Wnt transmembrane signaling and long‐term spatial memory

Abstract

Transmembrane signaling mechanisms are critical for regulating the plasticity of neuronal connections underlying the establishment of long-lasting memory (e.g., Linden and Routtenberg, 1989, Brain Res Rev. 14: 279–296; Sossin, 1996, Trends Neurosci 19: 215–218; Mayr and Montminy, 2001, Nat Rev Mol Cell Biol. 2: 599–609; Chen et al., 2011, Nature 469: 491–497). One signaling mechanism that has received surprisingly little attention in this regard is the well-known Wnt transmembrane signaling pathway even though this pathway in the adult plays a significant role, for example, in postsynaptic dendritic spine morphogenesis and presynaptic terminal neurotransmitter release (Inestrosa and Arenas, 2010, Nature Rev Neurosci 11: 77–86). The present report now provides the first evidence of Wnt signaling in spatial information storage processes. Importantly, this Wnt participation is specific and selective. Thus, spatial, but not cued, learning in a water maze selectively elevates the levels in hippocampus of Wnt 7 and Wnt 5a, but not the Wnt 3 isoform, indicating behavioral selectivity and isoform specificity. Wnt 7 elevation is subfield-specific: granule cells show an increase with no detectable change in CA3 neurons. Wnt 7 elevation is temporally specific: increased Wnt signaling is not observed during training, but is seen 7 days and, unexpectedly, 30 days later. If the Wnt elevation after learning is activity-dependent, then it may be possible to model this effect in primary hippocampal neurons in culture. Here we evaluate the consequence of potassium or glutamate depolarization on Wnt signaling. This represents, to our knowledge, the first demonstration of an activation-dependent elevation of Wnt levels. Additionally, the novel finding emerged of an increased number of Wnt-stained puncta in neuritis suggestive of trafficking from the cell body to neuronal processes, probably dendrites. It is proposed that Wnt signaling pathways, both canonical and non-canonical, regulate long-term information storage in a behavioral-, cellular- and isoform-specific manner.

Wnt Signaling Is Required for Long-Term Memory Formation

“…Furthermore, the expression level of wg mRNA is transiently elevated after spaced conditioning. These molecular results are consistent with those of Chen et al, 2006, Wayman et al, 2006, and Tabatadze et al, 2012, who showed that the expression of the ligands Wnt-3a, Wnt-2, Wnt-7, and Wnt-5a are elevated with increased neuronal activity or spatial memory.…”

Wnts in adult brain: from synaptic plasticity to cognitive deficiencies

“…The levels of Wnt7 in the hippocampus of animals trained in a water maze hidden platform, are enhanced in comparison to the animals trained with a visible platform (Tabatadze et al, 2012). Despite in the visible platform the memory acquisition is better, animals trained in the hidden platform have better retention memory after 30 days of training, that correlates with elevated levels of Wnt7 (Tabatadze et al, 2012).…”

Neurosteroids Involvement in the Epigenetic Control of Memory Formation and Storage

“…Several groups have examined whether learning regulates Wnt protein expression in the hippocampus. For instance, it has been demonstrated a specific Wnt5a and Wnt7 induction in some subregions such as the granule cell layer but not in CA3 neurons; conversely, the Wnt3 levels were not changed [71]. Different Wnt activation in response to various learning test (fear conditioning versus object recognition) was also found (see [65] for references).…”