Connective tissue growth factor regulates interneuron survival and information processing in the olfactory bulb

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 -