Ronald M Harris-Warrick

..These results support the hypothesis that aCINs play important roles in coordinating left-right movements during fictive locomotion and thus may be component neurons in the locomotor CPG in neonatal mice...

..However, coapplication of both blockers together fully occluded 5-HT's reduction of the calcium current. Thus, 5-HT decreases both N- and P/Q-type calcium current to excite neonatal CINs...

..It is not possible to model the function of neural networks without including the actions of neuromodulators...

..PIIH AB(S)-I overexpression enhanced PD neuron rhythmic firing in an amplitude-dependent manner above a minimal threshold two- to threefold increase in amplitude...

..Potassium currents control spike width and burst duration in many rhythmic motor systems. We are beginning to identify the genes that underlie these currents...

..Finally, spike-evoked and graded transmission at the same synapse can be oppositely affected by DA. These results emphasize the distributed nature of modulation in motor networks...

..Several examples are given of mechanisms for species-specific behavioral evolution that arise from mutations involving the structure, alternative splicing, level of expression, targeting and modulation of these important neural proteins...

..Since I(A) and I(h) influence neuronal activity in opposite directions, our results suggest a selective coregulation of these channels as a mechanism for constraining cell activity within appropriate physiological parameters...

..Our results suggest that I(Na(P)) is essential for the generation of the locomotor pattern and acts in part by regulating the frequency of interneuron firing in the central pattern generator for locomotion...

..Our data suggest that Hb9 INs participate in fictive locomotion, but the delayed onset of activity relative to ipsilateral motoneurons suggests that Hb9 INs are unlikely to be the sole intrasegmental rhythm-generating kernel of the CPG...

..The ability to measure the phase preferences of many neurons with cell type and spatial information should be widely applicable for studying other rhythmic neural circuits...

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..2006), suggest that dCINs and aCINs, but not adCINs, are excited by 5-HT and are rhythmically active during fictive locomotion. Thus, they may play important roles in the coordination of left-right movements during fictive locomotion...

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..5%, with no other strong changes in rhythm parameters. These results suggest that I(h) regulates the pyloric rhythm by accelerating AB pacemaker frequency, but that this effect can vary with the modulatory conditions...

..These results show that modulation of the strength and timing of a synaptic input can differentially affect the synapse's efficacy in the network...

..However, voltage-evoked local Ca(2+) accumulation can be differentially modulated to control Ca(2+)-dependent processes in functionally separate varicosities of a single neuron...

..Thus the contribution of specific calcium channel subtypes carrying the total ICa may vary between pyloric neuron classes, and DA may act on different calcium channel subtypes in the different pyloric neurons...

..The increased role of V2a interneurons at higher locomotor frequencies arises from increased synaptic drive to recruit subthreshold oscillating V2a neurons, and not from recruitment of a second set of silent V2a interneurons...

..This research demonstrates that dendritic calcium currents are targets of serotonin modulation in a group of spinal interneurons that are components of the mouse locomotor network...

..Thus an activity-independent homeostatic mechanism maintains constant neuronal activity in the face of dramatic increases in IA...

..Thus in a rhythmic network, the functional importance of synaptic modulation can only be understood in the context of parallel modulation of intrinsic properties...

..In this chapter, I focus on cellular and molecular mechanisms that could underlie rhythmogenesis in CPG networks, especially those that drive locomotion, respiration, and mastication...

..These experiments suggest that modulation of postsynaptic I(h) might play an important role in the control of synaptic strength in this rhythmogenic neural network...

..This will allow investigation of changes in mature neuronal properties in disease states or after spinal cord injury and allow prolonged recordings of responses to drug application that were previously impossible...

..This suggests that DA-induced release of calcium from intracellular stores activates I(CAN), which provides a depolarizing ramp current that underlies endogenous bursting in the AB neuron...

..Thus the network properties and functional correlates with locomotion of identified populations of interneurons can be studied simultaneously...

..Our results suggest an anatomical and physiological separation of CPG commissural interneurons in the ventral horn and demonstrate that it is possible to target specific interneuron subpopulations in the mammalian locomotor network...

..The AB neuron also shows a reversible 20% increase in the steady state I(K(V)). DA had no effect on I(K(V)) in PD, LP, VD, and IC neurons. The physiological roles of these currents and their modulation by DA are discussed...

..By showing how modulatory input sculpts a crustacean motor network to produce many behaviors, our work will serve as a model for studies of behavioral flexibility in other invertebrates and vertebrates alike. ..

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..It should also provide insights into the causes and possible treatments for psychiatric and other behavioral diseases in humans. ..

..The comparative viewpoints and emerging technologies that are emphasized at the ICN therefore have the potential to contribute to the diagnosis of nervous system diseases and the development of treatments. ..

..An eventual goal of our work is to provide a rational basis for post-injury neuromodulator therapy, to help maintain the locomotor networks in a functional state until regrowth of axons can be accomplished across the lesion. ..

..Our studies will allow us to assign physiological roles to specific K+ channel genes in determining both the intrinsic firing properties of identified neurons and the motor pattern generated by the pyloric network. ..

..This work will further our understanding of how a single anatomically defined neuronal network can be modulated to produce a series of related functional circuits, each generating a unique variant on the basic motor pattern...

..By showing how modulatory input sculpts a crustacean motor network to produce many behaviors, our work will serve as a model for studies of behavioral flexibility in other invertebrates and vertebrates alike...

..An eventual goal of our work is to provide a rational basis for post-injury neuromodulator therapy, to help maintain the locomotor networks in a functional state until regrowth of axons can be accomplished across the lesion. ..