scholarly journals Motor thalamus supports striatum-driven reinforcement

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Arnaud L Lalive ◽  
Anthony D Lien ◽  
Thomas K Roseberry ◽  
Christopher H Donahue ◽  
Anatol C Kreitzer
Keyword(s):  
Synaptic Plasticity ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Projection Neurons ◽  
Direct Pathway ◽  
Substantia Nigra Reticulata ◽  
Motor Thalamus ◽  
Self Stimulation ◽  
Stimulation Of

Reinforcement has long been thought to require striatal synaptic plasticity. Indeed, direct striatal manipulations such as self-stimulation of direct-pathway projection neurons (dMSNs) are sufficient to induce reinforcement within minutes. However, it’s unclear what role, if any, is played by downstream circuitry. Here, we used dMSN self-stimulation in mice as a model for striatum-driven reinforcement and mapped the underlying circuitry across multiple basal ganglia nuclei and output targets. We found that mimicking the effects of dMSN activation on downstream circuitry, through optogenetic suppression of basal ganglia output nucleus substantia nigra reticulata (SNr) or activation of SNr targets in the brainstem or thalamus, was also sufficient to drive rapid reinforcement. Remarkably, silencing motor thalamus—but not other selected targets of SNr—was the only manipulation that reduced dMSN-driven reinforcement. Together, these results point to an unexpected role for basal ganglia output to motor thalamus in striatum-driven reinforcement.

Role of the Subthalamic Nucleus in Cannabinoid Actions in the Substantia Nigra of the Rat

1997 ◽  
Vol 77 (3) ◽  
pp. 1635-1638 ◽  
Author(s):  
M. Clara Sañudo-Peña ◽  
J. Michael Walker
Keyword(s):  
Substantia Nigra ◽  
Subthalamic Nucleus ◽  
Cannabinoid Receptors ◽  
Excitatory Input ◽  
Physiological Regulation ◽  
Cannabinoid Antagonist ◽  
Substantia Nigra Reticulata ◽  
Cannabinoid Agonist ◽  
Stimulation Of

Sañudo-Peña, M. Clara and J. Michael Walker. Role of the subthalamic nucleus in cannabinoid actions in the substantia nigra of the rat. J. Neurophysiol. 77: 1635–1638, 1997. The effect of cannabinoids on the excitatory input to the substantia nigra reticulata (SNr) from the subthalamic nucleus was explored. For this purpose a knife cut was performed rostral to the subthalamic nucleus to isolate the subthalamic nucleus and the SNr from the striatum, a major source of cannabinoid receptors to the SNr. The data showed that the cannabinoid agonist WIN55,212-2 blocked the increase in the firing rate of SNr neurons induced by stimulation of the subthalamic nucleus with bicuculline. Furthermore, the cannabinoid antagonist SR141716A antagonized the effect of the cannabinoid agonist. This study showed that cannabinoids regulate not only the striatonigral pathway, as previously reported, but also the subthalamonigral pathway. The opposite influences of these two inputs to the SNr, inhibitory and excitatory respectively, suggest that endogenous cannabinoids play a major role in the physiological regulation of the SNr.

Lack of Spike-Count and Spike-Time Correlations in the Substantia Nigra Reticulata Despite Overlap of Neural Responses

2007 ◽  
Vol 98 (4) ◽  
pp. 2232-2243 ◽  
Author(s):  
Alon Nevet ◽  
Genela Morris ◽  
Guy Saban ◽  
David Arkadir ◽  
Hagai Bergman
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Information Transfer ◽  
Spike Timing ◽  
Spike Count ◽  
Unique Event ◽  
Correlated Activity ◽  
Different Types ◽  
Substantia Nigra Reticulata ◽  
Response Task

