The role of nitric oxide synthase in cortical plasticity is sex specific

Nitric oxide synthase-1 (NOS1) is involved in several forms of plasticity including hippocampal-dependent learning and memory, experience-dependent plasticity in the barrel cortex, and long-term potentiation (LTP) in the hippocampus and neocortex. NOS1 also contributes to ischemic damage during stroke and has a stronger deleterious effect in males than females. We therefore investigated whether the role of NOS1 in plasticity might also be sex specific. We tested LTP in the layer IV–II/III pathway between barrel columns and experience-dependent plasticity in the barrel cortex of αNOS1 knock-out mice and their wild-type littermates. We found that LTP was absent in male αNOS1 knock-out mice but not in females and that the residual LTP in females was not NO dependent. We also found that experience-dependent potentiation due to single whisker experience was significantly reduced in male αNOS1 knockouts but was unaffected in females. The αNOS1 knockout had a small effect on the development of the barrels, which were reduced in size by 20% compared with wild types, but this effect was not sex specific. We therefore conclude that neocortical plasticity mechanisms differ between males and females at the synaptic level, either in their basic plasticity induction pathways or in their ability to compensate for loss of αNOS1

Experience-dependent plasticity acts via GluR1 and a novel neuronal nitric oxide synthase-dependent synaptic mechanism in adult cortex

Synaptic plasticity directs development of the nervous system and is thought to underlie memory storage in adult animals. A great deal of our current understanding of the role of AMPA receptors in synaptic plasticity comes from studies on developing cortex and cell cultures. In the present study, we instead focus on plasticity in mature neurons in the neocortex of adult animals. We find that the glutamate receptor 1 (GluR1) subunit of the AMPA receptor is involved in experience-dependent plasticity in adult cortex in vivo and that it acts in addition to neuronal nitric oxide synthase (αNOS1), an enzyme that produces the rapid synaptic signaling molecule nitric oxide (NO). Potentiation of the spared whisker response, following single whisker experience, is ∼33% less in GluR1-null mutants than in wild types. We found that the remaining plasticity depended on αNOS1. Potentiation was reduced by >42% in the single αNOS1-null mutants and completely abolished in GluR1/αNOS1 double-knock-out mice. However, potentiation in GluR1/NOS3 double knock-outs occurred at similar levels to that seen in GluR1 single knock-outs. Synaptic plasticity in the layer IV to II/III pathway in vitro mirrored the results in vivo, in that LTP was present in GluR1/NOS3 double-knock-out mice but not in the GluR1/αNOS1 animals. While basal levels of NO in cortical slices depended on both αNOS1 and NOS3, NMDA receptor-dependent NO release only depended on αNOS1 and not on NOS3. These findings demonstrate that αNOS1 acts in concert with GluR1 to produce experience-dependent plasticity in the neocortex

Recent advances in psychoneuroimmunology: inflammation in psychiatric disorders

Psychiatric disorders are common and complex and their precise biological underpinnings remain elusive. Multiple epidemiological, molecular, genetic and gene expression studies suggest that immune system dysfunction may contribute to the risk for developing psychiatric disorders including schizophrenia, bipolar disorder, and major depressive disorder. However, the precise mechanisms by which inflammation-related events confer such risk are unclear. In this review, we examine the peripheral and central evidence for inflammation in psychiatric disorders and the potential molecular mechanisms implicated including inhibition of neurogenesis, apoptosis, the HPA-axis, the role of brain-derived neurotrophic factor and the interplay between the glutamatergic, dopaminergic and serotonergic neurotransmitter systems