High-frequency head impact causes chronic synaptic adaptation and long-term cognitive impairment in mice.

Repeated head impact exposure can cause memory and behavioral impairments. Here, we report that exposure to non-damaging, but high frequency, head impacts can alter brain function in mice through synaptic adaptation. High frequency head impact mice develop chronic cognitive impairments in the absence of traditional brain trauma pathology, and transcriptomic profiling of mouse and human chronic traumatic encephalopathy brain reveal that synapses are strongly affected by head impact. Electrophysiological analysis shows that high frequency head impacts cause chronic modification of the AMPA/NMDA ratio in neurons that underlie the changes to cognition. To demonstrate that synaptic adaptation is caused by head impact-induced glutamate release, we pretreated mice with memantine prior to head impact. Memantine prevents the development of the key transcriptomic and electrophysiological signatures of high frequency head impact, and averts cognitive dysfunction. These data reveal synapses as a target of high frequency head impact in human and mouse brain, and that this physiological adaptation in response to head impact is sufficient to induce chronic cognitive impairment in mice.

Valuation of Life With Disability: An International Comparison Study in Vietnam, Peru, and Haiti.

The authors measured perceived quality of life for 4 disabilities among 450 adults in 3 resource-limited countries, measuring mean utilities using time trade-off, and surveying participants on 35 sociocultural characteristics to compare utilities for disabilities by country and examine associated sociocultural characteristics. Mean utilities were >0 for mild and moderate, but <0 for severe and profound. Utilities differed across countries (P = .007, .000, .017, .000 for mild, moderate, severe, profound, respectively). Vietnamese utilities correlated with residence (P = .03, moderate), education (P = .03, severe), and number of children (P = .03, moderate). Peruvian utilities correlated with education (P = .05, mild; P = .05, severe), experience with disability (P = .001, mild), gender (P = .04, moderate; P = .03, profound), number of hospitalizations (P = .04, severe). In Haiti, the only correlate was rejection (P = .02, moderate). Culture-specific variables differentially shape perceptions of disability in developing countries, thereby affecting cost-effectiveness calculations. Given substantially negative perceptions, reducing major disability would improve cost-effectiveness of health-policy decisions more than reducing mortality.

Rapid concentration and isotopic measurements of ultra-trace 235U fission products with comparison to an ORIGEN isotope depletion model.

This article presents the application of an automated online separation-direct analysis method, RAPID (Rapid Analysis of Post-Irradiation Debris), for the simultaneous measurement of both radioactive and stable fission isotopes from an irradiated highly-enriched uranium target. Developed for the measurement of the concentration and isotopic composition of over 40 elements down to the femtogram level, the RAPID method possesses the sensitivity, stability, and precision required to achieve accurate, low-level analyses of elements of non-natural origin. The isotopic compositions and concentrations of key fission elements cesium, strontium, yttrium, lanthanum, cerium, praseodymium, neodymium, promethium, and samarium have been measured repeatedly over a six-week period. The validity of these measurements was confirmed using ORIGEN (Oak Ridge Isotope GENeration), an isotope depletion and decay modeling software, to within 1-3%.

Valuation of Quality of Life in Pediatric Disability in a Developing Country.

This article assessed how Indian providers and mothers value quality of life in pediatric disabilities, hypothesizing lower values with increasing disability, lower values among providers than mothers, and lower values among mothers with versus mothers without a disabled child. We asked 175 participants: "If born tomorrow, how many years of a disabled life ( y) would you trade to avoid life-long disability" for 4 hypothetical disabilities, calculating "utility" scores as: (life span - y) / life span, where death = 0 and full life without disability = 1. Providers' utilities were 0.67 (mild), 0.18 (moderate), -0.70 (severe), and -0.60 (profound); 0.67, 0, -0.77, and -0.88 for mothers without and 0.38, -0.49, -0.86, and -0.87 for mothers with a disabled child. Mothers without reported lower utilities than providers (severe and profound disability [ P ≤ .03]), and higher utilities than mothers (for mild and moderate disability [ P < .001]). Major disability is valued as a fate worse than death in India.

Maternal or neonatal infection: association with neonatal encephalopathy outcomes.

This corrects the article DOI: 10.1038/pr.2014.47.

The end of the unique myocardial band: Part I. Anatomical considerations.

