Facilitated c-Fos Induction in Mice Deficient for the AMPA Receptor-Associated Protein Ckamp44

Abstract

The recently identified Cystine-knot containing AMPAR-associated protein (Ckamp44) represents a novel AMPAR-related protein that critically controls AMPAR-mediated currents and short-term plasticity. However, the effects of the lack of this protein at network level are not entirely understood. Here we used c-Fos brain mapping to analyse whether the excitatory/inhibitory balance is altered in the absence of the Ckamp44. We found that Ckamp44(-/-) mice treated with an NMDAR antagonist exhibited a very robust c-Fos expression pattern, similar with that seen in mice lacking the GluN2A subunit of NMDAR treated with the same compound. This finding is unexpected, in particular, since Ckamp44 expression is strongest in dentate gyrus granule cells and less abundant in the rest of the brain.

Keywords: AMPA receptors; Ckamp44 (Shisa9); NMDA receptors; c-Fos.

Fig. 1

Induction of c-Fos in the brains of wild-type and Ckamp44 ^−/− mice. A, B Basal c-Fos expression of wild-type (A) and Ckamp44 ^−/− mice (B). C–E Brain induction of c-Fos expression upon MK-801 in wild-type (C), Ckamp44 ^−/− (D) and Grin2a ^−/− mice (E). Retrosplenial cortex (Rsp), piriform cortex (Pir), neocortex (Neo), CA1, CA3 and dentate gyrus (DG) of the hippocampus, basolateral amygdala (BLA), midline thalamic nuclei (MTN). Scale bar for CA1, CA3, and DG 200 μm. Scale bar for Pir, Rsp, Neo, MTN and BLA 250 μm

Fig. 2

Quantitative analysis of MK-801-induced c-Fos and parvalbumin expression in the CA1 and CA3 hippocampus of Ckamp44 ^−/− mice. Comparison of c-Fos expression induced by MK-801 in wild-type (WT), Ckamp44 ^−/−, Grin2a ^−/− and Gria1 ^−/− mice in the CA1 (a) and CA3 hippocampus (b) and retrosplenial cortex (c). In the CA3 hippocampus, there was only a tendency to more c-Fos-expressing cells in Ckamp44 ^−/− versus Grin2a ^−/− mice (p = 0.066). (d) Numbers of PV-expressing interneurons in the CA1, CA3 and DG of the hippocampus in Ckamp44 ^−/− versus wild-type mice. Statistical differences determined by one-way ANOVA followed by Bonferroni post hoc tests. *p < 0.05; **p < 0.01; ***p < 0.001, t, tendency. All groups were highly significant compared to saline (not depicted). WT Wild type, DG dentate gyrus, PV parvalbumin