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Modelling Feedback Excitation, Pacemaker Properties and Sensory Switching of Electrically Coupled Brainstem Neurons

Michael J Hull1,2, Stephen R Soffe2, David J Willshaw1

  • 1Institute for Adaptive and Neural Computation, University of Edinburgh, Edinburgh, United Kingdom.

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|January 30, 2016
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Summary

Networks of neurons with N-methyl-D-aspartate receptor (NMDAR) mediated feedback can sustain rhythmic firing. This neuronal rhythm generation can be switched on and off by brief synaptic inputs, crucial for behaviors like locomotion.

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Area of Science:

  • Neuroscience
  • Computational Neuroscience
  • Systems Neuroscience

Background:

  • Neuronal rhythm generation is fundamental for motor control.
  • Understanding how brief synaptic inputs initiate and cease rhythmic neuronal activity is key.

Purpose of the Study:

  • Investigate cellular and network properties enabling reliable neuronal rhythm generation.
  • Determine how rhythmic activity in brainstem neurons driving locomotion is switched on/off by sensory input.

Main Methods:

  • Computational modeling of 30 electrically-coupled conditional pacemaker neurons.
  • Simulations based on experimental estimates of neuron properties, population sizes, and synaptic connections.

Main Results:

  • Long-lasting glutamatergic excitation sustains rhythmic firing at swimming frequencies.
  • Electrical coupling is necessary for rhythm persistence; its absence breaks rhythm.
  • NMDAR voltage-dependency broadens synaptic feedback ranges for sustained rhythm.
  • Network activity can be switched on/off rapidly by brief synaptic excitation/inhibition.

Conclusions:

  • Networks with NMDAR-mediated feedback excitation can generate self-sustained activity after brief excitation.
  • Neuronal membrane channel kinetics limit activity frequency; inhibition stops activity.
  • Electrical coupling enables rhythmic activity at lower frequencies.
  • Excitatory synaptic feedback creates switchable, stable, sustained firing without inhibition.