The concept of the 'unique myocardial band', which proposes that the ventricular myocardial cone is arranged like skeletal muscle, provides an attractive framework for understanding haemodynamics. The original idea was developed by Francisco Torrent-Guasp. Using boiled hearts and blunt dissection, Torrent-Guasp created a single band of ventricular myocardium extending from the pulmonary trunk to the aortic root, with the band thus constructed encircling both ventricular cavities. Cooked hearts can, however, be dissected in many ways. In this review, we show that the band does not exist as an anatomical entity with defined borders. On the contrary, the ventricular cardiomyocytes are aggregated end to end and by their branching produce an intricate meshwork. Across the thickness of the left ventricular wall, the chains of cardiomyocytes exhibit a gradually changing helical angle, with a circumferential zone formed in the middle. There is no abrupt change in helical angle, as could be expected if the wall was constructed of opposing limbs of a single wrapped band, nor does the long axis of the cardiomyocytes consistently match with the long axis of the unique myocardial band. There are, furthermore, no connective tissue structures that could be considered to demarcate its purported boundaries. The unique myocardial band should be consistent with evolution, and although the ventricular wall of fish and reptiles has one or several distinct layers, a single band is not found. In 1965, Lev and Simpkins cautioned that the ventricular muscle mass of a cooked heart can be dissected almost at the whim of the anatomist. We suggest that the unique myocardial band should have ended there.

The end of the unique myocardial band: Part II. Clinical and functional considerations.

Two of the leading concepts of mural ventricular architecture are the unique myocardial band and the myocardial mesh model. We have described, in an accompanying article published in this journal, how the anatomical, histological and high-resolution computed tomographic studies strongly favour the latter concept. We now extend the argument to describe the linkage between mural architecture and ventricular function in both health and disease. We show that clinical imaging by echocardiography and magnetic resonance imaging, and electrophysiological studies, all support the myocardial mesh model. We also provide evidence that the unique myocardial band model is not compatible with much of scientific research.

Changes in overall ventricular myocardial architecture in the setting of a porcine animal model of right ventricular dilation.

BACKGROUND: Chronic pulmonary regurgitation often leads to myocardial dysfunction and heart failure. It is not fully known why secondary hypertrophy cannot fully protect against the increase in wall stress brought about by the increased end-diastolic volume in ventricular dilation. It has been assumed that mural architecture is not deranged in this situation, but we hypothesised that there might be a change in the pattern of orientation of the aggregations of cardiomyocytes, which would contribute to contractile impairment. METHODS: We created pulmonary valvular regurgitation by open chest, surgical suturing of its leaflets in seven piglets, performing sham operations in seven control animals. Using cardiovascular magnetic resonance imaging after 12 weeks of recovery, we demonstrated significantly increased right ventricular volumes in the test group. After sacrifice, diffusion tensor imaging of their hearts permitted measurement of the orientation of the cardiomyocytes. RESULTS: The helical angles in the right ventricle approached a more circumferential orientation in the setting of right ventricular RV dilation (p = 0.007), with an increased proportion of surface-parallel cardiomyocytes. In contrast, this proportion decreased in the left ventricle. Also in the left ventricle a higher proportion of E3 angles with a value around zero was found, and conversely a lower proportion of angles was found with a numerical higher value. In the dilated right ventricle the proportion of E3 angles around -90° is increased, while the proportion around 90° is decreased. CONCLUSION: Contrary to traditional views, there is a change in the orientation of both the left ventricular and right ventricular cardiomyocytes subsequent to right ventricular dilation. This will change their direction of contraction and hinder the achievement of normalisation of cardiomyocytic strain, affecting overall contractility. We suggest that the aetiology of the cardiac failure induced by right vetricular dilation may be partly explained by morphological changes in the myocardium itself.

Insights from echocardiography, magnetic resonance imaging, and microcomputed tomography relative to the mid-myocardial left ventricular echogenic zone.

