Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells.

Neurons are frequently classified into distinct types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 4,200 mouse visual cortical GABAergic interneurons and reconstructed the local morphologies of 517 of those neurons. We find that most transcriptomic types (t-types) occupy specific laminar positions within visual cortex, and, for most types, the cells mapping to a t-type exhibit consistent electrophysiological and morphological properties. These properties display both discrete and continuous variation among t-types. Through multimodal integrated analysis, we define 28 met-types that have congruent morphological, electrophysiological, and transcriptomic properties and robust mutual predictability. We identify layer-specific axon innervation pattern as a defining feature distinguishing different met-types. These met-types represent a unified definition of cortical GABAergic interneuron types, providing a systematic framework to capture existing knowledge and bridge future analyses across different modalities.

Percutaneous wide bore needle biopsy for spinal lesions using the kyphoplasty cannula-a technical note.

PURPOSE: Management of vertebral and discovertebral lesions depends on highly specific modalities like biopsy and histopathology. The transpedicular and transforaminal routes have gained popularity for obtaining samples for diagnosing these lesions. Sample inadequacy plays an important part in lowering the diagnostic accuracy. Present study introduces a technical modification by using a kyphoplasty cannula and pituitary forceps through it thus improving sample adequacy and diagnostic accuracy. METHODS: Seventy-one patients with radiological evidence of spinal lesions from T1 to S1 were included. After obtaining samples via the transpedicular route they were sent for aerobic, anaerobic, acid fast bacilli & fungal cultures, Mycobacterium Tuberculosis/Radio Immuno Frequency (MTB/RIF) Assay and histopathological examination. In lesions with minimal vertebral erosions the transforaminal route was used to obtain samples from the disc space. RESULTS: Sixty-eight patients (95.8%) had a definite diagnosis of which 37 patients (54.4%) tested positive for vertebral osteomyelitis/discitis. All the samples were found to be adequate on histopathological examination. The remaining 3 patients showed chronic inflammation and responded to oral and intravenous antibiotics. None of the patients underwent repeat biopsy. There were no perioperative complications. CONCLUSIONS: Percutaneous transpedicular biopsy has evolved as the intervention of choice in diagnosing radiologically proven vertebral body lesions. Our technique of using a pituitary forceps through a cannula is highly effective in getting an adequate representative sample with excellent accuracy in diagnosis. This procedure is beneficial for soft tissue lesions and for infective pathology especially discitis.

Joint inference of discrete cell types and continuous type-specific variability in single-cell datasets with MMIDAS.

Reproducible definition and identification of cell types is essential to enable investigations into their biological function, and understanding their relevance in the context of development, disease and evolution. Current approaches model variability in data as continuous latent factors, followed by clustering as a separate step, or immediately apply clustering on the data. We show that such approaches can suffer from qualitative mistakes in identifying cell types robustly, particularly when the number of such cell types is in the hundreds or even thousands. Here, we propose an unsupervised method, MMIDAS, which combines a generalized mixture model with a multi-armed deep neural network, to jointly infer the discrete type and continuous type-specific variability. Using four recent datasets of brain cells spanning different technologies, species, and conditions, we demonstrate that MMIDAS can identify reproducible cell types and infer cell type-dependent continuous variability in both uni-modal and multi-modal datasets.

Spinal Rosai-Dorfman disease-a report of 2 cases and review of literature.

INTRODUCTION: Rosai-Dorfman Disease (RDD) is a rare benign histiocytic disease that infrequently affects the spine. We report two cases of spinal RDD and review the relevant literature. This report addresses the various diagnostic dilemmas related to the evaluation of Spinal RDD and its treatment. CASE PRESENTATION: Case 1: A 32-year-old male presented with low back pain and left anterior thigh for last 8 months. On examination, there was sensory diminution on inner aspects of the thigh with an absent left knee jerk. CT/MRI scans revealed an extradural lesion at L2/3 with neural compression. PET scan showed several hypermetabolic lesions in ribs, humerus, femur, and vertebrae. He underwent en bloc excision of the extradural mass with L2-3 pedicle screw-rod fixation and was later managed with chemotherapy. Case 2: A 42-year-old male presented with spastic paraparesis with urinary incontinence for the last 4 weeks. On examination, he had a neurological level of T6. MRI scan revealed a lesion in posterior elements of T6-7 compressing the spinal cord. He underwent T6-7 laminectomy with decompression. In both cases, the diagnosis was confirmed by histopathology and further managed by Hemato-oncologist. They both did well at 1-year follow-up with improvement in neurology. DISCUSSION: Spinal RDD to date remains a large diagnostic dilemma with no pathognomonic clinical or radiological features; mimicking many osteolytic lesions in the spine. The diagnosis is purely histopathological and immunological. The lesion's complete surgical excision is the mainstay of treatment with a better prognosis and decreased chances of recurrences.

