scholarly journals AMPA Receptor-Dependent H2O2 Generation in Striatal Medium Spiny Neurons But Not Dopamine Axons: One Source of a Retrograde Signal That Can Inhibit Dopamine Release

2008 ◽  
Vol 100 (3) ◽  
pp. 1590-1601 ◽  
Author(s):  
Marat V. Avshalumov ◽  
Jyoti C. Patel ◽  
Margaret E. Rice
Keyword(s):  
Ampa Receptors ◽  
Dopamine Release ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
Indirect Evidence ◽  
Medium Spiny Neurons ◽  
Striatal Slices ◽  
Gyki 52466 ◽  
Spiny Neurons ◽  
Voltammetric Detection

Dopamine-glutamate interactions in the striatum are critical for normal basal ganglia-mediated control of movement. Although regulation of glutamatergic transmission by dopamine is increasingly well understood, regulation of dopaminergic transmission by glutamate remains uncertain given the apparent absence of ionotropic glutamate receptors on dopaminergic axons in dorsal striatum. Indirect evidence suggests glutamatergic regulation of striatal dopamine release is mediated by a diffusible messenger, hydrogen peroxide (H2O2), generated downstream from glutamatergic AMPA receptors (AMPARs). The mechanism of H2O2-dependent inhibition of dopamine release involves activation of ATP-sensitive K+ ( KATP) channels. However, the source of modulatory H2O2 is unknown. Here, we used whole cell recording, fluorescence imaging of H2O2, and voltammetric detection of evoked dopamine release in guinea pig striatal slices to examine contributions from medium spiny neurons (MSNs), the principal neurons of striatum, and dopamine axons to AMPAR-dependent H2O2 generation. Imaging studies of H2O2 generation in MSNs provide the first demonstration of AMPAR-dependent H2O2 generation in neurons in the complex brain-cell microenvironment of brain slices. Stimulation-induced increases in H2O2 in MSNs were prevented by GYKI-52466, an AMPAR antagonist, or catalase, an H2O2 metabolizing enzyme, but amplified by mercaptosuccinate (MCS), a glutathione peroxidase inhibitor. By contrast, dopamine release evoked by selective stimulation of dopamine axons was unaffected by GYKI-52466 or MCS, arguing against dopamine axons as a significant source of modulatory H2O2. Together, these findings suggest that glutamatergic regulation of dopamine release via AMPARs is mediated through retrograde signaling by diffusible H2O2 generated in striatal cells, including medium spiny neurons, rather than in dopamine axons.

scholarly journals Trafficking of calcium-permeable and calcium-impermeable AMPA receptors in nucleus accumbens medium spiny neurons co-cultured with prefrontal cortex neurons

2017 ◽  
Vol 116 ◽  
pp. 224-232 ◽  
Author(s):  
Craig T. Werner ◽  
Conor H. Murray ◽  
Jeremy M. Reimers ◽  
Niravkumar M. Chauhan ◽  
Kenneth K.Y. Woo ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Ampa Receptors ◽  
Medium Spiny Neurons ◽  
Spiny Neurons

scholarly journals Knock-Down of GPR88 in the Dorsal Striatum Alters the Response of Medium Spiny Neurons to the Loss of Dopamine Input and L-3-4-Dyhydroxyphenylalanine

2019 ◽  
Vol 10 ◽  
Author(s):  
Manuela Ingallinesi ◽  
Benjamin Galet ◽  
Jonathan Pegon ◽  
Nicole Faucon Biguet ◽  
Anh Do Thi ◽  
...  
Keyword(s):  
Dorsal Striatum ◽  
Medium Spiny Neurons ◽  
Knock Down ◽  
Spiny Neurons

scholarly journals Medium spiny neurons activity reveals the discrete segregation of mouse dorsal striatum

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Javier Alegre-Cortés ◽  
María Sáez ◽  
Roberto Montanari ◽  
Ramon Reig
Keyword(s):  
Dorsal Striatum ◽  
Medium Spiny Neurons ◽  
Extracellular Recordings ◽  
Electrophysiological Properties ◽  
Spiny Neurons ◽  
Behavioral Studies ◽  
Sensory Activity ◽  
Fast Oscillations ◽  
Anatomical Evidence

Behavioral studies differentiate the rodent dorsal striatum (DS) into lateral and medial regions; however, anatomical evidence suggests that it is a unified structure. To understand striatal dynamics and basal ganglia functions, it is essential to clarify the circuitry that supports this behavioral-based segregation. Here, we show that the mouse DS is made of two non-overlapping functional circuits divided by a boundary. Combining in vivo optopatch-clamp and extracellular recordings of spontaneous and evoked sensory activity, we demonstrate different coupling of lateral and medial striatum to the cortex together with an independent integration of the spontaneous activity, due to particular corticostriatal connectivity and local attributes of each region. Additionally, we show differences in slow and fast oscillations and in the electrophysiological properties between striatonigral and striatopallidal neurons. In summary, these results demonstrate that the rodent DS is segregated in two neuronal circuits, in homology with the caudate and putamen nuclei of primates.

scholarly journals Rhes protein transits from neuron to neuron and facilitates mutant huntingtin spreading in the brain.

