KCNA2 IgG autoimmunity in neuropsychiatric diseases.

BACKGROUND: Autoantibodies against the potassium voltage-gated channel subfamily A member 2 (KCNA2) have been described in a few cases of neuropsychiatric disorders, but their diagnostic and pathophysiological role is currently unknown, imposing challenges to medical practice. DESIGN / METHODS: We retrospectively collected comprehensive clinical and paraclinical data of 35 patients with KCNA2 IgG autoantibodies detected in cell-based and tissue-based assays. Patients' sera and cerebrospinal fluid (CSF) were used for characterization of the antigen, clinical-serological correlations, and determination of IgG subclasses. RESULTS: KCNA2 autoantibody-positive patients (n = 35, median age at disease onset of 65 years, range of 16-83 years, 74 % male) mostly presented with cognitive impairment and/or epileptic seizures but also ataxia, gait disorder and personality changes. Serum autoantibodies belonged to IgG3 and IgG1 subclasses and titers ranged from 1:32 to 1:10,000. KCNA2 IgG was found in the CSF of 8/21 (38 %) patients and in the serum of 4/96 (4.2 %) healthy blood donors. KCNA2 autoantibodies bound to characteristic anatomical areas in the cerebellum and hippocampus of mammalian brain and juxtaparanodal regions of peripheral nerves but reacted exclusively with intracellular epitopes. A subset of four KCNA2 autoantibody-positive patients responded markedly to immunotherapy alongside with conversion to seronegativity, in particular those presenting an autoimmune encephalitis phenotype and receiving early immunotherapy. An available brain biopsy showed strong immune cell invasion. KCNA2 autoantibodies occurred in less than 10 % in association with an underlying tumor. CONCLUSION: Our data suggest that KCNA2 autoimmunity is clinically heterogeneous. Future studies should determine whether KCNA2 autoantibodies are directly pathogenic or develop secondarily. Early immunotherapy should be considered, in particular if autoantibodies occur in CSF or if clinical or diagnostic findings suggest ongoing inflammation. Suspicious clinical phenotypes include autoimmune encephalitis, atypical dementia, new-onset epilepsy and unexplained epileptic seizures.

Seizure Semiology in Antibody-Associated Autoimmune Encephalitis.

BACKGROUND AND OBJECTIVES: To assess seizure characteristics in antibody (ab)-associated autoimmune encephalitis (ab + AE) with the 3 most prevalent abs against N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), and glutamic acid decarboxylase (GAD). METHODS: Multicenter nationwide prospective cohort study of the German Network for Research in Autoimmune Encephalitis. RESULTS: Three hundred twenty patients with ab + AE were eligible for analysis: 190 NMDAR+, 89 LGI1+, and 41 GAD+. Seizures were present in 113 (60%) NMDAR+, 69 (78%) LGI1+, and 26 (65%) GAD+ patients and as leading symptoms for diagnosis in 53 (28%) NMDAR+, 47 (53%) LGI+, and 20 (49%) GAD+ patients. Bilateral tonic-clonic seizures occurred with almost equal frequency in NMDAR+ (38/51, 75%) and GAD+ (14/20, 70%) patients, while being less common in LGI1+ patients (27/59, 46%). Focal seizures occurred less frequently in NMDAR+ (67/113; 59%) than in LGI1+ (54/69, 78%) or in GAD+ patients (23/26; 88%). An aura with déjà-vu phenomenon was nearly specific in GAD+ patients (16/20, 80%). Faciobrachial dystonic seizures (FBDS) were uniquely observed in LGI1+ patients (17/59, 29%). Status epilepticus was reported in one-third of NMDAR+ patients, but only rarely in the 2 other groups. The occurrence of seizures was associated with higher disease severity only in NMDAR+ patients. DISCUSSION: Seizures are a frequent and diagnostically relevant symptom of ab + AE. Whereas NMDAR+ patients had few localizing semiological features, semiology in LGI1+ and GAD+ patients pointed toward a predominant temporal seizure onset. FBDS are pathognomonic for LGI1 + AE. Status epilepticus seems to be more frequent in NMDAR + AE.

Informed DEcision for cerebrospinal fluid analysis after epiLeptic seizures- the IDEAL-score: A development and validation study.

