Input from the medial septum regulates adult hippocampal neurogenesis.
Neural progenitors in the subgranular zone of the hippocampal formation form a continuously proliferating cell population, generating new granule neurons throughout adult life. Between 10 days and 1 month after their formation, many of the newly generated cells die. The present study investigated whether a partial lesion of one of the main nuclei projecting to the hippocampus, the medial septum (MS), affects survival and differentiation of cells during this critical period. Rats were injected with BrdU and 5 days later excitotoxic lesion of the MS was applied by infusion of either 30 or 60 nmol of N-methyl-D-aspartate (NMDA). One week after the lesion, quantification of immunopositive cells revealed that the number of GABAergic cells was significantly reduced in both lesioned groups, whereas a decline in cholinergic cell number was observed only after injection of 60 nmol of NMDA. The partial septohippocampal denervation significantly reduced hippocampal neurogenesis. Survival of newly generated neurons was decreased by approximately 40%. The MS lesion did not affect proliferation of hippocampal progenitors. The present study points out the importance of a functional septohippocampal pathway for the regulation of hippocampal neurogenesis and highlights the potential role of GABA as a mediator in this phenomenon.
Van der Borght
Karin
K
Department of Molecular Neurobiology, Graduate School of Behavioural and Cognitive Neurosciences, University of Groningen, P.O. Box 14, 9750 AA Haren, The Netherlands. k.van.der.borght@rug.nl
Mulder
Jan
J
Keijser
Jan N
JN
Eggen
Bart J L
BJ
Luiten
Paul G M
PG
Van der Zee
Eddy A
EA
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002799:Cholinergic Fibers / Q000378:metabolism; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009434:Neural Pathways / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012686:Septal Nuclei / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D009498:Neurotoxins; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D000109:Acetylcholine