Electrophysiological Characterization of Substantia Nigra Pars Reticulata in Anesthetized Rats

doi:10.1007/s12204-022-2420-y

Abstract

Abstract: The substantia nigra pars reticulate (SNr), which plays a pivotal role in motor control, is the key structure in integrating information for cortex, basal ganglia and thalamus. Abnormal gait and posture deficits can be reversed by SNr deep brain stimulation (DBS) in certain Parkinson’s disease cases. However, functional characterization of SNr, which is the key for the optimization of DBS effect, remains elusive. In current study, we recorded extracellular single unit in SNr of urethane anesthetized rats. We have found that urethane can induce slow delta and theta oscillations in SNr local field potential. The high gamma oscillation observed is positively correlated with the occurrence of action potential. The putative GABAergic neurons have a mean firing rate of (20.82 ± 2.04) Hz, of which 65.2% display a regular firing pattern and 34.8% show irregular firing. Our results demonstrated the heterogeneous property of SNr and provided possible theoretical basis for promoting the next generation of DBS electrode design and optimization of clinical DBS parameters.

Key words: substantia nigra pars reticulate (SNr), local field potential, firing regularity, electrophysiology

CLC Number:

Q424

LIU Xinrui 1 (刘信锐), ZHANG Qianwen1 (张骞文), WANG Ying2 (王莹), CHEN Fujun1,3∗ (陈福俊). Electrophysiological Characterization of Substantia Nigra Pars Reticulata in Anesthetized Rats[J]. J Shanghai Jiaotong Univ Sci, 2022, 27(4): 505-511.

