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Comparing sequential stimuli is crucial for guiding complex behaviors. To understand mechanisms underlying sequential decisions, we compared neuronal responses in the prefrontal cortex (PFC), the lateral intraparietal (LIP), and medial intraparietal (MIP) areas in monkeys trained to decide whether sequentially presented stimuli were from matching (M) or nonmatching (NM) categories. We found that PFC leads M/NM decisions, whereas LIP and MIP appear more involved in stimulus evaluation and motor planning, respectively. Compared to LIP, PFC showed greater nonlinear integration of currently visible and remembered stimuli, which correlated with the monkeys’ M/NM decisions. Furthermore, multi-module recurrent networks trained on the same task exhibited key features of PFC and LIP encoding, including nonlinear integration in the PFC-like module, which was causally involved in the networks’ decisions. Network analysis found that nonlinear units have stronger and more widespread connections with input, output, and within-area units, indicating putative circuit-level mechanisms for sequential decisions.

Summary: BIN1, a member of the BAR adaptor protein family, is a significant late-onset Alzheimer disease risk factor. Here, we investigate BIN1 function in the brain using conditional knockout (cKO) models. Loss of neuronal Bin1 expression results in the select impairment of spatial learning and memory. Examination of hippocampal CA1 excitatory synapses reveals a deficit in presynaptic release probability and slower depletion of neurotransmitters during repetitive stimulation, suggesting altered vesicle dynamics in Bin1 cKO mice. Super-resolution and immunoelectron microscopy localizes BIN1 to presynaptic sites in excitatory synapses. Bin1 cKO significantly reduces synapse density and alters presynaptic active zone protein cluster formation. Finally, 3D electron microscopy reconstruction analysis uncovers a significant increase in docked and reserve pools of synaptic vesicles at hippocampal synapses in Bin1 cKO mice. Our results demonstrate a non-redundant role for BIN1 in presynaptic regulation, thus providing significant insights into the fundamental function of BIN1 in synaptic physiology relevant to Alzheimer disease. : BIN1 is a significant risk factor for late-onset Alzheimer disease. BIN1 has a general role in endocytosis and membrane dynamics in non-neuronal cells. De Rossi et al. show that BIN1 localizes to presynaptic terminals and plays an indispensable role in excitatory synaptic transmission by regulating neurotransmitter vesicle dynamics. Keywords: late-onset Alzheimer disease, BIN1, Morris water maze, synaptic physiology, release probability, super-resolution, dSTORM, STED, 3D EM reconstruction, Amphiphysin 2

Electrical stimulation of the brain is a valuable research tool and has shown therapeutic promise in the development of new sensory neural prosthetics. Despite its widespread use, we still do not fully understand how current passed through a microelectrode interacts with functioning neural circuits. Past behavioral studies have suggested that weak electrical stimulation (referred to as microstimulation) of sensory areas of cortex produces percepts that are similar to those generated by normal sensory stimuli. In contrast, electrophysiological studies using in vitro or anesthetized preparations have shown that neural activity produced by brief microstimulation is radically different and longer lasting than normal responses. To help reconcile these two aspects of microstimulation, we examined the temporal properties that microstimulation has on visual perception. We found that brief application of subthreshold microstimulation in the middle temporal (MT) area of visual cortex produced smaller and longer-lasting effects on motion perception compared with an equivalent visual stimulus. In agreement with past electrophysiological studies, a computer simulation reproduced our behavioral effects when the time course of a single microstimulation pulse was modeled with three components: an immediate fast strong excitatory component, followed by a weaker inhibitory component, and then followed by a long duration weak excitatory component. Overall, these results suggest the behavioral effects of microstimulation in our experiments were caused by the unique and long-lasting temporal effects microstimulation has on functioning cortical circuits. [ABSTRACT FROM AUTHOR]

