This grant is submitted in response to the NIMH Neural Systems Program announcement number 92-07 in order to develop a model with which to explore the relationships among the various sensory cortices, the basal ganglia, and the midbrain and their interactive role in attentive and orientation behaviors. The influence of cortex over midbrain behaviors has long served as a paradigm for understanding the manner in which 'higher' structures regulate subcortical sensorimotor behaviors. This relationship is underscored by observations that cortical and subcortical lesions often produce similar behavioral dysfunctions, presumably because they disrupt different portions of a common integrated system. However, the actual neuronal circuitry by which the cortex controls these behaviors via its influence on the neural activity of the midbrain (i.e., superior colliculus) is poorly understood. Currently, cortical influences on superior colliculus neurons have been overwhelmingly interpreted as being mediated solely via direct connections, an assumption reflecting the robust nature of direct corticotectal projections which have been detailed repeatedly. However, we believe that this issue requires serious reevaluation. It is likely that there is an indirect corticotectal pathway via the basal ganglia that will prove to be an important linkage between cortex and the superior colliculus. While there has long been theoretical support for this indirect pathway, as well as for the functional linkage between the basal ganglia and the superior colliculus, there has been little experimental effort devoted to establishing the relationship among these structures. New preliminary anatomical and physiological evidence is consistent with an indirect linkage. A new systems model is proposed for understanding cortical-superior colliculus relationships that is based on the premise that all sensory cortices exert their influences on superior colliculus neurons via direct and indirect pathways. The principal aim during this grant period will be to determine whether this multimodal systems model can be supported by anatomical and physiological evidence. These relationships are likely to have a direct impact on our understanding of how diseases of the basal ganglia disrupt attentive behavior, which is intimately related with the superior colliculus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS035008-04
Application #
2735684
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Program Officer
Broman, Sarah H
Project Start
1995-07-01
Project End
1999-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Jiang, Huai; Stein, Barry E; McHaffie, John G (2015) Multisensory training reverses midbrain lesion-induced changes and ameliorates haemianopia. Nat Commun 6:7263
Jiang, Huai; Stein, Barry E; McHaffie, John G (2011) Physiological evidence for a trans-basal ganglia pathway linking extrastriate visual cortex and the superior colliculus. J Physiol 589:5785-99
Redgrave, Peter; Coizet, Veronique; Comoli, Eliane et al. (2010) Interactions between the Midbrain Superior Colliculus and the Basal Ganglia. Front Neuroanat 4:
Jiang, Huai; Stein, Barry E; McHaffie, John G (2009) Cortical lesion-induced visual hemineglect is prevented by NMDA antagonist pretreatment. J Neurosci 29:6917-25
Fuentes-Santamaria, Veronica; Alvarado, Juan C; McHaffie, John G et al. (2009) Axon morphologies and convergence patterns of projections from different sensory-specific cortices of the anterior ectosylvian sulcus onto multisensory neurons in the cat superior colliculus. Cereb Cortex 19:2902-15
Coizet, VĂ©ronique; Graham, John H; Moss, Jonathan et al. (2009) Short-latency visual input to the subthalamic nucleus is provided by the midbrain superior colliculus. J Neurosci 29:5701-9
May, Paul J; McHaffie, John G; Stanford, Terrence R et al. (2009) Tectonigral projections in the primate: a pathway for pre-attentive sensory input to midbrain dopaminergic neurons. Eur J Neurosci 29:575-87
Fuentes-Santamaria, Veronica; McHaffie, John G; Stein, Barry E (2008) Maturation of multisensory integration in the superior colliculus: expression of nitric oxide synthase and neurofilament SMI-32. Brain Res 1242:45-53
Fuentes-Santamaria, Veronica; Alvarado, Juan Carlos; Stein, Barry E et al. (2008) Cortex contacts both output neurons and nitrergic interneurons in the superior colliculus: direct and indirect routes for multisensory integration. Cereb Cortex 18:1640-52
Gabriele, Mark L; Shahmoradian, Sarah H; French, Christopher C et al. (2007) Early segregation of layered projections from the lateral superior olivary nucleus to the central nucleus of the inferior colliculus in the neonatal cat. Brain Res 1173:66-77

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