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Despite the profound behavioral effects of the striatal dopamine (DA) activity and the inwardly rectifying potassium channel ( ) being a key determinant of striatal medium spiny neuron (MSN) activity that also profoundly affects behavior, previously reported DA regulations of Kir are conflicting and incompatible with MSN function in behavior. Here we show that in normal mice with an intact striatal DA system, the predominant effect of DA activation of D1Rs in D1-MSNs is to cause a modest depolarization and increase in input resistance by inhibiting Kir, thus moderately increasing the spike outputs from behavior-promoting D1-MSNs. In parkinsonian (DA-depleted) striatum, DA increases D1-MSN intrinsic excitability more strongly than in normal striatum, consequently strongly increasing D1-MSN spike firing that is behavior-promoting; this DA excitation of D1-MSNs is stronger when the DA depletion is more severe.
View Article and Find Full Text PDFMatrisomal components involved in regenerative wound healing in axolotl and : implications for biomaterial development.
Biomater Sci
September 2023
Department of Medical BioSciences, Radboud Research Institute, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Achieving regeneration in humans has been a long-standing goal of many researchers. Whereas amphibians like the axolotl () are capable of regenerating whole organs and even limbs, most mammals heal their wounds fibrotic scarring. Recently, the African spiny mouse ( sp.
View Article and Find Full Text PDFA Conditioned Place Preference for Heroin Is Signaled by Increased Dopamine and Direct Pathway Activity and Decreased Indirect Pathway Activity in the Nucleus Accumbens.
J Neurosci
March 2022
Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, Washington 98195
Repeated pairing of a drug with a neutral stimulus, such as a cue or context, leads to the attribution of the drug's reinforcing properties to that stimulus, and exposure to that stimulus in the absence of the drug can elicit drug-seeking. A principal role for the NAc in the response to drug-associated stimuli has been well documented. Direct and indirect pathway medium spiny neurons (dMSNs and iMSNs) have been shown to bidirectionally regulate cue-induced heroin-seeking in rats expressing addiction-like phenotypes, and a shift in NAc activity toward the direct pathway has been shown in mice following cocaine conditioned place preference (CPP).
View Article and Find Full Text PDFCyclic AMP-producing chemogenetic activation of indirect pathway striatal projection neurons and the downstream effects on the globus pallidus and subthalamic nucleus in freely moving mice.
J Neurochem
June 2018
Department of Pharmacology, University of Tennessee College of Medicine, Memphis, Tennessee, USA.
The indirect pathway striatal medium spiny projection neurons (iMSNs) are critical to motor and cognitive brain functions. These neurons express a high level of cAMP-increasing adenosine A2a receptors. However, the potential effects of cAMP production on iMSN spiking activity have not been established, and recording identified iMSNs in freely moving animals is challenging.
View Article and Find Full Text PDFStriatal Gα/cAMP Signal-Dependent Mechanism to Generate Levodopa-Induced Dyskinesia in Parkinson's Disease.
Front Cell Neurosci
November 2017
Department of Neurodegenerative Disorders Research, Institute of Biomedical Sciences, Graduate School of Medical Sciences, Tokushima University, Tokushima, Japan.
The motor symptoms of Parkinson's disease (PD) result from striatal dopamine (DA) deficiency due to a progressive degeneration of nigral dopaminergic cells. Although DA replacement therapy is the mainstay to treat parkinsonian symptoms, a long-term daily administration of levodopa often develops levodopa-induced dyskinesia (LID). LID is closely linked to the dysregulation of cyclic adenosine monophosphate (cAMP) signaling cascades in the medium spiny neurons (MSNs), the principal neurons of the striatum, which are roughly halved with striatonigral MSNs by striatopallidal MSNs.
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