BACKGROUND: The anatomical substrate for the mid-mural ventricular hyperechogenic zone remains uncertain, but it may represent no more than ultrasound reflected from cardiomyocytes orientated orthogonally to the ultrasonic beam. We sought to ascertain the relationship between the echogenic zone and the orientation of the cardiomyocytes. METHODS: We used 3D echocardiography, diffusion tensor imaging, and microcomputed tomography to analyze the location and orientation of cardiomyocytes within the echogenic zone. RESULTS: We demonstrated that visualization of the echogenic zone is dependent on the position of the transducer and is most clearly seen from the apical window. Diffusion tensor imaging and microcomputed tomography show that the echogenic zone seen from the apical window corresponds to the position of the circumferentially orientated cardiomyocytes. An oblique band seen in the parasternal view relates to cardiomyocytes orientated orthogonally to the ultrasonic beam. CONCLUSIONS: The mid-mural ventricular hyperechogenic zone represents reflected ultrasound from cardiomyocytes aligned orthogonal to the ultrasonic beam. The echogenic zone does not represent a space, a connective tissue sheet, a boundary between ascending and descending limbs of a hypothetical helical ventricular myocardial band, nor an abrupt change in cardiomyocyte orientation.

Antenatal Exposure to Magnesium Sulfate Is Associated with Reduced Cerebellar Hemorrhage in Preterm Newborns.

OBJECTIVE: To determine the association of antenatal magnesium sulfate with cerebellar hemorrhage in a prospective cohort of premature newborns evaluated by magnetic resonance imaging (MRI). STUDY DESIGN: Cross-sectional analysis of baseline characteristics from a prospective cohort of preterm newborns (<33 weeks gestation) evaluated with 3T-MRI shortly after birth. Exclusion criteria were clinical evidence of a congenital syndrome, congenital infection, or clinical status too unstable for transport to MRI. Antenatal magnesium sulfate exposure was abstracted from the medical records and the indication was classified as obstetric or neuroprotection. Two pediatric neuroradiologists, blinded to the clinical history, scored axial T2-weighted and iron susceptibility MRI sequences for cerebellar hemorrhage. The association of antenatal magnesium sulfate with cerebellar hemorrhage was evaluated using multivariable logistic regression, adjusting for postmenstrual age at MRI and known predictors of cerebellar hemorrhage. RESULTS: Cerebellar hemorrhage was present in 27 of 73 newborns (37%) imaged at a mean ± SD postmenstrual age of 32.4 ± 2 weeks. Antenatal magnesium sulfate exposure was associated with a significantly reduced risk of cerebellar hemorrhage. Adjusting for postmenstrual age at MRI, and predictors of cerebellar hemorrhage, antenatal magnesium sulfate was independently associated in our cohort with decreased cerebellar hemorrhage (OR, 0.18; 95% CI, 0.049-0.65; P = .009). CONCLUSION: Antenatal magnesium sulfate exposure is independently associated with a decreased risk of MRI-detected cerebellar hemorrhage in premature newborns, which could explain some of the reported neuroprotective effects of magnesium sulfate.

Stress increases GABAergic neurotransmission in CRF neurons of the central amygdala and bed nucleus stria terminalis.

Corticotrophin Releasing Factor (CRF) is a critical stress-related neuropeptide in major output pathways of the amygdala, including the central nucleus (CeA), and in a key projection target of the CeA, the bed nucleus of the stria terminalis (BnST). While progress has been made in understanding the contributions and characteristics of CRF as a neuropeptide in rodent behavior, little attention has been committed to determine the properties and synaptic physiology of specific populations of CRF-expressing (CRF(+)) and non-expressing (CRF(-)) neurons in the CeA and BnST. Here, we fill this gap by electrophysiologically characterizing distinct neuronal subtypes in CeA and BnST. Crossing tdTomato or channelrhodopsin-2 (ChR2-YFP) reporter mice to those expressing Cre-recombinase under the CRF promoter allowed us to identify and manipulate CRF(+) and CRF(-) neurons in CeA and BnST, the two largest areas with fluorescently labeled neurons in these mice. We optogenetically activated CRF(+) neurons to elicit action potentials or synaptic responses in CRF(+) and CRF(-) neurons. We found that GABA is the predominant co-transmitter in CRF(+) neurons within the CeA and BnST. CRF(+) neurons are highly interconnected with CRF(-) neurons and to a lesser extent with CRF(+) neurons. CRF(+) and CRF(-) neurons differentially express tonic GABA currents. Chronic, unpredictable stress increase the amplitude of evoked IPSCs and connectivity between CRF(+) neurons, but not between CRF(+) and CRF(-) neurons in both regions. We propose that reciprocal inhibition of interconnected neurons controls CRF(+) output in these nuclei.