Predictive and robust gene selection for spatial transcriptomics.

A prominent trend in single-cell transcriptomics is providing spatial context alongside a characterization of each cell's molecular state. This typically requires targeting an a priori selection of genes, often covering less than 1% of the genome, and a key question is how to optimally determine the small gene panel. We address this challenge by introducing a flexible deep learning framework, PERSIST, to identify informative gene targets for spatial transcriptomics studies by leveraging reference scRNA-seq data. Using datasets spanning different brain regions, species, and scRNA-seq technologies, we show that PERSIST reliably identifies panels that provide more accurate prediction of the genome-wide expression profile, thereby capturing more information with fewer genes. PERSIST can be adapted to specific biological goals, and we demonstrate that PERSIST's binarization of gene expression levels enables models trained on scRNA-seq data to generalize with to spatial transcriptomics data, despite the complex shift between these technologies.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types. We used image-based quantitative neuropathology to place 84 donors spanning the spectrum of AD pathology along a continuous disease pseudoprogression score and multiomic technologies to profile single nuclei from each donor, mapping their transcriptomes, epigenomes, and spatial coordinates to a common cell type reference with unprecedented resolution. Temporal analysis of cell-type proportions indicated an early reduction of Somatostatin-expressing neuronal subtypes and a late decrease of supragranular intratelencephalic-projecting excitatory and Parvalbumin-expressing neurons, with increases in disease-associated microglial and astrocytic states. We found complex gene expression differences, ranging from global to cell type-specific effects. These effects showed different temporal patterns indicating diverse cellular perturbations as a function of disease progression. A subset of donors showed a particularly severe cellular and molecular phenotype, which correlated with steeper cognitive decline. We have created a freely available public resource to explore these data and to accelerate progress in AD research at SEA-AD.org.

Connecting single-cell transcriptomes to projectomes in mouse visual cortex.

The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitions that include multiple cellular properties can offer additional insights into a neuron's role in brain circuits. While the Patch-seq method can investigate how transcriptomic properties relate to the local morphological and electrophysiological properties of cell types, linking transcriptomic identities to long-range projections is a major unresolved challenge. To address this, we collected coordinated Patch-seq and whole brain morphology data sets of excitatory neurons in mouse visual cortex. From the Patch-seq data, we defined 16 integrated morpho-electric-transcriptomic (MET)-types; in parallel, we reconstructed the complete morphologies of 300 neurons. We unified the two data sets with a multi-step classifier, to integrate cell type assignments and interrogate cross-modality relationships. We find that transcriptomic variations within and across MET-types correspond with morphological and electrophysiological phenotypes. In addition, this variation, along with the anatomical location of the cell, can be used to predict the projection targets of individual neurons. We also shed new light on infragranular cell types and circuits, including cell-type-specific, interhemispheric projections. With this approach, we establish a comprehensive, integrated taxonomy of excitatory neuron types in mouse visual cortex and create a system for integrated, high-dimensional cell type classification that can be extended to the whole brain and potentially across species.

Cell type matching in single-cell RNA-sequencing data using FR-Match.

