(from abstract): The lateral geniculate nucleus of the thalamus is the gateway to the striate cortex, representing the first opportunity for the visual system to regulate its own input dynamically. LGN relay cells possess a rich and complex repertoire of voltage and ligand gated conductances that are critical to this regulation. These are under the control of a variety of nonretinal inputs, chiefly a glutamatergic input from visual cortex and a cholinergic one from the parabrachial region (PBR) of the brainstem. One of the key conductances is a voltage dependent Ca current known as It and this determines response mode: burst mode during It activation and tonic mode during It inactivation. We found that these modes have profound consequences to visual information processing, and that they are controlled by the PBR input. We now focus our efforts on the corticogeniculate pathway, the largest input to LGN, but poorly understood and still an enigma. Although it provides more synaptic contacts to relay neurons than any other extrageniculate source, little is known of its effect on visual signal transmission or on the intrinsic membrane properties of LGN neurons. Prior examination of this pathway has yielded only limited insight into its role in retinogeniculate transmission: we propose a fresh attack on this vital problem. We shall not rely on a single approach, but instead we shall employ a multifaceted, parallel strategy that will examine the corticogeniculate pathway from the cellular level to intact circuitry. In vitro, we shall use intracellular recording in LGN slices to examine circuitry mediating corticogeniculate transmission, its underlying pharmacology, and its effects on intrinsic membrane properties of LGN cells. In many brain areas, different neurotransmitter systems may converge to modulate the same set of conductances, and we suspect the same to be true of the LGN. We shall supplement our brain slice experiments with whole cell patch recordings in dissociated LGN cells in order to examine the intracellular factors mediating LGN responses to corticogeniculate inputs, and the possible neurotransmitter convergence between the corticogeniculate and PBR pathways. In vitro, we shall pharmacologically activate and inactivate the corticogeniculate pathway in order to determine the spatial structure of the corticogeniculate influence and its effect on visual signal transmission. As a bonus to these studies, we shall also attempt to obtain cross-correlograms between single cortical and LGN cell pairs (among other pairs to be studied) to determine the effect of the corticogeniculate input at the single cell level. Our physiological inquiries will be complemented by anatomical studies of single corticogeniculate axons in order to determine the spatial extent of the cortical innervation of LGN, and to determine whether there are multiple subtypes of corticogeniculate projection cell. Furthermore, because the thalamic reticular nucleus is an essential link in the corticogeniculate input (this nucleus receives collateral input from corticogeniculate axons and projects to LGN, we shall study it as well. Our combined approaches will yield a comprehensive characterization of the corticogeniculate pathway and its role in visual signal transmission.
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