Brain-enriched guanylate kinase-associated protein (BEGAIN), a component of the post-synaptic density protein complexes, contributes to physiological plasticity, learning and memory

Abstract Brain-enriched guanylate kinase-associated protein (BEGAIN) is a neuropathic pain-related protein in the spinal dorsal horn that is highly enriched in the post-synaptic density (PSD) fraction. PSD proteins complexes containing N-methyl-d-aspartate (NMDA) receptors are known to be involved in synaptic plasticity in neuropathic pain. Since these PSD proteins are also participate in synaptic plasticity in learning and memory, BEGAIN is also expected to play a crucial role in this plasticity. To verify this, we first examined the distribution of BEGAIN in the brain. We found that BEGAIN was widely distributed in the brain and highly expressed in the dendritic regions of the hippocampus. Moreover, we also found that BEGAIN was concentrated in the PSD fraction of the hippocampus. Furthermore, immunoelectron microscopy confirmed that BEGAIN was localized at the asymmetric synapses. To determine the contribution of BEGAIN towards learning and memory, behavioral tests were performed using BEGAIN-knockout (KO) mice. Spatial reference memory and reversal learning in the Barns circular maze test along with contextual fear and cued fear memory in the contextual and cued fear conditioning test were significantly impaired in BEGAIN KO mice in comparison to the wild-type mice. Thus, this study reveals that BEGAIN is an excitatory postsynaptic molecule involved in learning and memory.