Reference cell atlases powered by single cell and spatial transcriptomics technologies are becoming available to study healthy and diseased tissue at single cell resolution. One important use of these data resources is to compare cell types from new dataset with cell types in the reference atlases to evaluate their phenotypic similarities and differences, for example, for identifying novel cell types under disease conditions. For this purpose, rigorously-validated computational algorithms are needed to perform these cell type matching tasks that can compare datasets from different experiment platforms and sample types. Here, we present significant enhancements to FR-Match (v2.0)-a multivariate nonparametric statistical testing approach for matching cell types in query datasets to reference atlases. FR-Match v2.0 includes a normalization procedure to facilitate cross-platform cluster-level comparisons (e.g., plate-based SMART-seq and droplet-based 10X Chromium single cell and single nucleus RNA-seq and spatial transcriptomics) and extends the pipeline to also allow cell-level matching. In the use cases evaluated, FR-Match showed robust and accurate performance for identifying common and novel cell types across tissue regions, for discovering sub-optimally clustered cell types, and for cross-platform and cross-sample cell type matching.

Upper Cervical Leiomyoma in an Adolescent Male.

Introduction: Leiomyomas are benign epithelial tumors with a female preponderance usually in the uterus, gastro-intestinal tract and skin. They are well-capsulated tumors with no mitotic activity and little pleomorphism. Primary leiomyoma in the upper cervical spine region is rare and the occurrence of these lesions in young immunocompetent males is extremely rare. Case Report: A 15-year-old male had swelling over the nape of the neck for 4 years with slight difficulty in neck movements for a few months. Asymptomatic 4 years back be developed a painless swelling at the nape of the neck on the right side initially the size of a pea which gradually increased size. A 10x8cm firm, on-tender and non-pulsatile swelling at the nape of the neck on the right extending from the occipital nuchal line and crossing the midline up to the posterior border of the sternomastoid. The skin over the swelling wasn't adherent and the swelling did not reduce on neck movements. Neck movements were terminally restricted with restriction on rotation towards the right. Routine X-ray's and magnetic resonance imaging were suggestive of a soft tissue mass in the inter-muscular plane on the posterior aspect more on the right side with a cystic component and causing thinning of the C2 lamina with no intraspinal extension. Biopsy was done. Findings were suggestive of a spindle cell benign tumor. Posterior en bloc excision was planned and the lesion blog with the entire capsule was excised and sent for histopathology which revealed the lesion was a leiomyoma. The patient has shown no clinical or radiological evidence of recurrence at 4 year fol-low-up. Conclusion: Leiomyomas in the upper cervical spine is extremely rare in adolescent immunocom-petent male.

Autologous mesenchymal stem cells in the treatment of spinal aneurysmal bone cyst.

PURPOSE: We retrospectively analyzed a cohort of patients treated at our Centre with bone marrow concentrated (BMC) injection for aneurysmal bone cyst (ABC) of the spine, in order to propose this treatment as a valid alternative for the management of ABCs. METHODS: Fourteen patients (6 male, 8 female) were treated between June 2014 to December 2019 with BMC injection for ABC of the spine. The mean age was 15.5 years. The mean follow up was 37.4 months (range 12-60 months). The dimension of the cyst and the degree of ossification were measured by Computed Tomography (CT) scans before the treatment and during follow-up visits. RESULTS: Six patients received a single dose of BMC, five patients received two doses and in three patients three doses of BMC were administered. The mean ossification of the cyst (expressed in Hounsfield units) increased statistically from 43.48 ± 2.36 HU to 161.71 ± 23.48 HU during follow-up time and the ossification was associated to an improvement of the clinical outcomes. The mean ossification over time was significantly higher in patients treated with a single injection compared to patients treated with multiple injections. No significant difference in ossification was found between cervical and non-cervical localization of the cyst. Moreover, the initial size of the cyst was not statistically associated with the degree of ossification during follow-up CONCLUSIONS: Results of this paper reinforce our previous evidence on the use of BMC as a valid alternative for spinal ABC management when SAE treatment is contraindicated or ineffective.

Aggressive Vertebral Hemangioma Causing Recurring Myelopathy -A Rare Case Report and Review of Literature.

