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The Journal of Neuroscience, December 26, 2007, 27(52):14392-14403; doi:10.1523/JNEUROSCI.3903-07.2007

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Development/Plasticity/Repair
Impaired Migration in the Rostral Migratory Stream But Spared Olfactory Function after the Elimination of Programmed Cell Death in Bax Knock-Out Mice

Woon Ryoung Kim,¹ Younghwa Kim,¹ Bokkee Eun,¹ Ok-hee Park,¹ Hyun Kim,¹ Kyungjin Kim,² Chang-Hwan Park,³ Sharon Vinsant,⁴ Ronald W. Oppenheim,⁴ and Woong Sun¹

¹Department of Anatomy, College of Medicine, Korea University, Sungbuk-Gu, Seoul 136-705, Korea, ²School of Biological Sciences, College of Natural Sciences, Seoul National University, Shilim-Dong, Kwanak-Gu, Seoul 151-742, Korea, ³Department of Microbiology, Hanyang University College of Medicine, Haeng Dang-Dong, Sung Dong-Gu, Seoul 133-791, Korea, and ⁴Department of Neurobiology and Anatomy and Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

Correspondence should be addressed to Dr. Woong Sun, Department of Anatomy, Korea University College of Medicine, Anam-dong, Sungbuk-gu, Seoul 136-705, Korea. Email: woongsun{at}korea.ac.kr

Rats and mice exhibit neurogenesis of olfactory bulb (OB) interneurons throughout adulthood. To homeostatically maintain stable neuron numbers, it is necessary to continuously remove a subset of OB neurons by programmed cell death (PCD). Here we demonstrate that Bax is critical for the elimination of OB neurons by showing that Bax-KO mice exhibit greatly reduced PCD in the OB. Despite the reduction of PCD, however, proliferation of progenitors and the size of the OB were virtually unaffected in Bax-knock-out (KO) mice. However, reducing PCD by Bax deletion affected the migration of a subset of adult-produced neurons by the disruption of glial tube formation as well as by premature detachment of neuroblasts from the migratory chain. Rescued cells aberrantly remained in the subventricular zone (SVZ)-rostral migratory stream (RMS), in which they differentiated into calretinin⁺ or GABA-expressing interneurons. Because of the migratory deficit, OB cell homeostasis involving new cell entry and PCD (neuronal turnover) was virtually absent in adult Bax-KO mice. Despite this, Bax-KO mice exhibited normal olfactory behaviors such as odor discrimination and olfactory memory which are thought to be influenced by adult neurogenesis. These results demonstrate that PCD is involved in the regulation of RMS migration and differentiation after OB neurogenesis, but that animals maintain normal olfactory function in the absence of PCD.

Key words: neurogenesis; Bax; cell death; olfactory bulb; migration; behaviors

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Received Aug. 23, 2006; revised Nov. 6, 2007; accepted Nov. 16, 2007.

Correspondence should be addressed to Dr. Woong Sun, Department of Anatomy, Korea University College of Medicine, Anam-dong, Sungbuk-gu, Seoul 136-705, Korea. Email: woongsun{at}korea.ac.kr

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