The Dendritic Spines of Interneurons Are Dynamic Structures Influenced by PSA-NCAM Expression

Abstract

Excitatory neurons undergo dendritic spine remodeling in response to different stimuli. However, there is scarce information about this type of plasticity in interneurons. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is a good candidate to mediate this plasticity as it participates in neuronal remodeling and is expressed by some mature cortical interneurons, which have reduced dendritic arborization, spine density, and synaptic input. To study the connectivity of the dendritic spines of interneurons and the influence of PSA-NCAM on their dynamics, we have analyzed these structures in a subpopulation of fluorescent spiny interneurons in the hippocampus of glutamic acid decarboxylase-enhanced green fluorescent protein transgenic mice. Our results show that these spines receive excitatory synapses. The depletion of PSA in vivo using the enzyme Endo-Neuraminidase-N (Endo-N) increases spine density when analyzed 2 days after, but decreases it 7 days after. The dendritic spine turnover was also analyzed in real time using organotypic hippocampal cultures: 24 h after the addition of EndoN, we observed an increase in the apparition rate of spines. These results indicate that dendritic spines are important structures in the control of the synaptic input of hippocampal interneurons and suggest that PSA-NCAM is relevant in the regulation of their morphology and connectivity.

Regulation of Spine Formation by ErbB4 in PV-Positive Interneurons

“…These observations indicate that ErbB4 in PV-positive neurons promotes spine formation during development. In support of our hypothesis is a recent finding that demonstrated a noncell-autonomous role for ErbB4 in spine formation (Del Pino et al, 2013).…”

“…As shown in Figure 5A, ErbB4 reduction was not apparent in early postnatal days (P0 and P7); however, significant reduction was observed in the hippocampus in P14 PV-ErbB4 Ϫ/Ϫ mice. This time course was consistent with that of PV promoter activity during development (del Río et al, 1994). Given that spine formation peaks in postnatal weeks 3-5 (Boyer et al, 1998), we next determined whether spine density was reduced during this stage in PV-ErbB4 Ϫ/Ϫ mice.…”

“…In support of this hypothesis was the observation that ErbB4 protein is reduced in PV-ErbB4 Ϫ/Ϫ mice at postnatal day 14, before the peak of spine formation (Boyer et al, 1998). GABA transmission in ErbB4 mutant mice increases the activity of pyramidal neurons Del Pino et al, 2013), which may lead to a compensatory reduction in spine formation. Consistent with this notion, in PV-ErbB4 Ϫ/Ϫ mice, spine reduction was observed in hippocampal CA1 and FrAL3 of the PFC, where PV-positive cells were abundant, but not in ORBL1 of the PFC, where few PV-positive cells were present (Fig.…”

“…During early development, GABA depolarizes immature neurons resulting from high intracellular Cl Ϫ concentration (Ben-Ari, 2002;Owens and Kriegstein, 2002). GABA-mediated depolarization is critical in the formation of spines and excitatory synapses (Ben-Ari et al, 1997;Akerman and Cline, 2006;Ge et al, 2006;Wang and Kriegstein, 2008). Thus, in ErbB4 mutant mice, impaired GABA release from interneurons during early development might lead to fewer spines and excitatory synapses.…”

“…Both Nrg1 and ErbB4, the only ErbB that can function as homodimer, have been identified as schizophrenia susceptibility genes (Stefansson et al, 2002;Yang et al, 2003;Silberberg et al, 2006;Sullivan et al, 2008;Walsh et al, 2008;Shi et al, 2009). Recent studies have revealed that NRG1 and ErbB4 play important roles in neural development as well as synaptic plasticity (Huang et al, 2000;Flames et al, 2004;Pitcher et al, 2008;Fazzari et al, 2010;Ting et al, 2011;Del Pino et al, 2013).…”