Dopamine increases NMDA-stimulated calcium flux in striatopallidal neurons through a matrix metalloproteinase-dependent mechanism.

Dopamine (DA) is a potent neuromodulator known to influence glutamatergic transmission in striatal medium spiny neurons (MSNs). It acts on D1- and D2-like DA receptors that are expressed on two distinct subpopulations. MSNs projecting to the substantia nigra express D1 receptors (D1Rs), while those projecting to the lateral globus pallidus express D2 receptors (D2Rs). D1R signalling in particular can increase excitatory transmission through varied protein kinase A-dependent, cell-autonomous pathways. Mechanisms by which D1R signalling could increase excitatory transmission in D2R-bearing MSNs have been relatively less explored. Herein, the possibility is considered that D1R agonists increase levels of soluble factors that subsequently influence N-methyl-D-aspartate (NMDA)-stimulated calcium flux in D2R neurons. This study focuses on matrix metalloproteinases (MMPs) and MMP-generated integrin binding ligands, important soluble effectors of glutamatergic transmission that may be elevated in the setting of excess DA. It was observed that DA and a D1R agonist, SKF81297, increase MMP activity in extracts from striatal slices, as determined by cleavage of the substrate ß-dystroglycan. Using mice engineered to express the calcium indicator GCaMP3 in striatopallidal D2R-bearing neurons, it was also observed that SKF81297 pretreatment of slices (60 min) potentiates NMDA-stimulated calcium increases in this subpopulation. Effects are diminished by pretreatment with an antagonist of MMP activity or an inhibitor of integrin-dependent signalling. Together, results suggest that DA signalling can increase excitatory transmission in D2R neurons through an MMP-dependent mechanism. Future studies may be warranted to determine whether D1R-stimulated MMP-dependent processes contribute to behaviours in which increased activity in striatopallidal MSNs plays a role.

Evidence for glycinergic GluN1/GluN3 NMDA receptors in hippocampal metaplasticity.

Hebbian, or associative, forms of synaptic plasticity are considered the molecular basis of learning and memory. However, associative synaptic modifications, including long-term potentiation (LTP) and depression (LTD), can form positive feedback loops which must be constrained for neural networks to remain stable. One proposed constraint mechanism is metaplasticity, a process whereby synaptic changes shift the threshold for subsequent plasticity. Metaplasticity has been functionally observed but the molecular basis is not well understood. Here, we report that stimulation which induces LTP recruits GluN2B-lacking GluN1/GluN3 NMDA receptors (NMDARs) to excitatory synapses of hippocampal pyramidal neurons. These unconventional receptors may compete against conventional GluN1/GluN2 NMDARs to favor synaptic depotentiation in response to subsequent "LTP-inducing" stimulation. These results implicate glycinergic GluN1/GluN3 NMDAR as molecular brakes on excessive synaptic strengthening, suggesting a role for these receptors in the brain that has previously been elusive.

Utilizing GCaMP transgenic mice to monitor endogenous Gq/11-coupled receptors.

The family of GCaMPs are engineered proteins that contain Ca(2+) binding motifs within a circularly permutated variant of the Aequorea Victoria green fluorescent protein (cp-GFP). The rapidly advancing field of utilizing GCaMP reporter constructs represents a major step forward in our ability to monitor intracellular Ca(2+) dynamics. With the use of these genetically encoded Ca(2+) sensors, investigators have studied activation of endogenous Gq types of G protein-coupled receptors (GPCRs) and subsequent rises in intracellular calcium. Escalations in intracellular Ca(2+) from GPCR activation can be faithfully monitored in space and time as an increase in fluorescent emission from these proteins. Further, transgenic mice are now commercially available that express GCaMPs in a Cre recombinase dependent fashion. These GCaMP reporter mice can be bred to distinct Cre recombinase driver mice to direct expression of this sensor in unique populations of cells. Concerning the central nervous system (CNS), sources of calcium influx, including those arising from Gq activation can be observed in targeted cell types like neurons or astrocytes. This powerful genetic method allows simultaneous monitoring of the activity of dozens of cells upon activation of endogenous Gq-coupled GPCRs. Therefore, in combination with pharmacological tools, this strategy of monitoring GPCR activation is amenable to analysis of orthosteric and allosteric ligands of Gq-coupled receptors in their endogenous environments.

