The lateral geniculate nucleus (LGN) serves as the primary thalamic relay for the transfer of retinal information to visual cortex. Despite the traditional view that the LGN plays a passive role in this information transfer, there is increasing evidence that the LGN serves a dynamic role in this process. In addition to sensory signaling, thalamocortical circuits play a role in alterations of behavioral states (e.g., sleep/wake, attention, and arousal), and certain pathophysiological conditions such as certain generalized epilepsies. The gating properties of thalamic nuclei, including the LGN, result from the integration of the intrinsic properties of thalamic neurons, synaptic organization and activity of thalamic pathways, and impinging influence of neuromodulators. Our long-range goals are to understand these various processes, and ultimately gain insight into how visual information is processed at the thalamic level. An understanding of these processes in the """"""""normal"""""""" state should provide insight to potential abnormalities that may give rise to pathological conditions. The proposed experiments will focus on the regulation of thalamocortical activity by a class of putative neuromodulators: neuropeptides. The thalamus receives a rich peptidergic innervation from brainstem, neocortical and thalamic neurons. These experiments involve a combined anatomical, physiological, and pharmacological approach to investigate the functional role of certain neuropeptides that are localized within thalamocortical circuits, including vasoactive intestinal peptide (VIP), substance P (SP), and cholecystokinin (CCK). Intracellular recordings using the whole cell configuration will be used to access the actions of these peptides on neurons in the LGN and thalamic reticular nucleus using an in vitro brain slice preparation. Extracellular recordings will be used to study the role of the peptides on thalamocortical circuit activity.
The specific aims are designed to determine the cellular mechanisms by which these neuropeptides alter excitability of individual thalamic neurons and their subsequent influence on synaptic transmission. Our working hypothesis is that certain neuropeptides serve as endogenous neuromodulators that are released in an activity-dependent manner and produce long-lasting changes in neuronal excitability, thereby having a significant role in the gating of visual information through the LGN. Our findings will provide not only new insights on the functional role of neuropeptides, but also how gating properties of the LGN are influenced by long-lasting modulatory influences

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY014024-05
Application #
7195011
Study Section
Visual Sciences B Study Section (VISB)
Program Officer
Oberdorfer, Michael
Project Start
2003-03-01
Project End
2010-02-28
Budget Start
2007-03-01
Budget End
2010-02-28
Support Year
5
Fiscal Year
2007
Total Cost
$289,035
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
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Aerts, Jordan T; Louis, Kathleen R; Crandall, Shane R et al. (2014) Patch clamp electrophysiology and capillary electrophoresis-mass spectrometry metabolomics for single cell characterization. Anal Chem 86:3203-8
Cox, Charles L (2014) Complex regulation of dendritic transmitter release from thalamic interneurons. Curr Opin Neurobiol 29:126-32
Paul, Kush; Cox, Charles L (2013) Age-dependent actions of dopamine on inhibitory synaptic transmission in superficial layers of mouse prefrontal cortex. J Neurophysiol 109:1323-32
Crandall, Shane R; Cox, Charles L (2013) Thalamic microcircuits: presynaptic dendrites form two feedforward inhibitory pathways in thalamus. J Neurophysiol 110:470-80
Paul, Kush; Venkitaramani, Deepa V; Cox, Charles L (2013) Dampened dopamine-mediated neuromodulation in prefrontal cortex of fragile X mice. J Physiol 591:1133-43
Crandall, Shane R; Cox, Charles L (2012) Local dendrodendritic inhibition regulates fast synaptic transmission in visual thalamus. J Neurosci 32:2513-22
Govindaiah, Gubbi; Venkitaramani, Deepa V; Chaki, Sulalita et al. (2012) Spatially distinct actions of metabotropic glutamate receptor activation in dorsal lateral geniculate nucleus. J Neurophysiol 107:1157-63
Yang, S; Yang, S; Cox, C L et al. (2012) Cell's intrinsic biophysical properties play a role in the systematic decrease in time-locking ability of central auditory neurons. Neuroscience 208:49-57

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