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Reduced cortical BDNF expression and aberrant memory in Carf knock-out mice
Kelli A McDowell1, Ashley N Hutchinson, Sarah J E Wong-Goodrich
1Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Summary
Calcium-response factor (CaRF) regulates brain-derived neurotrophic factor (BDNF) expression in specific brain regions. CaRF knockout mice show altered learning and memory, revealing its role in neural circuit function.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Transcription factors integrate cellular signals for synaptic development and plasticity.
- Calcium-response factor (CaRF) is a transcription factor linked to brain-derived neurotrophic factor (BDNF) gene expression.
Purpose of the Study:
- To investigate the in vivo function of CaRF using knockout (KO) mice.
- To characterize the role of CaRF in regulating BDNF expression and its impact on learning and memory.
Main Methods:
- Generation and analysis of Carf knockout mice.
- Measurement of BDNF mRNA and protein levels in different brain regions.
- Assessment of synaptic protein expression.
- Behavioral testing including Morris water maze, fear conditioning, and novel object recognition.
Main Results:
- Carf KO mice exhibit reduced cortical BDNF expression, indicating CaRF's region-selective regulation.
- Altered expression of GABAergic proteins in striatal synapses of Carf KO mice.
- Carf KO mice show impaired remote memory, enhanced reversal learning, and slower fear extinction.
Conclusions:
- CaRF is a critical regulator of BDNF expression in a brain region-specific manner.
- CaRF plays a significant role in the development and function of neural circuits involved in learning and memory.
- These findings highlight novel functions of CaRF in synaptic organization and cognitive processes.

