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The Journal of Neuroscience, March 5, 2008, 28(10):2633-2641; doi:10.1523/JNEUROSCI.5079-07.2008

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Cellular/Molecular
D1-Like Dopamine Receptor Activation Modulates GABAergic Inhibition But Not Electrical Coupling between Neocortical Fast-Spiking Interneurons

Stephen K. Towers and Shaul Hestrin

Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California 94305-5342

Correspondence should be addressed to Shaul Hestrin, Department of Comparative Medicine, Stanford University School of Medicine, Stanford, CA 94305-5342. Email: shestrin{at}stanford.edu

Dopamine, acting through D1 receptors, is thought to play an important role in cognitive functions of the frontal cortex such as working memory. D1 receptors are widely expressed in fast-spiking (FS) interneurons, a prominent class of inhibitory cells that exert a powerful control of neuronal firing through proximal synapses on their postsynaptic targets. FS cells are extensively mutually interconnected by both GABAA receptor-mediated synapses and gap junction-mediated electrical synapses, and networks of FS cells play a crucial role in the generation of rhythmic synchronous activity. Although recent studies have documented the effects of dopamine modulation of neocortical synaptic connections among excitatory cells and between excitatory and various inhibitory cells, the effects of dopamine receptor activation on GABAergic and electrical interactions among FS cells is not known. To resolve this, we recorded from pairs of FS cells in the infragranular layers of mouse neocortical slices and tested the effects of D1-like (D1/D5) receptor activation on these connections. We found that D1-like receptor activation modulated GABAergic but not electrical connections between them. A D1-like receptor agonist preserved the strength of electrical coupling but reduced the amplitude of IPSPs and IPSCs between FS cells. Our results suggest that D1-like receptor activation has synapse-specific effects within networks of FS cells, with potential implications for the generation of rhythmic activity in the neocortex.

Key words: dopamine; D1; electrical coupling; neocortex; FS interneurons; IPSPs

Received March 16, 2007; revised Jan. 15, 2008; accepted Jan. 16, 2008.

Correspondence should be addressed to Shaul Hestrin, Department of Comparative Medicine, Stanford University School of Medicine, Stanford, CA 94305-5342. Email: shestrin{at}stanford.edu






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