(2012) exist in the reward circuit, it would provide not only a potential mechanism for the “ghrelinergic” effects on reward but also a new paradigm for the rational development of therapeutic interventions for abnormal reward-seeking behaviors. “
“A major goal of neuroscience is to elucidate the molecular mechanisms mediating the different forms and phases of long-term synaptic plasticity that are thought to underlie learning and memory. Although many forms of synaptic plasticity have been described, four have been the most widely studied: (1) NMDA receptor (NMDAR)-dependent, transient early long-term potentiation (LTP), (2) NMDAR-dependent, persistent late LTP that requires Onalespib clinical trial new protein synthesis, (3) mGluR-dependent

long-term depression (LTD) that also requires new synthesis, and (4) NMDAR-dependent LTD. A current challenge to the field is to determine how these four forms of plasticity might mediate different aspects of behavior in the hopes of finding simple rules that may reframe the psychology of memory in neurophysiological and molecular terms. This requires understanding the core molecular mechanisms of these long-term synaptic modifications

in detail. The molecular mechanisms for any long-term form of synaptic plasticity can be divided into three phases: induction, triggering the plasticity; maintenance, sustaining it over time; and expression, transducing the mechanism of maintenance into a change PD0325901 solubility dmso in synaptic transmission. From the point of view of the search for the physical substrates of memory, the heart of the matter is maintenance. In recent years, significant progress has been made toward understanding the maintenance

of the two protein synthesis-dependent forms of synaptic plasticity. Whereas induction involves scores of signaling molecules, the critical requirement for new protein synthesis in the transition to maintenance constrains the complexity of the signaling network involved in sustaining modified synaptic Phosphoprotein phosphatase transmission in the maintenance phase. For example, in late LTP, PKMζ, a protein kinase C isoform that is uniquely synthesized as an autonomously active kinase by strong afferent stimulation, is the only kinase that has been found to maintain increases in synaptic transmission from hours to days after induction ( Sacktor, 2011). Because PKMζ is not involved in the maintenance of LTD, pharmacological and genetic tools that inhibit the kinase and block or reverse late LTP have been used to demonstrate a role for late-LTP maintenance in several forms of long-term memory ( Sacktor, 2011). Analogously, researchers are hot on the trail of a few suspects that are newly synthesized in mGluR-LTD, including arc, STEP, and MAP1b, which may maintain this form of synaptic depression ( Lüscher and Huber, 2010). In contrast, the core mechanisms that maintain the forms of synaptic plasticity that rely entirely on posttranslational modifications have been harder to pin down.