We have hypothesized that the external segment of the pallidum (GPe) is located at the center of the basal ganglia connections and plays a key role in the physiology and pathophysiology of the basal ganglia. To understand how the neuronal activity of the GPe is controlled under physiological and pathophysiological conditions, the nature of both the synaptic inputs to the GPe neurons and the properties of the postsynaptic membrane should be fully characterized. Anatomical knowledge as well as theories on the basal ganglia motor control predict that the stimulation of the cerebral cortex would induce powerful disynaptic, through the neostriatdum (Str), inhibition in the GPe. However, a striking observation obtained in monkey unit recording study as well as intracellular recording in anesthetized rats was that the cortical stimulation-induced inhibition in the GPe was weak and was dominated by the disynaptic excitation through the subthalamic nucleus (STN). When the STN was chemically blocked, cortical stimulation induced a long duration powerful inhibition in the GPe. Thus, aim 1 is to test a possibility that glutamatergic inputs suppress GABAergic inhibition in the GPe. The STN blockade also caused slow and strong oscillation of GPe neurons.
Aim 2 is to investigate the nature of the slow oscillation. Our experiments in the monkey also suggest that GPe neurons receive tonic excitatory input even after the STN blockade. The possible excitatory sources to the GPe, other than the STN, include the centromedian-parafascicular complex (CM-Pf) and the dorsal raphe nucleus.
Aim 3 is to study the anatomical and physiological properties of the CM-Pf inputs to the GPe.
Aim 4 is to investigate the effects of 5-HT agonists on the GPe neurons and also on the GABAergic synaptic transmissions in the GPe. Experiments will use whole cell recording method in rat brain slice preparations, unit recording method in awake monkeys and an anterograde neurotracing method in the rat. At the end of the proposed projects, we should be able to offer an anatomical and physiological basis for explaining how the synaptic inputs might control the neuronal activity of the GPe.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS042762-04
Application #
6824893
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Oliver, Eugene J
Project Start
2001-12-15
Project End
2006-11-30
Budget Start
2004-12-01
Budget End
2005-11-30
Support Year
4
Fiscal Year
2005
Total Cost
$227,525
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Chan, C Savio; Glajch, Kelly E; Gertler, Tracy S et al. (2011) HCN channelopathy in external globus pallidus neurons in models of Parkinson's disease. Nat Neurosci 14:85-92
Hashimoto, Kenji; Kita, Hitoshi (2008) Serotonin activates presynaptic and postsynaptic receptors in rat globus pallidus. J Neurophysiol 99:1723-32
Tachibana, Yoshihisa; Kita, Hitoshi; Chiken, Satomi et al. (2008) Motor cortical control of internal pallidal activity through glutamatergic and GABAergic inputs in awake monkeys. Eur J Neurosci 27:238-53
Kaneda, Katsuyuki; Kita, Takako; Kita, Hitoshi (2007) Repetitive activation of glutamatergic inputs evokes a long-lasting excitation in rat globus pallidus neurons in vitro. J Neurophysiol 97:121-33
Kita, Hitoshi; Chiken, Satomi; Tachibana, Yoshihisa et al. (2007) Serotonin modulates pallidal neuronal activity in the awake monkey. J Neurosci 27:75-83
Kita, Hitoshi (2007) Globus pallidus external segment. Prog Brain Res 160:111-33
Hashimoto, Kenji; Kita, Hitoshi (2006) Slow oscillatory activity of rat globus pallidus neurons in vitro. Eur J Neurosci 23:443-53
Kita, Hitoshi; Chiken, Satomi; Tachibana, Yoshihisa et al. (2006) Origins of GABA(A) and GABA(B) receptor-mediated responses of globus pallidus induced after stimulation of the putamen in the monkey. J Neurosci 26:6554-62
Kita, Hitoshi; Tachibana, Yoshihisa; Nambu, Atsushi et al. (2005) Balance of monosynaptic excitatory and disynaptic inhibitory responses of the globus pallidus induced after stimulation of the subthalamic nucleus in the monkey. J Neurosci 25:8611-9
Kaneda, K; Tachibana, Y; Imanishi, M et al. (2005) Down-regulation of metabotropic glutamate receptor 1alpha in globus pallidus and substantia nigra of parkinsonian monkeys. Eur J Neurosci 22:3241-54

Showing the most recent 10 out of 14 publications