Care practices and traditional beliefs related to neonatal jaundice in northern Vietnam: a population-based, cross-sectional descriptive study.

BACKGROUND: The National Hospital of Pediatrics in Vietnam performed >200 exchange transfusions annually (2006-08), often on infants presenting encephalopathic from lower-level hospitals. As factors delaying care-seeking are not known, we sought to study care practices and traditional beliefs relating to neonatal jaundice in northern Vietnam. METHODS: We conducted a prospective, cross-sectional, population-based, descriptive study from November 2008 through February 2010. We prospectively identified mothers of newborns through an on-going regional cohort study. Trained research assistants administered a 78-item questionnaire to mothers during home visits 14-28 days after birth except those we could not contact or whose babies remained hospitalized at 28 days. RESULTS: We enrolled 979 mothers; 99% delivered at a health facility. Infants were discharged at a median age of 1.35 days. Only 11% received jaundice education; only 27% thought jaundice could be harmful. During the first week, 77% of newborns were kept in dark rooms. Only 2.5% had routine follow-up before 14 days. Among 118 mothers who were worried by their infant's jaundice but did not seek care, 40% held non-medical beliefs about its cause or used traditional therapies instead of seeking care. Phototherapy was uncommon: 6 (0.6%) were treated before discharge and 3 (0.3%) on readmission. However, there were no exchange transfusions, kernicterus cases, or deaths. CONCLUSIONS: Early discharge without follow-up, low maternal knowledge, cultural practices, and use of traditional treatments may limit or delay detection or care-seeking for jaundice. However, in spite of the high prevalence of these practices and the low frequency of treatment, no bad outcomes were seen in this study of nearly 1,000 newborns.

Home-use icterometry in neonatal hyperbilirubinaemia: Cluster-randomised controlled trial in Vietnam.

AIM: To determine whether home-use icterometry improves parental recognition of neonatal jaundice, early care seeking and treatment to minimize risks of bilirubin encephalopathy. METHODS: Cluster-randomised controlled trial of community-level icterometry used at home by mothers in Chi Linh, Vietnam. Rural health-care workers identified and enrolled term newborns. Post-partum mothers received jaundice education and icterometry instructions and were cluster-randomised by commune. Cases received icterometers (icterometer group (IG)) and controls did not (control group (CG)). Subjects received mobile telephone calls from post-natal days 2-7 to determine maternal recognition by visual inspection and icterometer detection of jaundice (≥ 3.0 on five-point scale). Mothers without telephones, premature newborns (<35 weeks) or newborns hospitalised >5 days were excluded. RESULTS: Three hundred fifty-two subjects were enrolled (183 IG and 169 CG), of whom 11 (3.4%) were lost to telephone follow-up. Jaundice was recognised and/or detected in 94 (27%) of all newborns. Icterometry helped 11 mothers (6%) detect neonatal jaundice that was not visually recognised by IG mothers. Detection by IG mothers was not statistically greater than CG mothers (P = 0.09). Follow-up care seeking was 8% in both groups (P = 0.2), and 11% of jaundiced newborns received treatment (9% IG vs. 16% CG, P = 0.3). Newborns who received care had bilirubin measurements that averaged 257 µmol/L IG vs. 322 µmol/L CG (P = 0.3). There were no deaths. CONCLUSIONS: In this pilot study, home-use icterometry may help improve parental detection of jaundice in rural Vietnam. However, larger studies are necessary to determine the changes in recognition, care seeking and treatment.

Contrasting actions of group I metabotropic glutamate receptors in distinct mouse striatal neurones.

