The regulation of voluntary motor activity is presumed to involve brain pathways in the central nervous system that link the cerebral cortex and cerebellum. Clearly one of the most important of these pathways is the vast system of cortical axons that transmit information to the cerebellum via an obligatory synapse in the basilar pontine nuclei (BPN). However, recent work from this laboratory has suggested that the BPN might be more properly regarded as an integrating station for a wide variety of signals which are ultimately directed at the cerebellum. This notion is supported by (a) the presence of a population of GABA-ergic neurons in the BPN, (b) afferent projections from an unusually diverse aggregate of cell groups throughout the brain and spinal cord, as well as (c) feedback circuits from the cerebellum itself. Because of an interest in the regulation of voluntary motor behavior and the obvious involvement of such systems in a variety of neurological disorders ranging from developmental insults such as cerebral palsy to cerebral stroke, we propose to undertake several correlated anatomical and physiological studies which are designed to provide some degree of understanding of how the BPN might be involved in the control of motor behavior. More specifically, through the use of intracellular recording and the subsequent filling of the identified cell with HRP, we hope to resolve two long-standing fundamental questions pertaining to BPN circuitry; namely, are intrinsic, local circuit type neurons present in the BPN and , secondly, do some of the projection neurons give rise to axonal branches within the pontine gray before coursing into the cerebellum? In general, our experiments will represent an even mix of anatomy and physiology in the hope of clarifying not only the structure but also the functional parameters of BPN neurons. Additionally, our efforts will focus on a determination of the functional role played by the recently discovered GABA afferent projections to the BPN along with electron microscopic immunochemical studies designed to identify serotonergic, noradrenergic and glutaminergic synaptic boutons in the BPN. Taken together, the studies in this proposal will answer several long-standing questions regarding the intrinsic circuitry of the BPN and initiate much needed electrophysiological studies of BPN neurons and the recently discovered GABA-ergic afferent systems. Observations from these studies should provide fundamental insight into the actual functional role of the BPN as a processing center for various inputs directed ultimately at the cerebellum.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS012644-11
Application #
3394932
Study Section
Neurology A Study Section (NEUA)
Project Start
1978-07-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
11
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Overall Medical
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Lee, H S; Mihailoff, G A (1999) Fluorescent double-label study of lateral reticular nucleus projections to the spinal cord and periaqueductal gray in the rat. Anat Rec 256:91-8
Liu, H; Mihailoff, G A (1999) Hypothalamopontine projections in the rat: anterograde axonal transport studies utilizing light and electron microscopy. Anat Rec 255:428-51
Mihailoff, G A (1995) Orthograde axonal transport studies of projections from the zona incerta and pretectum to the basilar pontine nuclei in the rat. J Comp Neurol 360:301-18
Mihailoff, G A (1993) Cerebellar nuclear projections from the basilar pontine nuclei and nucleus reticularis tegmenti pontis as demonstrated with PHA-L tracing in the rat. J Comp Neurol 330:130-46
Mihailoff, G A; Border, B G (1990) Evidence for the presence of presynaptic dendrites and GABA-immunogold labeled synaptic boutons in the monkey basilar pontine nuclei. Brain Res 516:141-6
Lee, H S; Mihailoff, G A (1990) Convergence of cortical and cerebellar projections on single basilar pontine neurons: a light and electron microscopic study in the rat. Neuroscience 39:561-77
Border, B G; Mihailoff, G A (1990) GABAergic neural elements in the rat basilar pons: electron microscopic immunochemistry. J Comp Neurol 295:123-35
Mihailoff, G A; Kosinski, R J; Azizi, S A et al. (1989) Survey of noncortical afferent projections to the basilar pontine nuclei: a retrograde tracing study in the rat. J Comp Neurol 282:617-43
Kosinski, R J; Lee, H S; Mihailoff, G A (1988) A double retrograde fluorescent tracing analysis of dorsal column nuclear projections to the basilar pontine nuclei, thalamus, and superior colliculus in the rat. Neurosci Lett 85:40-6
Mihailoff, G A; Kosinski, R J; Border, B G et al. (1988) A review of recent observations concerning the synaptic organization of the basilar pontine nuclei. J Electron Microsc Tech 10:229-46

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