Daniel J. Uhlrich - US grants

The retino-geniculo-cortical pathway is considered the primary afferent pathway that subserves visual perception in most mammals. Recent evidence suggests that an important role of the lateral geniculate nucleus (LGN) in this pathway is to modulate or gate the transmission of visual information to visual cortex. This gain control is thought to reflect different behavioral states such as arousal, attention and eye movements. One source of this state-dependent influence is the brainstem. Three approaches are proposed to describe the anatomical and functional connections between the brainstem and LGN, and thus, elucidate the physiological basis of the state-dependent influences on visual perception. The first aim is to describe the light microscopic morphology of individual brainstem axons that project to the LGN. This will be accomplished by injecting, in separate experiments, the new anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L) into six specific cell groups in the brainstem (parabrachial nucleus, locus coeruleus, dorsal raphe nucleus, superior colliculus, parabigeminal nucleus and the nucleus of the optic tract) and serially reconstructing PHA-L labelled processes as they course through the ipsilateral LGN. This technique provides a far superior visualization of the terminal arborizations from thin axons than any previous anterograde tracing method. The second aim is to extend the PHA-L technique to the electron microscopic level. In particular, we will clarify issues about the circuitry through which individual brainstem axons influence LGN neurons. The third aim is to examine the functional consequences of these brainstem-LGN connections. This will be accomplished by observing the effects of electrical or chemical stimulation in the brainstem on the extracellular visual responses of LGN cells to grating and spot stimuli. Plans are described to analyze the effects of stimulation in three brainstem sites (parabrachial nucleus, locus coeruleus, and dorsal raphe nucleus) on the responses of the different functional cell types in the LGN (e.g., normal and lagged X-cells, Y-cells, projections cells, interneurons) and the adjacent perigeniculate nucleus.

The thalamic lateral geniculate nucleus (LGN) is found in the primary neural pathway between the eye and visual cortex, and it controls the flow of visual information to the brain in large measure through the influence of specific nuclei in the brainstem. Pathways from the brainstem can powerfully effect the LGN and are believed to reflect behavioral states, such as arousal or attention and the occurrence of eye movements. HOwever, the anatomy and physiology of these brainstem circuits are not well understood. This research will provide a comprehensive, multi-disciplinary description of the structural and functional influences of the brainstem on the LGN. In doing so, these studies will elucidate, more generally, the role of the thalamus in relaying sensory information to the e cortex, and they will aid in understanding the role of a key neural element underlying vision. Aims 1 and 3 are to demonstrate the effects of electrical and chemical activation of individual brainstem nuclei on the extra- and intracellular responses of LGN cells to visual stimuli. Aims 2 and 4 are to describe, at the light and electron microscopic level by means of retrograde and anterograde tracers, the morphology and ultrastructure of brainstem neurons that project to the LGN and other thalamic nuclei. Aim 5 is to confirm and describe key thalamic pathways through which the brainstem indirectly controls the LGN.

Nearly all sensory information destined for conscious perception is processed first in a central brain region called the thalamus before being sent to cerebral cortex. Sensory signals are actively modified in the thalamus as a function of behavioral state or events. Converging evidence suggests the thalamic reticular nucleus (TRN) is essential to this process; TRN receives input from myriad brain regions, and TRN impacts directly the thalamic neurons that pass the ascending sensory signals on to cortex. Modification of sensory signals in the thalamus has been demonstrated in association with the sleep-wake transition, but little is known about sensory modifications that occur within the awake brain. To address the challenge of understanding the function of TRN in the awake state, this project will determine sensory and non-sensory factors that activate TRN neurons and the consequences of TRN activation on transmission of visual information through the thalamic lateral geniculate nucleus. Preliminary electrophysiological recording, in conjunction with behavioral methods, suggests that TRN neurons have robust visual responses and significant non-visual reward and/or attention-related responses. The project will distinguish these and more fully define the role of TRN neurons in the awake, behaving state. This research will advance significantly understanding of the essential processes in the brain that underlie conscious perception of the world. The project will also provide training opportunities for undergraduate and graduate students within a program recognized nationally for its success in recruiting and retaining underrepresented students in graduate training.