CaMKII at a central synapse : α-calcium/calmodium protien kinase II and synaptic plasticity at CA3 Schaffer collateral -- CA1 synapses in the mammalian hippocampus

Long term potentiation (LTP) of synaptic transmission at the CA3-CA1 hippocampal synapse is a model synaptic plasticity mechanism that may underlie hippocampal dependent learning and memory. Inhibition of post-synaptic calcium/calmodulin protein kinase II (CaMKII) has been shown to block LTP, and a global knockout of the highly expressed a isoform of CaMKII caused an impairment in LTP and hippocampus dependent learning. We examined the role of CaMKII in CA3-CA1 LTP by selectively deleting [alpha]-CaMKII in adult hippocampal CA1 or CA3 pyramidal cells using conditional gene targeting. With this approach, we could investigate the locus of change that underlies LTP expression, as both pre- (CA3) and post- (CA1) synaptic CaMKII dependent mechanisms have been implicated, and further examine how CaMKII dependent plasticity contributes to learning and memory in a background of normal brain development. CA3-CA1 LTP is reduced in CA1 [alpha]-CaMKII knockout mice, suggesting that post-synaptic CaMKII is required for normal LTP. These mice are strikingly reminiscent of the a-CaMKII global knockout mice, demonstrating comparable LTP impairments and abnormal behaviors. In contrast, CA3 [alpha]-CaMKII knockout mice have normal LTP at CA3-CA1 synapses, suggesting that CaMKII phosphorylation of pre-synaptic synapsin I is not required for LTP expression. Contextual and cued fear conditioning were also normal in CA3 mutants, demonstrating that one form of hippocampus dependent learning is intact.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Brain and Cognitive Sciences.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2001

Author dc:creator

• Hinds, Heather L., 1969-

Advisor dc:contributor.advisor

• Susumu Tonegawa.

• Brain and Cognitive Sciences.

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/1721.1/8300

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8300