NeuroD2 regulates the development of hippocampal mossy fiber synapses

Abstract

BackgroundThe assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF) synapse.ResultsUsing NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice.ConclusionThese experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.

Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility

“…Little is known about the function of Dkkl1 in brain except that it bears sequence similarity to Dkk1 , an antagonist of canonical Wnt signaling, implicated broadly in neuronal development and survival (Oliva et al, 2013; Sibbe and Jarowyj, 2013). Neurod2 encodes a transcription factor that is important in neuronal differentiation and synapse maturation (Messmer et al, 2012; Olson et al, 2001; Wilke et al, 2012). Sdk1 is a cell-adhesion molecule that guides synapse formation in retina (Yamagata and Sanes, 2008; Yamagata et al, 2002), and recent work from our group has implicated Sdk1 in cocaine-induced spinogenesis in NAC (Scobie et al, 2014).…”

WNT/β-Catenin Pathway and Epigenetic Mechanisms Regulate the Pitt-Hopkins Syndrome and Schizophrenia Risk Gene TCF4

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Ethanol-related alterations in gene expression patterns in the developing murine hippocampus

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