It is now clear that the lateral geniculate nucleus (LGN) acts as a variable gateway or filter for the retina-to-cortex relay: when open, all information gets through; when closed, none does; and when partly open, some is relayed. The LGN, by thus controlling the flow of retinal information to cortex, represents a major neural substrate for many forms of visual attention. Our broad goal is to understand, at the cellular level, how this gating is controlled. We proposed to do so by complementary in vivo and in vitro intracellular recording of single neurons in the cat's LGN, the former performed in anesthetized animals and the latter from LGN slices. Two factors are key to this control of retinogeniculate gating. First, the LGN relay cells possess a number of voltage- and ligand-gated membrane conductances in addition to the conventional action potential, and the mix of these active at any time determines the gain of retinogeniculate transmission. A particularly important conductance is the low threshold Ca2+ spike, which is voltage dependent and can be self-regenerating; we shall test the hypothesis that, when active, it prevents normal retinogeniculate transmission. Other more subtle membrane properties will also be studied. Second, nonretinal inputs, which dominate synaptic input to LGN relay cells, act to control these conductances. Sources of these nonretinal inputs include: local, GABAergic, inhibitory neurons; ascending inputs from the brainstem (mostly midbrain), and descending inputs from visual cortex. We shall study the above mentioned membrane conductances, their control by various nonretinal synaptic transmission, and how they affect receptive field properties. In vivo studies of stimulation of differing membrane voltage (manipulated by current injection through the recording electrode) and activation of brainstem afferents. We shall also attend to any differences between X and Y cells, which are the LGN representatives of the two main parallel pathways from retina to cortex. In vitro studies will include analyses of the voltage- and time-dependents of the low threshold an assessment of putative neurotransmitters, their agonists and antagonists, and the postsynaptic receptor types. We shall also intracellularly label most cells in vitro to determine structure/function relationships, including any differences between interneurons and relay cells. Finally, we shall attempt simultaneous recording from two connected neurons to determine the synaptic physiology and pharmacology of these identified circuits.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY003038-13
Application #
3257356
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1979-07-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
13
Fiscal Year
1992
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Sherman, S Murray (2014) The function of metabotropic glutamate receptors in thalamus and cortex. Neuroscientist 20:136-49
Theyel, Brian B; Llano, Daniel A; Issa, Naoum P et al. (2011) In vitro imaging using laser photostimulation with flavoprotein autofluorescence. Nat Protoc 6:502-8
Lam, Ying-Wan; Sherman, S Murray (2011) Functional organization of the thalamic input to the thalamic reticular nucleus. J Neurosci 31:6791-9
Lam, Ying-Wan; Sherman, S Murray (2010) Functional organization of the somatosensory cortical layer 6 feedback to the thalamus. Cereb Cortex 20:13-24
Lee, Charles C; Sherman, S Murray (2010) Topography and physiology of ascending streams in the auditory tectothalamic pathway. Proc Natl Acad Sci U S A 107:372-7
Theyel, Brian B; Llano, Daniel A; Sherman, S Murray (2010) The corticothalamocortical circuit drives higher-order cortex in the mouse. Nat Neurosci 13:84-8
Petrof, Iraklis; Sherman, S Murray (2009) Synaptic properties of the mammillary and cortical afferents to the anterodorsal thalamic nucleus in the mouse. J Neurosci 29:7815-9
Llano, D A; Theyel, B B; Mallik, A K et al. (2009) Rapid and sensitive mapping of long-range connections in vitro using flavoprotein autofluorescence imaging combined with laser photostimulation. J Neurophysiol 101:3325-40
Lee, Charles C; Sherman, S Murray (2009) Glutamatergic inhibition in sensory neocortex. Cereb Cortex 19:2281-9
Varela, C; Sherman, S Murray (2009) Differences in response to serotonergic activation between first and higher order thalamic nuclei. Cereb Cortex 19:1776-86

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