Glutamate receptors play an essential role in mediating rapid excitatory synaptic activity in the vertebrate brain. It is possible that some disorders, such as epilepsy or anoxic damage, are related to changes in synaptic function, and ultimately, the properties of subsynaptic glutamate receptors. Thus, effective treatment for such disorders may come from an understanding of how the receptors are used and regulated. This information will also be needed to understand the control of signalling by rapid excitatory synapses. For example, in the auditory system, the ability to transmit rapid, ongoing, precisely timed signals is critical for conveying sensory information. Pharmacological experiments have indicated that antagonists of glutamate receptors block synaptic transmission between the large calyceal endings of the eighth cranial, or auditory, nerve fibers and postsynaptic cell bodies in the nucleus magnucellularis (NM) of the chicken, indicating that glutamate receptors mediate the response. These glutamate receptors are the focus of the proposed research. As the cells of the NM have few, if any, dendrites, and the major input for the auditory nerve is on the cell bodies, glutamate receptors on these cells must be restricted to the cell bodies. These receptors are therefore ideally situated for patch clamp studies on NM slices. Experiments are proposed to identify the subtypes of receptors, their role in the synaptic impulse and how the synaptic impulse is terminated, as well as the regulation of receptor distribution, kinetics and conductance by innervation and denervation. These experiments will be done under visual control at identified synaptic sites using video imaging techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS028901-04
Application #
2267279
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1991-05-01
Project End
1995-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Physiology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Lu, Hsin-Wei; Balmer, Timothy S; Romero, Gabriel E et al. (2017) Slow AMPAR Synaptic Transmission Is Determined by Stargazin and Glutamate Transporters. Neuron 96:73-80.e4
Irie, Tomohiko; Trussell, Laurence O (2017) Double-Nanodomain Coupling of Calcium Channels, Ryanodine Receptors, and BK Channels Controls the Generation of Burst Firing. Neuron 96:856-870.e4
Tang, Zheng-Quan; Trussell, Laurence O (2017) Serotonergic Modulation of Sensory Representation in a Central Multisensory Circuit Is Pathway Specific. Cell Rep 20:1844-1854
Lu, Hsin-Wei; Trussell, Laurence O (2016) Spontaneous Activity Defines Effective Convergence Ratios in an Inhibitory Circuit. J Neurosci 36:3268-80
Balmer, Timothy S; Trussell, Laurence O (2016) Quantum Disentanglement: Electrical Analysis of the Complex Roles of Ions in Filling Vesicles with Glutamate. Neuron 90:667-9
Borges-Merjane, Carolina; Trussell, Laurence O (2015) ON and OFF unipolar brush cells transform multisensory inputs to the auditory system. Neuron 85:1029-42
Tang, Zheng-Quan; Trussell, Laurence O (2015) Serotonergic regulation of excitability of principal cells of the dorsal cochlear nucleus. J Neurosci 35:4540-51
Apostolides, Pierre F; Trussell, Laurence O (2014) Chemical synaptic transmission onto superficial stellate cells of the mouse dorsal cochlear nucleus. J Neurophysiol 111:1812-22
Huang, Hai; Trussell, Laurence O (2014) Presynaptic HCN channels regulate vesicular glutamate transport. Neuron 84:340-6
Apostolides, Pierre F; Trussell, Laurence O (2014) Superficial stellate cells of the dorsal cochlear nucleus. Front Neural Circuits 8:63

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