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.

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.

Activation of Group III mGluRs Inhibits GABAergic and Glutamatergic Transmission in the Substantia Nigra Pars Reticulata

2001 ◽  
Vol 85 (5) ◽  
pp. 1960-1968 ◽  
Author(s):  
Marion Wittmann ◽  
Michael J. Marino ◽  
Stefania Risso Bradley ◽  
P. Jeffrey Conn
Keyword(s):  
Substantia Nigra ◽  
Synaptic Transmission ◽  
Globus Pallidus ◽  
Movement Disorders ◽  
Metabotropic Glutamate Receptors ◽  
Substantia Nigra Pars Reticulata ◽  
Projection Neurons ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Primary Output

The GABAergic projection neurons of the substantia nigra pars reticulata (SNr) exert an important influence on the initiation and control of movement. The SNr is a primary output nucleus of the basal ganglia (BG) and is controlled by excitatory inputs from the subthalamic nucleus (STN) and inhibitory inputs from the striatum and globus pallidus. Changes in the output of the SNr are believed to be critically involved in the development of a variety of movement disorders. Anatomical studies reveal that metabotropic glutamate receptors (mGluRs) are highly expressed throughout the BG. Interestingly, mRNA for group III mGluRs are highly expressed in STN, striatum, and globus pallidus, and immunocytochemical studies have shown that the group III mGluR proteins are present in the SNr. Thus it is possible that group III mGluRs play a role in the modulation of synaptic transmission in this nucleus. We performed whole cell patch-clamp recordings from nondopaminergic SNr neurons to investigate the effect of group III mGluR activation on excitatory and inhibitory transmission in the SNr. We report that activation of group III mGluRs by the selective agonist l(+)-2-amino-4-phosphonobutyric acid (l-AP4, 100 μM) decreases inhibitory synaptic transmission in the SNr. Miniature inhibitory postsynaptic currents studies and paired-pulse studies reveal that this effect is mediated by a presynaptic mechanism. Furthermore we found that l-AP4 (500 μM) also reduces excitatory synaptic transmission at the STN-SNr synapse by action on presynaptically localized group III mGluRs. The finding that mGluRs modulate the major inputs to SNr neurons suggests that these receptors may play an important role in motor function and could provide new targets for the development of pharmacological treatments of movement disorders.

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

Multisecond Oscillations in Firing Rate in the Basal Ganglia: Robust Modulation by Dopamine Receptor Activation and Anesthesia

1999 ◽  
Vol 81 (5) ◽  
pp. 2046-2055 ◽  
Author(s):  
David N. Ruskin ◽  
Debra A. Bergstrom ◽  
Yoshiki Kaneoke ◽  
Bindu N. Patel ◽  
Michael J. Twery ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Firing Rate ◽  
Dopamine Receptor ◽  
Cognitive Processes ◽  
Receptor Activation ◽  
Spike Trains ◽  
Significant Activity ◽  
Entopeduncular Nucleus ◽  
Periodic Oscillations

Multisecond oscillations in firing rate in the basal ganglia: robust modulation by dopamine receptor activation and anesthesia. Studies of CNS electrophysiology have suggested an important role for oscillatory neuronal activity in sensory perception, sensorimotor integration, and movement timing. In extracellular single-unit recording studies in awake, immobilized rats, we have found that many tonically active neurons in the entopeduncular nucleus ( n = 15), globus pallidus ( n = 31), and substantia nigra pars reticulata ( n = 31) have slow oscillations in firing rate in the seconds-to-minutes range. Basal oscillation amplitude ranged up to ±50% of the mean firing rate. Spectral analysis was performed on spike trains to determine whether these multisecond oscillations were significantly periodic. Significant activity in power spectra (in the 2- to 60-s range of periods) from basal spike trains was found for 56% of neurons in these three nuclei. Spectral peaks corresponded to oscillations with mean periods of ∼30 s in each nucleus. Multisecond baseline oscillations were also found in 21% of substantia nigra dopaminergic neurons. The dopamine agonist apomorphine (0.32 mg/kg iv, n = 10–15) profoundly affected multisecond oscillations, increasing oscillatory frequency (means of spectral peak periods were reduced to ∼15 s) and increasing the regularity of the oscillations. Apomorphine effects on oscillations in firing rate were more consistent from unit to unit than were its effects on mean firing rates in the entopeduncular nucleus and substantia nigra. Apomorphine modulation of multisecond periodic oscillations was reversed by either D1 or D2antagonists and was mimicked by the combination of selective D1 (SKF 81297) and D2 (quinpirole) agonists. Seventeen percent of neurons had additional baseline periodic activity in a faster range (0.4–2.0 s) related to ventilation. Multisecond periodicities were rarely found in neurons in anesthetized rats ( n = 29), suggesting that this phenomenon is sensitive to overall reductions in central activity. The data demonstrate significant structure in basal ganglia neuron spiking activity at unexpectedly long time scales, as well as a novel effect of dopamine on firing pattern in this slow temporal domain. The modulation of multisecond periodicities in firing rate by dopaminergic agonists suggests the involvement of these patterns in behaviors and cognitive processes that are affected by dopamine. Periodic firing rate oscillations in basal ganglia output nuclei should strongly affect the firing patterns of target neurons and are likely involved in coordinating neural activity responsible for motor sequences. Modulation of slow, periodic oscillations in firing rate may be an important mechanism by which dopamine influences motor and cognitive processes in normal and dysfunctional states.

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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