Oscillations in inspiratory synaptic inputs: role in controlling the repetitive firing behaviour of inspiratory motoneurons

Abstract

The transformation of neuronal input into patterns of action potential output, a key element of signal processing in the brain, is determined by the interaction between synaptic and intrinsic membrane properties. Traditional use of rectangular, ramp-like or sinusoidal waveforms to stimulate neurons has focussed attention on the role of intrinsic membrane properties and their modulation in determining repetitive firing behaviour. However, such studies do not address the role that dynamic features of endogenous synaptic inputs play in controlling output. Oscillations are prominent features of synaptic currents/potentials in many networks including those that provide rhythmic excitatory drive to motoneurons involved in behaviours such as locomotion and respiration [1,2,3]. Phrenic motoneurons (PMNs), for example, receive inspiratory currents of brainstem origin that oscillate with peak power in the 20–120 Hz bandwidth. These oscillations are ubiquitous throughout the respiratory network, in vivo [2,4] and in vitro [3,5], and although well-characterized, their function, if any, is not known. Using rhythmically active brainstem spinal cord preparations from neonatal rat and recently developed stimulation techniques [6], we explored the physiological significance to motor control of such oscillations by activating PMNs with native inspiratory synaptic currents that oscillate in the 20–50 Hz bandwidth. Action potentials arose predominantly from peaks of the current oscillations and the timing of spikes within trains was reproducible within 2%. Activation of neurons with low-pass filtered currents produced spike trains with considerably more variability; filtering also reduced the number of action potentials by 35%. Finally, the excitatory neuromodulator, phenylephrine, which significantly increased instantaneous firing frequency responses to filtered inspiratory or square-wave stimuli, had no effect on frequency evoked by endogenous (unfiltered) synaptic waveforms. Results indicate that oscillations in synaptic inputs generated by central respiratory circuits maximise neuronal output, and play a dominant role in controlling the timing of action potentials during behaviourally relevant repetitive firing, even in the presence of neuromodulators.