Genes in which rare, damaging variants substantially increase risk of developing schizophrenia have now been identified. These findings can influence how we think about mental illness in general as well as yielding specific insights into schizophrenia aetiology. Better understanding of underlying biology might eventually lead to improved treatments.

Cerebral malaria (CM) is the severe neurological complication causing acute non-traumatic encephalopathy in tropical countries. The mechanisms underlying the fatal cerebral complications are still not fully understood. Glutamate, a major excitatory neurotransmitter in the central nervous system of the mammalian brain, plays a key role in the development of neuronal cells, motor function, synaptic plasticity, learning and memory processes under normal physiological conditions. The subtypes of ionotropic glutamate receptor are N-methyl-D-aspartate receptors (NMDARs) which are involved in cellular mechanisms of learning and memory, synaptic plasticity and also mediate excitotoxic neuronal injury. In the present study, we found that glutamate level in synaptosomes, as well as expression of NMDAR, was elevated during the extreme condition of CM in C57BL6 mice. Arteether at 50 mg kg−1 × 1, 25 mg kg−1 × 2, days decreased the NMDAR expression and increased the overall survival of the experimental CM mice.

In the primate retina, parasol ganglion cells contribute to the primary visual pathway via the magnocellular division of the lateral geniculate nucleus, display ON and OFF concentric receptive field structure, nonlinear spatial summation, and high achromatic temporal–contrast sensitivity. Parasol cells may be homologous to the alpha-Y cells of nonprimate mammals where evidence suggests that N-methyl-D-aspartate (NMDA) receptor-mediated synaptic excitation as well as glycinergic disinhibition play critical roles in contrast sensitivity, acting asymmetrically in OFF- but not ON-pathways. Here, light-evoked synaptic currents were recorded in the macaque monkey retina in vitro to examine the circuitry underlying parasol cell receptive field properties. Synaptic excitation in both ON and OFF types was mediated by NMDA as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptors. The NMDA-mediated current–voltage relationship suggested high Mg2+ affinity such that at physiological potentials, NMDA receptors contributed ∼20% of the total excitatory conductance evoked by moderate stimulus contrasts and temporal frequencies. Postsynaptic inhibition in both ON and OFF cells was dominated by a large glycinergic “crossover” conductance, with a relatively small contribution from GABAergic feedforward inhibition. However, crossover inhibition was largely rectified, greatly diminished at low stimulus contrasts, and did not contribute, via disinhibition, to contrast sensitivity. In addition, attenuation of GABAergic and glycinergic synaptic inhibition left center–surround and Y-type receptive field structure and high temporal sensitivity fundamentally intact and clearly derived from modulation of excitatory bipolar cell output. Thus, the characteristic spatial and temporal–contrast sensitivity of the primate parasol cell arises presynaptically and is governed primarily by modulation of the large AMPA/kainate receptor-mediated excitatory conductance. Moreover, the negative feedback responsible for the receptive field surround must derive from a nonGABAergic mechanism.

We describe two cases of confirmed anti-NMDA receptor encephalitis; one patient initially presented with a clinical picture that resembled delirium and later appeared to present with a conversion reaction and the second patient presented with a first psychotic break followed by the clinical picture of neuroleptic malignant syndrome with catatonia. Neither patient had a previous history of psychiatric illness or recreational drug use. These cases illustrate the diagnostic and treatment challenges associated with this neuropsychiatric condition and underscore the role of psychosomatic medicine psychiatrists in diagnosing anti-NMDA receptor encephalitis.

We used an in vitro preparation of the ferret lateral geniculate nucleus (LGN) to examine the role of the NMDA class of excitatory amino acid (EAA) receptors in retinogeniculate transmission. Intracellular recordings revealed that blockade of NMDA receptors both shortened the time course and reduced the amplitude of fast and slow components of excitatory postsynaptic potentials (EPSPs) evoked by optic tract stimulation. The amplitude and width of the EPSPs mediated by NMDA receptors increased as membrane potential was depolarized towards spike threshold. Individual LGN cells were influenced to varying extents by blockade of NMDA receptors; NMDA and non-NMDA receptor blockade together attenuated severely the entire retinogeniculate EPSP. The dependence of all components of retinogeniculate EPSPs (and action potentials) on NMDA receptor activation supports the hypothesis that the NMDA receptor participates in fast (<10 ms) synaptic events underlying conventional retinogeniculate transmission. The voltage dependence of the NMDA receptor-gated conductance suggests strongly that the transmission of retinal information through the LGN is subject to modulation by extraretinal inputs that affect the membrane potential of LGN neurons.

Memory is the process by which organisms are able to record their experiences, and use this information to adapt their responses to the environment. As such, it is vital for survival. In recent years, the development of spatially and temporally selective techniques for the regulation of gene expression has allowed the molecular details of this process to emerge. Here we review the molecular mechanisms thought to underlie memory acquisition and storage, as well as discuss recent evidence regarding the mechanisms of subsequent memory consolidation.

