Alteration of Neuronal Excitability and Short-Term Synaptic Plasticity in the Prefrontal Cortex of a Mouse Model of Mental Illness.

Using a genetic mouse model that faithfully recapitulates a genetic alteration strongly associated with schizophrenia and other psychiatric disorders, we examined the impact of this mutation within the prefrontal cortex. Although cortical layering, cytoarchitecture, and proteome were found to be largely unaffected, electrophysiological examination of the mPFC revealed both neuronal hyperexcitability and alterations in short-term synaptic plasticity consistent with enhanced neurotransmitter release. Increased excitability of layer II/III pyramidal neurons was accompanied by consistent reductions in voltage-activated potassium currents near the action potential threshold as well as by enhanced recruitment of inputs arising from superficial layers to layer V.

Molecules, signaling, and schizophrenia.

Schizophrenia is one of the most common psychiatric disorders, but despite some progress in identifying the genetic factors implicated in its development, the molecular mechanisms underlying its etiology and pathogenesis remain poorly understood. However, accumulating evidence suggests that regardless of the underlying genetic complexity, the mechanisms of the disease may impact a small number of common signaling pathways. In this review, we discuss the evidence for a role of schizophrenia susceptibility genes in intracellular signaling cascades by focusing on three prominent candidate genes: AKT, PPP3CC (calcineurin), and DISC1.

Inhibition of phospholipase C disrupts cytoskeletal organization and gravitropic growth in Arabidopsis roots.

The phospholipase protein superfamily plays an important role in hormonal signalling and cellular responses to environmental stimuli. There is also growing evidence for interactions between phospholipases and the cytoskeleton. In this report we used a pharmacological approach to investigate whether inhibiting a member of the phospholipase superfamily, phospholipase C (PLC), affects microtubules and actin microfilaments as well as root growth and morphology of Arabidopsis thaliana seedlings.

Mast cells are necessary for the hypothermic response to LPS-induced sepsis.

As central nervous system residents, mast cells contain many cytokines and are localized primarily near large blood vessels in the diencephalon and within the leptomeninges, making them candidates for immune to neural "cross talk." Using mast cell-deficient Kit(W-sh/W-sh) mice, we assessed the role of these cells in the thermoregulatory component of the immune response to lipopolysaccharide (LPS). Kit(W-sh/W-sh) and wild-type (WT) mice differed in several respects in response to injection of a high dose of LPS (1 mg/kg ip).

A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition.

DISC1 is a strong candidate susceptibility gene for schizophrenia, bipolar disorder, and depression. Using a mouse strain carrying an endogenous Disc1 orthologue engineered to model the putative effects of the disease-associated chromosomal translocation we demonstrate that impaired Disc1 function results in region-specific morphological alterations, including alterations in the organization of newly born and mature neurons of the dentate gyrus. Field recordings at CA3/CA1 synapses revealed a deficit in short-term plasticity.

Coding for the initiation of pseudopregnancy by temporally patterned activation of amygdalar NMDA receptors.

Female rats modulate the number and interval between the intromissions the female receives during mating. This patterned vaginocervical stimulation (VCS) is critical for triggering long-term changes in prolactin (PRL) secretion necessary for pregnancy or pseudopregnancy (P/PSP). Previous work has shown that NMDA receptor activation in the posterodorsal medial amygdala (MEApd) is required at the time of mating for VCS to induce the twice-daily PRL surges characteristic of P/PSP.