Postsynaptic AMPA-type glutamate receptors (AMPARs) mediate most fast excitatory synaptic transmission and are crucial for many aspects of brain function, including learning, memory and cognition. The number, synaptic localization and subunit composition of synaptic AMPARs are tightly regulated by network activity and by the history of activity at individual synapses. Furthermore, aberrant AMPAR trafficking is implicated in neurodegenerative diseases. AMPARs therefore represent a prime target for drug development and the mechanisms that control their synaptic delivery, retention and removal are the subject of extensive research. Here, we review recent findings that have provided new insights into AMPAR trafficking and that might lead to the development of novel therapeutic strategies.

SummaryThe active zone (AZ) matrix of presynaptic terminals coordinates the recruitment of voltage-gated calcium channels (VGCCs) and synaptic vesicles to orchestrate neurotransmitter release. However, the spatial organization of the AZ and how it controls vesicle fusion remain poorly understood. Here, we employ super-resolution microscopy and ratiometric imaging to visualize the AZ structure on the nanoscale, revealing segregation between the AZ matrix, VGCCs, and putative release sites. Long-term blockade of neuronal activity leads to reversible AZ matrix unclustering and presynaptic actin depolymerization, allowing for enrichment of AZ machinery. Conversely, patterned optogenetic stimulation of postsynaptic neurons retrogradely enhanced AZ clustering. In individual synapses, AZ clustering was inversely correlated with local VGCC recruitment and vesicle cycling. Acute actin depolymerization led to rapid (5 min) nanoscale AZ matrix unclustering. We propose a model whereby neuronal activity modulates presynaptic function in a homeostatic manner by altering the clustering state of the AZ matrix.

The haemotropic mycoplasmas (haemoplasmas) are a group of bacteria that can induce anaemia in a wide variety of mammals, including domestic cats and wild felids. Different feline haemoplasma species of varying pathogenicity exist, with the more pathogenic Mycoplasma haemofelis (Mhf) capable of inducing severe haemolytic anaemia, whilst 'Candidatus Mycoplasma haemominutum' (CMhm) and 'Candidatus Mycoplasma turicensis' (CMt) are infrequently associated with clinical disease. Chronic haemoplasma infections are common and cats are frequently infected by two or more haemoplasmas, complicating the clinical picture. The natural route of transmission of haemoplasma infection between cats has not yet been determined; however, experimental transmission has been demonstrated via both oral and parenteral administration of infected blood. To date the haemoplasmas have been unable to be cultured in vitro, and accurate diagnosis is currently reliant on detection of bacterial DNA using PCR assays. Treatment of clinical haemoplasmosis is focussed on supportive care in combination with empirical treatment with antimicrobials (tetracyclines or fluoroquinolones). A significant number of asymptomatic cats are positive for haemoplasma infection. These cats may play a role in the maintenance of haemoplasma infection within a population, and need to be considered when choosing potential blood donors. Use of PCR assays has provided an accurate method of diagnosing haemoplasma infection and quantifying response to therapy, including in non-feline host animals, as presumed zoonotic haemoplasma infections are now being documented. Recent advances in genome sequencing techniques have allowed the whole genome sequences of the feline haemoplasmas Mhf and CMhm to be derived, as well as a number of non-feline haemoplasma species. These data have aided the identification of antigens for use in the development of serological tests, allowed the proteomic study of haemoplasmas and provided clues as to how the haemoplasmas can persist within the host. Future areas of study include investigation of their zoonotic potential, mechanisms of immune system evasion and transmission of these emerging pathogens.

BackgroundTick-borne haemoparasites Babesia vogeli and Anaplasma platys are common among the free-roaming canine populations associated with Aboriginal communities in Australia, whilst the prevalence of haemoplasmas, which are also suspected to be tick-borne, remained unexplored. The aim of this study was to determine the prevalence of haemoplasma infection in these populations, and to identify any correlation with other haemoparasites. Blood was collected from 39 dogs associated with four Aboriginal communities and screened for infection using PCR and serology. DNA was purified and PCR analyses for piroplasms, Anaplasmataceae family bacteria and haemoplasmas performed. Serum was analysed using a commercial haemoparasite ELISA. Prevalence of infection was compared between communities.ResultsSeventeen dogs (44%) were infected (PCR positive) with Mycoplasma haemocanis, eight (21%) with ‘Candidatus Mycoplasma haematoparvum’, 20 (51%) with A. platys, and 17 (44%) with B. vogeli. Two dogs were infected with a novel haemoplasma as determined by DNA amplification and sequencing. Two dogs (5%) were serologically positive for Dirofilaria immitis antigens, one (3%) was positive for Ehrlichia canis antibodies and nine (24nbsp;%) were positive for A. platys antibodies. Co-infections were frequent. Haemoplasma prevalence was highest (73%, 16/22) in Central Australia and lowest (22%, 2/9) in Western Australia (p = 0.017). In contrast, B. vogeli prevalence was low in Central Australia (18%, 4/22) but higher (78%, 7/9) in Western Australia (p = 0.003).ConclusionsThis is the first time haemoplasma infections, including a novel species, have been molecularly documented in Australian dogs. The wide regional variation in prevalence of some of the haemoparasite infections detected in this study warrants further investigation.

Case summary A 7-month-old Siberian cat was presented for investigation of acute onset multifocal neurological deficits. Neurological examination documented dull mental status and an ambulatory left hemiparesis. Serum biochemistry documented marked hyperglobulinaemia. MRI of the brain identified marked leptomeningeal contrast enhancement extending along the brainstem caudally to involve the cranial cervical spinal cord. MRI of the cervical spine further identified a subarachnoid diverticulum that extended from the level of the obex to the C2–C3 vertebrae. Cerebrospinal fluid quantitative RT-PCR was positive for the presence of feline coronavirus. Histopathology revealed pyogranulomatous meningitis and choroid plexitis, uveitis and nephritis. Relevance and novel information This article describes the first reported case of a subarachnoid diverticulum associated with feline infectious peritonitis.