Synaptic depression in conjunction with A-current channels promote phase constancy in a rhythmic network.

In many central pattern generators, pairs of neurons maintain an approximately fixed phase despite large changes in the frequency. The mechanisms underlying phase maintenance are not clear. Previous theoretical work suggested that inhibitory synapses that show short-term depression could play a critical role in this respect. In this work we examine how the interaction between synaptic depression and the kinetics of a transient potassium (A-like) current could be advantageous for phase constancy in a rhythmic network. To demonstrate the mechanism in the context of a realistic central pattern generator, we constructed a detailed model of the crustacean pyloric circuit. The frequency of the rhythm was modified by changing the level of a ligand-activated current in one of the pyloric neurons. We examined how the time difference of firing activities between two selected neurons in this circuit is affected by synaptic depression, A-current, and a combination of the two. We tuned the parameters of the model such that with synaptic depression alone, or A-current alone, phase was not maintained between these two neurons. However, when these two components came together, they acted synergistically to maintain the phase across a wide range of cycle periods. This suggests that synaptic depression may be necessary to allow an A-current to delay a postsynaptic neuron in a frequency-dependent manner, such that phase invariance is ensured.

[1]  E Marder,et al.  Modulators with Convergent Cellular Actions Elicit Distinct Circuit Outputs , 2001, The Journal of Neuroscience.

[2]  Farzan Nadim,et al.  Contribution of synaptic depression to phase maintenance in a model rhythmic network. , 2003, Journal of neurophysiology.

[3]  E Marder,et al.  A modulatory proctolin-containing neuron (MPN). II. State-dependent modulation of rhythmic motor activity , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  D. McCormick,et al.  Functional properties of a slowly inactivating potassium current in guinea pig dorsal lateral geniculate relay neurons. , 1991, Journal of neurophysiology.

[5]  Scott L. Hooper,et al.  The Pyloric Pattern of the Lobster (Panulirus interruptus) Stomatogastric Ganglion Comprises Two Phase-Maintaining Subsets , 1997, Journal of Computational Neuroscience.

[6]  M. A. Masino,et al.  Intersegmental coordination of rhythmic motor patterns. , 2003, Journal of neurophysiology.

[7]  E Marder,et al.  A modulatory proctolin-containing neuron (MPN). I. Identification and characterization , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  M. Moulins,et al.  Control by an identified modulatory neuron of the sequential expression of plateau properties of, and synaptic inputs to, a neuron in a central pattern generator , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[9]  J Schmidt,et al.  Pattern generation for walking and searching movements of a stick insect leg. I. Coordination of motor activity. , 2001, Journal of neurophysiology.

[10]  Scott L. Hooper,et al.  Phase Maintenance in the Pyloric Pattern of the Lobster (Panulirus interruptus) Stomatogastric Ganglion , 1997, Journal of Computational Neuroscience.

[11]  E Marder,et al.  Modulation of the lobster pyloric rhythm by the peptide proctolin , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  Charles J. Wilson,et al.  Contribution of a slowly inactivating potassium current to the transition to firing of neostriatal spiny projection neurons. , 1994, Journal of neurophysiology.

[13]  S. Hooper,et al.  Relating network synaptic connectivity and network activity in the lobster (Panulirus interruptus) pyloric network. , 2003, Journal of neurophysiology.

[14]  S. Gueron,et al.  Dopamine modulation of two subthreshold currents produces phase shifts in activity of an identified motoneuron. , 1995, Journal of neurophysiology.

[15]  E. Marder,et al.  Ionic currents of the lateral pyloric neuron of the stomatogastric ganglion of the crab. , 1992, Journal of neurophysiology.

[16]  S. Grillner Control of Locomotion in Bipeds, Tetrapods, and Fish , 1981 .

[17]  M. Taussig The Nervous System , 1991 .

[18]  D. Hartline,et al.  Pattern generation in the lobster (Panulirus) stomatogastric ganglion , 1979, Biological Cybernetics.

[19]  Eve Marder,et al.  Subharmonic Coordination in Networks of Neurons with Slow Conductances , 1994, Neural Computation.

[20]  T. Akasu,et al.  Slowly inactivating potassium current in cultured bull‐frog primary afferent and sympathetic neurones. , 1991, The Journal of physiology.

[21]  W. O. Friesen,et al.  Mechanisms of intersegmental coordination in leech locomotion , 1993 .

[22]  D. King Organization of crustacean neuropil. I. Patterns of synaptic connections in lobster stomatogastric ganglion , 1976, Journal of neurocytology.

[23]  E. Marder,et al.  Principles of rhythmic motor pattern generation. , 1996, Physiological reviews.

[24]  M. Moulins,et al.  Muscarinic modulation of a pattern-generating network: control of neuronal properties , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  D. King Organization of crustacean neuropil. II. Distribution of synaptic contacts on identified motor neurons in lobster stomatogastric ganglion , 1976, Journal of neurocytology.

[26]  E. Marder,et al.  Selective regulation of current densities underlies spontaneous changes in the activity of cultured neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[27]  R. Harris-Warrick,et al.  Strychnine eliminates alternating motor output during fictive locomotion in the lamprey , 1984, Brain Research.

[28]  R. Harris-Warrick,et al.  Dopamine modulation of transient potassium current evokes phase shifts in a central pattern generator network , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  E. Marder,et al.  A mechanism for production of phase shifts in a pattern generator. , 1984, Journal of neurophysiology.

[30]  Johan F. Storm,et al.  Temporal integration by a slowly inactivating K+ current in hippocampal neurons , 1988, Nature.

[31]  E. Marder,et al.  Contribution of individual ionic currents to activity of a model stomatogastric ganglion neuron. , 1992, Journal of neurophysiology.

[32]  Ronald L Calabrese,et al.  Model of intersegmental coordination in the leech heartbeat neuronal network. , 2002, Journal of neurophysiology.

[33]  J. Freschi Proctolin activates a slow, voltage-dependent sodium current in motoneurons of the lobster cardiac ganglion , 1989, Neuroscience Letters.

[34]  Jordan,et al.  Maintenance of motor pattern phase relationships in the ventilatory system of the crab , 1997, The Journal of experimental biology.

[35]  Farzan Nadim,et al.  Dynamic Interaction of Oscillatory Neurons Coupled with Reciprocally Inhibitory Synapses Acts to Stabilize the Rhythm Period , 2004, The Journal of Neuroscience.

[36]  Eve Marder,et al.  The Functional Consequences of Changes in the Strength and Duration of Synaptic Inputs to Oscillatory Neurons , 2003, The Journal of Neuroscience.

[37]  C. Morris,et al.  Voltage oscillations in the barnacle giant muscle fiber. , 1981, Biophysical journal.