I am interested in how information is processed in neural tissue. Specifically I am interested in how single neurons integrate and process incoming inputs and how this processing could contribute to network function. I am currently studying neurons in the globus pallidus, a nucleus in the group of subcortical structures called the basal ganglia. The basal ganglia are involved in motor control as well as higher cognitive functions.

To understand how these neurons synthesize their many excitatory and inhibitory inputs in order to create a single output spike train it is necessary to characterizing both the synaptic input to these cells and the distribution of active conductances which could contribute to the processing of these inputs.

To characterize short term plasticity in the synaptic input to these cells I am currently using the in vitro rat brain slice preparation and whole cell patch clamp recordings. Present studies are characterizing synaptic plasticity in the inputs to these cells. In these experiments postsynaptic globus pallidus cells are recorded from while either excitatory or inhibitory inputs are activated by extracellular stimulation. The postsynaptic potentials or currents are then recorded in response to stimulation at varying intervals or in response to in vivo-like input patterns. Preliminary data is also being made to determine if globus pallidus axon collaterals make functional contacts on adjacent cells. This possibility is being examined using simultaneous recordings from pairs of cells.

In order to examine the distribution of active conductances in these neurons, light and electron microscopy of immunolabeld tissue is being used. Recently, antibodies against a variety of voltage-gated ion channels have become commercially available. I am currently testing antibodies against voltage-gated sodium channels in fixed rat brain tissue. Future plans include using other ion channel antibodies including those directed against calcium channels. Electron microscopy of tissue labeled with these antibodies and revealed with either peroxidase reaction product or gold particles will provide detailed information about the subcellular distribution of these conductances.

Finally, I hope to synthesize this data using compartmental models of globus pallidus neurons based on the morphology of intracellularly filled cells. Compartmental models based on physiological recordings and created with ion channel distributions taken from anatomical studies can be tested with controlled synaptic input. These models could offer insight into how these cells process information because controlled sets of well defined inputs can be applied and the role of individual factors such as particular conductances can be examined in ways that are not experimentally accessible.

Predictions from these models can be tested with physiological recordings using various techniques including uncaging of neurotransmitter at controlled distances along the dendrite and blockers of specific ion channels. Additionally, precise patterns of synaptic conductances can be applied to these neurons using the technique of dynamic current clamping and preliminary data has been collected with this approach.