LIM-Kinase1 and CREB regulation of synaptic plasticity and memory
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1
University of Toronto, Department of Physiology, Canada
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2
The Hospital for Sick Children, Neurosciences and Mental Health, Canada
Regulation of neuronal structural plasticity is known to be important for learning and memory. LIM-Kinase 1 (LIMK1) is an important regulator of postsynaptic structural morphology by its regulation of actin dynamics by regulating the activity of actin depolymerizing factor (ADF)/cofilin. Previous studies from our lab have shown that LIMK1 knockout mice exhibit abnormal dendritic spine morphology as well as altered hippocampal early long-term potentiation (E-LTP). In addition, a recent study has found that LIMK1 can directly interact with and phosphorylate CREB in hippocampal neuroprogenitor cells. CREB is an important and well-studied transcription factor that facilitates the changes from short-term memory to long-term memory. CREB activation is also known to be important in late long-term potentiation (L-LTP). Based on this evidence we proposed that LIMK1 might play a role in long-term memory and long-term synaptic plasticity via regulation of CREB in mature hippocampal neurons. Accordingly, we have shown that LIMK1 exists in an immunocomplex with CREB in mature hippocampal slices. Moreover, mice lacking LIMK1 were shown to be deficient in L-LTP induced by high frequency stimulation, and L-LTP induced by strong theta burst stimulation. This evidence suggests a role for LIMK1 in L-LTP and long-term synaptic plasticity via regulation of CREB. In addition, mice lacking LIMK1 did not perform as well in fear conditioning tests. LIMK1 knockout mice exhibited less freezing than wild-type littermate controls in the contextual memory test. These results suggest that LIMK1 plays a role in long-term memory. Taken together, these results are indicative of a role for LIMK1 in a long-term memory and long-term synaptic plasticity via regulation of CREB.
Conference:
B.R.A.I.N. platform in Physiology poster day 2009, Toronto, ON, Canada, 16 Dec - 16 Dec, 2009.
Presentation Type:
Poster Presentation
Topic:
Poster presentations
Citation:
Todorovski
Z and
Jia
Z
(2009). LIM-Kinase1 and CREB regulation of synaptic plasticity and memory.
Front. Neurosci.
Conference Abstract:
B.R.A.I.N. platform in Physiology poster day 2009.
doi: 10.3389/conf.neuro.03.2009.17.046
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Received:
18 Dec 2009;
Published Online:
18 Dec 2009.
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Correspondence:
Zarko Todorovski, University of Toronto, Department of Physiology, Toronto, Canada, zarko.todorovski@utoronto.ca