Dr. Yoland Smith: Yerkes

Xiaotao Jin

I earned my Ph.D. from Dr. Brunken's laboratory at Boston College in 1996 and received postdoctoral training in the laboratory of Dr. Nigel Daw at Yale University and Dr. Stuart Lipton at Burnham Research Institute. I have joined the lab as an Instructor in 2002. My current project is to study ultrastructural expression, distribution and functions of kainate receptors (GluR6/7) in the rat globus pallidus GP) using electron microscope and patch-clamp techniques (whole-cell recording). These studies represent a first step to a better understanding of the role of kainate receptors in normal basal ganglia functions and help characterize the potential implications of these receptors in the pathophysiology of basal ganglia disorders. Here are some of the issues I am interested in about kainate receptors.

1. Ultrastructural localization of (GluR6/7) in rat globus pallidus. Results of this work will provide the direct evidence to show the localization of KARs at ultrastructural level. These results will help us to understand the functions of KARs in the rat GP. Consistent with our primate data, pre- and postsynaptic GluR6/7 labeling are found in adult and young rat GP. Figure 1. is an example of GluR6/7 labeled dendrite.

glur 6/7 em image

Figure 1.
GluR6/7 labeled dendrite of
Young rat GP neuron.

2. Functional expression of GluR6/7 at postsynaptic GP neurons. I have recorded two groups of GP neurons (Types I and II). The type II neurons (Figure 2) are the most commonly recorded cells encountered in the rat GP. In line with my EM data, whole-cell recording demonstrate a dose-depend Inward current activated by kainate in presence of D-AP5 and TTX. This current is largely mediated through activation of KARs because it is not blocked by the selective AMPA receptor antagonists, GYKI 52466 and SYM 2206, but significantly reduced by AMPA/KARs antagonists CNQX (Figure 3). Current experiments are testing synaptic activation of GluR6/7.

recording gp neurons

Figure 2.
Electrophysiological (A) and morphological.
(B) characteristics of type II GP neurons.

Fig 3.
Inward (A) and mean amplitude of current activated by kainate (B).

3. Does activation of GluR6/7 modulate the glutamatergic synaptic transmission in rat GP? The rationale of this project is that pre-synaptic kainate receptors modulate release of glutamate from glutamatergic terminals in GP. The experiments, therefore, examine the effect of kainate on evoked and paired pulse of EPSC.

4. Does activation of GluR6/7 modulate GABAergic synaptic transmission in rat GP? Based on the findings collected in young rats showing the presynaptic GluR6/7 receptors in GP (Jin and Smith, 2003), I will test if GluR6/7 activation modulates the evoked IPSC.

5. What possible molecular mechanisms underlie kainate receptors involvement in the modulation of glutamatergic and GABAergic transmission in rat GP?

biotin image