2021 ◽  
Author(s):  
Uri Nimrod Ramirez Jarquin ◽  
Manish Sharma ◽  
Neelam Shahani ◽  
Yunqing Li ◽  
Siddaraju Boregowda ◽  
...  
Keyword(s):  
Protein Transport ◽  
Brain Slices ◽  
Brain Regions ◽  
Medium Spiny Neurons ◽  
Striatal Neurons ◽  
Spiny Neurons ◽  
Tunneling Nanotube ◽  
Intact Brain ◽  
Cortical Regions ◽  
The Brain

Rhes (RASD2) is a thyroid hormone-induced gene that regulates striatal motor activity and promotes neurodegeneration in Huntington disease (HD) and tauopathy. Previously, we showed that Rhes moves between cultured striatal neurons and transports the HD protein, polyglutamine-expanded huntingtin (mHTT) via tunneling nanotube (TNT)-like membranous protrusions. However, similar intercellular Rhes transport has not yet been demonstrated in the intact brain. Here, we report that Rhes induces TNT-like protrusions in the striatal medium spiny neurons (MSNs) and transported between dopamine-1 receptor (D1R)-MSNs and D2R-MSNs of intact striatum and organotypic brain slices. Notably, mHTT is robustly transported within the striatum and from the striatum to the cortical areas in the brain, and Rhes deletion diminishes such transport. Moreover, we also found transport of Rhes to the cortical regions following restricted expression in the MSNs of the striatum. Thus, Rhes is a first striatum-enriched protein demonstrated to move and transport mHTT between neurons and brain regions, providing new insights on interneuronal protein transport in the brain.

scholarly journals Differences in Nicotine Encoding Dopamine Release between the Striatum and Shell Portion of the Nucleus Accumbens

2018 ◽  
Vol 28 (3) ◽  
pp. 248-261 ◽  
Author(s):  
Yuan-Hao Chen ◽  
Bon-Jour Lin ◽  
Tsung-Hsun Hsieh ◽  
Tung-Tai Kuo ◽  
Jonathan Miller ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
High Frequency ◽  
Dopamine Release ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
High Frequency Stimulation ◽  
Sprague Dawley ◽  
Frequency Stimulation ◽  
Da Release

The aim of this work was to determine the effect of nicotine desensitization on dopamine (DA) release in the dorsal striatum and shell of the nucleus accumbens (NAc) from brain slices. In vitro fast-scan cyclic voltammetry analysis was used to evaluate dopamine release in the dorsal striatum and the NAc shell of Sprague–Dawley rats after infusion of nicotine, a nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (Mec), and an α4β2 cholinergic receptor antagonist (DHβe). DA release related to nicotine desensitization in the striatum and NAc shell was compared. In both structures, tonic release was suppressed by inhibition of the nicotine receptor (via Mec) and the α4β2 receptor (via DHβe). Paired-pulse ratio (PPR) was facilitated in both structures after nicotine and Mec infusion, and this facilitation was suppressed by increasing the stimulation interval. After variable frequency stimulation (simulating phasic burst), nicotine infusion induced significant augmentation of DA release in the striatum that was not seen in the absence of nicotine. In contrast, nicotine reduced phasic DA release in NAc, although frequency augmentation was seen both with and without nicotine. Evaluation of DA release evoked by various trains (high-frequency stimulation (HFS) 100 Hz) of high-frequency stimulation revealed significant enhancement after a train of three or more pulses in the striatum and NAc. The concentration differences between tonic and phasic release related to nicotine desensitization were more pronounced in the NAc shell. Nicotine desensitization is associated with suppression of tonic release of DA in both the striatum and NAc shell that may occur via the α4β2 subtype of nAChR, whereas phasic frequency-dependent augmentation and HFS-related gating release is more pronounced in the striatum than in the NAc shell. Differences between phasic and tonic release associated with nicotine desensitization may underlie processing of reward signals in the NAc shell, and this may have major implications for addictive behavior.

scholarly journals Age-dependent effects of protein restriction on dopamine release

2020 ◽  
Vol 46 (2) ◽  
pp. 394-403
Author(s):  
Fabien Naneix ◽  
Kate Z. Peters ◽  
Andrew M. J. Young ◽  
James E. McCutcheon
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Physiological State ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
Protein Restriction ◽  
Fast Scan Cyclic Voltammetry ◽  
Health And Development ◽  
Late Maturation ◽  
The Impact

