TY - JOUR
T1 - Connective tissue growth factor regulates interneuron survival and information processing in the olfactory bulb
AU - Khodosevich, Konstantin
AU - Lazarini, Françoise
AU - von Engelhardt, Jakob
AU - Kaneko, Hiroshi
AU - Lledo, Pierre-Marie
AU - Monyer, Hannah
N1 - Copyright © 2013 Elsevier Inc. All rights reserved.
PY - 2013/9/18
Y1 - 2013/9/18
N2 - Neurogenesis underlies plastic changes in defined neuronal circuits in the postnatal and adult brain. Here we identify connective tissue growth factor (CTGF) as a critical factor in the mouse olfactory bulb (OB) in determining the efficiency of incorporation of postnatally born inhibitory neurons, thus gating the output of glomeruli, the first relay station of olfactory processing in the brain. In the OB, CTGF expression was restricted to prenatally born external tufted cells. CTGF enhanced the proapoptotic activity of glial-derived TGF-β2, decreasing the survival of periglomerular inhibitory neurons. Changes in CTGF expression levels in the OB led to modifications in local neuronal circuitry and olfactory behaviors. We show that the odorant-specific recruitment of distinct glomeruli resulted in enhanced local CTGF expression levels in the activated glomeruli. Collectively our data reveal a molecular mechanism controlling the survival of defined postnatally born neurons, thus adapting neuronal integration to the sensory experiences.
AB - Neurogenesis underlies plastic changes in defined neuronal circuits in the postnatal and adult brain. Here we identify connective tissue growth factor (CTGF) as a critical factor in the mouse olfactory bulb (OB) in determining the efficiency of incorporation of postnatally born inhibitory neurons, thus gating the output of glomeruli, the first relay station of olfactory processing in the brain. In the OB, CTGF expression was restricted to prenatally born external tufted cells. CTGF enhanced the proapoptotic activity of glial-derived TGF-β2, decreasing the survival of periglomerular inhibitory neurons. Changes in CTGF expression levels in the OB led to modifications in local neuronal circuitry and olfactory behaviors. We show that the odorant-specific recruitment of distinct glomeruli resulted in enhanced local CTGF expression levels in the activated glomeruli. Collectively our data reveal a molecular mechanism controlling the survival of defined postnatally born neurons, thus adapting neuronal integration to the sensory experiences.
KW - Analysis of Variance
KW - Animals
KW - Animals, Newborn
KW - Bromodeoxyuridine/metabolism
KW - Cell Line, Transformed
KW - Cell Survival/genetics
KW - Connective Tissue Growth Factor/genetics
KW - Discrimination (Psychology)/physiology
KW - Female
KW - Gene Expression Regulation/genetics
KW - Humans
KW - Interneurons/physiology
KW - Luminescent Proteins/genetics
KW - Lysine/analogs & derivatives
KW - Male
KW - Memory, Long-Term/physiology
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - MicroRNAs/genetics
KW - Nerve Tissue Proteins/genetics
KW - Odorants
KW - Olfactory Bulb/cytology
KW - Organ Culture Techniques
KW - Protein-Serine-Threonine Kinases/genetics
KW - RNA, Small Interfering/genetics
KW - Receptors, Odorant/genetics
KW - Receptors, Transforming Growth Factor beta/genetics
KW - Sensory Thresholds/physiology
KW - Smell/genetics
KW - Synaptic Potentials/genetics
KW - Transfection
KW - tau Proteins/genetics
U2 - 10.1016/j.neuron.2013.07.011
DO - 10.1016/j.neuron.2013.07.011
M3 - Journal article
C2 - 23993699
SN - 0896-6273
VL - 79
SP - 1136
EP - 1151
JO - Neuron
JF - Neuron
IS - 6
ER -