, response to hyperpolarization. We find that at hyperpo- electrotonically compact dendrites characteristic of SNc larized potentials, some dopamine neurons respond to dopamine neurons are also necessary for the production brief somatic current injections with a long-lasting of the HI-ADP. In particular, reducing the membrane depolarizing plateau that is accompanied by a large cal- input resistance of the model cell eliminated the HI-ADP. cium transient in the dendrites. Because this depolariz- Confirming this prediction, our experimental data show ing plateau requires prior hyperpolarization, we will that reducing the input resistance of SNc dopamine neu- refer to it as a hyperpolarization induced afterdepolari- rons through activation of G-protein coupled inwardly- zation (HI-ADP). rectifying potassium channels (GIRKs) abolished the Using electrophysiology and calcium imaging, we found HI-ADP and reduced the concomitant dendritic calcium that pharmacological block of T-type calcium currents transient. In conclusion, we have shown that T-type calcium chan- with TTA-P2 completely eliminated the dendritic calcium nels and electrotonically compact dendrites are essential transient and greatly reduced the size of the HI-ADP. In contrast, blocking L-type calcium channels with nifedipine for generating a HI-ADP in SNc dopamine neurons. did not significantly alter the dendritic calcium or size of These HI-ADPs represent an interesting response to the HI-ADP. To further investigate the involvement of hyperpolarization that may be unique to SNc dopamine dendritic T-currents in generating the HI-ADP, we devel- neurons having the specific combination of high T-type oped a multi-compartmental, multi-channel model of an channel density and tight electrotonically compact den- drites. This particular combination of characteristics may allow SNc dopamine neurons to respond to inhibition or * Correspondence: rebekah.evans@nih.gov the release of inhibition with an increased ability to burst. NINDS, NIH, Bethesda, MD 20892, USA © 2015 Evans and Khaliq This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Evans and Khaliq BMC Neuroscience 2015, 16(Suppl 1):P123 Page 2 of 2 http://www.biomedcentral.com/1471-2202/16/S1/P123 Published: 18 December 2015 References 1. Henny P, Brown MTC, Northrop A, Faunes M, Ungless MA, Magill PJ, Bolam JP: Structural correlates of heterogeneous in vivo activity of midbrain dopaminergic neurons. Nat Neurosci 2012, 15:613-619. 2. Schultz W, Dayan P, Montague PR: A neural substrate of prediction and reward. Science 1997, 275:1593-1599. 3. Lobb CJ, Wilson CJ, Paladini CA: A dynamic role for GABA receptors on the firing pattern of midbrain dopaminergic neurons. J Neurophysiol 2010, 104:403-413. 4. Tateno T, Robinson HPC: The mechanism of ethanol action on midbrain dopaminergic neuron firing: a dynamic-clamp study of the role of I(h) and GABAergic synaptic integration. J Neurophysiol 2011, 106:1901-1922. doi:10.1186/1471-2202-16-S1-P123 Cite this article as: Evans and Khaliq: T-type calcium channels trigger a hyperpolarization induced afterdepolarization in substantia nigra dopamine neurons. BMC Neuroscience 2015 16(Suppl 1):P123. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png BMC Neuroscience Springer Journals

T-type calcium channels trigger a hyperpolarization induced afterdepolarization in substantia nigra dopamine neurons

Evans, Rebekah; Khaliq, Zayd
BMC Neuroscience , Volume 16 (1) – Dec 18, 2015
Download PDF
2 pages

Loading next page...
 
/lp/springer-journals/t-type-calcium-channels-trigger-a-hyperpolarization-induced-Cv00M2gV5k

References (4)

Publisher
Springer Journals
Copyright
Copyright © 2015 by Evans and Khaliq
Subject
Biomedicine; Neurosciences; Neurobiology; Animal Models
eISSN
1471-2202
DOI
10.1186/1471-2202-16-S1-P123
Publisher site
See Article on Publisher Site

