Neocortical neurons in vivo receive periodic stimuli due to feedforward input from the periphery as well as local cellular and circuit properties. In order to understand how neurons process such information, the responses of neurons to periodic sine wave current stimuli of varying frequencies and amplitudes were investigated. Sine wave stimuli were injected into pyramidal cells of young adult ferret visual cortical slices in vitro using sharp microelectrodes. To simulate higher resting membrane potentials observed in vivo a slight depolarizing current was injected to bring the neuron just to threshold. Initially, neurons discharged at least one action potential per sine wave cycle, but as the frequency was increased, a point was reached where this one-to-one responsiveness was lost. This critical frequency was dependent upon the injected sine wave amplitude and the magnitude of the underlying steady-state depolarization, and was correlated with spike width. Larger steady-state depolarizations and thinner action potentials corresponded to higher critical frequencies. Thus, when a neuron was very active it could respond in a one-to-one fashion over a greater range of frequencies than with the smallest DC offset.The results suggest that the frequency-following characteristics of individual cortical neurons can be modulated by the activity state of the neuron itself.
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