Allan Gulledge, Dartmouth Medical School

Reciprocal control of corticofugal output by serotonin and acetylcholine

Pyramidal neurons in the mouse medial prefrontal cortex comprise two broad subclasses of neurons defined by their long-distance axonal projections: intratelencephalic neurons, which include commissural/callosal (COM) projection neurons, and corticofugal neurons, which include those projecting to the pons (CPn neurons). COM and CPn neurons are differentially regulated by modulatory neurotransmitters, including serotonin (5-HT) and acetylcholine (ACh). While CPn neurons are universally inhibited via Gi/o-coupled 5-HT1A (1A) receptors, COM neurons are excited via Gq- coupled 5-HT2A (2A) receptors. Further, although both neuron subpopulations express Gq-coupled M1 muscarinic ACh receptors, ACh preferentially enhances the excitability of CPn neurons. This suggests that 5-HT and ACh may exert opposing influences on corticofugal output to the brainstem. Consistent with this hypothesis, we find that release of endogenous ACh selectively and persistently increases action potential output in CPn neurons (for many 10’s of seconds) through at least three distinct mechanisms, including suppression of M- current and activation of a calcium-permeable conductance. These findings suggest that 5-HT and ACh exert reciprocal control over corticofugal output to the brainstem.

Additional Information

Colloquium Talk in the GRK 1589 "Sensory Computation in Neural Systems"

Organized by

Susana Contreras / Susanne Schreiber