Modulation of the input/output function of rat piriform cortex pyramidal cells

1. In transverse brain slice preparations of rat piriform cortex, we characterized the repetitive firing properties of layer II pyramidal cells in control conditions (n = 78) and during perfusion of the cholinergic agonist carbachol (n = 26), with the ultimate goal of developing realistic computational simulations of the cholinergic modulation of the input/output function of these neurons. The response of neurons to prolonged (1 s) intracellular current injections was examined at a full range of current injection amplitudes providing three-dimensional plots of firing frequency versus current amplitude versus time. 2. All neurons showed adaptation in response to intracellular current injection, with repetitive generation of action potentials at frequencies that were highest at the onset of the pulse and that decreased considerably thereafter. Substantial differences were observed between cells with regard to their rates of adaptation and the maximal number of action potentials they could generate during the current pulse. 3. The adaptation characteristics of each neuron were quantified by plotting the number of action potentials generated in 1 s as a function of the normalized current injection amplitude and measuring the area beneath this plot of the number of spikes versus current injection amplitude (S-I plot). This value was termed S-I value and allowed neurons to be plotted on a continuum including neurons showing strong adaptation (S-I value <8.0) and neurons showing weak adaptation (S-I value >8.0). The group showing weak adaptation contained 36% of the cells in control solution and 93.8% of the cells in 20 μM carbachol. 4. Neurons showing strong adaptation did not differ significantly from neurons showing weak adaptation in control conditions in measurements of resting potential, input resistance, threshold, and spike amplitude. Only a small difference was found in frequencies of firing measured soon after pulse onset (after 100 ms). This implies that differences in S-I values are primarily due to different rates of adaptation in later parts of the response. 5. Perfusion with solution containing the cholinergic agonist carbachol (2-100 μM) or 0 Ca²⁺ and 200 μM cadmium resulted in a substantial increase in the S-I values of neurons showing strong adaptation but had only a small effect on their initial firing rates. The effect on weakly adapting cells was smaller. In the presence of 20 μM carbachol, neurons showed a distribution shifted predominantly toward weak adaptation (n = 26). 6. On the basis of these findings we constructed two computational models of pyramidal neurons: model 1, showing strong adaptation; and model 2, showing weak adaptation. These models differ in the maximal conductance of the M current and the afterhyperpolarization current. The S-I values of these two models provided a representation of typical values in the population of neurons in control solution and the population of neurons recorded during cholinergic modulation. Use of these single-cell simulations allows a more realistic representation of the effect of acetylcholine on the input/output function of neurons in a network biophysical simulation. This allows exploration of the role of acetylcholine in associative memory function, as described in the accompanying paper.