BACKGROUND: This observational study was done to develop a score based on clinical predictors that enables a guided decision for the necessity of cerebrospinal fluid (CSF) analysis after first unprovoked epileptic seizures and to validate this score in a retrospective patient cohort. METHODS: Clinical predictors were identified by two panels of epilepsy experts and selected according to content validity ratios. Based on these predictors a score was created and applied to a cohort of patients with first epileptic seizures. RESULTS: The "IDEAL score" consists of 9 items (fever, prolonged disturbance of consciousness, headache, imaging results, cognitive dysfunction, status epilepticus, malignancy, autoimmune encephalitis symptoms) that are collected at two different time points (< 3 h [A-score]; > 3 h [B-score] after hospital admittance). A CSF analysis is recommended, if at least one clinical finding is present, either one of the items evaluated during the acute phase (A-score) or later in the diagnostic process (B-score). In 41 patients (13%) CSF analysis provided essential clues to the cause of the seizure. The combined IDEAL score reached a sensitivity of 98%, a specificity of 53%, a positive predictive value of 24% and a negative predictive value of 99% in this patient cohort. CONCLUSIONS: A CSF analysis after first epileptic seizures provided decisive etiological findings in only 13% of all investigated patients. The IDEAL score offers clinicians a simple and easy-to-implement algorithm to assess the necessity of a CSF analysis, and to prevent unnecessary diagnostic procedures.

Characterization of Hippocampal Adult-borne Granule Cells in a Transient Cerebral Ischemia Model.

Long-term consequences of stroke significantly impair the quality of life in a growing population of stroke survivors. Hippocampal adult neurogenesis has been hypothesized to play a role in the pathophysiology of cognitive and neuropsychiatric long-term sequelae of stroke. Reliable animal models of stroke are paramount to understanding their biomechanisms and to advancing therapeutic strategies. We present a detailed protocol of a transient cerebral ischemia model which does not cause direct ischemic damage in the hippocampus, allowing investigations into the pathophysiology of long-term neurocognitive deficits of stroke. Furthermore, we describe a protocol for obtaining acute hippocampal slices for the purpose of electrophysiological and morphological characterization of adult-borne granule cells. Particularities relating to performing electrophysiological recordings from small cells, such as immature adult-borne granule cells, are also discussed. The present protocol may be complemented by multi-modal investigations (behavioral, morpho-structural, biochemical), to hopefully facilitate research and advances into the long-term sequelae of stroke and the discovery of new therapeutic opportunities.

Sepsis promotes gliogenesis and depletes the pool of radial glia like stem cells in the hippocampus.

Sepsis associated encephalopathy (SAE) is a major complication of patients surviving sepsis with a prevalence up to 70%. Although the initial pathophysiological events of SAE are considered to arise during the acute phase of sepsis, there is increasing evidence that SAE leads to persistent brain dysfunction with severe cognitive decline in later life. Previous studies suggest that the hippocampal formation is particularly involved leading to atrophy in later stages. Thereby, the underlying cellular mechanisms are only poorly understood. Here, we hypothesized that endogenous neural stems cells and adult neurogenesis in the hippocampus are impaired following sepsis and that these changes may contribute to persistent cognitive dysfunction when the animals have physically fully recovered. We used the murine sepsis model of peritoneal contamination and infection (PCI) and combined different labeling methods of precursor cells with confocal microscopy studies to assess the neurogenic niche in the dentate gyrus at day 42 postsepsis. We found that following sepsis i) gliogenesis is increased, ii) the absolute number of radial glia-like cells (type 1 cells), which are considered the putative stem cells, is significantly reduced, iii) the generation of new neurons is not significantly altered, while iv) the synaptic spine maturation of new neurons is impaired with a shift to expression of more immature and less mature spines. In conclusion, sepsis mainly leads to depletion of the neural stem cell pool and enhanced gliogenesis in the dentate gyrus which points towards an accelerated aging of the hippocampus due to septic insult.

Current and Desired Quality of Life in People with Parkinson's Disease: the Calman Gap Increases with Depression.

