Astrocyte and Neuronal Panx1 Support Long-Term Reference Memory in Mice

Pannexin 1 (Panx1) is an ubiquitously expressed protein that forms plasma membrane channels permeable to anions and moderate-sized signaling molecules (e.g., ATP, glutamate). In the nervous system, activation of Panx1 channels has been extensively shown to contribute to distinct neurological disorders (epilepsy, chronic pain, migraine, neuroAIDS, etc.), but knowledge of the extent to which these channels have a physiological role remains restricted to three studies supporting their involvement in hippocampus dependent learning. Given that Panx1 channels may provide an important mechanism for activity-dependent neuron-glia interaction, we used Panx1 transgenic mice with global and cell-type specific deletions of Panx1 to interrogate their participation in working and reference memory. Using the eight-arm radial maze, we show that long-term spatial reference memory, but not spatial working memory, is deficient in Panx1-null mice and that both astrocyte and neuronal Panx1 contribute to the consolidation of long-term spatial memory. Field potential recordings in hippocampal slices of Panx1-null mice revealed an attenuation of both long-term potentiation (LTP) of synaptic strength and long-term depression (LTD) at Schaffer collateral-CA1 synapses without alterations of basal synaptic transmission or pre-synaptic paired-pulse facilitation. Our results implicate both neuronal and astrocyte Panx1 channels as critical players for the development and maintenance of long-term spatial reference memory in mice

Developmental Time Course of SNAP-25 Isoforms Regulate Hippocampal Long-Term Synaptic Plasticity and Hippocampus-Dependent Learning

SNAP-25 is essential to activity-dependent vesicle fusion and neurotransmitter release in the nervous system. During early development and adulthood, SNAP-25 appears to have differential influences on short- and long-term synaptic plasticity. The involvement of SNAP-25 in these processes may be different at hippocampal and neocortical synapses because of the presence of two different splice variants, which are developmentally regulated. We show here that the isoform SNAP-25a, which is expressed first developmentally in rodent brain, contributes to developmental regulation of the expression of both long-term depression (LTD) and long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in the hippocampus. In one month old mice lacking the developmentally later expressed isoform SNAP-25b, Schaffer collateral-CA1 synapses showed faster release kinetics, decreased LTP and enhanced LTD. By four months of age, SNAP-25b-deficient mice appeared to have compensated for the lack of the adult SNAP-25b isoform, now exhibiting larger LTP and no differences in LTD compared to wild type mice. Interestingly, learning a hippocampus-dependent task reversed the reductions in LTP, but not LTD, seen at one month of age. In four month old adult mice, learning prevented the compensatory up-regulation of LTD that we observed prior to training. These findings support the hypothesis that SNAP-25b promotes stronger LTP and weakens LTD at Schaffer collateral-CA1 synapses in young mice, and suggest that compensatory mechanisms can reverse alterations in synaptic plasticity associated with a lack of SNAP-25b, once mice reach adulthood

Developmental Time Course of SNAP-25 Isoforms Regulate Hippocampal Long-Term Synaptic Plasticity and Hippocampus-Dependent Learning

SNAP-25 is essential to activity-dependent vesicle fusion and neurotransmitter release in the nervous system. During early development and adulthood, SNAP-25 appears to have differential influences on short- and long-term synaptic plasticity. The involvement of SNAP-25 in these processes may be different at hippocampal and neocortical synapses because of the presence of two different splice variants, which are developmentally regulated. We show here that the isoform SNAP-25a, which is expressed first developmentally in rodent brain, contributes to developmental regulation of the expression of both long-term depression (LTD) and long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in the hippocampus. In one month old mice lacking the developmentally later expressed isoform SNAP-25b, Schaffer collateral-CA1 synapses showed faster release kinetics, decreased LTP and enhanced LTD. By four months of age, SNAP-25b-deficient mice appeared to have compensated for the lack of the adult SNAP-25b isoform, now exhibiting larger LTP and no differences in LTD compared to wild type mice. Interestingly, learning a hippocampus-dependent task reversed the reductions in LTP, but not LTD, seen at one month of age. In four month old adult mice, learning prevented the compensatory up-regulation of LTD that we observed prior to training. These findings support the hypothesis that SNAP-25b promotes stronger LTP and weakens LTD at Schaffer collateral-CA1 synapses in young mice, and suggest that compensatory mechanisms can reverse alterations in synaptic plasticity associated with a lack of SNAP-25b, once mice reach adulthood

