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- Title
Inositol 1,4,5-Triphosphate Drives Glutamatergic and Cholinergic Inhibition Selectively in Spiny Projection Neurons in the Striatum.
- Authors
Clements, Michael A.; Swapna, Immani; Morikawa, Hitoshi
- Abstract
The striatum is critically involved in the selection of appropriate actions in a constantly changing environment. The spiking activity of striatal spiny projection neurons (SPNs), driven by extrinsic glutamatergic inputs, is shaped by local GABAergic and cholinergic net-works. For example, it is well established that different types of GABAergic interneurons, activated by extrinsic glutamatergic and local cholinergic inputs, mediate powerful feedforward inhibition of SPN activity. In this study, using mouse striatal slices, we show that glutamatergic and cholinergic inputs exert direct inhibitory regulation of SPN activity via activation of metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors. While pressure ejection of the group I mGluR (mGluRl/5) agonist DHPG [(S)-3,5-dihydroxyphenylglycine] equally engages both mGluRI and mGluR5 subtypes, the mGluR-dependent component of IPSCs elicited by intrastriatal electrical stimulation is almost exclusively mediated by the mGluRI subtype. Ca2+ release from intracellular stores specif-ically through inositol 1,4,5-triphospahte receptors (IP3Rs) and not ryanodine receptors (RyRs) mediates this form of inhibition by gating two types of Ca2+-activated K+ channels (i.e., small-conductance SK channels and large-conductance BK channels). Conversely, spike-evoked Ca2+ influx triggers Ca2+ release solely through RyRs to generate SK-dependent slow after hyperpolarizations, demon-strating functional segregation of IP3Rs and RyRs. Finally, IP3-induced Ca2+ release is uniquely observed in SPNs and not in different types of interneurons in the striatum. These results demonstrate that IP3-mediated activation of SK and BK channels provides a robust mechanism for glutamatergic and cholinergic inputs to selectively suppress striatal output neuron activity.
- Subjects
INOSITOL trisphosphate; EXCITATORY amino acid agents; CHOLINERGIC mechanisms; NEURONS; GLUTAMATE receptors; BRAIN stimulation; CHOLINERGIC receptors
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 6, p2697
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4759-12.2013