title: Saccadic burst cell membrane dysfunction is responsible for saccadic oscillations.
abstract: Saccadic oscillations threaten clear vision by causing image motion on the retina. They are either purely horizontal (ocular flutter) or multidimensional (opsoclonus). We propose that ion channel dysfunction in the burst cell membrane is the underlying abnormality. We have tested this hypothesis by simulating a neuromimetic computational model of the burst neurons. This biologically realistic model mimics the physiologic properties and anatomic connections in the brainstem saccade generator. A rebound firing after sustained inhibition, called post-inhibitory rebound (PIR), and reciprocal inhibition between premotor saccadic burst neurons are the key features of this conceptual scheme. PIR and reciprocal inhibition make the circuits that generate the saccadic burst inherently unstable and can lead to oscillations unless stabilized by external inhibition. Our simulations suggest that alterations in membrane properties that lead to an increase in PIR, a reduction in external glycinergic inhibition, or both can cause saccadic oscillations.
authors.affiliation: Department of Neurology, The Johns Hopkins University, Baltimore, Maryland 21287, USA. ashaikh@dizzy.med.jhu.edu
authors.forename: Aasef G
authors.initials: AG
authors.lastname: Shaikh
authors.forename: Stefano
authors.initials: S
authors.lastname: Ramat
authors.forename: Lance M
authors.initials: LM
authors.lastname: Optican
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Miura
authors.forename: R John
authors.initials: RJ
authors.lastname: Leigh
authors.forename: David S
authors.initials: DS
authors.lastname: Zee
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology*; D006801:Humans; D009434:Neural Pathways / Q000033:anatomy & histology / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D015835:Ocular Motility Disorders / Q000503:physiopathology*; D011149:Pons / Q000033:anatomy & histology / Q000502:physiology*; D012438:Saccades / Q000502:physiology*