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Most everyday memories including many episodic-like memories that we may form automatically in the hippocampus (HPC) are forgotten, while some of them are retained for a long time by a memory stabilization process, called initial memory consolidation. Specifically, the retention of everyday memory is enhanced, in humans and animals, when something novel happens shortly before or after the time of encoding. Converging evidence has indicated that dopamine (DA) signaling via D1/D5 receptors in HPC is required for persistence of synaptic plasticity and memory, thereby playing an important role in the novelty-associated memory enhancement. In this review paper, we aim to provide an overview of the key findings related to D1/D5 receptor-dependent persistence of synaptic plasticity and memory in HPC, especially focusing on the emerging evidence for a role of the locus coeruleus (LC) in DA-dependent memory consolidation. We then refer to candidate brain areas and circuits that might be responsible for detection and transmission of the environmental novelty signal and molecular and anatomical evidence for the LC-DA system. We also discuss molecular mechanisms that might mediate the environmental novelty-associated memory enhancement, including plasticity-related proteins that are involved in initial memory consolidation processes in HPC. [ABSTRACT FROM AUTHOR]

Amyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD), as oligomeric Aβ induces loss of postsynaptic AMPA receptors (AMPARs) leading to cognitive deficits. The loss of postsynaptic AMPARs is mediated through the clathrin-dependent endocytosis pathway, in which endophilin2 is one of the important regulatory proteins. Endophilin2, which is enriched in both the pre- and postsynaptic membrane, has previously been reported to be important for recycling of synaptic vesicles at the presynaptic membrane. However, the role of endophilin2 in oligomeric Aβ-induced postsynaptic AMPAR endocytosis is not well understood. In this study, we show that endophilin2 does not affect constitutive AMPAR endocytosis. Endophilin2 knockdown, but not overexpression, resisted oligomeric Aβ-induced AMPAR dysfunction. Moreover, endophilin2 colocalized and interacted with GluA1, a subunit of AMPAR, to regulate oligomeric Aβ-induced AMPAR endocytosis. Thus, we have determined a role of endophilin2 in oligomeric Aβ-induced postsynaptic AMPAR dysfunction, indicating possible directions for preventing the loss of AMPARs in cognitive impairment and providing evidence for the clinical treatment of AD. [ABSTRACT FROM AUTHOR]

Establishing novel episodic memories and stable spatial representations depends on an exquisitely choreographed, multistage process involving the online encoding and offline consolidation of sensory information, a process that is largely dependent on the hippocampus. Each step is influenced by distinct neural network states that influence the pattern of activation across cellular assemblies. In recent years, the occurrence of hippocampal sharp wave ripple (SWR) oscillations has emerged as a potentially vital network phenomenon mediating the steps between encoding and consolidation, both at a cellular and network level by promoting the rapid replay and reactivation of recent activity patterns. Such events facilitate memory formation by optimising the conditions for synaptic plasticity to occur between contingent neural elements. In this paper, we explore the ways in which SWRs and other network events can bridge the gap between spatiomnemonic processing at cellular/synaptic and network levels in the hippocampus. [ABSTRACT FROM AUTHOR]

The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD) in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex. [ABSTRACT FROM AUTHOR]