STDP in the Developing Sensory Neocortex

Spike timing-dependent plasticity (STDP) has been proposed as a mechanism for optimizing the tuning of neurons to sensory inputs, a process that underlies the formation of receptive field properties and associative memories. The properties of STDP must adjust during development to enable neurons to optimally tune their selectivity for environmental stimuli, but these changes are poorly understood. Here we review the properties of STDP and how these may change during development in primary sensory cortical layers 2/3 and 4, initial sites for intracortical processing. We provide a primer discussing postnatal developmental changes in synaptic proteins and neuromodulators that are thought to influence STDP induction and expression. We propose that STDP is shaped by, but also modifies, synapses to produce refinements in neuronal responses to sensory inputs

Presynaptic NMDA Receptor Mechanisms for Enhancing Spontaneous Neurotransmitter Release

NMDA receptors (NMDARs) are required for experience-driven plasticity during formative periods of brain development and are critical for neurotransmission throughout postnatal life. Most NMDAR functions have been ascribed to postsynaptic sites of action, but there is now an appreciation that presynaptic NMDARs (preNMDARs) can modulate neurotransmitter release in many brain regions, including the neocortex. Despite these advances, the cellular mechanisms by which preNMDARs can affect neurotransmitter release are largely unknown. Here we pharmacologically interrogated preNMDAR functions to determine how these receptors promote spontaneous neurotransmitter release in mouse primary visual cortex. Our results provide three new insights into the mechanisms by which preNMDARs can function. First, preNMDARs can tonically enhance spontaneous neurotransmitter release with minimal extracellular Ca2+ or with major sources of intracellular Ca2+ blocked. Second, lowering extracellular Na+ levels significantly reduces the contribution of preNMDARs to spontaneous transmitter release. Third, preNMDAR enhance transmitter release in part through protein kinase C (PKC) signaling. These data demonstrate that preNMDARs can act through novel pathways to promote neurotransmitter release in the absence of action potentials

A population-based observational study of diabetes during pregnancy in Victoria, Australia, 1999-2008

Objectives: This paper reports secular trends in diabetes in pregnancy in Victoria, Australia and examines the effect of including or excluding women with pre-existing diabetes on gestational diabetes (GDM) prevalence estimates

COVID-19 Vaccine Uptake and Its Impacts in a Cohort of Gay and Bisexual Men in Australia

Successful use of biomedical forms of HIV risk-reduction may have predisposed many gay and bisexual men (GBM) to vaccination against COVID-19, which may, in turn, affect their sexual behavior. A total of 622 Australian GBM provided weekly data on COVID-19 vaccination history and sexual behaviour between 17 January 2021 and 22 June 2021. We identify factors associated with COVID-19 vaccination, and compare sexual behavior before and since vaccination. Mean age was 47.3 years (SD 14.0). At least one-dose vaccination coverage had reached 57.2%, and 61.3% reported that the majority of their friends intended to be vaccinated. Vaccinated men reported a mean of 1.11 (SD 2.10) weekly non-relationship sex partners before vaccination and 1.62 (SD 3.42) partners following vaccination. GBM demonstrated high confidence in COVID-19 vaccines. Their sexual activity increased following vaccination suggesting that greater sexual freedom may be a specific motivation for vaccine uptake among some men

Developmental Switch in the Contribution of Presynaptic and Postsynaptic NMDA Receptors to Long-Term Depression

NMDA receptor (NMDAR) activation is required for many forms of learning and memory as well as sensory system receptive field plasticity, yet the relative contribution of pre- and postsynaptic NMDARs over cortical development remains unknown. Here we demonstrate a rapid developmental loss of functional presynaptic NMDARs in the neocortex. Presynaptic NMDARs enhance neurotransmitter release at synapses onto visual cortex pyramidal cells in young mice (P21). Immuno-electron microscopy revealed that the loss of presynaptic NMDAR function is likely due in part to a 50% reduction in the prevalence of presynaptic NMDARs. Coincident with the observed loss of presynaptic NMDAR function, there is an abrupt change in the mechanisms of timing-dependent long-term depression (tLTD). Induction of tLTD before the onset of the critical period requires activation of pre- but not postsynaptic NMDARs, while the induction of tLTD in older mice requires activation of postsynaptic NMDARs. By demonstrating that both pre- and postsynaptic NMDARs contribute to the induction of synaptic plasticity, and that their relative roles shift over development, our findings define a novel, and perhaps general, property of synaptic plasticity in emerging cortical circuits

How to have sex in a pandemic: the development of strategies to prevent COVID-19 transmission in sexual encounters among gay and bisexual men in Australia

