Author Correction: Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention.

Neocortical choline acetyltransferase (ChAT)-expressing interneurons are a subclass of vasoactive intestinal peptide (ChAT-VIP) neurons of which circuit and behavioural function are unknown. Here, we show that ChAT-VIP neurons directly excite neighbouring neurons in several layers through fast synaptic transmission of acetylcholine (ACh) in rodent medial prefrontal cortex (mPFC). Both interneurons in layers (L)1-3 as well as pyramidal neurons in L2/3 and L6 receive direct inputs from ChAT-VIP neurons mediated by fast cholinergic transmission. A fraction (10-20%) of postsynaptic neurons that received cholinergic input from ChAT-VIP interneurons also received GABAergic input from these neurons. In contrast to regular VIP interneurons, ChAT-VIP neurons did not disinhibit pyramidal neurons. Finally, we show that activity of these neurons is relevant for behaviour and they control attention behaviour distinctly from basal forebrain ACh inputs. Thus, ChAT-VIP neurons are a local source of cortical ACh that directly excite neurons throughout cortical layers and contribute to attention.

Functional Architecture and Encoding of Tactile Sensorimotor Behavior in Rat Posterior Parietal Cortex.

The posterior parietal cortex (PPC) in rodents is reciprocally connected to primary somatosensory and vibrissal motor cortices. The PPC neuronal circuitry could thus encode and potentially integrate incoming somatosensory information and whisker motor output. However, the information encoded across PPC layers during refined sensorimotor behavior remains largely unknown. To uncover the sensorimotor features represented in PPC during voluntary whisking and object touch, we performed loose-patch single-unit recordings and extracellular recordings of ensemble activity, covering all layers of PPC in anesthetized and awake, behaving male rats. First, using single-cell receptive field mapping, we revealed the presence of coarse somatotopy along the mediolateral axis in PPC. Second, we found that spiking activity was modulated during exploratory whisking in layers 2-4 and layer 6, but not in layer 5 of awake, behaving rats. Population spiking activity preceded actual movement, and whisker trajectory endpoints could be decoded by population spiking, suggesting that PPC is involved in movement planning. Finally, population spiking activity further increased in response to active whisker touch but only in PPC layers 2-4. Thus, we find layer-specific processing, which emphasizes the computational role of PPC during whisker sensorimotor behavior.SIGNIFICANCE STATEMENT The posterior parietal cortex (PPC) is thought to merge information on motor output and sensory input to orchestrate interaction with the environment, but the function of different PPC microcircuit components is poorly understood. We recorded neuronal activity in rat PPC during sensorimotor behavior involving motor and sensory pathways. We uncovered that PPC layers have dedicated function: motor and sensory information is merged in layers 2-4; layer 6 predominantly represents motor information. Collectively, PPC activity predicts future motor output, thus entailing a motor plan. Our results are important for understanding how PPC computationally processes motor output and sensory input. This understanding may facilitate decoding of brain activity when using brain-machine interfaces to overcome loss of function after, for instance, spinal cord injury.

Dorsomedial prefrontal cortex neurons encode nicotine-cue associations.

The role of medial prefrontal cortex (mPFC) in regulating nicotine taking and seeking remains largely unexplored. In this study we took advantage of the high time-resolution of optogenetic intervention by decreasing (Arch3.0) or increasing (ChR2) the activity of neurons in the dorsal and ventral mPFC during 5-s nicotine cue presentations in order to evaluate their contribution to cued nicotine seeking and taking. Wistar rats were trained to self-administer intravenous nicotine in 1 h self-administration sessions twice a day for a minimum of 10 days. Subsequently, dmPFC or vmPFC neuronal activity was modulated during or following presentation of the 5-s nicotine cue, both under extinction and self-administration conditions. We also used in vivo electrophysiology to record the activity of dmPFC neurons during nicotine self-administration and extinction tests. We show that optogenetic inhibition of dmPFC neurons during, but not following, response-contingent presentations of the nicotine cue increased nicotine seeking. We found no effect on nicotine self-administration or on food seeking in an extinction test. We also show that this effect is specific to dmPFC, because optogenetic inhibition of vmPFC had no effect on nicotine seeking and taking. In vivo recordings revealed that dmPFC network neuronal activity was modulated more strongly following nicotine cue presentation in extinction, compared to following nicotine self-administration. Our results strongly suggest that a population of neurons within the dmPFC is involved in encoding the incentive value of nicotine-associated cues.

Neural Representation of Motor Output, Context and Behavioral Adaptation in Rat Medial Prefrontal Cortex During Learned Behavior.

