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.
Showing the most recent 10 out of 80 publications
