A method for activating neurons using endogenous synaptic waveforms.

Abstract

Neuronal input-output functions are traditionally studied using rectangular or ramp waveforms of injected current. These waveforms are easy to produce and responses to them easy to quantify; thus they have been central to our understanding of the roles that membrane properties play in controlling repetitive firing. However, since smooth rectangular step and ramp waveforms lack the dynamic features of endogenous synaptic input, their use has the potential to underemphasize the importance of input patterns in controlling physiological patterns of neuronal output. To activate neurons with current waveforms that replicate natural synaptic input, we developed a method for acquiring, digitally manipulating and reinjecting endogenous synaptic currents. We demonstrate, by applying this technique to phrenic motoneurons (PMNs) in rhythmically-active in vitro preparations from neonatal rats, that stimulation of neurons with endogenous current waveforms produces responses that mimic those produced by spontaneous synaptic inputs. Acquired waveforms can be reinjected repeatedly to produce consistent responses, and can also be amplified or filtered prior to reinjection to yield a range of information including standard descriptors of firing behavior such as frequency/current plots. This technique provides a valuable tool for analysing characteristics of the synaptic waveform important in generating neuronal output and how synaptic factors interact with membrane properties to control repetitive firing.