The auditory system localizes sound in azimuth by computing interaural time delays. In the avian auditorybrainstem, nucleus magnocellularis (NM)is the first central nucleus in this temporal coding pathway. NMcontains highly specialized anatomic, synaptic, and intrinsic properties that play key roles in shapinginhibitory responses and maintaining temporal fidelity in NM. The development of these specializations ispoorly understood.
The first aim i s to describe the time-course of the development of inhibition in chick NMusing in vitro electrophysiological techniques..
The second aim i s to understand the developmentalimportance of afferent excitatory inputs in the development of inhibition using otocyst removal followed byphysiological recordings.
The third aim will examine role of Kv1.1 in developing the normal NM phenotypeusing RNA interference techniques. Plasmids encoding RNAs designed to interfere with the Kcnal, theKv1.1 gene, and an EGFP reporter gene will be electroporated in ovo in early embryos. The physiology oftransfected cells will be examined through development. These manipulations are hypothesized to alter thenormal development of NM anatomy and physiological responses to excitatory and inhibitory inputs.
Howard, Mackenzie A; Rubel, Edwin W (2010) Dynamic spike thresholds during synaptic integration preserve and enhance temporal response properties in the avian cochlear nucleus. J Neurosci 30:12063-74 |
Howard, MacKenzie A; Burger, R Michael; Rubel, Edwin W (2007) A developmental switch to GABAergic inhibition dependent on increases in Kv1-type K+ currents. J Neurosci 27:2112-23 |