Mice: A Preclinical Model of -Related Neurodevelopmental Disorder.

Objective: -related neurodevelopmental disorder ( -NDD) is characterized by clinically significant variation in the gene, which encodes the obligatory GluN1 subunit of N-methyl-D-aspartate receptors (NMDARs). The identified p.Tyr647Ser (Y647S) variant - carried by a 33-year-old female with seizures and intellectual disability - is located in the M3 helix in the GluN1 transmembrane domain.

Sex-dependence of synaptic depression induced by activation of metabotropic glutamate receptors in rat hippocampus.

The modulation of synaptic efficacy by group I metabotropic glutamate receptors is dysregulated in several neurodevelopmental and neurodegenerative disorders impacting cognitive function. The progression and severity of these and other disorders are affected by biological sex, and differences in metabotropic glutamate receptor signalling have been implicated in this effect. In this study, we have examined whether there are any sex-dependent differences in a form of long-term depression of synaptic responses that is triggered by application of the group I metabotropic glutamate receptor agonist 3,5-dihydroxyphenylglycine (DHPG).

(2,6)- and (2,6)-hydroxynorketamine inhibit the induction of NMDA receptor-dependent LTP at hippocampal CA1 synapses in mice.

The ketamine metabolite (2,6)-hydroxynorketamine has been proposed to have rapid and persistent antidepressant actions in rodents, but its mechanism of action is controversial. We have compared the ability of ()-ketamine with the (2,6)- and (2,6)-isomers of hydroxynorketamine to affect the induction of -methyl-d-aspartate receptor-dependent long-term potentiation in the mouse hippocampus. Following pre-incubation of these compounds, we observed a concentration-dependent (1-10 μM) inhibition of long-term potentiation by ketamine and a similar effect of (2,6)-hydroxynorketamine.

The Hippocampus Is the Place to Be: Opioid Receptors and LTP.

Nam et al. (2019) genetically modulate the expression of astrocytic μ-opioid receptors to reveal they are necessary for drug-induced conditioned place preference. These receptors trigger a mechanism involving metabotropic glutamate receptors to enhance hippocampal long-term potentiation, linking the conditioning to the location.

Differential ability of the dorsal and ventral rat hippocampus to exhibit group I metabotropic glutamate receptor-dependent synaptic and intrinsic plasticity.

Background: The hippocampus is critically involved in learning and memory processes. Although once considered a relatively homogenous structure, it is now clear that the hippocampus can be divided along its longitudinal axis into functionally distinct domains, responsible for the encoding of different types of memory or behaviour. Although differences in extrinsic connectivity are likely to contribute to this functional differentiation, emerging evidence now suggests that cellular and molecular differences at the level of local hippocampal circuits may also play a role.

The NMDA receptor as a target for cognitive enhancement.

NMDA receptors (NMDARs) play an important role in neural plasticity including long-term potentiation and long-term depression, which are likely to explain their importance for learning and memory. Cognitive decline is a major problem facing an ageing human population, so much so that its reversal has become an important goal for scientific research and pharmaceutical development. Enhancement of NMDAR function is a core strategy toward this goal.