Whole-cell recordings of tiger salamander ganglion cells were obtained using a superfused retinal slice preparation. Membrane current fluctuations were recorded under voltage-clamp conditions with cells usually held at −70 mV. Current fluctuations at rest (Mg2+ = 1 mM) were reduced by adding d-2-amino-7-phosphonoheptanoate (d-AP7). Resting fluctuations were increased by adding N-methyl-D-aspartate (NMDA) or by removing extracellular Mg2+. These increased fluctuations were blocked by d-AP7. Blocking NMDA receptors under control conditions also reduced a tonic inward current by −1 to −15 pA. Fluctuation analysis of current noise shows that the noise power spectrum measured in the presence of NMDA is similar to that measured under Mg2+-free conditions. We conclude that NMDA receptors are active in cells held at −70 mV even in the presence of 1 mM Mg2+. We believe this activation is due to the presence of endogenous glutamate in the retina. The observations of this study strongly suggest that NMDA receptors contribute to the resting noise and conductance properties of retinal ganglion cells. Our results suggest NMDA receptors are activated by an ambient level of extracellular glutamate whose source has yet to be determined.

The response properties of postreceptoral sensory neurones are determined by the properties of their input neurones, by intrinsic membrane properties, and by the properties of neurotransmitter receptors on the soma and dendritic tree. We previously showed that inhibitory neurotransmitter (GABAA and glycine) receptors on a well-characterised sensory neurone, the parasol ganglion cell in the primate retina, are segregated towards the distal part of the dendritic tree. Here we studied the distribution of excitatory ionotropic glutamate receptor subunits on the dendrites of parasol cells in the retina of a New World monkey, the marmoset, Callithrix jacchus. Individual ganglion cells were intracellularly injected in an in vitro retinal wholemount preparation. Ionotropic glutamate receptor subunits, including AMPA (GluR1-4), kainate (GluR6/7), NMDA (NR1C2′) subunits, and the orphan receptors δ1 and δ2 were visualized with immunocytochemical methods. Immunoreactive puncta that colocalized with the dendrites of ganglion cells were analyzed using standard and/or confocal light microscopy. Colocalized puncta were present on parasol dendrites for all subunits studied, but their density was much lower (approximately 1/5) than previously reported for inhibitory (GABA and glycine) receptors. Segregation of the glutamate receptor clusters (GluR1, GluR6/7 subunits) to the peripheral dendrites was less marked than that shown for GABA and glycine receptor clusters. No sign of segregation of colocalized puncta to the peripheral part of the dendritic field was seen with antibodies to the GluR2, GluR2/3, GluR4, δ1/2, or NR1C2′ subunits. The results suggest that although there is diverse expression of glutamate receptor subtypes, the glutamatergic synapses form only a small proportion of the total synaptic input to primate ganglion cells. They further suggest that the processes which control distribution of excitatory and inhibitory synapses on the dendritic field of ganglion cells are, at least to some extent, independent.

In normal adult cats, a monoclonal antibody directed toward the NR-1 subunit of the N-methyl-d-aspartate (NMDA) receptor (Pharmingen, clone 54.1) produced dense cellular and neuropil labeling throughout all layers of the lateral geniculate nucleus (LGN) and adjacent thalamic nuclei, including the thalamic reticular, perigeniculate, medial intralaminar, and ventral lateral geniculate nuclei. Cellular staining revealed well-defined somata, and in some cases proximal dendrites. NMDAR-1 cell labeling was also evident in the LGN of early postnatal kittens, suggesting that developing LGN cells possess this receptor subunit at or before eye opening. Within the A-layers of the adult LGN, staining encompassed a wide range of soma sizes. Soma size comparisons of NMDAR-1 stained cells with those stained with an antibody directed toward a nonphosphorylated neurofilament protein (SMI-32), which selectively stains Y-relay cells (Bickford et al., 1998), or an antibody to glutamic acid decarboxylase (GAD), which stains for GABAergic interneurons, suggested that NMDA receptors are utilized by relay cells and interneurons. NMDAR-1 staining was also observed in the LGN of cats with early monocular lid suture. Although labeling was apparent in both deprived and nondeprived A-layers of LGN, the distribution of soma sizes was significantly different. In the deprived A-layers of LGN, staining was limited to small- and medium-sized cells. Cells with relatively large soma were lacking. However, cell density measurements as well as soma size comparisons with cells stained for Nissl substance suggested these differences were due to deprivation-induced cell shrinkage and not to a loss of NMDAR-1 staining in Y-cells. Taken together, these results suggest that NMDA receptors are utilized by both relay cells and interneurons in LGN and that alterations in early visual experience do not necessarily affect the expression of NMDA receptors in the LGN.