Cortical cell assemblies and their underlying connectivity: An in silico study.

Recent developments in experimental techniques have enabled simultaneous recordings from thousands of neurons, enabling the study of functional cell assemblies. However, determining the patterns of synaptic connectivity giving rise to these assemblies remains challenging. To address this, we developed a complementary, simulation-based approach, using a detailed, large-scale cortical network model. Using a combination of established methods we detected functional cell assemblies from the stimulus-evoked spiking activity of 186,665 neurons. We studied how the structure of synaptic connectivity underlies assembly composition, quantifying the effects of thalamic innervation, recurrent connectivity, and the spatial arrangement of synapses on dendrites. We determined that these features reduce up to 30%, 22%, and 10% of the uncertainty of a neuron belonging to an assembly. The detected assemblies were activated in a stimulus-specific sequence and were grouped based on their position in the sequence. We found that the different groups were affected to different degrees by the structural features we considered. Additionally, connectivity was more predictive of assembly membership if its direction aligned with the temporal order of assembly activation, if it originated from strongly interconnected populations, and if synapses clustered on dendritic branches. In summary, reversing Hebb's postulate, we showed how cells that are wired together, fire together, quantifying how connectivity patterns interact to shape the emergence of assemblies. This includes a qualitative aspect of connectivity: not just the amount, but also the local structure matters; from the subcellular level in the form of dendritic clustering to the presence of specific network motifs.

Thalamic control of sensory processing and spindles in a biophysical somatosensory thalamoreticular circuit model of wakefulness and sleep.

Thalamoreticular circuitry plays a key role in arousal, attention, cognition, and sleep spindles, and is linked to several brain disorders. A detailed computational model of mouse somatosensory thalamus and thalamic reticular nucleus has been developed to capture the properties of over 14,000 neurons connected by 6 million synapses. The model recreates the biological connectivity of these neurons, and simulations of the model reproduce multiple experimental findings in different brain states. The model shows that inhibitory rebound produces frequency-selective enhancement of thalamic responses during wakefulness. We find that thalamic interactions are responsible for the characteristic waxing and waning of spindle oscillations. In addition, we find that changes in thalamic excitability control spindle frequency and their incidence. The model is made openly available to provide a new tool for studying the function and dysfunction of the thalamoreticular circuitry in various brain states.

Perioperative Outcomes of Transurethral Resection, Open Prostatectomy, and Laser Therapy in the Surgical Treatment of Benign Prostatic Obstruction: A "Real-World" Data Analysis from the URO-Cert Prostate Centers.

INTRODUCTION: The aim of the study is to compare length of hospital stay, transfusion rates, and re-intervention rates during hospitalization for transurethral resection of the prostate (TUR-P), open prostatectomy (OP), and laser therapy (LT) for surgical treatment of benign prostatic obstruction (BPO). METHODS: URO-Cert is an organization, in which clinical data of prostatic diseases from 2 university, 19 public, and 3 private hospitals and 270 office-based urologists are collected in order to document treatment quality. Data on diagnostics, therapy, and course of disease are recorded web based. The analysis includes datasets from 2005 to 2017. RESULTS: Of 10,420 patients, 8,389 were treated with TUR-P, 1,334 with OP, and 697 with LT. Median length of hospital stay was 6 days (IQR: 4-7) for TUR-P, 9 days (IQR: 7-11) for OP, and 5 days (IQR: 4-6) for LT (p < 0.001). Risk for a hospital stay ≥7 days was higher for OP versus TUR-P (OR: 7.25; 95% CI = 6.27-8.36; p < 0.001) and LT (OR: 17.89; 95% CI = 14.12-22.65; p < 0.001) and higher for TUR-P versus LT (OR: 2.47; 95% CI = 2.03-3.01; p < 0.001). OP had a significantly higher risk for transfusions than TUR-P (OR: 2.44; 95% CI = 1.74-3.41; p < 0.001) and LT (OR: 3.32; 95% CI = 1.56-7.01; p < 0.001). Transfusion rates were not significantly different between TUR-P and LT (OR: 1.36; 95% CI = 0.66-2.79; p = 0.51). Risk of re-intervention was not different between all 3 approaches. CONCLUSION: OP was associated with higher transfusion rates and longer hospital stay than TUR-P and LT. Risk of transfusion was not different between TUR-P and LT, but TUR-P was inferior to LT concerning length of hospital stay. Re-intervention rates during hospitalization did not differ between the groups.

Cortical reliability amid noise and chaos.

Typical responses of cortical neurons to identical sensory stimuli appear highly variable. It has thus been proposed that the cortex primarily uses a rate code. However, other studies have argued for spike-time coding under certain conditions. The potential role of spike-time coding is directly limited by the internally generated variability of cortical circuits, which remains largely unexplored. Here, we quantify this internally generated variability using a biophysical model of rat neocortical microcircuitry with biologically realistic noise sources. We find that stochastic neurotransmitter release is a critical component of internally generated variability, causing rapidly diverging, chaotic recurrent network dynamics. Surprisingly, the same nonlinear recurrent network dynamics can transiently overcome the chaos in response to weak feed-forward thalamocortical inputs, and support reliable spike times with millisecond precision. Our model shows that the noisy and chaotic network dynamics of recurrent cortical microcircuitry are compatible with stimulus-evoked, millisecond spike-time reliability, resolving a long-standing debate.