The role of Polo-like kinase 2 in synaptic function and plasticity

Homeostatic forms of plasticity keep the spiking output of neurons within an optimal range in the face of changing activity levels of the surrounding network, but little is known about the underlying molecular mechanisms, particularly during heightened activity. We report in Chapter 2 that in hippocampal neurons experiencing elevated activity, the activity-inducible protein kinase, Polo-like kinase 2 (Plk2), was required for synaptic scaling in dissociated culture and for reducing membrane excitability in slice culture-two principal compensatory mechanisms underlying homeostatic plasticity. Inhibition of Plk2 activity in slice culture during elevated activity resulted in increased dendritic spine size and density as well as a "run-up" in synaptic strength that prevented subsequent LTP. Thus, the homeostatic functions of Plk2 allow synapses to remain within a modifiable range during prolonged heightened network activity. In Chapter 3, we show that the homeostatic prevention of run-up during elevated activity also depended on CDK5, which acted as a "priming" kinase for the phospho-dependent binding of PIk2 to its substrate SPAR, a postsynaptic RapGAP.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Seeburg, Daniel P. (Daniel Philip)

Advisor dc:contributor.advisor

• Morgan Sheng.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/38993

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/38993