Selecting behavioral outputs in a dynamic environment is the outcome of integrating multiple information streams and weighing possible action outcomes with their value. Integration depends on the medial prefrontal cortex (mPFC), but how mPFC neurons encode information necessary for appropriate behavioral adaptation is poorly understood. To identify spiking patterns of mPFC during learned behavior, we extracellularly recorded neuronal action potential firing in the mPFC of rats performing a whisker-based "Go"/"No-go" object localization task. First, we identify three functional groups of neurons, which show different degrees of spiking modulation during task performance. One group increased spiking activity during correct "Go" behavior (positively modulated), the second group decreased spiking (negatively modulated) and one group did not change spiking. Second, the relative change in spiking was context-dependent and largest when motor output had contextual value. Third, the negatively modulated population spiked more when rats updated behavior following an error compared to trials without integration of error information. Finally, insufficient spiking in the positively modulated population predicted erroneous behavior under dynamic "No-go" conditions. Thus, mPFC neuronal populations with opposite spike modulation characteristics differentially encode context and behavioral updating and enable flexible integration of error corrections in future actions.

The posterior parietal cortex as integrative hub for whisker sensorimotor information.

Our daily life consists of a continuous interplay between incoming sensory information and outgoing motor plans. Particularly during goal-directed behavior and active exploration of the sensory environment, brain circuits are merging sensory and motor signals. This is referred to as sensorimotor integration and is relevant for locomotion, vision or tactile exploration. The somatosensory (tactile) system is an attractive modality to study sensorimotor integration in health and disease, motivated by the need for revolutionary technology that builds upon conceptual understanding of sensorimotor integration, such as brain-machine-interfaces and neuro-prosthetics. In this perspective, we focus on the rat whisker system and put forward the posterior parietal cortex as a potential circuit where sensorimotor integration could occur during active somatosensation.

Graft Site Morbidity in Elbow Ligament Reconstruction Procedures: A Systematic Review.

BACKGROUND: It is unclear which tendon harvest for ulnar or lateral collateral ligament reconstruction has the lowest graft site morbidity rate. PURPOSES: To obtain graft site morbidity rates after tendon harvest for ulnar and lateral collateral ligament reconstruction procedures. STUDY DESIGN: Systematic review/Meta-analysis. METHODS: Studies were eligible if (1) patients had undergone elbow ligament reconstruction procedures; (2) original data for at least 5 patients were available; (3) the article was written in English, German, or Dutch; (4) a full-text article was available; and (5) information about graft site morbidity was available. The review excluded studies about complicated elbow ligament reconstruction procedures due to initial fractures, revision procedures, or circumferential graft techniques; animal studies; (systematic) reviews; and expert opinions. Because the majority of studies were case reports, no selection form or overall scoring system to evaluate methodological quality was used. RESULTS: The review included 619 patients with an ulnar or lateral collateral ligament reconstruction procedure. The autograft types used included palmaris longus tendon (58%), gracilis tendon (24%), semitendinosus tendon (8%), triceps tendon (7%), toe extensor tendon (<2%), plantaris tendon (<2%), extensor carpi radialis longus tendon (<1%), and Achilles tendon (<1%). CONCLUSION: Graft site morbidity occurred in 1% of the patients after an ulnar or lateral collateral ligament reconstruction procedure. This study did not have enough samples of all the autograft types to conclude that autograft type and graft site morbidity are unrelated.

Sustained Attentional States Require Distinct Temporal Involvement of the Dorsal and Ventral Medial Prefrontal Cortex.

Attending the sensory environment for cue detection is a cognitive operation that occurs on a time scale of seconds. The dorsal and ventral medial prefrontal cortex (mPFC) contribute to separate aspects of attentional processing. Pyramidal neurons in different parts of the mPFC are active during cognitive behavior, yet whether this activity is causally underlying attentional processing is not known. We aimed to determine the precise temporal requirements for activation of the mPFC subregions during the seconds prior to cue detection. To test this, we used optogenetic silencing of dorsal or ventral mPFC pyramidal neurons at defined time windows during a sustained attentional state. We find that the requirement of ventral mPFC pyramidal neuron activity is strictly time-locked to stimulus detection. Inhibiting the ventral mPFC 2 s before or during cue presentation reduces response accuracy and hampers behavioral inhibition. The requirement for dorsal mPFC activity on the other hand is temporally more loosely related to a preparatory attentional state, and short lapses in pyramidal neuron activity in dorsal mPFC do not affect performance. This only occurs when the dorsal mPFC is inhibited during the entire preparatory period. Together, our results reveal that a dissociable temporal recruitment of ventral and dorsal mPFC is required during attentional processing.

Juxtasomal biocytin labeling to study the structure-function relationship of individual cortical neurons.