Purpose of the Study: Posterior Wallaby I is a fixed polyethylene tibial plateau prosthesis enabling preservation of the posterior cruciate ligament (PCL). Its asymmetrical and divergent femoral condyles articulate with also asymmetrical tibial plateaus. The purpose of this prospective study was to analyze outcome of the first 425 Wallaby I prosthesis of the Guepar group implanted for first-intention treatment., Materials and Methods: These 425 prostheses were implanted from December 1992 to February 1995 by senior and junior surgeons. Mean patient age at implantation was 70.5 years. 91% had primary or secondary osteoarthritis and only 8.9% had inflammatory rheumatoid disease. The mean preoperative IKS score was 25.34 points and the IKS function score was 29.04. 10.35% of knees were aligned normally (mechanical axis between 2 degrees varus and 3 degrees valgus) according to the IKS criteria (Ewald), 24% presented valgus > or = 4 degrees and 65.6% varus > or = 3 degrees. All tibial and patellar components (except one) were cemented, 5.8% of the femoral pieces were inserted without cement. All but 11 patellae were resurfaced. Clinical outcome was assessed with the IKS score and radiological outcome with the IKS criteria. The patella was considered to be tilted when the alpha angle was > 5 degrees and dislocated when the AA' distance was > 5 mm. The chi-square test was used for comparison of quantitative variables (significance set at 0.05)., Results: Early postoperative complications were rare: two infections cured with debridement-lavage and antibiotics without removal of the prosthesis, one peronal nerve palsy which regressed partially, ten late unions without clinical consequence (particularly in the inflammatory rheumatoid patients). Twenty-six prostheses were followed less than one year (eight patients died and eighteen were lost to follow-up) and 84 less than five years (27 patients died and 57 lost to follow-up before five years). 315 prostheses were followed for more than five years (5-9 years) with a mean follow-up of 6.3 years. Among the 399 prostheses followed for one year or more, we noted: four infections including three requiring change of the prosthesis (one cured by arthroscopic lavage), two aseptic loosenings which were revised (one global one tibial), one tibial loosening and three patellar loosenings which were not revised, and two femoral ossifications limiting joint motion but improved by arthrolysis and resection of the ossifications. Three patients experienced anterior pain requiring secondary patellar resurfacing in two and section of the lateral patellar wing in one. Ninteen patellar fractures (4.7%) were noted, including 17 with no significant functional impact which were not revised. The mean IKS knee score among prostheses followed for five years was 90.5 points, with mean motion 110.5 degrees. Mean IKS function score was 61.63 points. 72.9% of the knees were aligned, 22.2% in varus and 4.9% in valgus. The mechanical axis of 94.3% of the knees was between 5 degrees varus and 5 degrees valgus. Prosthesis survival at eight years (Kaplan-Meier method) was 97.7% considering all reasons for prosthesis removal and 98.5% for removal for aseptic loosening., Conclusion: This prospective multicentric study demonstrated that the results obtained with the Wallaby I prosthesis are as good as those obtained with other prostheses sparing the PCL and published in the literature. Preservation of the PCL enables better knee stability, correct motion (110.5 degrees in our series) with almost no radiological wear of the tibial polyethylene at eight years. The only worrisome complication is patellar fracture.

The prosthesis has two components. The femoral component is metallic surfacing the condyle and a tibial plateau in polyethylene replaces the original one. The prosthesis can be uni or bi-condylar. Operative technique has to be very precise and the position of the prosthesis needs accuracy. The advantages are: minimal bone resection, small implant harmonic action with the knee joint as a whole. 20 patients with I8 months follow up are reviewed, problems are infections and pain in the patello-femoral joint. The results on pain and walking are good. Stability depends on accurate indications.

The authors have studied a series of 521 fractures of the tibia treated by blind intramedullary nailing without reaming. Union by the 120th day was obtained in 93.3% of cases. Malunion was uncommon and was related to an inadequate initial reduction. A secondary procedure was only necessary in two cases of malunion. In closed fractures, no case suffered infection. In compound fractures, 4.3% became infected (5 osteitis, 4 septic non-union) but all cases were cured by secondary procedures. Aseptic non-union occurred in 2.3% of cases. The authors recommend the use of nails of at least 8 mm diameter driven down to the region of the lower articular surface. In patients with a narrow medullary canal, or in fractures of the lower third of the tibia, the authors consider that reaming would have given better results. In other types of fracture reaming is more hazardous than useful.