Sex-Biased Effects on Hippocampal Circuit Development by Perinatal SERT Expression in CA3 Pyramidal Neurons

Neurodevelopmental disorders ranging from autism to intellectual disability display sex-biased prevalence and phenotypical presentations. Despite increasing knowledge about temporospatial cortical map development and genetic variants linked to neurodevelopmental disorders, when and how sex-biased neural circuit derailment may arise in diseased brain remain unknown. Here, we identify in mice that serotonin uptake transporter (SERT) in non-serotonergic neurons - hippocampal and prefrontal pyramidal neurons - confers sex-biased effects specifically during neural circuit development. A set of gradient-patterned CA3 pyramidal neurons transiently express SERT to clear extracellular serotonin, coinciding with hippocampal synaptic circuit establishment. Ablating pyramidal neuron SERT (SERTPyramidΔ) alters dendritic spine developmental trajectory in the hippocampus, and precipitates sex-biased impairments in long-term activity-dependent hippocampal synaptic plasticity and cognitive behaviors. Transcriptomic analyses identify sex-biased alterations in gene sets associated with autism, dendritic spine structure, synaptic function and male-specific enrichment of dysregulated genes in glial cells in early postnatal SERTPyramidΔ hippocampus. Our data suggest that SERT function in these pyramidal neurons underscores a temporal- and brain region-specific regulation of normal sex-dimorphic circuit development and a source for sex-biased vulnerability to cognitive and behavioral impairments. This article has an associated \u27The people behind the papers\u27 interview

Socioeconomic Characteristics of Pediatric Traumatic Brain Injury Patients

BACKGROUND: Traumatic brain injuries (TBIs) play a significant role in pediatric mortality and morbidity. Environment may play a role in the type, severity, and outcome of pediatric TBI (pTBI). Our objective was to characterize the impact of poor socioeconomic status (PSES) on the incidence, treatment, and outcomes of pTBI patients. METHODS: The Kids\u27 Inpatient Database (KID) was queried from 2016 to 2019 for with TBI using International Classification of Disease, 10th revision (ICD 10) codes. Data defining demographics, complications, procedures, and outcomes was extracted. PSES was defined as Medicaid insurance and Q1 median income category. RESULTS: 26,417 patients had pTBI. 11,040 (41.8 %) of pTBI patients were on Medicaid insurance. 13,119 and 8165 (30.9 %) were in Q1 median income category. Land transport caused the majority of pTBI (41 %). Patients on Medicaid or Q1 median income were more likely to experience assault (OR 2.927, CI 95 % 2.455-3.491, p \u3c 0.001 OR 2.033, CI 95 % 1.722-2.4000 p \u3c 0.001 respectively). On propensity matched analysis, PSES was associated with increased mortality (OR 1.667, 95 % CI 1.322-2.100, p \u3c 0.01), length of stay (LOS) (OR 1.369, 95 % CI 1.201-1.559, p \u3c 0.01), and major complicated trauma (OR 1.354 95 % CI 1.090-1.682 p = 0.007). Total hospital charges were higher in pTBI patients on Medicaid ($112,101.52, +/-$203,716.35) versus non-Medicaid ($109,064.37 +/-$212,057.98) (p \u3c 0.001). CONCLUSION: PSES is correlated with increased mortality, complications, and longer LOS. Healthcare coverage and clinical training should take these disparities into account to provide improved care and optimize healthcare resource utilization. LEVEL OF EVIDENCE: Level IV, Retrospective Database

Frailty as a Predictor of Outcomes in Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