Although many studies reported on decreases in sexual partner numbers among gay and bisexual-identifying men in the early period of the COVID-19 pandemic, few studies have explored COVID-19 risk-reduction strategies. Drawing on free-text responses in an online survey (from April to July 2020), we describe the ways in which men sought to minimise the risk of COVID-19 in sexual encounters. Partner selection was an important strategy, in particular, restricting sex to men they already knew. Accounts also indicate how participants assessed risk from potential sex partners based on symptoms, residential location, recent travel, work role, and number of other sexual contacts. Less common were in situ practices, such as avoiding kissing. Participants’ responses provide insight into creative community-based responses in the early months of the pandemic, some of which have resonances with early responses to HIV. Findings are discussed in relation to the concepts of ‘lay epidemiology’ and ‘counterpublic health’. In particular, we examine how risks and health are experienced and valued in relation to local knowledges, meanings, and practices; and how practices emerge in response to dominant public health discourses that produce an idealised public based on (hetero)normative assumptions

Conditional Knock-Out of Kir4.1 Leads to Glial Membrane Depolarization, Inhibition of Potassium and Glutamate Uptake, and Enhanced Short-Term Synaptic Potentiation

During neuronal activity, extracellular potassium concentration ([

Relationship Between Sexual Behaviors with Non-committed Relationship Partners and COVID-19 Restrictions and Notification Rates: Results from a Longitudinal Study of Gay and Bisexual Men in Australia

Introduction: COVID-19 related lockdowns have impacted the sexual activity of gay and bisexual men (GBM). We investigated trends in sexual behaviors and the COVID-19 context in which they occurred (COVID-notification rates and jurisdictional restrictions) to understand changes in the duration and severity of periods of lockdown on the sexual behavior of Australian GBM. Methods: In an online, prospective observational study of 831 GBM from May 2020 to May 2021, we investigated associations between changes in sexual behavior among Australian GBM, lockdowns, and COVID-19 notification rates through weekly surveys from May 2020 to May 2021. Results: The mean age was 45.71 years (SD: 13.93). Most identified as gay (89.0%) and 10.2% were living with HIV. There was an overall increase in the mean weekly number of non-committed relationship partners (0.53–0.90, p < 0.001). The state of Victoria experienced a significant extended COVID-19 outbreak, accompanied by severe lockdown restrictions. In response, Victorian men’s partner numbers shifted three times, while elsewhere there was an overall gradually increasing trend. Conclusions: Less severe outbreaks with shorter lockdown periods, involving fewer and geographically contained, COVID-19 notifications were accompanied by non-significant changes in sex with non-relationship partners than more severe outbreaks over extended periods and larger geographical areas

COVID-19 Testing in a Weekly Cohort Study of Gay and Bisexual Men: The Impact of Health-Seeking Behaviors and Social Connection

Gay, bisexual, and other men who have sex with men (GBM) have developed community norms for regular HIV/STI testing. We investigated factors associated with self-reported COVID-19 testing in response to reported COVID-19 cases and public health restrictions. Participants responded to weekly cohort surveys between 10th May 2021 and 27th September 2021. We used the Andersen-Gill extensions to the Cox proportional hazards model for multivariable survival data to predict factors influencing COVID-19 testing. Mean age of the 942 study participants was 45.6 years (SD: 13.9). In multivariable analysis, GBM were more likely to report testing during periods of high COVID-19 caseload in their state of residence; if they were younger; university educated; close contact of someone with COVID-19; or reported coping with COVID-19 poorly. COVID-19 testing was higher among men who: were more socially engaged with other GBM; had a higher proportion of friends willing to vaccinate against COVID-19; and were willing to contact sexual partners for contact tracing. Social connection with other gay men was associated with COVID-19 testing, similar to what has been observed throughout the HIV epidemic, making community networks a potential focus for the promotion of COVID-19 safe practices

Pinceau Organization in the Cerebellum Requires Distinct Functions of Neurofascin in Purkinje and Basket Neurons during Postnatal Development

Basket axon collaterals synapse onto the Purkinje soma/axon initial segment (AIS) area to form specialized structures, the pinceau, which are critical for normal cerebellar function. Mechanistic details of how the pinceau become organized during cerebellar development are poorly understood. Loss of cytoskeletal adaptor protein Ankyrin G (AnkG) results in mislocalization of the cell adhesion molecule Neurofascin (Nfasc) at the Purkinje AIS and abnormal organization of the pinceau. Loss of Nfasc in adult Purkinje neurons leads to slow disorganization of the Purkinje AIS and pinceau morphology. Here we utilized mouse conditional knockout techniques to show that selective loss of Nfasc specifically in Purkinje neurons during early development prevented maturation of the AIS and resulted in loss of Purkinje neuron spontaneous activity and pinceau disorganization. Loss of Nfasc in both Purkinje and basket neurons caused abnormal basket axon collateral branching and targeting to Purkinje soma/AIS, leading to extensive pinceau disorganization, Purkinje neuron degeneration and severe ataxia. Our studies reveal that the Purkinje Nfasc is required for AIS maturation and for maintaining stable contacts between basket axon terminals and the Purkinje AIS during pinceau organization, while the basket neuron Nfasc in combination with Purkinje Nfasc is required for proper basket axon collateral outgrowth and targeting to Purkinje soma/AIS. Thus, cerebellar pinceau organization requires coordinated mechanisms involving specific Nfasc functions in both Purkinje and basket neurons