This project examines the cellular basis of signal transformations that occur in vestibular reflexes. Studies of the vestibuloocular reflex have revealed short and long-term multiplicative changes in reflex gain. Functional considerations suggest similar changes should occur in the vestibulocollic reflex. The principal aim of this project is to understand and quantitate the fundamental cellular mechanisms involved in such reflex modulations using an in vitro mouse brain slice preparation. We will study the electrophysiological and pharmacological properties of vestibular afferent input to medial vestibular nucleus (MVN) neurons in these slices. focusing on the kinetic behavior of the ionotrophic glutamate receptors (NMDA and AMPA) which underlie the synaptic currents elicited by repetitive (physiologic) activation of vestibular afferents. These studies will employ both whole-cell recordings of the synaptic currents, and excised patch recordings of single and macroscopic glutamate receptor-mediated currents. We will then study the modulation of this glutamatergic afferent input to vestibular nucleus neurons by cerebellar projections, examining the cellular mechanisms by which GABAergic cerebellar afferents sculpt the response of vestibular reflex interneurons to vestibular afferent inputs. Neuroanatomical labeling techniques will be used to reveal the projections of neurons that are studied so that we can relate our data to afferent activation and cerebellar modulation of speciflt- vestibuloocular and vestibulospinal reflexes. Data obtained from experimental portions of this study will then be used to generate models of vestibular signal processing in the MVN. which will provide key. insights into the neuronal substrates of signal transformations in these vestibular reflexes. Understanding of these reflexes is important since they are essential to maintain the clear vision and stable posture required to carry out many activities of daily living.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC003197-04
Application #
6137873
Study Section
Hearing Research Study Section (HAR)
Program Officer
Platt, Christopher
Project Start
1997-01-01
Project End
2001-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
4
Fiscal Year
2000
Total Cost
$183,017
Indirect Cost
Name
Northwestern University at Chicago
Department
Physiology
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Billups, Daniela; Liu, Ying-Bing; Birnstiel, Susanne et al. (2002) NMDA receptor-mediated currents in rat cerebellar granule and unipolar brush cells. J Neurophysiol 87:1948-59
Nunzi, M G; Birnstiel, S; Bhattacharyya, B J et al. (2001) Unipolar brush cells form a glutamatergic projection system within the mouse cerebellar cortex. J Comp Neurol 434:329-41