Research ReportHippocampal infusions of MARCKS peptides impair memory of rats on the radial-arm maze

In vitro hippocampal studies by Gay et al. (2008) demonstrated that a myristoylated alanine-rich C kinase substrate (MARCKS) peptide comprising the phosphorylation site or effector domain of the protein acts as a powerful inhibitor of α7 nicotinic acetylcholine receptors (nAChRs), which are known to be critically involved in memory function. However, behavioral consequences of hippocampal MARCKS peptide infusions have not been investigated. The purpose of the current study was to determine if local infusions in the rat ventral hippocampus of long (comprising amino acids 151-175) and short (amino acids 159-165) forms of MARCKS peptides could affect memory performance in the 16-arm radial maze. Our results demonstrated a dramatic impairment of both working (changing) and reference (constant) memory with MARCKS151-175 only. The shorter MARCKS peptide did not affect memory performance. This is in line with in vitro results reported by Gay et al. (2008) that long, but not short, MARCKS peptides inhibit α7 nAChRs. We also found that the effect of the MARCKS151-175 peptide was dose-dependent, with a robust memory impairment at 10 μg/side, and smaller inconsistent effects at lower doses. Our present behavioral study, together with the earlier in vitro study by Gay et al. (2008), suggests that effector domain MARCKS peptides could play a significant role in memory regulation and impairment.