John Harting - US grants

While the mammalian superior colliculus is undoubtedly involved in many functions of which we know nothing about, it can be said that it does send control signals of some kind to brainstem and spinal cord systems concerned with eye and head position. The proposed studies are part of a long-range analysis of the basic pathways and circuitry which enable the colliculus to perform, or at least participate in these function(s). To reach this goal, neuroanatomical tracing methods will be used to explore the spatial relationships which exist between particular afferents to the superficial layers and the cells of origin of particular superficial collicular tectofugal systems. Emerging data indicate that collicular layers are divisible into sublayers on the basis of connectional and physiological criteria. Such sublaminae could be the sites of input-output linkages between particular afferents and efferents. Such a plan would allow different types of incoming information to distribute to select sets of collicular targets. Studies of the intermediate and deep layers will focus upon determining whether functionally related "patchy" inputs overlap and upon determining the local geometry of output systems. As part of our interest in collicular connectivity and function, we will study the geniculocortical components of a small-celled circuit over which fine-fibered retinal and tectal input reaches supragranular cortical layers. Finally, we will analyze the projection of the parabigeminal nucleus in the primate Macaca mulatta.

The centromedian nucleus (CM-Pf) projects to striatal (caudate and putamen) neurons that are key components of basal ganglia pathways that regulate movement. It is well documented that diseases involving basal ganglia circuitry result in the debilitating deficits associated with Parkinson s and Huntington s disease, but the role of the CM-PF-striatal projection in these deficits has not been explored. The single hypothesis to be tested is that the projections from the cerebral cortex drive the response properties of CM-Pf neurons. Thus we predict that cortical terminals are closely associated with the inhibitory entopeduncular terminals on the proximal dendrites of CM-PF-striatal neurons. Such a finding would suggest that these excitatory cortical drivers could play a role in determining the amount of inhibition flowing out of the basal ganglia (entopeduncluar nucleus). Disease involving the nigrostriatal dopaminergic pathway results in increased inhibition flowing out of the basal ganglia to the motor thalamus and, in turn, the motor cortex. One possible way of turning up the amount of excitation reaching striatal neurons would be to increase the firing of the CM-PF-striatal excitatory projection via the excitatory cortical driver. This could ultimately lower the amount of inhibition leaving the basal ganglia for the motor thalamus and possible help to alleviate some of the Parkinsonian deficits. The fining that cortex is driving CM-PF neurons would modify and extend current models in which the outflow of the basal ganglia is thought to dominate CM-PF function. If Rls in CM-Pf come from the cortex, and share the major synaptic relationships of primary afferents in other thalamic nuclei, we will have a strong argument for changing contemporary views regarding the functions of the CM-Pf (and possibly other intralaminar nuclei) and its role in motor activity. Our findings will be incorporated into current models of basal ganglia circuits, which themselves have shortcomings that necessitate revisions and updating (Wichmann and DeLong 96).

DESCRIPTION(adapted from applicant's abstract): The thalamic reticular nucleus (TRN) is a sheet of GABAergic neurons surrounding the dorsal thalamus. The caudal portion of the TRN is the "visual sector," and its cells are innervated by axon collaterals of thalamocortical and corticothalamic axons and have profound inhibitory effects on cells in the visual thalamic nuclei: the lateral geniculate nucleus (LGN) and pulvinar. The TRN can modify not only the transfer of the ascending retinal information relayed through the LGN to primary visual cortex, but also cortico-cortical information that is routed through the pulvinar. Current evidence suggests that the TRN plays a role in selective visual attention, and that TRN pathology can lead to attentional disorders. However, in view of the very limited information about the functional organization of the visual circuits that involve the TRN, direct evidence about 1'RN function is still extremely limited. The overriding aim of this proposal is to make clear for the first time the connectional organization of the visual TRN in a primate, Galago. We propose to use a number of contemporary light and electron microscopic neuroanatomical tracing methods to extend previous work that divided the visual TRN into inner and outer tiers. We will test three broad hypotheses about the organization of the visual TRN. 1) The outer tier of the TRN is precisely organized topographically and is involved in the modulation of visual information ascending through the LGN. 2) The innermost component of the outer tier (i.e. a "central" tier) is a specialized region wherein activity related to the visual periphery converges to influence neural activity related to the central visual field. This conceivably could play a role in visual orienting responses or selective attention. 3) The pulvinar-related inner tier has little or no topographical organization and is a point of convergence for inputs from many extrastriate cortical areas. Thus, the inner tier plays a role in cortico-cortical communication between higher visual cortical areas. Successful completion of the proposed experiments will elevate our understanding of the functional organization of the visual TRN and will provide the necessary basis for future functional studies