89. Loss of extinction in CA1-NMDA receptor deficient mice: A novel model for PTSD?

Pathway-specificity in N-methyl-d-aspartate receptor-mediated synaptic inputs onto subplate neurons

The subplate plays an important role in forming neuronal connections during early cortical development. We characterized by the use of whole-cell and cell-attached patch-clamp recordings in coronal brain slices from newborn mice (postnatal day [P] 0-3) the functional properties of two major pathways onto subplate neurons (SPn), the thalamocortical and the intra-subplate synaptic input. The two afferent pathways were stimulated extracellularly with bipolar electrodes placed in the thalamus and the subplate, respectively. Synaptically evoked and pharmacologically isolated N-methyl-d-aspartate receptor (NMDAR) -mediated responses with an onset latency of approximately 6 ms could be reliably re…

Rapid developmental switch in the mechanisms driving early cortical columnar networks

The immature cerebral cortex self-organizes into local neuronal clusters long before it is activated by patterned sensory inputs. In the cortical anlage of newborn mammals, neurons coassemble through electrical or chemical synapses either spontaneously or by activation of transmitter-gated receptors. The neuronal network and the cellular mechanisms underlying this cortical self-organization process during early development are not completely understood. Here we show in an intact in vitro preparation of the immature mouse cerebral cortex that neurons are functionally coupled in local clusters by means of propagating network oscillations in the beta frequency range. In the newborn mouse, this…

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Abstract Background Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results NNVs were more favourable in su…

D1/D5 modulation of synaptic NMDA receptor currents.

Converging evidence suggests that salience-associated modulation of behavior is mediated by the release of monoamines and that monoaminergic activation of D1/D5receptors is required for normal hippocampal-dependent learning and memory. However, it is not understood how D1/D5modulation of hippocampal circuits can affect salience-associated learning and memory. We have observed in CA1 pyramidal neurons that D1/D5receptor activation elicits a bidirectional long-term plasticity of NMDA receptor-mediated synaptic currents with the polarity of plasticity determined by NMDA receptor, NR2A/B subunit composition. This plasticity results in a decrease in the NR2A/NR2B ratio of subunit composition. Sy…

Bone Trauma Causes Massive but Reversible Changes in Spinal Circuitry.

Abstract Bone fracture with subsequent immobilization of the injured limb can cause complex regional pain syndrome (CRPS) in humans. Mechanisms of CRPS are still not completely understood but bone fracture with casting in mice leads to a similar post-traumatic inflammation as seen in humans and might therefore be an analog to human CRPS. In this article we report behavioral and spinal electrophysiological changes in mice that developed swelling of the paw, warming of the skin, and pain in the injured limb after bone fracture. The receptive field sizes of spinal neurons representing areas of the hind paws increased after trauma and recovered over time—as did the behavioral signs of inflammat…