In mouse striatum, metabotropic glutamate receptor (mGluR) activation leads to several modulatory effects in synaptic transmission. These effects range from dampening of glutamate release from excitatory terminals to depolarization of divergent classes of interneurones. We compared the action of group I mGluR activation on several populations of striatal neurones using a combination of genetic identification, electrophysiology, and Ca(2+) imaging techniques. Patch-clamp recordings from spiny projection neurones (SPNs) and various interneurone populations demonstrated that the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) robustly depolarizes several interneurone classes that form GABAergic synapses onto SPNs. We further utilized the genetic reporter mouse strain Ai38, which expresses the calcium indicator protein GCaMP3 in a Cre-dependent manner. Breeding Ai38 mice with various neurone selective, promoter-driven Cre recombinase mice resulted in GCaMP3 expression in defined cell populations in striatum. Consistent with our electrophysiological findings, group I agonist applications increased intracellular levels of calcium ([Ca(2+)]i) in all interneurone populations tested. We also found that acute DHPG application evoked a transient, rapid increase in [Ca(2+)]i from only a small percentage of identifiable SPNs. Surprisingly, this fast [Ca(2+)]i response exhibited a robust enhancement or sensitization, in a calcium-dependent fashion. Following several procedures to increase [Ca(2+)]i, the vast majority of SPNs responded with rapid changes in [Ca(2+)]i to mGluR agonists in a time-dependent fashion. These findings extend our understanding on group I mGluR influence of striatal output via powerful, local GABAergic connections in addition to [Ca(2+)]i dynamics that impact on activity or spike-timing-dependent forms of synaptic plasticity.

Maternal or neonatal infection: association with neonatal encephalopathy outcomes.

BACKGROUND: Perinatal infection may potentiate brain injury among children born preterm. The objective of this study was to examine whether maternal and/or neonatal infection are associated with adverse outcomes among term neonates with encephalopathy. METHODS: This study is a cohort study of 258 term newborns with encephalopathy whose clinical records were examined for signs of maternal infection (chorioamnionitis) and infant infection (sepsis). Multivariate regression was used to assess associations between infection, pattern, and severity of injury on neonatal magnetic resonance imaging, as well as neurodevelopment at 30 mo (neuromotor examination, or Bayley Scales of Infant Development, second edition mental development index <70 or Bayley Scales of Infant Development, third edition cognitive score <85). RESULTS: Chorioamnionitis was associated with lower risk of moderate-severe brain injury (adjusted odds ratio: 0.3; 95% confidence interval: 0.1-0.7; P = 0.004) and adverse cognitive outcome in children when compared with no chorioamnionitis. Children with signs of neonatal sepsis were more likely to exhibit watershed predominant injury than those without (P = 0.007). CONCLUSION: Among neonates with encephalopathy, chorioamnionitis was associated with a lower risk of brain injury and adverse outcomes, whereas signs of neonatal sepsis carried an elevated risk. The etiology of encephalopathy and timing of infection and its associated inflammatory response may influence whether infection potentiates or mitigates injury in term newborns.

Distinct roles of synaptic and extrasynaptic GABAAreceptors in striatal inhibition dynamics.

Striatonigral and striatopallidal projecting medium spiny neurons (MSNs) express dopamine D1 (D1+) and D2 receptors (D2+), respectively. Both classes receive extensive GABAergic input via expression of synaptic, perisynaptic, and extrasynaptic GABAA receptors. The activation patterns of different presynaptic GABAergic neurons produce transient and sustained GABAA receptor-mediated conductance that fulfill distinct physiological roles. We performed single and dual whole cell recordings from striatal neurons in mice expressing fluorescent proteins in interneurons and MSNs. We report specific inhibitory dynamics produced by distinct activation patterns of presynaptic GABAergic neurons as source of synaptic, perisynaptic, and extrasynaptic inhibition. Synaptic GABAA receptors in MSNs contain the α2, γ2, and a ß subunit. In addition, there is evidence for the developmental increase of the α1 subunit that contributes to faster inhibitory post-synaptic current (IPSC). Tonic GABAergic currents in MSNs from adult mice are carried by extrasynaptic receptors containing the α4 and δ subunit, while in younger mice this current is mediated by receptors that contain the α5 subunit. Both forms of tonic currents are differentially expressed in D1+ and D2+ MSNs. This study extends these findings by relating presynaptic activation with pharmacological analysis of inhibitory conductance in mice where the ß3 subunit is conditionally removed in fluorescently labeled D2+ MSNs and in mice with global deletion of the δ subunit. Our results show that responses to low doses of gaboxadol (2 µM), a GABAA receptor agonist with preference to δ subunit, are abolished in the δ but not the ß3 subunit knock out mice. This suggests that the ß3 subunit is not a component of the adult extrasynaptic receptor pool, in contrast to what has been shown for tonic current in young mice. Deletion of the ß3 subunit from D2+ MSNs however, removed slow spontaneous IPSCs, implicating its role in mediating synaptic input from striatal neurogliaform interneurons.