Introduction: Vertebral hemangiomas although benign vascular lesions few of these may be ag-gressive causing osseous, extra-osseous and/or epidural expansions with recurrence rate as low as 3%. It should be considered as one of the important differentials while dealing with lytic lesions in the dorsal spine causing compressive myelopathy. Case Report: A 16-year-old female came with an acute history of paraparesis with bladder in-volvement. She was diagnosed of vertebral hemangioma of D9 for which she underwent surgical decompression and fixation. At present, she had paraparesis with a sensory level of D10 on exami-nation. After radiological investigations (X-ray and MRI) she had high intensity signals in the extra osseous portion of D9 with significant neural compression indicating recurrence of vertebral he-mangioma. She underwent decompression with long segment instrumentation with prior arterial embolization. Histopathology features were suggestive of hemangioma and our diagnosis of recur-rence was confirmed. At 2 weeks, the patient had improved neurology with partial sensory recovery and Grade 2 power in the right lower limb and Grade 1 power in the left lower limb. Histopathology report confirmed the diagnosis of hemangioma indicating recurrence. At 6 months follow-up after aggressive rehabilitation, the patient was spastic and improved to Grade 3 power in the left lower limb and Grade 4 power in the right lower limb. The sphincteric control was also found to be fair at 1 year follow-up. Discussion: Vertebral hemangiomas when causing progressive neurological deficit warrant surgical decompression. The choice of intervention depends on location and extent of the tumor. Due to their high vascularity, it is advisable for to preoperatively carry out arterial embolization. Conclusion: Although commonly asymptomatic, vertebral hemangiomas may present as compressive myelopathy. Therefore, they should be detected early, intervened and followed up regularly to detect recurrence to prevent worsening of neurology and function.

Consistent cross-modal identification of cortical neurons with coupled autoencoders.

Consistent identification of neurons in different experimental modalities is a key problem in neuroscience. Although methods to perform multimodal measurements in the same set of single neurons have become available, parsing complex relationships across different modalities to uncover neuronal identity is a growing challenge. Here we present an optimization framework to learn coordinated representations of multimodal data and apply it to a large multimodal dataset profiling mouse cortical interneurons. Our approach reveals strong alignment between transcriptomic and electrophysiological characterizations, enables accurate cross-modal data prediction, and identifies cell types that are consistent across modalities.

Surgery Versus Radiofrequency Ablation in the Management of Spinal Osteoid Osteomas: A Spine Oncology Referral Center Comparison Analysis of 138 Cases.

BACKGROUND: Osteoid osteomas (OOs) are benign bone forming tumors that, usually, occur in the extremities, with about 10% of them arising in the spine more commonly in the posterior elements. The aim of this study is to evaluate the long-term results of patients suffering from spinal OO treated with surgery and radiofrequency ablation. METHODS: This was a retrospective comparison analysis of data prospectively collected from 2 cohorts of consecutive patients diagnosed with OO of the spine treated at the same Institute from November 2002 to February 2019. The first cohort included patients submitted to an intralesional extracapsular excision of the lesion (surgery group); the second cohort included patients submitted to radiofrequency ablation (RFA group). RESULTS: The surgery group showed a local recurrence rate of 1.7% versus a recurrence rate of 12.5% in the RFA group with a statistically significant difference in the disease-free survival at longest follow-up (P = 0.012). No statistically significant differences were observed in local recurrence rate stratified for level and site of lesion. No complications were observed in both groups at the time of first procedure. CONCLUSIONS: Surgery and RFA are both safe and effective interventional procedures for the management of spinal OO, although RFA is associated with a greater recurrence rate. Treatment should be tailored according to the relationship of lesions with neural structures and to advantages and disadvantages of each technique.

Anatomic Considerations of Anterior Transarticular Screw Fixation for Atlantoaxial Instability.

