The Journal of Neuroscience, November 2, 2005, ():
Cholinergic Inhibition of Neocortical Pyramidal Neurons
J. Neurosci. Gulledge and Stuart
25: 10308
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Files in this Data Supplement:
- supplemental material
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Supplementary Figure 1. Model of cholinergic inhibition of neocortical neurons. A, A cartoon diagram of a rat’s brain depicting cholinergic input from neurons in the basal forebrain nuclei to neocortical pyramidal neurons in the somatosensory cortex. B, Shown is a model of the intracellular signalling mechanisms that mediate cholinergic inhibition of neocortical pyramidal neurons. First, ACh binds to M1-type mAChRs to activate the Gq–phospholipase C pathway that liberates IP3 from phospholipids in the plasma membrane. IP3 subsequently releases calcium from IP3-sensitive stores to increase cytoplasmic free calcium. The rise in intracellular calcium, which is amplified further by calcium-induced calcium release from ryanodine receptors, activates SK-type calcium-activated potassium conductances to hyperpolarize neurons. It is possible that the natural bifurcation of the Gq signalling cascade may allow M1 receptors to gate both hyperpolarizing and depolarizing responses to ACh. While the IP3 pathway leads to hyperpolarization via SK-channel activation, PLC generation of diacylglycerols and subsequent activation of PKC may play a role in generating M1 receptor-mediated depolarization. It is also possible that IP3 signalling also directly plays a role in generating depolarization. Finally, calcium entry through voltage-gated calcium channels refills internal calcium stores to facilitate repetitive cholinergic responses over time.
- supplemental material
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Supplementary Video 1. Calcium imaging of cholinergic response. Video of layer 5 pyramidal neuron (left) filled with Oregon Green BAPTA-6F. The timing of acetylcholine application (100 µM, 5 ms) is indicated with an orange circle. The voltage response of this neuron (right) shows a hyperpolarization from the resting potential that corresponds in time to the increase in fluorescence.
- supplemental material
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Supplementary Video 2. Calcium imaging of the cholinergic response in a neuron firing action potentials. Video of layer 5 pyramidal neuron (left) filled with Oregon Green BAPTA-6F and firing action potentials in response to 300 pA of somatic current injection. The timing of acetylcholine application (100 µM, 5 ms) is indicated with an orange circle. The voltage response of this neuron (right) shows a pronounced inhibition of action potential firing that corresponds in time to the increase in fluorescence. Data are from the same neuron as in Supplementary Video 1
