Many animal behaviors involve the generation of rhythmic patterns and movements. These rhythmic patterns are commonly mediated by neural networks that produce an oscillatory activity pattern, where different neurons maintain a relative phase relationship. This thesis examines the relationships between the cellular and synaptic properties that give rise to stable activity in the form of phase maintenance, across different frequencies in a well-suited model system, the pyloric network of the crab Cancer borealis. The pyloric network has endogenously oscillating ‘pacemaker’ neurons that inhibit ‘follower’ neurons, which in turn feed back onto the pacemaker neurons. The focus of this thesis was to determine the methods by which phase maintenance is achieved in an oscillatory network. This thesis examines the idea that phase maintenance occurs through the actions of intrinsic properties of isolated neurons or through the dynamics of their synaptic connections or both. A combination of pharmacological and electrophysiological techniques a used to show how identified membrane properties and short-term synaptic plasticity are involved with phase maintenance over a range of biologically relevant oscillation frequencies.
To examine whether network stability is due to the characteristic stable activity of the identified pyloric neuron types, the hypothesis that phase maintenance is an inherent property of synaptically-isolated individual neurons in the pyloric network was first tested. A set of parameters were determined (frequency-dependent activity profile) to define the response of each isolated pyloric neuron to sinusoidal input at different frequencies. The parameters that define the activity profile are: burst onset phase, burst end phase, resonance frequency and intra-burst spike frequency. Each pyloric neuron type was found to possess a unique activity profile, indicating that the individual neuron types are tuned to produce a particular activity pattern at different frequencies depending on their role in the network. To elucidate the biophysical properties underlying the frequency-dependent activity profiles of the neurons, the hyperpolarization activated current (Ih) was measured and found to possess frequency-dependent properties. This implies that Ih has a different influence on the activity phase of pyloric neurons at different frequencies. Additionally, it was found that the Ih contribution to the burst onset phase depends on the neuron type: in the pacemaker group neurons (PD) it had no influence on the burst onset phase at any frequency whereas in follower neurons it acted to advance the onset phase in one neuron type (LP) and, paradoxically, to delay it in a different neuron type (PY). The results from this part of the study provided evidence that stability is due in part to the intrinsic neuronal properties but that these intrinsic properties do not fully explain network stability.
To address the contribution of pyloric synapses to network stability, the mechanisms by which synapses promote phase maintenance were investigated. An artificial synapse that mimicked the feedforward PD to LP synapse, was used so that the synaptic parameters could be varied in a controlled manner in order to examine the influence of the properties of this synapse on the postsynaptic LP neuron. It was found that a static synapse with fixed parameters (such as strength and peak phase) across frequencies cannot result in a constant activity phase in the LP neuron. However, if the synaptic strength decreases and the peak phase is delayed as a function of frequency, the LP neuron can maintain a constant activity phase across a large range of frequencies. These dynamic changes in the strength and peak phase of the PD to LP synapse are consistent with the short-term plasticity properties previously reported for this synapse.
In the pyloric network, the follower neuron LP provides the sole transmitter-mediated feedback to the pacemaker neurons. To understand the role of this synapse in network stability, this synapse was blocked and replaced by an artificial synapse using the dynamic clamp technique. Different parameters of the artificial synapse, including strength, peak phase, duration and onset phase were found to affect the pyloric cycle period. The most effective parameters that influence cycle period were the synaptic duration and its onset phase.
Overall this study demonstrated that both the intrinsic properties of individual neurons and the dynamic properties of the synapses are essential in producing stable activity phases in this oscillatory network. The insight obtained from this thesis can provide a general understanding of the contribution of intrinsic properties to neuronal activity phase and how short-term synaptic dynamics can act to promote phase maintenance in oscillatory networks.
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