References 36

[1]	ZHOU F M, LEE C R. Intrinsic and integrative properties of substantia nigra pars reticulata neurons [J].Neuroscience, 2011, 198: 69-94.
[2]	CONDé H. Organization and physiology of the substantia nigra [J]. Experimental Brain Research, 1992,88(2): 233-248.
[3]	RICHARDS C D, SHIROYAMA T, KITAI S T. Elec-Trophysio logical and immunocytochemical characterization of GABA and dopamine neurons in the substantia nigra of the rat [J]. Neuroscience, 1997, 80(2):545-557.
[4]	DENIAU J M, MAILLY P, MAURICE N, et al. Thepars reticulata of the substantia nigra: A window to basal Ganglia output [J]. Progress in Brain Research,2007, 160: 151-172.
[5]	M A C L E O D N K , J A M E S T A , K I L P A T R I C K I C , e tal. Evidence for a GABAergic nigrothalamic pathwayin the rat. II. Electrophysiological studies [J]. Experimental Brain Research, 1980, 40(1): 55-61.
[6]	FRIEND D M, KRA VITZ A V. Working together:Basal Ganglia pathways in action selection [J]. Trendsin Neurosciences, 2014, 37(6): 301-303.
[7]	H I K O S A K A O , K I M H F , Y A S U D A M , e t a l . B a s a lGanglia circuits for reward value-guided behavior [J].Annual Review of Neuroscience, 2014, 37: 289-306.
[8]	SCHOLTEN M, KLEMT J, HEILBRONN M, et al.Effects of subthalamic and nigral stimulation on gaitkinematics in Parkinson’s disease [J]. Frontiers in Neurology, 2017, 8: 543-543.
[9]	WINDELS F, KIYATKIN E A. GABAergic mechanisms in regulating the activity state of substantianigra pars reticulata neurons [J]. Neuroscience, 2006,140(4): 1289-1299.
[10]	W ANG Y, ZHANG Q J, LIU J, et al. Changes in firingrate and pattern of GABAergic neurons in subregions of the substantia nigra pars reticulata in rat models of Parkinson’s disease [J]. Brain Research, 2010, 1324:54-63.
[11]	DENIAU J M, CHEV ALIER G. The lamellar organization of the rat substantia nigra pars reticulata: Distribution of projection neurons [J]. Neuroscience, 1992,46(2): 361-377.
[12]	WILTSCHKO A B, GAGE G J, BERKE J D. Wavelet filtering before spike detection preserves wave form shape and enhances single-unit discrimination [J].Journal of Neuroscience Methods, 2008, 173(1): 34-40.
[13]	REY H G, PEDREIRA C, QUIAN QUIROGA R.Past, present and future of spike sorting techniques[J]. Brain Research Bulletin, 2015, 119: 106-117.
[14]	TAUBE J S. Interspike interval analyses reveal irregular firing patterns at short, but not long, intervals inrat head direction cells [J]. Journal of Neurophysiology,2010, 104(3): 1635-1648.
[15]	WEIR K, BLANQUIE O, KILB W, et al. Comparison of spike parameters from optically identified GABAer-gic and glutamatergic neurons in sparse cortical cultures [J]. Frontiers in Cellular Neuroscience, 2015, 8:460.
[16]	MAURICE N, THIERRY A M, GLOWINSKI J, et al.Spontaneous and evoked activity of substantia nigrapars reticulata neurons during high-frequency stimulation of the subthalamic nucleus [J]. Journal of Neuroscience, 2003, 23(30): 9929-9936.
[17]	SANO H, CHIKEN S, HIKIDA T, et al. Signalsthrough the striatopallidal indirect pathway stopmovements by phasic excitation in the substantia nigra[J]. Journal of Neuroscience, 2013, 33(17): 7583-7594.
[18]	MURER M G, RIQUELME L A, TSENG K Y, et al.Substantia nigra pars reticulata single unit activity innormal and 60HDA-lesioned rats: Effects of intrastriatal apomorphine and subthalamic lesions [J]. Synapse,1997, 27(4): 278-293.
[19]	HUH Y, CHO J. Urethane anesthesia depresses activities of thalamocortical neurons and alters its response to nociception in terms of dual firing modes [J]. Frontiers in Behavioral Neuroscience, 2013, 7: 141.
[20]	HARA K, HARRIS R A. The anesthetic mechanism ofurethane: The effects on neurotransmitter-gated ion channels [J]. Anesthesia and Analgesia, 2002, 94(2):313-318.
[21]	DAYAL V, LIMOUSIN P, FOLTYNIE T. Subthalamicnucleus deep brain stimulation in Parkinson’s disease:The effect of varying stimulation parameters [J]. Journal of Parkinson ’s Disease, 2017, 7(2): 235-245.
[22]	THEV ATHASAN W, DEBU B, AZIZ T, et al. Pedun-culopontine nucleus deep brain stimulation in Parkin-son’s disease: A clinical review [J]. Movement Disorders, 2018, 33(1): 10-20.
[23]	CASTRIOTO A, MORO E. New targets for deep brain stimulation treatment of Parkinson’s disease [J]. Ex-pert Review of Neurotherapeutics, 2013, 13(12): 1319-1328.
[24]	FOLLETT K A, TORRES-RUSSOTTO D. Deep brain stimulation of globus pallidus interna, subthalamic nucleus, and pedunculopontine nucleus for Parkinson’s disease: Which target? [J]. Parkinsonism and Related Disorders, 2012, 18 (Sup.1): S165-S167.
[25]	BROSIUS S N, GONZALEZ C L, SHURESH J, et al.Reversible improvement in severe freezing of gait from Parkinson’s disease with unilateral interleaved subtha-lamic brain stimulation [J]. Parkinsonism and Related Disorders, 2015, 21(12): 1469-1470.
[26]	DOR V AL A D, GRILL W M. Deep brain stimulation of the subthalamic nucleus reestablishes neuronal in-formation transmission in the 6-OHDA rat model of Parkinsonism [J]. Journal of Neurophysiology, 2014,111(10): 1949-1959.
[27]	LI H, MCCONNELL G C. Intraoperative microelec-trode recordings in substantia nigra pars reticulata inanesthetized rats [J]. Frontiers in Neuroscience, 2020,14: 367.
[28]	HOWELL B, GRILL W M. Evaluation of high-perimeter electrode designs for deep brain stimulation [J]. Journal of Neural Engineering, 2014, 11(4):046026.
[29]	AKEJU O, BROWN E N. Neural oscillations demonstrate that general anesthesia and sedative states areneuro physiologically distinct from sleep [J]. Current Opinion in Neurobiology, 2017, 44: 178-185.
[30]	LEWIS L D, CHING S, WEINER V S, et al. Localcortical dynamics of burst suppression in the anaes-thetized brain [J]. Brain, 2013, 136(9): 2727-2737.
[31]	AKEJU O, SONG A H, HAMILOS A E, et al. Elec-troencephalogram signatures of ketamine anesthesia-induced unconsciousness [J]. Clinical Neurophysiology,2016, 127(6): 2414-2422.
[32]	C H E R Y R , G U R D E N H , M A R T I N C . A n e s t h e t i cregimes modulate the temporal dynamics of local field potential in the mouse olfactory bulb [J]. Journal of Neurophysiology, 2014, 111(5): 908-917.
[33]	HOMAYOUN H, MOGHADDAM B. NMDA receptorhypo function produces opposite effects on prefrontal cortex interneurons and pyramidal neurons [J]. Journal of Neuroscience, 2007, 27(43): 11496-11500.
[34]	R A Y S , H S I A O S S , C R O N E N E , e t a l . Effect of stimulus intensity on the spike-local field potential relationship in the secondary somatosensory cortex [J].Journal of Neuroscience, 2008, 28(29): 7334-7343.
[35]	PARASTARFEIZABADI M, KOUZANI A Z. Advances in closed-loop deep brain stimulation devices[J]. Journal of Neuro engineering and Rehabilitation,2017, 14(1): 79.
[36]	HABETS J G V, HEIJMANS M, KUIJF M L, et al. An update on adaptive deep brain stimulation in Parkin-son’s disease [J]. Movement Disorders, 2018, 33(12):1834-1843.