Notch and NGF/p75^NTR control dendrite morphology and the balance of excitatory/inhibitory synaptic input to hippocampal neurones through Neurogenin 3

Abstract

We have previously shown that dendrite morphology of cultured hippocampal neurones is controlled by Notch receptor activation or binding of nerve growth factor (NGF) to its low affinity receptor p75 NTR , i.e. processes that up-regulate the expression of the Homologue of enhancer of split 1 and 5. Thus, the increased expression of these genes decreases the number of dendrites, whereas abrogation Neurotrophins have been shown to regulate dendrite morphology in a variety of experimental models (Mcallister et al. 1995(Mcallister et al. , 1997Baker et al. 1998;Jin et al. 2003). As neurotrophins are released in an activity-dependent manner, they may be fundamental in orchestrating the structural modifications that developing and mature neuronal circuits undergo (Whitford et al. 2002). However, the signalling pathways underlying the effects of neurotrophins on dendrite morphology are not fully understood. While most studies in this area have emphasized the importance of the Trk receptors, there is evidence that nerve growth factor (NGF) regulates dendrite morphology by binding to p75 NTR , the common neurotrophin receptor (Salama-Cohen et al. 2005) Address correspondence and reprint requests to Dr A. Rodríguez-Tébar, Instituto Cajal, CSIC, Avenue. Doctor Arce, 37, 28002 Madrid, Spain. E-mail: rodriguez@cajal.csic.esAbbreviations used: DIV, days in vitro; EGFP, enhanced green fluorescent protein; E/I, ratio, ratio of excitatory to inhibitory; GAD, glutamic acid decarboxylase; Hes, homologue of enhancer of split; Mash1: mouse achaete scute homologue 1; MAP, microtubule-associated protein; NGF, nerve growth factor; Ngn3, neurogenin 3; p75-Ab, p75 NTR blocking antibody; ROI, region of interest; Syp, synaptophysin; VgluT, vesicular glutamate transporter; VIAAT, vesicular inhibitory amino acid transporter.

Altered Balance of Glutamatergic/GABAergic Synaptic Input and Associated Changes in Dendrite Morphology after BDNF Expression in BDNF-Deficient Hippocampal Neurons

“…A role of p75 NTR in the regulation of dendritic branching was shown recently in hippocampal neurons (Hartmann et al, 2004;Zagrebelsky et al, 2005;Salama-Cohen et al, 2006). These studies suggest that, in general, p75 NTR functions as a negative modulator of dendritic branching and spine density.…”

“…org as supplemental material), whereas an antibody against p75 NTR (Huber and Chao, 1995) failed to change the number of Sypϩ terminals (supplemental Fig. 2e, available at www.jneurosci.org as supplemental material); however, in contrast to the blocking effect of p75-Ab on synaptic responses to exogenous NGF (Salama-Cohen et al, 2006), the synaptogenic action of tBDNF remained unaltered.…”

“…Returning to the shorter expression time of 16 h, we examined the effects of tBDNF on "dendrite elongation" (i.e., the number of dendritic trees exceeding the ROI limits) and "dendrite initiation" (i.e., the number of primary dendrites per neuron or the number of branch points per ROI). At the time of fixation (DIV6), dendrites could already be distinguished from axons (see Materials and Methods), and previous quantitative analysis of these cultures showed that Ͼ95% of their combined dendritic length displays immunoreactivity for MAP2 (Salama-Cohen et al, 2006).…”

“…Our methods for the evaluation of dendritic morphology and presynaptic terminal identification in dissociated cell cultures have been described previously (Henneberger et al, 2005;Salama-Cohen et al, 2005, 2006. Briefly, labeled neurons were visualized by standard epifluorescence under a Plan-Neofluar 63ϫ oil objective with a numerical aperture of 1.3 (Zeiss, Oberkochen, Germany).…”

MiRNA expression analysis during normal zebrafish development and following inhibition of the Hedgehog and Notch signaling pathways

“…The Notch intracellular domain then translocates to the nucleus where it mediates transcriptional activation or repression of target genes. The role of Notch signaling in establishing neuronal outgrowth and differentiation is fairly well characterized (Teo et al, 2005;Salama-Cohen et al, 2006), whereas the involvement in somite formation is less well known. Notch signaling has been implicated in proper polarization of developing embryos with a loss of somite boundaries being associated with Notch mutants (Holley, 2002).…”