The Effects of CREB-mediated BDNF Expression on Memory- and Anxiety-related Behaviours in the Adult Mouse

• Main Author: Florczynski, Matthew
• Other Authors: Josselyn, Sheena
• Language: en_ca
• Published: 2012
• Subjects: transgenic mice; memory; anxiety; motor learning; fear conditioning; water maze; CREB; BDNF; behaviour; activity-dependent; 0317
• Online Access: http://hdl.handle.net/1807/33420

Experience drives changes in gene expression that mold and reorganize neuronal circuits. In response to neuronal activity, the transcription factor CREB binds to a regulatory site on Bdnf promoter IV to modulate BDNF protein levels. CREB and BDNF are extensively implicated in animal behaviour, but the role of the interaction between these proteins has not been studied. I used transgenic mice carrying mutations at the CREB binding site of Bdnf promoter IV (CREmKI mutation) to specifically disrupt this interaction. F1 (N = 52) and F2 (N = 69) mice underwent a battery of behavioural tests. All mice showed normal motor learning and spatial memory. Critically, F1 mutants showed impaired auditory fear memory, while F2 mutants showed heightened anxiety. I suspect that differences in Bdnf expression and compensatory effects contributed to discrepancies between the two generations. My findings highlight the relevance of BDNF expression levels for memory- and anxiety-related behaviours.