Abstract

Evans and Khaliq BMC Neuroscience 2015, 16(Suppl 1):P123 http://www.biomedcentral.com/1471-2202/16/S1/P123 POSTER PRESENTATION Open Access T-type calcium channels trigger a hyperpolarization induced afterdepolarization in substantia nigra dopamine neurons Rebekah C Evans , Zayd M Khaliq From 24th Annual Computational Neuroscience Meeting: CNS*2015 Prague, Czech Republic. 18-23 July 2015 Dopamine neuron dendrites integrate synaptic informa- SNc dopamine neuron in Genesis simulation software. tion arriving from a diverse set of cell classes including This model contains a spherical soma with two dendritic excitatory and inhibitory neurons. The majority of trees extending from it, each containing identical primary, synapses formed onto substantia nigra (SNc) dopamine secondary and tertiary branches. Our simulations showed that a high density of dendritic T-type calcium channels is neurons (>70 %) arrive from inhibitory GABAergic neu- rons [1]. Activation of GABA receptors pauses tonic fir- critical to the generation of the HI-ADP. Specifically, we ing and hyperpolarizes cells. Although the pause in found that reducing the T-type channel conductance by dopamine neuron firing has behavioral relevance during half throughout the entire cell completely abolished the reward omission [2], the hyperpolarization may also HI-ADP. On the other hand, removing T-type channels enable burst firing through disinhibition [3] or engage- from only one dendritic tree slightly reduced, but did not ment of voltage-gated ion channels [4]. However, it is eliminate the HI-ADP. These simulations show that a not clear how hyperpolarization influences dendritic high, localized density of T-type channels is more impor- integration. Here we use detailed single-cell computa- tant to the generation of the HI-ADP than the total num- tional modeling, patch-clamp electrophysiology, and ber of T-type channels in the cell. two-photon calcium imaging to investigate the dendritic Further simulations predict that the tightly coupled, response to hyperpolarization. We find that at hyperpo- electrotonically compact dendrites characteristic of SNc larized potentials, some dopamine neurons respond to dopamine neurons are also necessary for the production brief somatic current injections with a long-lasting of the HI-ADP. In particular, reducing the membrane depolarizing plateau that is accompanied by a large cal- input resistance of the model cell eliminated the HI-ADP. cium transient in the dendrites. Because this depolariz- Confirming this prediction, our experimental data show ing plateau requires prior hyperpolarization, we will that reducing the input resistance of SNc dopamine neu- refer to it as a hyperpolarization induced afterdepolari- rons through activation of G-protein coupled inwardly- zation (HI-ADP). rectifying potassium channels (GIRKs) abolished the Using electrophysiology and calcium imaging, we found HI-ADP and reduced the concomitant dendritic calcium that pharmacological block of T-type calcium currents transient. In conclusion, we have shown that T-type calcium chan- with TTA-P2 completely eliminated the dendritic calcium nels and electrotonically compact dendrites are essential transient and greatly reduced the size of the HI-ADP. In contrast, blocking L-type calcium channels with nifedipine for generating a HI-ADP in SNc dopamine neurons. did not significantly alter the dendritic calcium or size of These HI-ADPs represent an interesting response to the HI-ADP. To further investigate the involvement of hyperpolarization that may be unique to SNc dopamine dendritic T-currents in generating the HI-ADP, we devel- neurons having the specific combination of high T-type oped a multi-compartmental, multi-channel model of an channel density and tight electrotonically compact den- drites. This particular combination of characteristics may allow SNc dopamine neurons to respond to inhibition or * Correspondence: rebekah.evans@nih.gov the release of inhibition with an increased ability to burst. NINDS, NIH, Bethesda, MD 20892, USA © 2015 Evans and Khaliq This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Evans and Khaliq BMC Neuroscience 2015, 16(Suppl 1):P123 Page 2 of 2 http://www.biomedcentral.com/1471-2202/16/S1/P123 Published: 18 December 2015 References 1. Henny P, Brown MTC, Northrop A, Faunes M, Ungless MA, Magill PJ, Bolam JP: Structural correlates of heterogeneous in vivo activity of midbrain dopaminergic neurons. Nat Neurosci 2012, 15:613-619. 2. Schultz W, Dayan P, Montague PR: A neural substrate of prediction and reward. Science 1997, 275:1593-1599. 3. Lobb CJ, Wilson CJ, Paladini CA: A dynamic role for GABA receptors on the firing pattern of midbrain dopaminergic neurons. J Neurophysiol 2010, 104:403-413. 4. Tateno T, Robinson HPC: The mechanism of ethanol action on midbrain dopaminergic neuron firing: a dynamic-clamp study of the role of I(h) and GABAergic synaptic integration. J Neurophysiol 2011, 106:1901-1922. doi:10.1186/1471-2202-16-S1-P123 Cite this article as: Evans and Khaliq: T-type calcium channels trigger a hyperpolarization induced afterdepolarization in substantia nigra dopamine neurons. BMC Neuroscience 2015 16(Suppl 1):P123. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit

Journal

BMC Neuroscience – Springer Journals

Published: Dec 18, 2015

There are no references for this article.