Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits
Fig 4
Acetylcholine- and noradrenaline-mediated disinhibition facilitates back-propagation of EPSPs and action potentials into the dendrites of CA3 pyramidal cells.
A) Sketch of CA3 pyramidal cell and positioning within the layers of the hippocampus. Synaptic inputs are shown with location of contact (red—recurrent CA3-CA3 synapse, blue—feed-forward inhibitory synapse, gray—mossy fiber synapse). SLM–stratum lacunosum moleculare, SR–stratum radiatum, SL–stratum lucidum, SP–stratum pyramidale, SO–stratum oriens. B) Example traces produced by the biophysical CA3 neuron model of action potentials generated at the soma from summated mossy fiber EPSPs presented at 20 Hz (top), back-propagation into the radial oblique dendrites (middle), and dendritic calcium influx (bottom), in control and with acetylcholine (ACh) or noradrenaline (NA)-mediated disinhibition of feed-forward inhibition. C) Back-propagating action potential amplitude before (left) and after (middle) cholinergic or noradrenergic modulation, and the difference in amplitude (right) distributed across an example CA3 pyramidal cell. D) The number of stimuli required to generate a back-propagating action potential across all cell morphologies. Only dendrites that had back-propagating action potentials in control conditions are shown. E) The proportion of oblique dendrites in stratum radiatum reached by a back-propagating action potential per stimulus for all cell morphologies. F) Histogram of differences in back-propagating action potential amplitudes with and without acetylcholine disinhibition in stratum radiatum oblique dendritic compartments (< 1 μm diameter) from 15 cells. G) Distribution of back-propagating action potential amplitudes in stratum radiatum oblique dendrites for a range of excitation-inhibition ratios in 15 cells. In our simulations the effect of acetylcholine was modelled as a change in this ratio (the absence of acetylcholine, gI/gE = 3; in the presence of acetylcholine, gI/gE = 1). H) The probability of successful action potential back-propagation (bAP amplitude > 40 mV) in oblique dendrites in 15 cells as a function of excitation-inhibition ratio.