Essential role for TrkB receptors in hippocampus-mediated learning

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB regulate bot h short-term synaptic functions and long-term potentiation (LTP) of brain s ynapses, raising the possibility that BDNF/TrkB may be involved in cognitiv e functions. We have generated conditionally gene targeted mice in which th e knockout of the trkB gene is restricted to the forebrain and occurs only during postnatal development. Adult mutant mice show increasingly impaired learning behavior or inappropriate coping responses when facing complex and /or stressful learning paradigms but succeed in simple passive avoidance le arning. Homozygous mutants show impaired LTP at CA1 hippocampal synapses. I nterestingly, heterozygotes show a partial but substantial reduction of LTP but appear behaviorally normal. Thus, CA1 LTP may need to be reduced below a certain threshold before behavioral defects become apparent.