Degeneration of dopamine (DA) neurons in Parkinson's disease (PD) causes hypokinesia, but DA replacement therapy can elicit exaggerated voluntary and involuntary behaviors that have been attributed to enhanced DA receptor sensitivity in striatal projection neurons. Here we reveal that in hemiparkinsonian mice, striatal D1 receptor-expressing medium spiny neurons (MSNs) directly projecting to the substantia nigra reticulata (SNr) lose tonic presynaptic inhibition by GABAB receptors. The absence of presynaptic GABAB response potentiates evoked GABA release from MSN efferents to the SNr and drives motor sensitization. This alternative mechanism of sensitization suggests a synaptic target for PD pharmacotherapy.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559856 | PMC |
| http://dx.doi.org/10.1016/j.neuron.2015.08.022 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Selective Colocalization of GHSR and GLP-1R in a Subset of Hypothalamic Neurons and Their Functional Interaction.
Endocrinology
November 2024
Laboratory of Neurophysiology, Multidisciplinary Institute of Cell Biology [IMBICE; Argentine Research Council (CONICET); Scientific Research Commission, Province of Buenos Aires (CIC-PBA); National University of La Plata], B1906APO La Plata, Buenos Aires, Argentina.
The GH secretagogue receptor (GHSR) and the glucagon-like peptide-1 receptor (GLP-1R) are G protein-coupled receptors with critical, yet opposite, roles in regulating energy balance. Interestingly, these receptors are expressed in overlapping brain regions. However, the extent to which they target the same neurons and engage in molecular crosstalk remains unclear.
View Article and Find Full Text PDFInvestigating the Mechanisms Involved in Scopolamine-induced Memory Degradation.
Arch Razi Inst
June 2024
Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
In the present study, the mechanisms involved in scopolamine-induced memory impairment have been investigated. The molecular events that take place during memory mostly include mechanisms that are seen in the acquisition phase. Results showed that one of the mechanisms of memory destruction caused by scopolamine, in addition to weakening the cholinergic system, is the indirect effect of scopolamine on other neurotransmitter systems, including the glutamatergic system.
View Article and Find Full Text PDFReversible cerebral vasoconstriction syndrome in a methylphenidate-treated patient: a case report.
BMC Neurol
December 2024
Pharmacovigilance, Pharmacoepidemiology and Drug Information Centre, Department of Clinical Pharmacology, Rennes University Hospital, Rennes, 35033, France.
Background: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe headaches, often thunderclap headaches, and a multifocal constriction of the cerebral arteries. Although RCVS can occur spontaneously, some cases occur after exposure to drugs. We describe the first case of RCVS in which methylphenidate, a drug with vasoconstrictive properties, is the only suspected drug.
View Article and Find Full Text PDFHaloperidol-Induced Catalepsy and Its Correlations with Acetylcholinesterase Activity in Different Brain Structures of Mice.
Neurol 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 PDFPharmacological blocking of spinal GABA receptors in monkeys reduces sensory transmission to the spinal cord, thalamus, and cortex.
Cell Rep
December 2024
Rehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neural Basis of Cognition, Pittsburgh, PA, USA; Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:
A century of research established that GABA inhibits proprioceptive inputs presynaptically to sculpt spinal neural inputs into skilled motor output. Recent results in mice challenged this theory by showing that GABA can also facilitate action potential conduction in proprioceptive afferents. Here, we tackle this controversy in monkeys, the most human-relevant animal model, and show that GABA receptors (GABARs) indeed facilitate sensory inputs to spinal motoneurons and interneurons and that this mechanism also influences sensory transmission to supraspinal centers.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!