Abstract
The transcription factor neuronal PAS domain-containing protein 4 (Npas4) is an inducible immediate early gene which regulates the formation of inhibitory synapses, and could have a significant regulatory role during cortical circuit formation. However, little is known about basal Npas4 mRNA expression during postnatal development. Here, postnatal and adult mouse brain sections were processed for isotopic in situ hybridization using an Npas4 specific cRNA antisense probe. In adults, Npas4 mRNA was found in the telencephalon with very restricted or no expression in diencephalon or mesencephalon. In most telencephalic areas, including the anterior olfactory nucleus (AON), piriform cortex, neocortex, hippocampus, dorsal caudate putamen (CPu), septum and basolateral amygdala nucleus (BLA), basal Npas4 expression was detected in scattered cells which exhibited strong hybridization signal. In embryonic and neonatal brain sections, Npas4 mRNA expression signals were very low. Starting at postnatal day 5 (P5), transcripts for Npas4 were detected in the AON, CPu and piriform cortex. At P8, additional Npas4 hybridization was found in CA1 and CA3 pyramidal layer, and in primary motor cortex. By P13, robust mRNA expression was located in layers IV and VI of all sensory cortices, frontal cortex and cingulate cortex. After onset of expression, postnatal spatial mRNA distribution was similar to that in adults, with the exception of the CPu, where Npas4 transcripts became gradually restricted to the most dorsal part. In conclusion, the spatial distribution of Npas4 mRNA is mostly restricted to telencephalic areas, and the temporal expression increases with developmental age during postnatal development, which seem to correlate with the onset of activity-driven excitatory transmission.
Highlights
neuronal PAS domain-containing protein 4 (Npas4) is a member of the PAS family of proteins, a family of signal transduction molecules characterized by a conserved basic-helix-loop-helix motif and pas domain
The highest hybridization intensity was detected in the anterior olfactory nucleus (AON), piriform cortex, frontal cortex, cingulate cortex, auditory cortex and hippocampus
Low levels of expression were detected in the dorsal caudate putamen (CPu), amygdala and in retrosplenial cortex
Summary
Npas is a member of the PAS family of proteins, a family of signal transduction molecules characterized by a conserved basic-helix-loop-helix motif and pas domain. Npas acts as an early-response transcription factor that, when induced by excitatory neuronal activity, regulates the formation of inhibitory synapses onto excitatory and inhibitory neurons (Lin et al, 2008; Coutellier et al, 2012; Bloodgood et al, 2013). In the adult mammalian brain, Npas mRNA is found in limbic structures, cortex, and striatum (Moser et al, 2004; Ooe et al, 2004; Shamloo et al, 2006). Basal brain expression is low, it is rapidly upregulated in response to stimuli causing intense excitatory activity suggesting a role in cortical plasticity (Flood et al, 2004; Shamloo et al, 2006; Ploski et al, 2010; Bloodgood et al, 2013; Kaliszewska and Kossut, 2015). Npas is upregulated in response to acute stress (Drouet et al, 2015), but in contrast, is down-regulated after chronic restraint stress or light deprivation (Yun et al, 2010; Karpova et al, 2010)
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