scholarly journals Cholinergic Projections to the Substantia Nigra Pars Reticulata Inhibit Dopamine Modulation of Basal Ganglia through the M4 Muscarinic Receptor

Neuron ◽  
2017 ◽  
Vol 96 (6) ◽  
pp. 1358-1372.e4 ◽  
Author(s):  
Mark S. Moehle ◽  
Tristano Pancani ◽  
Nellie Byun ◽  
Samantha E. Yohn ◽  
George H. Wilson ◽  
...  
Author(s):  
Charles J. Wilson

The subthalamo-pallidal system constitutes the second layer of circuitry in the basal ganglia, downstream of the striatum. It consists of four nuclei. Two of them, the external segment of the globus pallidus (GPe) and subthalamic nucleus (STN), make their connections primarily within the basal ganglia. The others, the internal segment of the globus pallidus (GPi) and the substantia nigra pars reticulata (SNr), are the output nuclei of the basal ganglia. Collectively, their axons distribute collaterals to all the targets of the basal ganglia. Rare interneurons have been reported in each of them from studies of Golgi-stained preparations, but they have not so far been confirmed using more modern methods. The circuit as described here is based primarily on studies of the axonal arborizations of neurons stained individually by intracellular or juxtacellular labeling.


2006 ◽  
Vol 96 (3) ◽  
pp. 1581-1591 ◽  
Author(s):  
Fu-Wen Zhou ◽  
Jian-Jun Xu ◽  
Yu Zhao ◽  
Mark S. LeDoux ◽  
Fu-Ming Zhou

The substantia nigra pars reticulata (SNr) is a key basal ganglia output nucleus. Inhibitory outputs from SNr are encoded in spike frequency and pattern of the inhibitory SNr projection neurons. SNr output intensity and pattern are often abnormal in movement disorders of basal ganglia origin. In Parkinson’s disease, histamine innervation and histamine H3 receptor expression in SNr may be increased. However, the functional consequences of these alterations are not known. In this study, whole cell patch-clamp recordings were used to elucidate the function of different histamine receptors in SNr. Histamine increased SNr inhibitory projection neuron firing frequency and thus inhibitory output. This effect was mediated by activation of histamine H1 and H2 receptors that induced inward currents and depolarization. In contrast, histamine H3 receptor activation hyperpolarized and inhibited SNr inhibitory projection neurons, thus decreasing the intensity of basal ganglia output. By the hyperpolarization, H3 receptor activation also increased the irregularity of the interspike intervals or changed the pattern of SNr inhibitory neuron firing. H3 receptor–mediated effects were normally dominated by those mediated by H1 and H2 receptors. Furthermore, endogenously released histamine provided a tonic, H1 and H2 receptor–mediated excitation that helped keep SNr inhibitory projection neurons sufficiently depolarized and spiking regularly. These results suggest that H1 and H2 receptors and H3 receptor exert opposite effects on SNr inhibitory projection neurons. Functional balance of these different histamine receptors may contribute to the proper intensity and pattern of basal ganglia output and, as a consequence, exert important effects on motor control.


2015 ◽  
Vol 113 (6) ◽  
pp. 1681-1696 ◽  
Author(s):  
Masaharu Yasuda ◽  
Okihide Hikosaka

Gaze is strongly attracted to visual objects that have been associated with rewards. Key to this function is a basal ganglia circuit originating from the caudate nucleus (CD), mediated by the substantia nigra pars reticulata (SNr), and aiming at the superior colliculus (SC). Notably, subregions of CD encode values of visual objects differently: stably by CD tail [CD(T)] vs. flexibly by CD head [CD(H)]. Are the stable and flexible value signals processed separately throughout the CD-SNr-SC circuit? To answer this question, we identified SNr neurons by their inputs from CD and outputs to SC and examined their sensitivity to object values. The direct input from CD was identified by SNr neuron's inhibitory response to electrical stimulation of CD. We found that SNr neurons were separated into two groups: 1) neurons inhibited by CD(T) stimulation, located in the caudal-dorsal-lateral SNr (cdlSNr), and 2) neurons inhibited by CD(H) stimulation, located in the rostral-ventral-medial SNr (rvmSNr). Most of CD(T)-recipient SNr neurons encoded stable values, whereas CD(H)-recipient SNr neurons tended to encode flexible values. The output to SC was identified by SNr neuron's antidromic response to SC stimulation. Among the antidromically activated neurons, many encoded only stable values, while some encoded only flexible values. These results suggest that CD(T)-cdlSNr-SC circuit and CD(H)-rvmSNr-SC circuit transmit stable and flexible value signals, largely separately, to SC. The speed of signal transmission was faster through CD(T)-cdlSNr-SC circuit than through CD(H)-rvmSNr-SC circuit, which may reflect automatic and controlled gaze orienting guided by these circuits.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Andrew Lutas ◽  
Carolina Lahmann ◽  
Magali Soumillon ◽  
Gary Yellen

Certain neuron types fire spontaneously at high rates, an ability that is crucial for their function in brain circuits. The spontaneously active GABAergic neurons of the substantia nigra pars reticulata (SNr), a major output of the basal ganglia, provide tonic inhibition of downstream brain areas. A depolarizing 'leak' current supports this firing pattern, but its molecular basis remains poorly understood. To understand how SNr neurons maintain tonic activity, we used single-cell RNA sequencing to determine the transcriptome of individual mouse SNr neurons. We discovered that SNr neurons express the sodium leak channel, NALCN, and that SNr neurons lacking NALCN have impaired spontaneous firing. In addition, NALCN is involved in the modulation of excitability by changes in glycolysis and by activation of muscarinic acetylcholine receptors. Our findings suggest that disruption of NALCN could impair the basal ganglia circuit, which may underlie the severe motor deficits in humans carrying mutations in NALCN.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Mario J Lintz ◽  
Gidon Felsen

How movements are selected is a fundamental question in systems neuroscience. While many studies have elucidated the sensorimotor transformations underlying stimulus-guided movements, less is known about how internal goals – critical drivers of goal-directed behavior – guide movements. The basal ganglia are known to bias movement selection according to value, one form of internal goal. Here, we examine whether other internal goals, in addition to value, also influence movements via the basal ganglia. We designed a novel task for mice that dissociated equally rewarded internally-specified and stimulus-guided movements, allowing us to test how each engaged the basal ganglia. We found that activity in the substantia nigra pars reticulata, a basal ganglia output, predictably differed preceding internally-specified and stimulus-guided movements. Incorporating these results into a simple model suggests that internally-specified movements may be facilitated relative to stimulus-guided movements by basal ganglia processing.


Author(s):  
Edith G. McGeer ◽  
William A. Staines ◽  
Patrick L. McGeer

ABSTRACTThe literature is reviewed on the afferents and efferents of the caudate/putamen, globus pallidus and substantia nigra, and on the neurotransmitters occurring in the various tracts. Emphasis is placed upon the diverse roles played by GABA and glutamate as transmitters in motor pathways and upon the probability that the substantia nigra pars reticulata plays a pivotal role in the output of the basal ganglia. Excessive stimulation of the projection from the pedunculopontine tegmental area to the substantia nigra is shown to cause destruction of dopaminergic neurons in the latter nucleus, suggesting another possible mechanism for cell death in Parkinson’s disease.


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