Activity-Dependent Internalization of Glun2B-Containing NMDARS Is Required For Synaptic Incorporation of Glun2A And Synaptic Plasticity.

NMDA-type glutamate receptors are heterotetrameric complexes composed of two GluN1 and two GluN2 subunits. The precise composition of the GluN2 subunits determines the channel's biophysical properties and influences its interaction with postsynaptic scaffolding proteins and signaling molecules involved in synaptic physiology and plasticity. The precise regulation of NMDAR subunit composition at synapses is crucial for proper synaptogenesis, neuronal circuit development, and synaptic plasticity, a cellular model of memory formation.

Office-based ureteric stent removal is achievable, improves clinical flexibility and quality of care, whilst also keeping surgeons close to their patients.

Introduction: Diagnostic pressure on endoscopy suites can result in stent removal not receiving the required priority and unnecessary morbidity for patients. As well as using stents with extraction strings, the introduction of a portable single-use flexible cystoscope for ureteric stent removal (Isiris™), offered an opportunity to negotiate these issues by relocating stent removal to the office/clinic. This study aimed to determine whether such flexibility reduced stent dwell time with the assumption this would improve patient experience and decrease associated complications.

Role for 2D image generated 3D face models in the rehabilitation of facial palsy.

The outcome for patients diagnosed with facial palsy has been shown to be linked to rehabilitation. Dense 3D morphable models have been shown within the computer vision to create accurate representations of human faces even from single 2D images. This has the potential to provide feedback to both the patient and medical expert dealing with the rehabilitation plan.

Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice(1,2,3).

Corticostriatal signaling participates in sensitized responses to drugs of abuse, where short-term increases in dopamine availability provoke persistent, yet reversible, changes in glutamate release. Prior studies in mice show that amphetamine withdrawal promotes a chronic presynaptic depression in glutamate release, whereas an amphetamine challenge reverses this depression by potentiating corticostriatal activity in direct pathway medium spiny neurons. This synaptic plasticity promotes corticostriatal activity and locomotor sensitization through upstream changes in the activity of tonically active cholinergic interneurons (ChIs).

Acetylcholine encodes long-lasting presynaptic plasticity at glutamatergic synapses in the dorsal striatum after repeated amphetamine exposure.

Locomotion and cue-dependent behaviors are modified through corticostriatal signaling whereby short-term increases in dopamine availability can provoke persistent changes in glutamate release that contribute to neuropsychiatric disorders, including Parkinson's disease and drug dependence. We found that withdrawal of mice from repeated amphetamine treatment caused a chronic presynaptic depression (CPD) in glutamate release that was most pronounced in corticostriatal terminals with a low probability of release and lasted >50 d in treated mice. An amphetamine challenge reversed CPD via a dopamine D1-receptor-dependent paradoxical presynaptic potentiation (PPP) that increased corticostriatal activity in direct pathway medium spiny neurons.

Overinhibition of corticostriatal activity following prenatal cocaine exposure.

Objective: Prenatal cocaine exposure (PCE) can cause persistent neuropsychological and motor abnormalities in affected children, but the physiological consequences of PCE remain unclear. Conclusions drawn from clinical studies can sometimes be confounded by polysubstance abuse and nutritional deprivation. However, existing observations suggest that cocaine exposure in utero, as in adults, increases synaptic dopamine and promotes enduring dopamine-dependent plasticity at striatal synapses, altering behaviors and basal ganglia function.

Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors.

The striatum regulates motor control, reward and learning. Abnormal function of striatal GABAergic medium spiny neurons (MSNs) is believed to contribute to the deficits in these processes that are observed in many neuropsychiatric diseases. The orphan G protein-coupled receptor GPR88 is robustly expressed in MSNs and is regulated by neuropharmacological drugs, but its contribution to MSN physiology and behavior is unclear.

Regulation of prefrontal excitatory neurotransmission by dopamine in the nucleus accumbens core.

Interactions between dopamine and glutamate signalling within the nucleus accumbens core are required for behavioural reinforcement and habit formation. Dopamine modulates excitatory glutamatergic signals from the prefrontal cortex, but the precise mechanism has not been identified. We combined optical and electrophysiology recordings in murine slice preparations from CB1 receptor-null mice and green fluorescent protein hemizygotic bacterial artificial chromosome transgenic mice to show how dopamine regulates glutamatergic synapses specific to the striatonigral and striatopallidal basal ganglia pathways.

Molecular determinants controlling NMDA receptor synaptic incorporation.

Synaptic incorporation of NMDA receptors (NMDARs) is regulated by GluN2 subunits with different rules controlling GluN2A- and GluN2B-containing receptors; whereas GluN2B-containing receptors are constitutively incorporated into synapses, GluN2A incorporation is activity-dependent. We expressed electrophysiologically tagged NMDARs in rat hippocampal slices to identify the molecular determinants controlling the mode of synaptic incorporation of NMDARs. Expressing chimeric GluN2 subunits, we identified a putative N-glycosylation site present in GluN2B, but not in GluN2A, as necessary and sufficient to drive NMDARs into synapses in an activity-independent manner.

Dynamic regulation of NMDA receptor transmission.

N-methyl-D-aspartate receptors (NMDARs) are critical for establishing, maintaining, and modifying glutamatergic synapses in an activity-dependent manner. The subunit composition, synaptic expression, and some of the properties of NMDARs are regulated by synaptic activity, affecting processes like synaptic plasticity. NMDAR transmission is dynamic, and we were interested in studying the effect of acute low or null synaptic activity on NMDA receptors and its implications for synaptic plasticity.

John Wesley (1708-91).

John Wesley was a competent physician, quite capable of the diagnosis and care of patients. His Primitive Physic provides a picture of therapy in the eighteenth century but he rejected the bleeding and purging which were common at that time. He was ahead of his time in his emphasis on hygiene, cleanliness and simple living.

Sir George Newman (1870-1948).

George Newman (1870-1948) was a major figure in the development of public health and school medicine in the years between World Wars I and II. From a Quaker background, he became first Chief Medical Officer to the Board of Education and then Chief Medical Officer to the Ministry of Health. In these posts he wrote many reports to the minister concerned and stimulated others.

Novel imaging strategy for the detection of fat embolism after arthroplasty.

Introduction: Respiratory complications are common after arthroplasty with fat emboli and thromboembolic disease (PTE) being the most serious. As fat embolism from bone marrow should contain reticuloendothelial cells, we hypothesized that these cells take up colloid in the lung. A prospective tomographic study of 99m Tc phytate and perfusion was performed within 24 h after arthroplasty.

Bone scintigraphy in acetabular labral tears.

Background: Acetabular labral tears are an increasingly recognized cause of hip pain in young adults with hip dysplasia and older patients with degenerative disease of the hips.

Methods: The authors analyzed retrospectively bone scintigraphy in 27 patients with acetabular labral tears diagnosed by MRI/arthroscopy. Analysis was also made of scintigraphy in 30 patients without labral tears being investigated for other causes of hip pain for comparison.

James Alison Glover (1874-963), OBE (1919) CBE (1941) MD (1905) DPH (1905) FRCP (1933).

James Allison Glover served in the Boer War and World War I. In 1917 he was appointed to the Cerebro-spinal Laboratory in London. There, his work on cerebrospinal fever resulted in the "spacing out" of beds in huts and earned him the name of "good friend of the private soldier".