This is the readme for the models for the paper: Prescott SA, Ratte S, De Koninck Y, Sejnowski TJ. Pyramidal neurons switch from integrators in vitro to resonators under in vivo-like conditions. J. Neurophysiol. In press. Abstract: During wakefulness, pyramidal neurons in the intact brain are bombarded by synaptic input that causes tonic depolarization, increased membrane conductance (i.e. shunting), and noisy fluctuations in membrane potential; by comparison, pyramidal neurons in acute slices typically experience little background input. Such differences in operating conditions can compromise extrapolation of in vitro data to explain neuronal operation in vivo. For instance, pyramidal neurons have been identified as integrators (i.e. class 1 neurons according to Hodgkin's classification of intrinsic excitability) based on in vitro experiments, but that classification is inconsistent with the ability of hippocampal pyramidal neurons to oscillate/resonate at theta frequency since intrinsic oscillatory behavior is limited to class 2 neurons. Using long depolarizing stimuli and dynamic clamp to reproduce in vivo-like conditions in slice experiments, we show that CA1 hippocampal pyramidal cells switch from integrators to resonators, i.e. from class 1 to class 2 excitability. The switch is explained by increased outward current contributed by the M-type potassium current I(M), which shifts the balance of inward and outward currents active at perithreshold potentials and thereby converts the spike initiating mechanism as predicted by dynamical analysis of our computational model. Perithreshold activation of I(M) is enhanced by the depolarizing shift in spike threshold caused by shunting and/or sodium channel inactivation secondary to tonic depolarization. Our conclusions were validated by multiple comparisons between simulation and experimental data. Thus, even so-called "intrinsic" properties may differ qualitatively between in vitro and in vivo conditions. Model Notes: The Morris-Lecar-type model included here shows how spike initiating dynamics can be influenced by external factors like the level of background synaptic input. High levels of synaptic input cause shunting (i.e. increased membrane conductance) and tonic depolarization which can cause activation/inactivation of voltage-sensitive currents. In this study, we show that shunting and/or tonic depolarization can convert a neuron exhibiting class 1 excitability (spike initiation through a saddle-node on invariant circle bifurcation) to class 2 excitability (spike initiation through a subcritical Hopf bifurcation). One importance consequence is that class 2 neurons can oscillate/resonate whereas class 1 neurons cannot. In the first model, ML(noNainactivation).ode, there is no sodium channel inactivation. Try varying gshunt and/or gM to add/remove shunting and adaptation from the model. Be sure to include small-amplitude noise (sigma>0) in order to see noise-induced oscillations. In the second model, ML(withNainactivation).ode, sodium channel inactivation is included. Strength of inactivation is controlled by alpha_h; set alpha_h to 1 to turn off this mechanism. In this model, other parameters have been adjusted to correspond to those described in Figure 9B of the paper. The main idea is that shunting and/or tonic depolarization (causing inactivation of sodium channels or activation of M channels) will lead to depolarizing shift in voltage threshold. Shifting threshold influences how strongly certain currents will activate at voltages just below threshold. Increased subthreshold activation of the delayed-rectifier potassium current can lead to high-frequency oscillations. Increased subtheshold activation of the M-type potassium current can lead to theta-frequency oscillations. An important conclusion of this study is that although M-type potassium current is present in CA1 pyramidal neurons, that current may not be strongly activated at subthrehsold potentials under in vitro conditions whereas it would more strongly activated under in vivo conditions because of the shift in threshold caused by background synaptic input. The resulting shift in balance of inward and outward currents near threshold can qualitatively change the spike initiating mechanism, with important consequences for the integrative properties of the neuron. The code contains numerous comments that help explain the model. For more information about XPP, visit http://www.scholarpedia.org/article/XPPAUT or http://www.math.pitt.edu/~bard/xpp/xpp.html.