scholarly journals The leak channel NALCN controls tonic firing and glycolytic sensitivity of substantia nigra pars reticulata neurons

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Andrew Lutas ◽  
Carolina Lahmann ◽  
Magali Soumillon ◽  
Gary Yellen
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Acetylcholine Receptors ◽  
Muscarinic Acetylcholine Receptors ◽  
Substantia Nigra Pars Reticulata ◽  
Motor Deficits ◽  
Tonic Firing ◽  
Leak Channel ◽  
Individual Mouse ◽  
Severe Motor

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.

Subthalamo-Pallidal Circuit

2017 ◽  
pp. 143-150
Author(s):  
Charles J. Wilson
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Substantia Nigra Pars Reticulata ◽  
Modern Methods

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.

scholarly journals The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Jennifer Brown ◽  
Wei-Xing Pan ◽  
Joshua Tate Dudman
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Feedback Inhibition ◽  
Gain Control ◽  
Feedback Gain ◽  
Projection Neurons ◽  
Tonic Firing ◽  
Canonical Models ◽  
Firing Rates ◽  
Engineered Systems

Dysfunction of the basal ganglia produces severe deficits in the timing, initiation, and vigor of movement. These diverse impairments suggest a control system gone awry. In engineered systems, feedback is critical for control. By contrast, models of the basal ganglia highlight feedforward circuitry and ignore intrinsic feedback circuits. In this study, we show that feedback via axon collaterals of substantia nigra projection neurons control the gain of the basal ganglia output. Through a combination of physiology, optogenetics, anatomy, and circuit mapping, we elaborate a general circuit mechanism for gain control in a microcircuit lacking interneurons. Our data suggest that diverse tonic firing rates, weak unitary connections and a spatially diffuse collateral circuit with distinct topography and kinetics from feedforward input is sufficient to implement divisive feedback inhibition. The importance of feedback for engineered systems implies that the intranigral microcircuit, despite its absence from canonical models, could be essential to basal ganglia function.

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 ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Muscarinic Receptor ◽  
Substantia Nigra Pars Reticulata ◽  
M4 Muscarinic Receptor ◽  
Cholinergic Projections ◽  
Dopamine Modulation

Opposite Functions of Histamine H1 and H2 Receptors and H3 Receptor in Substantia Nigra Pars Reticulata

2006 ◽  
Vol 96 (3) ◽  
pp. 1581-1591 ◽  
Author(s):  
Fu-Wen Zhou ◽  
Jian-Jun Xu ◽  
Yu Zhao ◽  
Mark S. LeDoux ◽  
Fu-Ming Zhou
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Inhibitory Neuron ◽  
Projection Neuron ◽  
Receptor Activation ◽  
Histamine Receptors ◽  
Receptor Expression ◽  
Substantia Nigra Pars Reticulata ◽  
Projection Neurons ◽  
Neuron Firing

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.

scholarly journals Functional territories in primate substantia nigra pars reticulata separately signaling stable and flexible values

2015 ◽  
Vol 113 (6) ◽  
pp. 1681-1696 ◽  
Author(s):  
Masaharu Yasuda ◽  
Okihide Hikosaka
Keyword(s):  
Electrical Stimulation ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Signal Transmission ◽  
Inhibitory Response ◽  
Substantia Nigra Pars Reticulata ◽  
Visual Objects ◽  
Direct Input ◽  
Antidromic Response ◽  
Stimulation Of

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.

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