STUDY DESIGN: Cadaveric, observational study. PURPOSE: Atlantoaxial instability (AAI) is characterized by excessive movement at the C1-C2 junction between the atlas and axis. An anterior surgical approach to expose the upper cervical spine for internal fixation and bone grafting has been developed to fix AAI. Currently, no anatomic information exists on the anterior transarticular atlantoaxial screw or screw and plate fixation between C1 and C2 in the Indian population. The objective of this study is to assess the anatomic landmarks of C1-C2 vertebrae: entry point, trajectory, screw length, and safety of the procedure. OVERVIEW OF LITERATURE: Methods outlined by Magerl and Harms are the optimal approaches among the dorsal techniques. Contraindications for these techniques include aberrant location of vertebral arteries, fractures of C1-C2 posterior structures. In these cases, anterior transarticular fixation is an alternative. Several available screw insertion trajectories have been reported. Biomechanical studies have demonstrated that adequate rigidity of this fixation is comparable with posterior fusion techniques. METHODS: Direct measurements using Vernier calipers and a goniometer were recorded from 30 embalmed human cadavers. The primary parameters measured were the minimum and maximum lateral and posterior angulations of the screw in the sagittal and coronal planes, respectively, and optimum screw length, if it was placed accurately. RESULTS: The posterior and lateral angles of screw placement in the coronal and sagittal planes ranged from 16° to 30° (mean±standard deviation [SD], 23.93°±3.93°) and 8° to 17° (mean±SD, 13.3°±2.26°), respectively. The optimum screw length was 25-38 mm (mean±SD, 28.76±3.69 mm). CONCLUSIONS: If the screw was inserted without lateral angulation, the spinal canal or cord could be violated. If a longer screw was inserted with greater posterior angulation, the vertebral artery at the posterior or posterolateral aspect of the C1 superior facet could be violated. Thus, 26° and 30° of lateral and posterior angulations, respectively, are the maximum angles permissible to avoid injury of the vertebral artery and violations of the spinal canal or atlanto-occipital joint.

Anterior Release and Anterior Reconstruction for a Neglected Osteoporotic Odontoid Fracture.

A 70 years old lady presented to us with history of a fall 3 months prior. She had suffered a type 2 odontoid fracture with atlantoaxial dislocation, that was not reducible by traction. She had symptoms of neck pain with inability to hold the neck upright. The patient was subsequently planned for anterior release and reduction of odontoid fracture dislocation with posterior stabilization in the same sitting. The patient was treated with cervical skeletal traction and immobilized. However, she developed occipital sore during the period and was mobilized with brace after which she developed myelopathic symptoms and gait disturbance due to the collapse of fracture segment. The patient was planned for anterior release and fixation with contoured reconstruction plate fixing C1 lateral mass to the lateral mass on the right side and C1 lateral mass to C2 body on the left side primarily with distraction of the C1-C2 joint by autologous tricortical iliac bone graft. The posterior stabilization was planned after healing of the sore, and the patient was counseled for the same. However, the patient was lost on follow-up and returned at 3-month postoperative period with collapse of the graft, resubluxation of C1-C2 segment, and failure of anterior fixation. The standard modality of treatment for such cases includes an anterior release of contracted soft tissues and ligaments and posterior stabilization with fusion in a single setting. However, it is the posterior fixation that stabilizes the fracture and prevents it from redislocation. Anterior fixation as a stand-alone treatment in osteoporotic bone has high risks of failure due to severe posterior tensile stresses. This article describes the importance of posterior fixation in osteoporotic bone based on our experience.

Single-cell transcriptomic evidence for dense intracortical neuropeptide networks.

Seeking new insights into the homeostasis, modulation and plasticity of cortical synaptic networks, we have analyzed results from a single-cell RNA-seq study of 22,439 mouse neocortical neurons. Our analysis exposes transcriptomic evidence for dozens of molecularly distinct neuropeptidergic modulatory networks that directly interconnect all cortical neurons. This evidence begins with a discovery that transcripts of one or more neuropeptide precursor (NPP) and one or more neuropeptide-selective G-protein-coupled receptor (NP-GPCR) genes are highly abundant in all, or very nearly all, cortical neurons. Individual neurons express diverse subsets of NP signaling genes from palettes encoding 18 NPPs and 29 NP-GPCRs. These 47 genes comprise 37 cognate NPP/NP-GPCR pairs, implying the likelihood of local neuropeptide signaling. Here, we use neuron-type-specific patterns of NP gene expression to offer specific, testable predictions regarding 37 peptidergic neuromodulatory networks that may play prominent roles in cortical homeostasis and plasticity.

Cadaveric study for ideal dorsal pedicle screw entry point.

