Astrocytes are increasingly appreciated to possess underestimated and important roles in modulating neuronal circuits. Astrocytes in striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators, including GABA and adenosine. However, here we reveal that striatal astrocytes occupy a cell type-specific anatomical and functional relationship with cholinergic interneurons (ChIs), through which they rapidly excite ChIs and govern dopamine release via nicotinic acetylcholine receptors on subsecond timescales. We identify that ChI somata are in unexpectedly close proximity to astrocyte somata, in mouse and human, forming a "soma-to-soma" satellite-like configuration not typically observed for other striatal neurons. We find that transient depolarization of astrocytes in mouse striatum reversibly regulates ChI excitability by decreasing extracellular calcium. These findings reveal a privileged satellite astrocyte-interneuron interaction for striatal ChIs operating on subsecond timescales via regulation of extracellular calcium dynamics to shape downstream striatal circuit activity and dopamine signaling.
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http://dx.doi.org/10.1038/s41467-024-54253-7 | DOI Listing |
J Biol Chem
December 2024
Laboratory of Reproductive Neurobiology, HUN-REN Institute of Experimental Medicine, Budapest, 1083 Hungary. Electronic address:
We developed a versatile 'IHC/LCM-Seq' method for spatial transcriptomics of immunohistochemically detected neurons collected with laser-capture microdissection (LCM). IHC/LCM-Seq uses aluminon and polyvinyl sulfonic acid for inventive RNA-preserving strategies to maintain RNA integrity in free-floating sections of 4% formaldehyde-fixed brains. To validate IHC/LCM-Seq, we first immunostained and harvested striatal cholinergic interneurons with LCM.
View Article and Find Full Text PDFNetw Neurosci
December 2024
Science for Life Laboratory, Department of Computer Science, KTH Royal Institute of Technology, Stockholm, Sweden.
Striatum, the input stage of the basal ganglia, is important for sensory-motor integration, initiation and selection of behavior, as well as reward learning. Striatum receives glutamatergic inputs from mainly cortex and thalamus. In rodents, the striatal projection neurons (SPNs), giving rise to the direct and the indirect pathway (dSPNs and iSPNs, respectively), account for 95% of the neurons, and the remaining 5% are GABAergic and cholinergic interneurons.
View Article and Find Full Text PDFNeurol Int
December 2024
Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of ABC (UFABC), São Bernardo do Campo 09606-070, Brazil.
Background/objectives: Antipsychotic medicines are used to treat several psychological disorders and some symptoms caused by dementia and schizophrenia. Haloperidol (Hal) is a typical antipsychotic usually used to treat psychosis; however, its use causes motor or extrapyramidal symptoms (EPS) such as catalepsy. Hal blocks the function of presynaptic D2 receptors on cholinergic interneurons, leading to the release of acetylcholine (ACh), which is hydrolyzed by the enzyme acetylcholinesterase (AChE).
View Article and Find Full Text PDFNeurobiol Dis
December 2024
Department of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada. Electronic address:
Background: Altered balance between striatal direct and indirect pathways contributes to early motor, cognitive and psychiatric symptoms in Huntington disease (HD). While degeneration of striatal D2-type dopamine receptor (D2)-expressing indirect pathway medium spiny neurons (iMSNs) occurs prior to that of D1-type dopamine receptor (D1)-expressing direct pathway neurons, altered corticostriatal synaptic function precedes degeneration. D2-mediated signaling on iMSNs reduces their excitability and promotes endocannabinoid (eCB) synthesis, suppressing glutamate release from cortical afferents.
View Article and Find Full Text PDFSci Adv
December 2024
Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.
Striatal cholinergic interneurons (CINs) are key to regulating behavioral flexibility, involving both extinguishing learned actions and adopting new ones. However, the mechanisms driving these processes remain elusive. In this study, we initially demonstrate that chronic alcohol consumption disrupts the burst-pause dynamics of CINs and impairs behavioral flexibility.
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