Compartment-Specific Modulation of GABAergic Synaptic Transmission by μ-Opioid Receptor in the Mouse Striatum with Green Fluorescent Protein-Expressing Dopamine Islands

• DOI: 10.1523/jneurosci.2993-07.2007
• Publication Date: 2007-09-05T16:39:17Z
• Authors: Masami Miura; Sachiko Saino-Saito; Masao Masuda; Kazuto Kobayashi; Toshihiko Aosaki
• Keywords: Patch-Clamp Techniques; Tyrosine 3-Monooxygenase; Dopamine; Narcotic Antagonists; Green Fluorescent Proteins; Receptors, Opioid, mu; Excitatory Postsynaptic Potentials; Mice, Transgenic; Cyclic AMP-Dependent Protein Kinases; Immunohistochemistry; Synaptic Transmission; Corpus Striatum; Analgesics, Opioid; Mice; 03 medical and health sciences; Organ Culture Techniques; 0302 clinical medicine; Inhibitory Postsynaptic Potentials; Animals; Enzyme Inhibitors; gamma-Aminobutyric Acid

The striatum is a heterogeneous mosaic of two neurochemically, developmentally, and functionally distinct compartments: the μ-opioid receptor (MOR)-enriched striosomes and the matrix. Preferential activation of the striosomes and persistent suppression of the matrix have recently been suggested to represent neural correlates of motor stereotypy. However, little is known concerning the physiological properties of the striosomes. We made patch-clamp recordings from medium spiny neurons in identified MOR-immunoreactive “dopamine islands” as striosomes in a slice preparation taken from transgenic mice expressing green fluorescent protein in tyrosine hydroxylase mRNA-containing neurons. Striosomal neurons differed electrophysiologically from cells in the matrix in having significantly less hyperpolarized resting membrane potentials and larger input resistances, suggesting developmental differences between the two types of cells. Moreover, corticostriatal EPSCs were inhibited by MOR activation to similar extents in the two compartments, although inhibition of IPSCs was observed only in the striosomes. This MOR-induced inhibition of IPSCs was presynaptically mediated, because MOR agonist invariably decreased IPSC amplitudes when postsynaptic G-protein was inactivated, significantly increased the paired-pulse ratio of the IPSCs, and decreased the frequency but not the amplitude of miniature IPSCs. These effects of MOR were mediated principally by 4-aminopyridine-sensitive K+conductance via a cAMP-dependent pathway, which was further augmented by previous blockade of the protein kinase C cascade. These findings suggest that MOR activation by endogenous and/or exogenous MOR-selective opioid substances differentially regulates the activities of the striosome and matrix compartments and thus plays an important role in motivated behavior and learning.