Changes in Excitability Properties of Ventromedial Motor Thalamic Neurons in 6-OHDA Lesioned Mice

Overview

Journal eNeuro

Specialty Neurology

Date 2021 Jan 29

PMID 33509950

Citations 5

Authors

Edyta K Bichler

Francesco Cavarretta

Dieter Jaeger

Affiliations

Soon will be listed here.

Abstract

The activity of basal ganglia input receiving motor thalamus (BGMT) makes a critical impact on motor cortical processing, but modification in BGMT processing with Parkinsonian conditions has not be investigated at the cellular level. Such changes may well be expected because of homeostatic regulation of neural excitability in the presence of altered synaptic drive with dopamine depletion. We addressed this question by comparing BGMT properties in brain slice recordings between control and unilaterally 6-hydroxydopamine hydrochloride (6-OHDA)-treated adult mice. At a minimum of one month after 6-OHDA treatment, BGMT neurons showed a highly significant increase in intrinsic excitability, which was primarily because of a decrease in M-type potassium current. BGMT neurons after 6-OHDA treatment also showed an increase in T-type calcium rebound spikes following hyperpolarizing current steps. Biophysical computer modeling of a thalamic neuron demonstrated that an increase in rebound spiking can also be accounted for by a decrease in the M-type potassium current. Modeling also showed that an increase in sag with hyperpolarizing steps found after 6-OHDA treatment could in part but not fully be accounted for by the decrease in M-type current. These findings support the hypothesis that homeostatic changes in BGMT neural properties following 6-OHDA treatment likely influence the signal processing taking place in the BG thalamocortical network in Parkinson's disease.

Citing Articles

Modeling Synaptic Integration of Bursty and β Oscillatory Inputs in Ventromedial Motor Thalamic Neurons in Normal and Parkinsonian States.

Cavarretta F, Jaeger D eNeuro. 2023; 10(12).

PMID: 37989589 PMC: 10726287. DOI: 10.1523/ENEURO.0237-23.2023.

T-type calcium channels as therapeutic targets in essential tremor and Parkinson's disease.

Matthews L, Puryear C, Correia S, Srinivasan S, Belfort G, Pan M Ann Clin Transl Neurol. 2023; 10(4):462-483.

PMID: 36738196 PMC: 10109288. DOI: 10.1002/acn3.51735.

Oscillatory waveform sharpness asymmetry changes in motor thalamus and motor cortex in a rat model of Parkinson's disease.

Parr-Brownlie L, Itoga C, Walters J, Underwood C Exp Neurol. 2022; 354:114089.

PMID: 35461830 PMC: 11345867. DOI: 10.1016/j.expneurol.2022.114089.

Input Zone-Selective Dysrhythmia in Motor Thalamus after Dopamine Depletion.

Nakamura K, Sharott A, Tanaka T, Magill P J Neurosci. 2021; 41(50):10382-10404.

PMID: 34753740 PMC: 8672689. DOI: 10.1523/JNEUROSCI.1753-21.2021.

Revisiting the "Paradox of Stereotaxic Surgery": Insights Into Basal Ganglia-Thalamic Interactions.

Magnusson J, Leventhal D Front Syst Neurosci. 2021; 15:725876.

PMID: 34512279 PMC: 8429495. DOI: 10.3389/fnsys.2021.725876.

References

Murer M, Riquelme L, Tseng K, Pazo J . Substantia nigra pars reticulata single unit activity in normal and 60HDA-lesioned rats: effects of intrastriatal apomorphine and subthalamic lesions. Synapse. 1998; 27(4):278-93. DOI: 10.1002/(SICI)1098-2396(199712)27:4<278::AID-SYN2>3.0.CO;2-9. View

Chan C, Shigemoto R, Mercer J, Surmeier D . HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons. J Neurosci. 2004; 24(44):9921-32. PMC: 6730257. DOI: 10.1523/JNEUROSCI.2162-04.2004. View

Bosch-Bouju C, Hyland B, Parr-Brownlie L . Motor thalamus integration of cortical, cerebellar and basal ganglia information: implications for normal and parkinsonian conditions. Front Comput Neurosci. 2013; 7:163. PMC: 3822295. DOI: 10.3389/fncom.2013.00163. View

DeLong M . Primate models of movement disorders of basal ganglia origin. Trends Neurosci. 1990; 13(7):281-5. DOI: 10.1016/0166-2236(90)90110-v. View

