Effects of inhibition and dendritic saturation in simulated neocortical pyramidal cells.

1. We have used compartmental models of reconstructed pyramidal neurons from layers 2 and 5 of cat visual cortex to investigate the nonlinear summation of excitatory synaptic input and the effectiveness of inhibitory input in countering this excitation. 2. In simulations that match the conditions of a recent experiment, dendritic saturation was significant for physiological levels of synaptic activation: a compound excitatory postsynaptic potential (EPSP) electrically evoked during a depolarization caused by physiological synaptic activation was decreased by up to 80% compared with an EPSP evoked at rest. 3. Synaptic inhibition must be coactivated with excitation to quantitatively match the experimental results. The experimentally observed coactivation of inhibition with excitation produced additional current shunts that amplified the decrease in test EPSP amplitude. About 30% of the experimentally observed decrease in EPSP amplitude was caused by decreases in input resistance (Rin) due to synaptic conductance changes; a reduced driving force accounted for the remaining decrease. 4. The amount of inhibition was then increased by nearly an order of magnitude, to approximately 10% of the total number of inhibitory synapses on a typical cortical pyramidal cell. The sustained firing of this many inhibitory inputs was sufficient to completely suppress the firing of a neuron receiving strong excitatory input. However, this level of inhibition produced a very large reduction in Rin. Such large reductions in Rin have not been observed experimentally, suggesting that inhibition in cortex does not act to veto (shunt) strong, sustained excitatory input (of order 100 ms). 5. We propose instead that strong, transient activation (< 10 ms) of a neuron's inhibitory inputs, sufficient to briefly prevent firing, is used to shape the temporal structure of the cell's output spike train. Specifically, cortical inhibition may serve to synchronize the firing of groups of pyramidal cells during optimal stimulation.