Frailty is an emerging concept in clinical practice used to predict outcomes and dictate treatment algorithms. Frail patients, especially older adults, are at higher risk for adverse outcomes. Aneurysmal subarachnoid hemorrhage (aSAH) is a neurosurgical emergency associated with high morbidity and mortality rates that have previously been shown to correlate with frailty. However, the relationship between treatment selection and post-treatment outcomes in frail aSAH patients is not established. We conducted a meta-analysis of the relevant literature in accordance with PRISMA guidelines. We searched PubMed, Embase, Web of Science, and Google Scholar using Subarachnoid hemorrhage AND frailty and subarachnoid hemorrhage AND frail as search terms. Data on cohort age, frailty measurements, clinical grading systems, and post-treatment outcomes were extracted. Of 74 studies identified, four studies were included, with a total of 64,668 patients. Percent frailty was 30.4% under a random-effects model in all aSAH patients ( \u3c 0.001). Overall mortality rate of aSAH patients was 11.7% when using a random-effects model ( \u3c 0.001). There was no significant difference in mortality rate between frail and non-frail aSAH patients, but this analysis only included two studies and should be interpreted cautiously. Age and clinical grading, rather than frailty, independently predicted outcomes and mortality in aSAH patients

Life-long Brain Compensatory Responses to Galactic Cosmic Radiation Exposure

Galactic cosmic radiation (GCR) composed of high-energy, heavy particles (HZE) poses potentially serious hazards to long-duration crewed missions in deep space beyond earth\u27s magnetosphere, including planned missions to Mars. Chronic effects of GCR exposure on brain structure and cognitive function are poorly understood, thereby limiting risk reduction and mitigation strategies to protect against sequelae from exposure during and after deep-space travel. Given the selective vulnerability of the hippocampus to neurotoxic insult and the importance of this brain region to learning and memory, we hypothesized that GCR-relevant HZE exposure may induce long-term alterations in adult hippocampal neurogenesis, synaptic plasticity, and hippocampal-dependent learning and memory. To test this hypothesis, we irradiated 3-month-old male and female mice with a single, whole-body dose of 10, 50, or 100 cGy 56Fe ions (600 MeV, 181 keV/μm) at Brookhaven National Laboratory. Our data reveal complex, dynamic, time-dependent effects of HZE exposure on the hippocampus. Two months post exposure, neurogenesis, synaptic plasticity and learning were impaired compared to sham-irradiated, age-matched controls. By six months post-exposure, deficits in spatial learning were absent in irradiated mice, and synaptic potentiation was enhanced. Enhanced performance in spatial learning and facilitation of synaptic plasticity in irradiated mice persisted 12 months post-exposure, concomitant with a dramatic rebound in adult-born neurons. Synaptic plasticity and spatial learning remained enhanced 20 months post-exposure, indicating a life-long influence on plasticity and cognition from a single exposure to HZE in young adulthood. These findings suggest that GCR-exposure can persistently alter brain health and cognitive function during and after long-duration travel in deep space

Neuroendovascular Surgery Applications in Craniocervical Trauma

Cerebrovascular injuries resulting from blunt or penetrating trauma to the head and neck often lead to local hemorrhage and stroke. These injuries present with a wide range of manifestations, including carotid or vertebral artery dissection, pseudoaneurysm, occlusion, transection, arteriovenous fistula, carotid-cavernous fistula, epistaxis, venous sinus thrombosis, and subdural hematoma. A selective review of the literature from 1989 to 2023 was conducted to explore various neuroendovascular surgical techniques for craniocervical trauma. A PubMed search was performed using these terms: endovascular, trauma, dissection, blunt cerebrovascular injury, pseudoaneurysm, occlusion, transection, vasospasm, carotid-cavernous fistula, arteriovenous fistula, epistaxis, cerebral venous sinus thrombosis, subdural hematoma, and middle meningeal artery embolization. An increasing array of neuroendovascular procedures are currently available to treat these traumatic injuries. Coils, liquid embolics (onyx or n-butyl cyanoacrylate), and polyvinyl alcohol particles can be used to embolize lesions, while stents, mechanical thrombectomy employing stent-retrievers or aspiration catheters, and balloon occlusion tests and super selective angiography offer additional treatment options based on the specific case. Neuroendovascular techniques prove valuable when surgical options are limited, although comparative data with surgical techniques in trauma cases is limited. Further research is needed to assess the efficacy and outcomes associated with these interventions