Lundblad M, Picconi B, Lindgren H, Cenci M . A model of L-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function. Neurobiol Dis. 2004; 16(1):110-23. DOI: 10.1016/j.nbd.2004.01.007. View

Ramcharan E, Gnadt J, Sherman S . Burst and tonic firing in thalamic cells of unanesthetized, behaving monkeys. Vis Neurosci. 2000; 17(1):55-62. DOI: 10.1017/s0952523800171056. View

Chu H, McIver E, Kovaleski R, Atherton J, Bevan M . Loss of Hyperdirect Pathway Cortico-Subthalamic Inputs Following Degeneration of Midbrain Dopamine Neurons. Neuron. 2017; 95(6):1306-1318.e5. PMC: 5679443. DOI: 10.1016/j.neuron.2017.08.038. View

Kuramoto E, Ohno S, Furuta T, Unzai T, Tanaka Y, Hioki H . Ventral medial nucleus neurons send thalamocortical afferents more widely and more preferentially to layer 1 than neurons of the ventral anterior-ventral lateral nuclear complex in the rat. Cereb Cortex. 2013; 25(1):221-35. DOI: 10.1093/cercor/bht216. View

Llinas R, Jahnsen H . Electrophysiology of mammalian thalamic neurones in vitro. Nature. 1982; 297(5865):406-8. DOI: 10.1038/297406a0. View

10.

Albin R, Young A, Penney J . The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989; 12(10):366-75. DOI: 10.1016/0166-2236(89)90074-x. View

11.

Brazhnik E, Novikov N, McCoy A, Cruz A, Walters J . Functional correlates of exaggerated oscillatory activity in basal ganglia output in hemiparkinsonian rats. Exp Neurol. 2014; 261:563-77. PMC: 4318574. DOI: 10.1016/j.expneurol.2014.07.010. View

12.

Devergnas A, Chen E, Ma Y, Hamada I, Pittard D, Kammermeier S . Anatomical localization of Cav3.1 calcium channels and electrophysiological effects of T-type calcium channel blockade in the motor thalamus of MPTP-treated monkeys. J Neurophysiol. 2015; 115(1):470-85. PMC: 4760490. DOI: 10.1152/jn.00858.2015. View

13.

Hu W, Tian C, Li T, Yang M, Hou H, Shu Y . Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation. Nat Neurosci. 2009; 12(8):996-1002. DOI: 10.1038/nn.2359. View

14.

Ha G, Lee J, Kwak H, Song K, Kwon J, Jung S . The Ca-activated chloride channel anoctamin-2 mediates spike-frequency adaptation and regulates sensory transmission in thalamocortical neurons. Nat Commun. 2016; 7:13791. PMC: 5187435. DOI: 10.1038/ncomms13791. View

15.

Magnin M, Morel A, Jeanmonod D . Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients. Neuroscience. 2000; 96(3):549-64. DOI: 10.1016/s0306-4522(99)00583-7. View

16.

Iavarone E, Yi J, Shi Y, Zandt B, OReilly C, Van Geit W . Experimentally-constrained biophysical models of tonic and burst firing modes in thalamocortical neurons. PLoS Comput Biol. 2019; 15(5):e1006753. PMC: 6541309. DOI: 10.1371/journal.pcbi.1006753. View

17.

Kuramoto E, Furuta T, Nakamura K, Unzai T, Hioki H, Kaneko T . Two types of thalamocortical projections from the motor thalamic nuclei of the rat: a single neuron-tracing study using viral vectors. Cereb Cortex. 2009; 19(9):2065-77. DOI: 10.1093/cercor/bhn231. View

18.

Chu H, Atherton J, Wokosin D, Surmeier D, Bevan M . Heterosynaptic regulation of external globus pallidus inputs to the subthalamic nucleus by the motor cortex. Neuron. 2015; 85(2):364-76. PMC: 4304914. DOI: 10.1016/j.neuron.2014.12.022. View

19.

Sherman S, Guillery R . The role of the thalamus in the flow of information to the cortex. Philos Trans R Soc Lond B Biol Sci. 2003; 357(1428):1695-708. PMC: 1693087. DOI: 10.1098/rstb.2002.1161. View

20.

Atherton J, Kitano K, Baufreton J, Fan K, Wokosin D, Tkatch T . Selective participation of somatodendritic HCN channels in inhibitory but not excitatory synaptic integration in neurons of the subthalamic nucleus. J Neurosci. 2010; 30(47):16025-40. PMC: 3073577. DOI: 10.1523/JNEUROSCI.3898-10.2010. View