OBJECTIVE: To determine the entry for the dorsal pedicular screw in relation to the notch present at the junction of base of the lateral margin of superior articular process with superior border of transverse process in dorsal spine. The advantage of this technique is a constant and easily identifiable entry point which does not involve partial resection of the inferior facet, thus maintaining stability and maintaining the well defined transverse and sagittal screw angles and decreasing the incidence of medial and inferior pedicle violation. MATERIALS AND METHODS: The study was carried out using ten cadavers (four male and six female). Spinal column was dissected completely from cadavers. Before the experiment, normal anatomy was confirmed on all cadavers excluding cases of spinal deformity. Dissection was done by the spine surgeons taking care to preserve all the bony landmarks near the entry point. This study was carried out bilaterally on pedicles between the first and twelfth thoracic (T) vertebrae. RESULTS: The relation of the superior articular notch and transverse process to the thoracic spine pedicles was studied. It was found that superior third of the pedicle was related to the superior articular notch and the transverse process in the first five thoracic vertebrae. The relation of these structures to the pedicle of the sixth thoracic vertebra was somewhat equally distributed between the superior and middle third of the pedicle. From the 7th to 12th thoracic vertebrae the superior articular process and transverse process were related to the middle third of the pedicle in almost all the cases. It is important to note that the inferior 1/3rd of the pedicle was not related to these landmarks at any of the levels. CONCLUSION: We conclude that the ideal pedicle entry point described here should be considered by surgeons during thoracic pedicle screw instrumentation. The notch at the base of the superior articular process will always remain constant and therefore an important anatomical landmark in guiding the screw toward the entry of the pedicle.

Radial Artery Pseudoaneurysm in a Post-operative Case of Midshaft Radius Fracture.

INTRODUCTION: Pseudoaneurysms of arteries are not uncommon complications of vessel handling during surgery. Early identification and management is important to prevent disastrous complications such as rupture and thrombosis. CASE REPORT: We describe a case of a 28-year-old male who developed a pseudoaneurysm of the radial artery after being operated by plating for a mid-shaft radius fracture. He presented 2 weeks after surgery with swelling over the forearm which was confirmed to be a pseudoaneurysm after computed tomography angiography. It was treated with surgical excision and end-to-end anastomosis. CONCLUSION: A high index of suspicion must be maintained about the occurrence of this complication secondary to both trauma and surgery.

Computer assisted detection of axonal bouton structural plasticity in in vivo time-lapse images.

The ability to measure minute structural changes in neural circuits is essential for long-term in vivo imaging studies. Here, we propose a methodology for detection and measurement of structural changes in axonal boutons imaged with time-lapse two-photon laser scanning microscopy (2PLSM). Correlative 2PLSM and 3D electron microscopy (EM) analysis, performed in mouse barrel cortex, showed that the proposed method has low fractions of false positive/negative bouton detections (2/0 out of 18), and that 2PLSM-based bouton weights are correlated with their volumes measured in EM (r = 0.93). Next, the method was applied to a set of axons imaged in quick succession to characterize measurement uncertainty. The results were used to construct a statistical model in which bouton addition, elimination, and size changes are described probabilistically, rather than being treated as deterministic events. Finally, we demonstrate that the model can be used to quantify significant structural changes in boutons in long-term imaging experiments.

Effects of homeostatic constraints on associative memory storage and synaptic connectivity of cortical circuits.

The impact of learning and long-term memory storage on synaptic connectivity is not completely understood. In this study, we examine the effects of associative learning on synaptic connectivity in adult cortical circuits by hypothesizing that these circuits function in a steady-state, in which the memory capacity of a circuit is maximal and learning must be accompanied by forgetting. Steady-state circuits should be characterized by unique connectivity features. To uncover such features we developed a biologically constrained, exactly solvable model of associative memory storage. The model is applicable to networks of multiple excitatory and inhibitory neuron classes and can account for homeostatic constraints on the number and the overall weight of functional connections received by each neuron. The results show that in spite of a large number of neuron classes, functional connections between potentially connected cells are realized with less than 50% probability if the presynaptic cell is excitatory and generally a much greater probability if it is inhibitory. We also find that constraining the overall weight of presynaptic connections leads to Gaussian connection weight distributions that are truncated at zero. In contrast, constraining the total number of functional presynaptic connections leads to non-Gaussian distributions, in which weak connections are absent. These theoretical predictions are compared with a large dataset of published experimental studies reporting amplitudes of unitary postsynaptic potentials and probabilities of connections between various classes of excitatory and inhibitory neurons in the cerebellum, neocortex, and hippocampus.