RCAN1 Regulates Bidirectional Synaptic Plasticity.

Synaptic plasticity, with its two most studied forms, long-term potentiation (LTP) and long-term depression (LTD), is the cellular mechanism underlying learning and memory. Although it has been known for two decades that bidirectional synaptic plasticity necessitates a corresponding bidirectional regulation of calcineurin activity, the underlying molecular mechanism remains elusive. Using organotypic hippocampal slice cultures, we show here that phosphorylation of the endogenous regulator-of-calcineurin (RCAN1) by GSK3β underlies calcineurin activation and is a necessary event for LTD induction, while phosphorylation of RCAN1 at a PKA site blocks calcineurin activity, thereby allowing LTP induction.

How internalised stigma reduces self-esteem in schizophrenia: the crucial role of off-line metacognition.

Stigma is widely recognised as a major barrier to recovery. In schizophrenia, internalised stigma (IS) strongly impacts self-esteem, but the mechanisms underlying this phenomenon remain poorly understood. In this study, we suggest that IS alters self-esteem by leading people to perceive their cognitive functioning as inefficient.

NMDA-receptor activation but not ion flux is required for amyloid-beta induced synaptic depression.

Alzheimer disease is characterized by a gradual decrease of synaptic function and, ultimately, by neuronal loss. There is considerable evidence supporting the involvement of oligomeric amyloid-beta (Aβ) in the etiology of Alzheimer's disease. Historically, AD research has mainly focused on the long-term changes caused by Aβ rather than analyzing its immediate effects.