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

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.

Download Full-text

Correction: Song et al., “Selective Role of RGS9-2 in Regulating Retrograde Synaptic Signaling of Indirect Pathway Medium Spiny Neurons in Dorsal Striatum”

Journal of Neuroscience ◽

10.1523/jneurosci.2281-18.2018 ◽

2018 ◽

Vol 38 (43) ◽

pp. 9302-9302

Keyword(s):

Dorsal Striatum ◽

Medium Spiny Neurons ◽

Indirect Pathway ◽

Synaptic Signaling ◽

Spiny Neurons

Download Full-text

Experience-related remapping of temporal encoding by striatal ensembles

10.1101/2021.03.12.435177 ◽

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.

Download Full-text

Transcriptional Diversity of Medium Spiny Neurons in the Primate Striatum

10.1101/2020.10.25.354159 ◽

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.

Download Full-text

Mushroom spine dynamics in medium spiny neurons of dorsal striatum associated with memory of moderate and intense training

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1613680113 ◽

2016 ◽

Vol 113 (42) ◽

pp. E6516-E6525 ◽

Cited By ~ 24

Author(s):

Paola C. Bello-Medina ◽

Gonzalo Flores ◽

Gina L. Quirarte ◽

James L. McGaugh ◽

Roberto A. Prado Alcalá

Keyword(s):

Memory Consolidation ◽

Dorsal Striatum ◽

Inhibitory Avoidance ◽

Brain Structures ◽

Brain Regions ◽

Medium Spiny Neurons ◽

Spine Density ◽

Spiny Neurons ◽

Intense Training ◽

Transfer Of Information

A growing body of evidence indicates that treatments that typically impair memory consolidation become ineffective when animals are given intense training. This effect has been obtained by treatments interfering with the neural activity of several brain structures, including the dorsal striatum. The mechanisms that mediate this phenomenon are unknown. One possibility is that intense training promotes the transfer of information derived from the enhanced training to a wider neuronal network. We now report that inhibitory avoidance (IA) induces mushroom spinogenesis in the medium spiny neurons (MSNs) of the dorsal striatum in rats, which is dependent upon the intensity of the foot-shock used for training; that is, the effect is seen only when high-intensity foot-shock is used in training. We also found that the relative density of thin spines was reduced. These changes were evident at 6 h after training and persisted for at least 24 h afterward. Importantly, foot-shock alone did not increase spinogenesis. Spine density in MSNs in the accumbens was also increased, but the increase did not correlate with the associative process involved in IA; rather, it resulted from the administration of the aversive stimulation alone. These findings suggest that mushroom spines of MSNs of the dorsal striatum receive afferent information that is involved in the integrative activity necessary for memory consolidation, and that intense training facilitates transfer of information from the dorsal striatum to other brain regions through augmented spinogenesis.

Download Full-text

Dopamine response gene pathways in dorsal striatum MSNs from a gene expression viewpoint: cAMP-mediated gene networks

10.1101/757500 ◽

2019 ◽

Author(s):

Vladimir Babenko ◽

Anna Galyamina ◽

Igor Rogozin ◽

Dmitry Smagin ◽

Natalia Kudryavtseva

Keyword(s):

Gene Networks ◽

Cpg Island ◽

Dorsal Striatum ◽

Gene Clusters ◽

Alternative Transcript ◽

Medium Spiny Neurons ◽

Main Body ◽

Social Conflicts ◽

Spiny Neurons ◽

Genes Expression

AbstractA mouse model of chronic social conflicts was used to analyze dorsal striatum neurons implicated in cAMP-mediated phosphorylation activation pathways specific for Medium Spiny Neurons (MSNs). Based on expression correlation analysis, we succeeded in dissecting Drd1- and Drd2-dopaminoceptive neurons (D1 and D2, correspondingly) gene pathways. We also found that D1 neurons feature previously reported two states, passive and active ones, represented in our analysis by distinct, negatively correlated gene clusters.The correlation based gene pathways strongly corroborate the phosphorylation cascades highlighted in the previous studies, implying that the expression-based viewpoint corresponds to phosphorylation/dephosphorylation interplay in each type of neurons. Notably, D2 neurons showed the largest Ppp1r1b (encoding DARPP-32) expression modulation impact, implying that Ppp1r1b expression dynamics is mostly associated with neuroendocrine response mediated by Penk/Pdyn genes expression in D2 neurons.We observed that under defeat stress in chronic social conflicts mice exhibited reduced motor activity as well as overall depression of dopamine-mediated MSNs activity, while aggressive mice exhibited motor hyperactivity and an increase in both D1-active phase and D2 MSNs genes expression.Based on alternative transcript isoforms expression analysis, it was assumed that many genes (Drd1, Adora1, Pde10, Ppp1r1b, Gnal), specifically those in D1 neurons, apparently remain transcriptionally repressed via the reversible mechanism of promoter CpG island silencing, resulting in alternative promoter usage following profound reduction in their expression rate.Significance statementMedium Spiny Neurons (MSNs) comprise the main body of dorsal striatum neurons and represent dopaminoceptive GABAergic neurons. The cAMP- mediated cascade of excitation and inhibition responses involved in dopaminergic neurotransmission is crucial for neuroscience research due to its involvement in the motor and behavioral functions. In particular, all types of addictions are related to MSNs. Shedding the light on the mechanics of the above-mentioned cascade is of primary importance for this research domain. In this paper MSNs steady states will be elucidated based on pooled tissue RNA-Seq data not explicitly outlined before and connected with dynamic dopamine neurotransmission cycles.

Download Full-text

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

10.1101/2020.02.21.959692 ◽

2020 ◽

Author(s):

J. Alegre-Cortés ◽

M. Sáez ◽

R. Montanari ◽

R. Reig

Keyword(s):

Basal Ganglia ◽

Dorsal Striatum ◽

Medium Spiny Neurons ◽

Extracellular Recordings ◽

Electrophysiological Properties ◽

Spiny Neurons ◽

Sensory Activity ◽

Fast Oscillations ◽

Anatomical Evidence

AbstractBehavioural 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 behavioural-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.

Download Full-text

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

Journal of Neurophysiology ◽

10.1152/jn.90548.2008 ◽

2008 ◽

Vol 100 (3) ◽

pp. 1590-1601 ◽

Cited By ~ 32

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.

Download Full-text