Format

Send to

Choose Destination
Cell Rep. 2015 Nov 17;13(7):1353-1365. doi: 10.1016/j.celrep.2015.10.009. Epub 2015 Nov 5.

Coordinated Regulation of Synaptic Plasticity at Striatopallidal and Striatonigral Neurons Orchestrates Motor Control.

Author information

1
Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
2
Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy; Life Science Department, University of Milan, 20133 Milano, Italy.
3
IRCCS, Mario Negri Institute for Pharmacological Research, 20156 Milano, Italy; Neuroscience and Mental Health Research Institute, Division of Neuroscience, School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
4
Neuroscience and Mental Health Research Institute, Division of Neuroscience, School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK; Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute and University, 20132 Milano, Italy.
5
Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy. Electronic address: raffaella.tonini@iit.it.

Abstract

The basal ganglia play a critical role in shaping motor behavior. For this function, the activity of medium spiny neurons (MSNs) of the striatonigral and striatopallidal pathways must be integrated. It remains unclear whether the activity of the two pathways is primarily coordinated by synaptic plasticity mechanisms. Using a model of Parkinson's disease, we determined the circuit and behavioral effects of concurrently regulating cell-type-specific forms of corticostriatal long-term synaptic depression (LTD) by inhibiting small-conductance Ca(2+)-activated K(+) channels (SKs) of the dorsolateral striatum. At striatopallidal synapses, SK channel inhibition rescued the disease-linked deficits in endocannabinoid (eCB)-dependent LTD. At striatonigral cells, inhibition of these channels counteracted a form of adenosine-mediated LTD by activating the ERK cascade. Interfering with eCB-, adenosine-, and ERK signaling in vivo alleviated motor abnormalities, which supports that synaptic modulation of striatal pathways affects behavior. Thus, our results establish a central role of coordinated synaptic plasticity at MSN subpopulations in motor control.

PMID:
26549453
DOI:
10.1016/j.celrep.2015.10.009
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center