Hopes and expectations often differ from current experiences. This so-called Calman gap influences quality of life (QoL). We investigated this gap in 77 elderly patients with Parkinson's disease (PD), 25 patients with epilepsy, and 39 age-matched healthy older adults using a novel QoL questionnaire, where current and desired states were marked on a visual analogue scale. We studied the relationships between (1) epidemiological factors, (2) current and desired QoL, as well as the difference between the latter two. Current QoL was determined by depression, education level, living situation, and condition (PD, epilepsy, control). In contrast, desired QoL was essentially determined by the presence of a disease (condition), education level, and age, but not by depression. In particular, the presence of PD, lower education level, and higher age was correlated with lower expectations. In patients with PD, the gap between the current and desired QoL was largest for pain and physical functions. Accordingly, the significant effects of depression were observed only for mean current QoL, but not for desired QoL. Therefore, depression mainly influences current but not desired QoL in patients with PD. Depressed patients with PD had significantly worse QoL than PD patients without depression, although they both had almost the same desired QoL and hence, depressed PD patients had a larger Calman gap between current and desired QoL.

Can commercially available wearable EEG devices be used for diagnostic purposes? An explorative pilot study.

Electroencephalography (EEG) is a core element in the diagnosis of epilepsy syndromes and can help to monitor antiseizure treatment. Mobile EEG (mEEG) devices are increasingly available on the consumer market and may offer easier access to EEG recordings especially in rural or resource-poor areas. The usefulness of consumer-grade devices for clinical purposes is still underinvestigated. Here, we compared EEG traces of a commercially available mEEG device (Emotiv EPOC) to a simultaneously recorded clinical video EEG (vEEG). Twenty-two adult patients (11 female, mean age 40.2 years) undergoing noninvasive vEEG monitoring for clinical purposes were prospectively enrolled. The EEG recordings were evaluated by 10 independent raters with unmodifiable view settings. The individual evaluations were compared with respect to the presence of abnormal EEG findings (regional slowing, epileptiform potentials, seizure pattern). Video EEG yielded a sensitivity of 56% and specificity of 88% for abnormal EEG findings, whereas mEEG reached 39% and 85%, respectively. Interrater reliability coefficients were better in vEEG as compared to mEEG (ϰ = 0.50 vs. 0.30), corresponding to a moderate and fair agreement. Intrarater reliability between mEEG and vEEG evaluations of simultaneous recordings of a given participant was moderate (ϰ = 0.48). Given the limitations of our exploratory pilot study, our results suggest that vEEG is superior to mEEG, but that mEEG can be helpful for diagnostic purposes. We present the first quantitative comparison of simultaneously acquired clinical and mobile consumer-grade EEG for a clinical use-case.

Data on adherence to medication in neurological patients using the German Stendal Adherence to Medication Score (SAMS).

This article presents demographic, socio-economic and detailed adherence to medication data from 429 patients with neurological disorders. Adherence to medication was assessed using the German Stendal Adherence to Medication Score (SAMS). The SAMS questionnaire includes 18 questions forming a cumulative scale (0 - 72) in which 0 indicates complete adherence and 72 complete non-adherence. The SAMS covers different aspects of adherence/non-adherence, such as intentional modification of medication, missing knowledge about reasons/dosage/timing of medication and forgetting to take medication. The dataset allows determining different reasons and clusters of adherence to medication. The dataset can be used as by clinicians, pharmacists and academia for further research and as reference. The dataset can also be used in a large range of other topics where demographic and socio-economic parameters are relevant. The data presented herein is associated with the research article "Clusters of non-adherence to medication in neurological patients" [1] and available on Mendeley https://data.mendeley.com/datasets/ny2krr3vgg/1.

Clusters of non-adherence to medication in neurological patients.

BACKGROUND: Non-adherence to medication is a common and serious problem in health care. To develop more effective interventions to improve adherence, there is a need for a better understanding of the individual types of non-adherence. OBJECTIVE: To determine clusters of non-adherence in neurological patients using a complex adherence questionnaire. METHODS: In this observational, monocentric study 500 neurological patients (consecutive sampling) were recruited in the Department of Neurology at the Jena University Hospital, Germany (outpatient clinic, wards) over a period of 5 months. Patients with severe dementia or delirium who were unable to complete the questionnaire were excluded. Due to missing adherence data, in total, 429 patients with common neurological disorders were analyzed. Different types and clusters of non-adherence using the German Stendal Adherence to Medication Score (SAMS) were determined. RESULTS: For the 429 patients, the mean age was 63 years (SD = 16), 189 were female. According to the SAMS total score 74 (17.2%) were fully adherent, 252 (58.7%) showed moderate non-adherence and 103 (24%) showed clinically significant non-adherence. Principal component analysis with Varimax rotation revealed three independent factors explaining 60.5% of the SAMS variance. The bulk of non-adherence was attributed to modifications of medication (41.7%) and forgetting to take the medication (33.2%) followed by lack of knowledge 25.1% about reasons, dosages and time of administration for the medication. CONCLUSIONS: Intentional non-adherence was the primary self-reported behavior identified among non-adherent neurological participants. Many patients modified their prescribed medication due to various reasons, such as side effects or lacking effect. Different clusters require different interventions. While for the cluster ´forgetfulness' the reduction of poly-medication and a behavioral approach with reminders seems reasonable, patients in cluster ´missing knowledge' and cluster ´modifications' may need an educational approach.

