RESUMEN
Malfunctioning synaptic plasticity is one of the major mechanisms contributing to the development of chronic pain. We studied spike-timing dependent depression (tLTD) in the anterior cingulate cortex (ACC) of male mice, a brain region involved in processing emotional aspects of pain. tLTD onto layer 5 pyramidal neurons depended on postsynaptic calcium-influx through GluN2B-containing NMDARs and retrograde signaling via nitric oxide to reduce presynaptic release probability. After chronic constriction injury of the sciatic nerve, a model for neuropathic pain, tLTD was rapidly impaired; and this phenotype persisted even beyond the time of recovery from mechanical sensitization. Exclusion of GluN2B-containing NMDARs from the postsynaptic site specifically at projections from the anterior thalamus to the ACC caused the tLTD phenotype, whereas signaling downstream of nitric oxide synthesis remained intact. Thus, transient neuropathic pain can leave a permanent trace manifested in the disturbance of synaptic plasticity in a specific afferent pathway to the cortex.SIGNIFICANCE STATEMENT Synaptic plasticity is one of the main mechanisms that contributes to the development of chronic pain. Most studies have focused on potentiation of excitatory synaptic transmission, but very little is known about the reduction in synaptic strength. We have focused on the ACC, a brain region associated with the processing of emotional and affective components of pain. We studied spike-timing dependent LTD, which is a biologically plausible form of synaptic plasticity, that depends on the relative timing of presynaptic and postsynaptic activity. We found a long-lasting and pathway-specific suppression of the induction mechanism for spike-timing dependent LTD from the anterior thalamus to the ACC, suggesting that this pathology might be involved in altered emotional processing in pain.
Asunto(s)
Dolor Crónico , Neuralgia , Animales , Dolor Crónico/metabolismo , Depresión , Giro del Cíngulo/fisiología , Masculino , Ratones , Neuralgia/metabolismo , Plasticidad Neuronal , Óxido Nítrico/metabolismoRESUMEN
During the COVID-19 pandemic, the importance of ventilation was widely stressed and new protocols of ventilation were implemented in school buildings worldwide. In the Netherlands, schools were recommended to keep the windows and doors open, and after a national lockdown more stringent measures such as reduction of occupancy were introduced. In this study, the actual effects of such measures on ventilation and thermal conditions were investigated in 31 classrooms of 11 Dutch secondary schools, by monitoring the indoor and outdoor CO2 concentration and air temperature, both before and after the lockdown. Ventilation rates were calculated using the steady-state method. Pre-lockdown, with an average occupancy of 17 students, in 42% of the classrooms the CO2 concentration exceeded the upper limit of the Dutch national guidelines (800 ppm above outdoors), while 13% had a ventilation rate per person (VRp) lower than the minimum requirement (6 l/s/p). Post-lockdown, the indoor CO2 concentration decreased significantly while for ventilation rates significant increase was only found in VRp, mainly caused by the decrease in occupancy (average 10 students). The total ventilation rate per classrooms, mainly induced by opening windows and doors, did not change significantly. Meanwhile, according to the Dutch national guidelines, thermal conditions in the classrooms were not satisfying, both pre- and post-lockdown. While opening windows and doors cannot achieve the required indoor environmental quality at all times, reducing occupancy might not be feasible for immediate implementation. Hence, more controllable and flexible ways for improving indoor air quality and thermal comfort in classrooms are needed.
RESUMEN
BACKGROUND: In fall 2020 when schools in the Netherlands operated under a limited set of COVID-19 measures, we conducted outbreaks studies in four secondary schools to gain insight in the level of school transmission and the role of SARS-CoV-2 transmission via air and surfaces. METHODS: Outbreak studies were performed between 11 November and 15 December 2020 when the wild-type variant of SARS-CoV-2 was dominant. Clusters of SARS-CoV-2 infections within schools were identified through a prospective school surveillance study. All school contacts of cluster cases, irrespective of symptoms, were invited for PCR testing twice within 48 h and 4-7 days later. Combined NTS and saliva samples were collected at each time point along with data on recent exposure and symptoms. Surface and active air samples were collected in the school environment. All samples were PCR-tested and sequenced when possible. RESULTS: Out of 263 sampled school contacts, 24 tested SARS-CoV-2 positive (secondary attack rate 9.1%), of which 62% remained asymptomatic and 42% had a weakly positive test result. Phylogenetic analysis on 12 subjects from 2 schools indicated a cluster of 8 and 2 secondary cases, respectively, but also other distinct strains within outbreaks. Of 51 collected air and 53 surface samples, none were SARS-CoV-2 positive. CONCLUSION: Our study confirmed within school SARS-CoV-2 transmission and substantial silent circulation, but also multiple introductions in some cases. Absence of air or surface contamination suggests environmental contamination is not widespread during school outbreaks.