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Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex
Daniel W Sparks1, Michael K Tian1, Derya Sargin1
1Department of Physiology, University of Toronto, Toronto, ON, Canada.
Frontiers in Neural Circuits
|January 23, 2018
Summary
Acetylcholine (ACh) and serotonin (5-HT) oppositely modulate prefrontal cortex layer 6 neurons, impacting attention. This study reveals the neurophysiology behind their opposing influences on attention processing.
Area of Science:
- Neuroscience
- Cellular Neuroscience
- Systems Neuroscience
Background:
- The prefrontal cortex is crucial for attention, receiving input from cholinergic and serotonergic systems.
- Acetylcholine (ACh) and serotonin (5-HT) show opposing effects on attention, but the neural mechanisms are unclear.
- Medial prefrontal layer 6 pyramidal neurons are key targets due to their role in corticothalamic and cortical interneuron modulation.
Purpose of the Study:
- To investigate the opposing neurophysiological effects of ACh and 5-HT on medial prefrontal layer 6 pyramidal neurons.
- To elucidate the mechanisms underlying the opposing neuromodulation by ACh and 5-HT in attention circuits.
Main Methods:
- Whole-cell recordings in acute mouse brain slices.
- Application of exogenous ACh and 5-HT agonists.
- Optogenetic stimulation of endogenous ACh and 5-HT release in transgenic mice.
Main Results:
- Individual layer 6 pyramidal neurons exhibited bidirectional responses to ACh and 5-HT, with opposing effects on excitability.
- Optogenetically evoked endogenous ACh and 5-HT confirmed these opposing modulatory effects.
- Serotonin (5-HT) significantly suppressed acetylcholine (ACh)-induced excitation in these neurons.
Conclusions:
- Medial prefrontal layer 6 pyramidal neurons are a substrate for opposing neuromodulation by ACh and 5-HT.
- These findings provide insight into the neurophysiological basis of attention regulation by cholinergic and serotonergic systems.
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