Comparison of anonymous versus nonanonymous responses to a medication adherence questionnaire in patients with Parkinson's disease.

PURPOSE: Adherence to medication can be assessed by various self-report questionnaires. One could hypothesize that survey respondents tend to answer questions in a manner that will be viewed favorably by others. We aimed to answer if anonymous and nonanonymous responses to a questionnaire on medication adherence differ. PATIENTS AND METHODS: Adherence was assessed with the German Stendal Adherence with Medication Score (SAMS), which includes 18 questions with responses based on a 5-point Likert scale. Anonymous data from 40 subjects were collected during a symposium for patients with Parkinson's disease (PD), and nonanonymous data were obtained from 40 outpatient-clinic PD patients at the Department of Neurology. RESULTS: The two groups (anonymous self-reported questionnaire and nonanonymous) did not differ in terms of demographical characteristics and the SAMS sum score. However, anonymously collected data showed significant higher scoring for the item 6 ("Do you forget your medications?") than the data collected nonanonymously (P=0.017). All other items of the SAMS did not significantly differ between both groups. CONCLUSION: Overall assessment of adherence does not depend on whether the patient remains anonymous or not. There seems to be no relevant social desirability bias in nonanonymous responses.

Stroke Accelerates and Uncouples Intrinsic and Synaptic Excitability Maturation of Mouse Hippocampal DCX+ Adult-Born Granule Cells.

Stroke robustly stimulates adult neurogenesis in the hippocampal dentate gyrus. It is currently unknown whether this process induces beneficial or maladaptive effects, but morphological and behavioral studies have reported aberrant neurogenesis and impaired hippocampal-dependent memory following stroke. However, the intrinsic function and network incorporation of adult-born granule cells (ABGCs) after ischemia is unclear. Using patch-clamp electrophysiology, we evaluated doublecortin-positive (DCX+) ABGCs as well as DCX- dentate gyrus granule cells 2 weeks after a stroke or sham operation in DCX/DsRed transgenic mice of either sex. The developmental status, intrinsic excitability, and synaptic excitability of ABGCs were accelerated following stroke, while dendritic morphology was not aberrant. Regression analysis revealed uncoupled development of intrinsic and network excitability, resulting in young, intrinsically hyperexcitable ABGCs receiving disproportionately large glutamatergic inputs. This aberrant functional maturation in the subgroup of ABGCs in the hippocampus may contribute to defective hippocampal function and increased seizure susceptibility following stroke.SIGNIFICANCE STATEMENT Stroke increases hippocampal neurogenesis but the functional consequences of the postlesional response is mostly unclear. Our findings provide novel evidence of aberrant functional maturation of newly generated neurons following stroke. We demonstrate that stroke not only causes an accelerated maturation of the intrinsic and synaptic parameters of doublecortin-positive, new granule cells in the hippocampus, but that this accelerated development does not follow physiological dynamics due to uncoupled intrinsic and synaptic maturation. Hyperexcitable immature neurons may contribute to disrupted network integration following stroke.

The first seizure as an indicator of epilepsy.

PURPOSE OF REVIEW: Optimal treatment of a possible first seizure depends on the determination if the paroxysmal event was an epileptic seizure and was on an accurate assessment of the recurrence risk. This review summarizes evidence from the last 5 years addressing the following questions: Is it an epileptic seizure? Is it a first seizure? When does a first seizure indicate epilepsy? RECENT FINDINGS: The acts of taking and interpreting the history from patients and witnesses continue to be the most important tools in the diagnosis of first seizures. Assessment tools based on factual questions and the observation of patients' conversational behaviour can contribute to the differentiation of patients with epileptic seizures from those who have experienced other types of transient loss of consciousness (TLOC). At present, only about 40% of patients are seen after their very first seizure. Tests have a limited role in the initial diagnosis of a seizure but help to determine the recurrence risk based on the cause. A remote symptomatic cause and detection of epileptiform discharges are associated with a recurrence risk of at least 60% and allow a diagnosis of epilepsy after a first seizure. The risk of recurrence after an acute symptomatic first seizure is well below 60%. SUMMARY: Expert history-taking continues to be the most important tool in the diagnosis of a first seizure. Cause is the most important determinant of the recurrence risk. Unfortunately, there is currently no formula enabling a precise calculation of an individualized recurrence risk.

