Abstract
Serotonin (5-HT) regulates attention by neurobiological mechanisms that are not well understood. Layer 6 (L6) pyramidal neurons of prefrontal cortex play an important role in attention and express 5-HT receptors, but the serotonergic modulation of this layer and its excitatory output is not known. Here, we performed whole-cell recordings and pharmacological manipulations in acute brain slices from wild-type and transgenic mice expressing either eGFP or eGFP-channelrhodopsin in prefrontal L6 pyramidal neurons. Excitatory circuits between L6 pyramidal neurons and L5 GABAergic interneurons, including a population of interneurons essential for task attention, were investigated using optogenetic techniques. Our experiments show that prefrontal L6 pyramidal neurons are subject to strong serotonergic inhibition and demonstrate direct 5-HT–sensitive connections between prefrontal L6 pyramidal neurons and two classes of L5 interneurons. This work helps to build a neurobiological framework to appreciate serotonergic disruption of task attention and yields insight into the disruptions of attention observed in psychiatric disorders with altered 5-HT receptors and signaling.
Footnotes
Authors report no conflict of interest.
This work was supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada, the Canada Research Chair in Developmental Cortical Physiology, an Early Researcher Award from the Province of Ontario, and the Canadian Foundation for Innovation (EKL); a Banting and Best Canada Graduate Scholarship from CIHR (MKT); a Brain and Behavior Research Foundation NARSAD Young Investigator Grant; the van Ameringen Foundation (EFS), and Canada Research Chairs (Chaires de recherche du Canada (EKL)).
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