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 well understood. Here, we performed whole-cell recordings and pharmacological manipulations in acute brain slices from wildtype 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.
Significance Statement: While serotonin shapes and biases attention, the mechanisms underlying this phenomenon are not well understood. Layer 6 (L6) pyramidal neurons of medial prefrontal cortex play a critical role in performance on attention tasks, but their serotonergic modulation is unclear. Using electrophysiology and optogenetic techniques, we investigated the effects of serotonin on L6 pyramidal neurons and their local cortical circuits. We discovered a direct and serotonin-sensitive functional link from prefrontal L6 pyramidal neurons to GABAergic interneurons in L5, two populations of neurons essential for attention.
Authors report no conflict of interest.
Canada Research Chairs (Chaires de recherche du Canada) ; Canada Research Chair in Developmental Cortical Physiology