Adult hippocampal neurogenesis poststroke: More new granule cells but aberrant morphology and impaired spatial memory.

Stroke significantly stimulates neurogenesis in the adult dentate gyrus, though the functional role of this postlesional response is mostly unclear. Recent findings suggest that newborn neurons generated in the context of stroke may fail to correctly integrate into pre-existing networks. We hypothesized that increased neurogenesis in the dentate gyrus following stroke is associated with aberrant neurogenesis and impairment of hippocampus-dependent memory. To address these questions we used the middle cerebral artery occlusion model (MCAO) in mice. Animals were housed either under standard conditions or with free access to running wheels. Newborn granule cells were labelled with the thymidine analoque EdU and retroviral vectors. To assess memory performance, we employed a modified version of the Morris water maze (MWM) allowing differentiation between hippocampus dependent and independent learning strategies. Newborn neurons were morphologically analyzed using confocal microscopy and Neurolucida system at 7 weeks. We found that neurogenesis was significantly increased following MCAO. Animals with MCAO needed more time to localize the platform and employed less hippocampus-dependent search strategies in MWM versus controls. Confocal studies revealed an aberrant cell morphology with basal dendrites and an ectopic location (e.g. hilus) of new granule cells born in the ischemic brain. Running increased the number of new neurons but also enhanced aberrant neurogenesis. Running, did not improve the general performance in the MWM but slightly promoted the application of precise spatial search strategies. In conclusion, ischemic insults cause hippocampal-dependent memory deficits which are associated with aberrant neurogenesis in the dentate gyrus indicating ischemia-induced maladaptive plasticity in the hippocampus.

Interactions of Human Autoantibodies with Hippocampal GABAergic Synaptic Transmission - Analyzing Antibody-Induced Effects ex vivo.

Autoantibodies (aAB) to the presynaptic located enzyme glutamate decarboxylase 65 (GAD65) are a characteristic attribute for a variety of autoimmune diseases of the central nervous system including subtypes of limbic encephalitis, stiff person-syndrome, cerebellar ataxia, and Batten's disease. Clinical signs of hyperexcitability and improvement of disease symptoms upon immunotherapy in some of these disorders suggest a possible pathogenic role of associated aAB. Recent experimental studies report inconsistent results regarding a direct pathogenic influence of anti-GAD65 aAB affecting inhibitory synaptic transmission in central GABAergic pathways. We here provide a method for direct evaluation of aAB-induced pathomechanisms in the intact hippocampal network. Purified patient IgG fractions containing aAB to GAD65 together with fixable lipophilic styryl dyes (FMdyes) are stereotactically injected into the hilus and the dentate gyrus in anesthetized mice. Twenty-four hours after intrahippocampal injection, acute hippocampal slices are prepared and transferred to a patch-clamp recording setup equipped with a fluorescence light source. Intraneural incorporated FMdyes show correct injection site for patch-clamp recording. Whole-cell patch-clamp recordings are performed from granule cells in the dentate gyrus and extracellular stimulation is applied in the border area of the dentate gyrus-hilus region to stimulate GABAergic afferents arising from parvalbumin positive basket cells. GABA-A receptor mediated inhibitory postsynaptic currents (IPSC) and miniature IPSC are recorded after blocking glutamatergic transmission. This approach allows investigation of potential aAB-induced effects on GABA-A receptor signaling ex vivo in an intact neuronal network. This offers several advantages compared to experimental procedures used in previous studies by in vitro AB preincubation of primary neurons or slice preparations. Furthermore, this method requires only small amounts of patient material that are often limited in rare diseases.

Two distinct populations of doublecortin-positive cells in the perilesional zone of cortical infarcts.