AbstractDespite the essential role of protein intake for health and development, very little is known about the impact of protein restriction on neurobiological functions, especially at different stages of the lifespan. The dopamine system is a central actor in the integration of food-related processes and is influenced by physiological state and food-related signals. Moreover, it is highly sensitive to dietary effects during early life periods such as adolescence due to its late maturation. In the present study, we investigated the impact of protein restriction either during adolescence or adulthood on the function of the mesolimbic (nucleus accumbens) and nigrostriatal (dorsal striatum) dopamine pathways using fast-scan cyclic voltammetry in rat brain slices. In the nucleus accumbens, protein restriction in adults increased dopamine release in response to low and high frequency trains of stimulation (1–20 Hz). By contrast, protein restriction during adolescence decreased nucleus accumbens dopamine release. In the dorsal striatum, protein restriction at adulthood has no impact on dopamine release but the same diet during adolescence induced a frequency-dependent increase in stimulated dopamine release. Taken together, our results highlight the sensitivity of the different dopamine pathways to the effect of protein restriction, as well as their vulnerability to deleterious diet effects at different life stages.

scholarly journals Experience-related remapping of temporal encoding by striatal ensembles

2021 ◽  
Author(s):  
R. Austin. Bruce ◽  
Matthew A. Weber ◽  
Rachael A. Volkman ◽  
Mayu Oya ◽  
Eric B. Emmons ◽  
...  
Keyword(s):  
Dorsal Striatum ◽  
Interval Timing ◽  
Medium Spiny Neurons ◽  
Differential Modulation ◽  
Temporal Control ◽  
Related Activity ◽  
Spiny Neurons ◽  
Timing Task ◽  
Temporal Encoding ◽  
Temporal Control Of Movement

AbstractTemporal control of action is key for a broad range of behaviors and is disrupted in human diseases such as Parkinson’s disease and schizophrenia. A brain structure that is critical for temporal control is the dorsal striatum. Experience and learning can influence dorsal striatal neuronal activity, but it is unknown how these neurons change with experience in contexts which require precise temporal control of movement. We investigated this question by recording from medium-spiny neurons (MSNs) in the dorsal striatum of mice as they gained experience controlling their actions in time. We leveraged an interval timing task optimized for mice which required them to “switch” response ports after enough time had passed without receiving a reward. We report three main results. First, we found that time-related ramping activity and response-related activity increased with more experience. Second, temporal decoding by MSN ensembles improved with experience and was predominantly driven by time-related ramping activity. Finally, we found that some MSNs had differential modulation on error trials. These findings enhance our understanding of dorsal striatal temporal processing by demonstrating how MSN ensembles can evolve with experience. Our results can be linked to temporal habituation and illuminate striatal flexibility during interval timing, which may be relevant for human disease.

scholarly journals Transcriptional Diversity of Medium Spiny Neurons in the Primate Striatum

2020 ◽  
Author(s):  
Jing He ◽  
Michael Kleyman ◽  
Jianjiao Chen ◽  
Aydin Alikaya ◽  
Kathryn M. Rothenhoefer ◽  
...  
Keyword(s):  
Dorsal Striatum ◽  
Cell Types ◽  
Specific Information ◽  
Medium Spiny Neurons ◽  
Striatal Neurons ◽  
Cell Type ◽  
Indirect Pathway ◽  
Spiny Neurons ◽  
Single Nucleus ◽  
Cell Type Specific

AbstractThe striatum is the neural interface between dopamine reward signals and cortico-basal ganglia circuits responsible for value assignments, decisions, and actions. Medium spiny neurons (MSNs) make up the vast majority of striatal neurons and are traditionally classified as two distinct types: direct- and indirect-pathway MSNs. The direct- and indirect-pathway model has been useful for understanding some aspects of striatal functions, but it accounts for neither the anatomical heterogeneity, nor the functional diversity of the striatum. Here, we use single nucleus RNA-sequencing and Fluorescent In-Situ Hybridization to explore MSN diversity in the Rhesus macaque striatum. We identified MSN subtypes that correspond to the major subdivisions of the striatum. These include dorsal striatum subtypes associated with striosome and matrix compartments, as well as ventral striatum subtypes associated with the shell of the nucleus accumbens. We also describe a cell type that is anatomically restricted to “Neurochemically Unique Domains in the Accumbens and Putamen (NUDAPs)”. Together, these results help to advance nonhuman primate studies into the genomics era. The identified cell types provide a comprehensive blueprint for investigating cell type-specific information processing, and the differentially expressed genes lay a foundation for achieving cell type-specific transgenesis in the primate striatum.

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