, 2009 and Hayar et al., 2004). CTGF acts via glial-derived TGF-β2, whose activity it potentiates, promoting SMAD-dependent apoptosis of newborn neurons in the glomerular

layer via TGF-βRs. CTGF expression is enhanced by olfactory stimulation, thus leading to an activity-dependent potentiation of TGF-β2 signaling. At the functional level, changes in inhibitory neuron number modify the excitation/inhibition balance in stimulated glomeruli and OB output cells (i.e., mitral cells), thus affecting olfactory behavior. It is of note that the regulation of CTGF-mediated cell survival occurs in a region- and cell-type-specific manner. Thus, within the OB, only the survival of periglomerular cells, but

not granule Volasertib supplier cells, is subject to CTGF regulation. Regulation of CTGF expression by olfactory stimuli changes apoptosis in the glomerular layer and thus adjusts the number of surviving inhibitory neurons according to olfactory cues in the environment. Since each odor often activates Bioactive Compound Library only few glomeruli, this adjustment of inhibitory drive provides a mechanism for glomerulus-specific plasticity. Thus, activation of distinct glomeruli increases CTGF expression, thereby reducing the number of interneurons in these glomeruli, whereas inactive glomeruli exhibit lower CTGF levels and hence more periglomerular interneurons. At the behavioral level the increased number of interneurons very likely lowers the threshold for odorant detection and enhances olfactory discrimination. The CTGF-dependent behavioral phenotype that we describe here is in accordance with results reported in a recent study, in which the authors demonstrated that an increase in mitral cell inhibition enhances odor discrimination, whereas a decrease in mitral cell inhibition interferes with odor discrimination (Abraham et al., 2010). The mechanism by which almost enhanced inhibition may

result in better performance is most likely due to the fact that augmented inhibition causes better synchronization of mitral cell activity (Giridhar et al., 2011 and Schoppa, 2006), thereby enhancing the recruitment of downstream cortical targets (Giridhar et al., 2011). Increased inhibition was shown to synchronize the activity not only of mitral cells in mice (Giridhar et al., 2011 and Schoppa, 2006) but also of antennal lobe projection neurons in locusts (functional analogs of mitral cells) (MacLeod and Laurent, 1996). These studies and our own are compatible with the following scenarios, according to which CTGF levels modulate the olfactory detection threshold: (1) low CTGF levels augment the number of periglomerular interneurons, leading to an increase in odorant sensitivity; i.e.