Variant Brain-Derived Neurotrophic Factor (Val66Met) Alters Adult Olfactory Bulb Neurogenesis and Spontaneous Olfactory Discrimination

• DOI: 10.1523/jneurosci.4387-07.2008
• Publication Date: 2008-03-05T17:34:17Z
• Authors: Kevin G. Bath; Nathalie Mandairon; Deqiang Jing; Rithwick Rajagopal; Ruchi Kapoor; Zhe-Yu Chen; Tanvir Khan; Catia C. Proenca; Rosemary Kraemer; Thomas A. Cleland; Barbara L. Hempstead; Moses V. Chao; Francis S. Lee
• Keywords: Olfactory memory

Neurogenesis, the division, migration, and differentiation of new neurons, occurs throughout life. Brain derived neurotrophic factor (BDNF) has been identified as a potential signaling molecule regulating neurogenesis in subventricular zone (SVZ), but its functional consequences vivo have not well defined. We report marked unexpected deficits survival proliferation newly born cells adult knock-in mice containing variant form BDNF [a valine (Val) to methionine (Met) substitution at position 66 prodomain (Val66Met)], genetic mutation shown lead selective impairment activity-dependent secretion. Utilizing knock-out mouse lines, we tyrosine receptor kinase B (TrkB) critical molecules for observed impairments neurogenesis, with p75 showing no effect on cell or survival. then localized activated TrkB discrete population cells, type A migrating neuroblasts, demonstrate decrease phosphorylation SVZ Val66Met mutant mice. With these findings, identify signaling, potentially through activity dependent release BDNF, step neuroblasts. behavioral task be sensitive disruptions olfactory bulb specific spontaneous discrimination, general sensitivity habituation stimuli Through observations, novel links between , which may contribute significant function.