A Key Role for Nectin-1 in the Ventral Hippocampus in Contextual Fear Memory

Abstract

Nectins are cell adhesion molecules that are widely expressed in the brain. Nectin expression shows a dynamic spatiotemporal regulation, playing a role in neural migratory processes during development. Nectin-1 and nectin-3 and their heterophilic trans-interactions are important for the proper formation of synapses. In the hippocampus, nectin-1 and nectin-3 localize at puncta adherentia junctions and may play a role in synaptic plasticity, a mechanism essential for memory and learning. We evaluated the potential involvement of nectin-1 and nectin-3 in memory consolidation using an emotional learning paradigm. Rats trained for contextual fear conditioning showed transient nectin-1—but not nectin-3—protein upregulation in synapse-enriched hippocampal fractions at about 2 h posttraining. The upregulation of nectin-1 was found exclusively in the ventral hippocampus and was apparent in the synaptoneurosomal fraction. This upregulation was induced by contextual fear conditioning but not by exposure to context or shock alone. When an antibody against nectin-1, R165, was infused in the ventral-hippocampus immediately after training, contextual fear memory was impaired. However, treatment with the antibody in the dorsal hippocampus had no effect in contextual fear memory formation. Similarly, treatment with the antibody in the ventral hippocampus did not interfere with acoustic memory formation. Further control experiments indicated that the effects of ventral hippocampal infusion of the nectin-1 antibody in contextual fear memory cannot be ascribed to memory non-specific effects such as changes in anxiety-like behavior or locomotor behavior. Therefore, we conclude that nectin-1 recruitment to the perisynaptic environment in the ventral hippocampus plays an important role in the formation of contextual fear memories. Our results suggest that these mechanisms could be involved in the connection of emotional and contextual information processed in the amygdala and dorsal hippocampus, respectively, thus opening new venues for the development of treatments to psychopathological alterations linked to impaired contextualization of emotions.

BDNF-TrkB signaling through Erk1/2MAPK phosphorylation mediates the enhancement of fear memory induced by glucocorticoids

“… 54 Recent evidences using both pharmacological and genetic approaches targeting the MR indicate that these receptors are also able to regulate contextual fear memory 55 with a specific role in retrieval of emotional information. 56 Some of the effects of GC could also be mediated by cell adhesion molecules (CAMs), such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) 57 , 58 or nectin-1, 59 catecholamines in particular the stress hormone norepinephrine, 60 or interleukins 61 that also contribute to the modulation of contextual fear memory.…”

Localization of nectin‐2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage‐gated A‐type K+ channel Kv4.2 in the medial habenula

“…This asymmetric localization of nectin‐1 and nectin‐3 is involved in the selective interaction of axons and dendrites cooperatively with afadin and N‐cadherin (Togashi et al, ). Nectin‐1 is implicated in contextual fear memory consolidation in the hippocampus (Fantin, van der Kooij, Grosse, Krummenacher, & Sandi, ), whereas nectin‐3 is implicated in cognitive impairment induced by stress via corticotropin‐releasing hormone receptor 1 on the hippocampal CA3 pyramidal cells (Wang et al, ). Nectin‐1 and nectin‐3 are expressed in Cajal‐Retzius cells and neocortical projection neurons, respectively, in the developing brain, and the nectin‐1‐ and nectin‐3‐mediated interaction between Cajal‐Retzius cells and migrating neurons is critical for radial migration of neurons cooperatively with afadin and N‐cadherin (Gil‐Sanz et al, ).…”

Novel homozygous mutation, c.400C>T (p.Arg134*), in the PVRL1 gene underlies cleft lip/palate‐ectodermal dysplasia syndrome in an Asian patient

“…Nectin‐1 can serve as a receptor for wild‐type herpes simplex virus‐1 and ‐2 in human cells of epithelial and neuronal origin . Nectin‐1 is expressed in keratinocytes, neurons, the developing face and plate, and various other organs. In mice lacking the PVRL1 gene ( Pvrl1 −/−), the expression of loricrin, a differentiation marker and a major component of cornified cell envelopes in the epidermis, is downregulated and newborn pups have shiny and slightly reddish skin .…”

“…In mice lacking the PVRL1 gene ( Pvrl1 −/−), the expression of loricrin, a differentiation marker and a major component of cornified cell envelopes in the epidermis, is downregulated and newborn pups have shiny and slightly reddish skin . Cell–cell adhesion mediated by nectin‐1 has also been demonstrated to have a pivotal role in the nervous system . These observations suggest pathological roles of PVRL1 mutations in CLPED1.…”