BACKGROUND: Recovery following stroke depends on cellular plasticity in the perilesional zone (PZ). Doublecortin (DCX), a protein mainly labeling immature neurons in neurogenic niches is also highly expressed in the vicinity of focal cortical infarcts. Notably, the number of DCX+ cells positively correlates with the recovery of functional deficits after stroke though the nature and origin of these cells remains unclear. RESULTS: In the present study, we aimed to characterize the population of DCX+ cells in the vicinity of ischemic infarcts in a mouse model in detail. Employing a photothrombosis model, distinct immunohistochemical techniques, stereology and confocal microscopy, we show that: i) DCX+ cells in the perilesional zone do not constitute a homogenous population and two cell types, stellate and polar cells can be distinguished according to their morphology. ii) Stellate cells are mainly located in the lateral and medial vicinity of the insult and express astrocytic markers. iii) Polar cells are found almost exclusively in the corpus callosum region including in the preserved deep cortical layers close to the subventricular zone (SVZ). Further, they do not show any colocalisation of glial markers. Polar morphology and distribution suggest a migration towards the lesion. CONCLUSIONS: In summary, our findings provide evidence that in mice DCX+ cells in the perilesional zone of cortical infarcts comprise a distinct cell population and the majority of cells are of glial nature.

Serial FDG PET/CT in autoimmune encephalitis with faciobrachial dystonic seizures.

Autoimmune encephalitis (AE) is increasingly recognized as a nonparaneoplastic disorder with autoantibodies to neuronal proteins. Although MRI is frequently unremarkable, PET imaging might contribute to identification of affected brain regions in distinct AE. We report on serial FDG PET in a 72-year-old man with particular AE subtype, with potassium channel complex antibodies and prodromal stage with dystonic seizures. Serial FDG PET/CT revealed that besides limbic structures, basal ganglia are centrally involved and presumably play a key role in the generation of dystonic seizures.

Connexin expression by radial glia-like cells is required for neurogenesis in the adult dentate gyrus.

In the adult dentate gyrus, radial glia-like cells represent putative stem cells generating neurons and glial cells. Here, we combined patch-clamp recordings, biocytin filling, immunohistochemistry, single-cell transcript analysis, and mouse transgenics to test for connexin expression and gap junctional coupling of radial glia-like cells and its impact on neurogenesis. Radial glia-like cells were identified in mice expressing EGFP under control of the nestin and gfap promoters. We show that a majority of Radial glia-like cells are coupled and express Cx43. Neuronal precursors were not coupled. Mice lacking Cx30 and Cx43 in GFAP-positive cells displayed almost complete inhibition of proliferation and a significant decline in numbers of radial glia-like cells and granule neurons. Inducible virus-mediated ablation of connexins in the adult hippocampus also reduced neurogenesis. These findings strongly suggest the requirement of connexin expression by radial glia-like cells for intact neurogenesis in the adult brain and point to possible communication pathways of these cells.

Satellite NG2 progenitor cells share common glutamatergic inputs with associated interneurons in the mouse dentate gyrus.

Several studies have provided evidence that NG2-expressing (NG2(+)) progenitor cells are anatomically associated to neurons in gray matter areas. By analyzing the spatial distribution of NG2(+) cells in the hilus of the mouse dentate gyrus, we demonstrate that NG2(+) cells are indeed closely associated to interneurons. To define whether this anatomical proximity reflected a specific physiological interaction, we performed patch-clamp recordings on hilar NG2(+) cells and interneurons between 3 and 21 postnatal days. We first observed that hilar NG2(+) cells exhibit spontaneous glutamatergic EPSCs (sEPSCs) whose frequency and amplitude increase during the first 3 postnatal weeks. At the same time, the rise time and decay time of sEPSCs significantly decreased, suggesting that glutamatergic synapses in NG2(+) cells undergo a maturation process that is reminiscent of what has been reported in neurons during the same time period. We also observed that hilar interneurons and associated NG2(+) cells are similarly integrated into the local network, receiving excitatory inputs from both granule cells and CA3 pyramidal neurons. By performing pair recordings, we found that bursts of activity induced by GABAergic antagonists were strongly synchronized between both cell types and that the amplitude of these bursts was positively correlated. Finally, by applying carbachol to increase EPSC activity, we observed that closely apposed cells were more likely to exhibit synchronized EPSCs than cells separated by >200 microm. The finding that NG2(+) cells are sensing patterns of activity arising in closely associated neurons suggests that NG2(+) cell function is finely regulated by the local network.