Previous studies of single neurons in the substantia nigra reticulata (SNr) have shown that many of them respond to similar events. These results, as well as anatomical studies, suggest that SNr neurons share inputs and thus may have correlated activity. Different types of correlation can exist between pairs of neurons. These are traditionally classified as either spike-count (“signal” and “noise”) or spike-timing (spike-to-spike and joint peristimulus time histograms) correlations. These measures of neuronal correlation are partially independent and have different implications. Our purpose was to probe the computational characteristics of the basal ganglia output nuclei through an analysis of these different types of correlation in the SNr. We carried out simultaneous multiple-electrode single-unit recordings in the SNr of two monkeys performing a probabilistic delayed visuomotor response task. A total of 113 neurons (yielding 355 simultaneously recorded pairs) were studied. Most SNr neurons responded to one or more task-related events, with instruction cue (69%) and reward (63%) predominating. Response-match analysis, comparing peristimulus time histograms, revealed a significant overlap between response vectors. However, no measure of average correlation differed significantly from zero. The lack of significant SNr spike-count population correlations appears to be an exceptional phenomenon in the brain, perhaps indicating unique event-related processing by basal ganglia output neurons to achieve better information transfer. The lack of spike-timing correlations suggests that the basal high-frequency discharge of SNr neurons is not driven by the common inputs and is probably intrinsic.

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 Parallel Movement-suppressing Striatal Output Pathways

2020 ◽  
Author(s):  
Qiaoling Cui ◽  
Xixun Du ◽  
Isaac Y. M. Chang ◽  
Arin Pamukcu ◽  
Varoth Lilascharoen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Body Movement ◽  
Disease Model ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Striatal Projection Neurons ◽  
6 Hydroxydopamine

AbstractThe classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known. In this study, we interrogated the organization principles of striatopallidal projections and how they are involved in full-body movement in mice (both males and females). In contrast to the canonical motor-promoting role of dSPNs in the dorsomedial striatum (DMSdSPNs), optogenetic stimulation of dSPNs in the dorsolateral striatum (DLSdSPNs) suppressed locomotion. Circuit analyses revealed that dSPNs selectively target Npas1+ neurons in the GPe. In a chronic 6-hydroxydopamine lesion model of Parkinson’s disease, the dSPN-Npas1+ projection was dramatically strengthened. As DLSdSPN-Npas1+ projection suppresses movement, the enhancement of this projection represents a circuit mechanism for the hypokinetic symptoms of Parkinson’s disease that has not been previously considered.Significance statementIn the classic basal ganglia model, the striatum is described as a divergent structure—it controls motor and adaptive functions through two segregated, opponent output streams. However, the experimental results that show the projection from direct-pathway neurons to the external pallidum have been largely ignored. Here, we showed that this striatopallidal sub-pathway targets a select subset of neurons in the external pallidum and is motor-suppressing. We found that this sub-pathway undergoes plastic changes in a Parkinson’s disease model. In particular, our results suggest that the increase in strength of this sub-pathway contributes to the slowness or reduced movements observed in Parkinson’s disease.

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.

scholarly journals Cortically Activated Interneurons Shape Spatial Aspects of Cortico-Accumbens Processing

2009 ◽  
Vol 101 (4) ◽  
pp. 1876-1882 ◽  
Author(s):  
Aaron J. Gruber ◽  
Elizabeth M. Powell ◽  
Patricio O'Donnell
Keyword(s):  
Basal Ganglia ◽  
Projection Neurons ◽  
Behavioral Outcome ◽  
Excitatory Response ◽  
Local Inhibition ◽  
Naturally Occurring ◽  
Parallel Loops ◽  
Winner Take All ◽  
Take All ◽  
Stimulation Of

Basal ganglia circuits are organized as parallel loops that have been proposed to compete in a winner-take-all fashion to determine the appropriate behavioral outcome. However, limited experimental support for strong lateral inhibition mechanisms within striatal regions questions this model. Here, stimulation of the prefrontal cortex (PFC) using naturally occurring bursty patterns inhibited firing in most nucleus accumbens (NA) projection neurons. When an excitatory response was observed for one stimulation site, neighboring PFC sites evoked inhibition in the same neuron. Furthermore, PFC stimulation activated interneurons, and PFC-evoked inhibition was blocked by GABAA antagonists in corticoaccumbens slice preparations. Thus bursting PFC activity recruits local inhibition in the NA, shaping responses of projection neurons with a topographical arrangement that allows inhibition among parallel corticoaccumbens channels. The data indicate a high order of information processing within striatal circuits that should be considered in models of basal ganglia function and disease.

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