The cerebral cortex is characterized by multiple layers and many distinct cell-types that together as a network are responsible for many higher cognitive functions including decision making, sensory-guided behavior or memory. To understand how such intricate neuronal networks perform such tasks, a crucial step is to determine the function (or electrical activity) of individual cell types within the network, preferentially when the animal is performing a relevant cognitive task. Additionally, it is equally important to determine the anatomical structure of the network and the morphological architecture of the individual neurons to allow reverse engineering the cortical network. Technical breakthroughs available today allow recording cellular activity in awake, behaving animals with the valuable option of post hoc identifying the recorded neurons. Here, we demonstrate the juxtasomal biocytin labeling technique, which involves recording action potential spiking in the extracellular (or loose-patch) configuration using conventional patch pipettes. The juxtasomal recording configuration is relatively stable and applicable across behavioral conditions, including anesthetized, sedated, awake head-fixed, and even in the freely moving animal. Thus, this method allows linking cell-type specific action potential spiking during animal behavior to reconstruction of the individual neurons and ultimately, the entire cortical microcircuit. In this video manuscript, we show how individual neurons in the juxtasomal configuration can be labeled with biocytin in the urethane-anaesthetized rat for post hoc identification and morphological reconstruction.

Impact of implant size on cement filling in hip resurfacing arthroplasty.

Larger proportions of cement within femoral resurfacing implants might result in thermal bone necrosis. We postulate that smaller components are filled with proportionally more cement, causing an elevated failure rate. A total of 19 femoral heads were fitted with polymeric replicas of ReCap (Biomet) resurfacing components fixed with low-viscosity cement. Two specimens were used for each even size between 40 and 56 mm and one for size 58 mm. All specimens were imaged with computed tomography, and the cement thickness and bone density were analyzed. The average cement mantle thickness was 2.63 mm and was not correlated with the implant size. However, specimen with low bone density had thicker cement mantles regardless of size. The average filling index was 36.65% and was correlated to both implant size and bone density. Smaller implants and specimens with lower bone density contained proportionally more cement than larger implants. According to a linear regression model, bone density but not implant size influenced cement thickness. However, both implant size and bone density had a significant impact on the filling index. Large proportions of cement within the resurfacing head have the potential to generate thermal bone necrosis and implant failure. When considering hip resurfacing in patients with a small femoral head and/or osteoporotic bone, extra care should be taken to avoid thermal bone necrosis, and alternative cementing techniques or even cementless implants should be considered. This study should help delimiting the indications for hip resurfacing and to choose an optimal cementing technique taking implant size into account.

Layer-specific high-frequency action potential spiking in the prefrontal cortex of awake rats.

Cortical pyramidal neurons show irregular in vivo action potential (AP) spiking with high-frequency bursts occurring on sparse background activity. Somatic APs can backpropagate from soma into basal and apical dendrites and locally generate dendritic calcium spikes. The critical AP frequency for generation of such dendritic calcium spikes can be very different depending on cell type or brain area involved. Previously, it was shown in vitro that calcium electrogenesis can be induced in L(ayer) 5 pyramidal neurons of prefrontal cortex (PFC). It remains an open question whether somatic burst spiking and the resulting dendritic calcium electrogenesis also occur in morphologically more compact L2/3 pyramidal neurons. Furthermore, it is not known whether critical frequencies that trigger dendritic calcium electrogenesis occur in PFC under awake conditions in vivo. Here, we addressed these issues and found that pyramidal neurons in both PFC L2/3 and L5 in awake rats spike APs in short bursts but with different probabilities. The critical frequency (CF) for calcium electrogenesis in vitro was layer-specific and lower in L5 neurons compared to L2/3. Taking the in vitro CF as a predictive measure for dendritic electrogenesis during in vivo spontaneous activity, supracritical bursts in vivo were observed in a larger fraction of L5 neurons compared to L2/3 neurons but with similar incidence within these subpopulations. Together, these results show that in PFC of awake rats, AP spiking occurs at frequencies that are relevant for dendritic calcium electrogenesis and suggest that in awake rat PFC, dendritic calcium electrogenesis may be involved in neuronal computation.

Novel flicker-sensitive visual circuit neurons inhibited by stationary patterns.

Many animals use visual motion cues for navigating within their surroundings. Both flies and vertebrates compute local motion by temporal correlation of neighboring photoreceptors, via so-called elementary motion detectors (EMDs). In the fly lobula plate and the vertebrate visual cortex the output from many EMDs is pooled in neurons sensitive to wide-field optic flow. Although the EMD has been the preferred model for more than 50 years, recent work has highlighted its limitations in describing some visual behaviors, such as responses to higher-order motion stimuli. Non-EMD motion processing may therefore serve an important function in vision. Here, we describe a novel neuron class in the fly lobula plate that clearly does not derive its input from classic EMDs. The centrifugal stationary inhibited flicker excited (cSIFE) neuron is strongly excited by flicker, up to very high temporal frequencies. The non-EMD driven flicker sensitivity leads to strong, nondirectional responses to high-speed, wide-field motion. Furthermore, cSIFE is strongly inhibited by stationary patterns, within a narrow wavelength band. cSIFE's outputs overlap with the inputs of well described optic flow-sensitive lobula plate tangential cells (LPTCs). Driving cSIFE affects the active dendrites of LPTCs, and cSIFE may therefore play a large role in motion vision.

Octopaminergic modulation of contrast sensitivity.

Sensory systems adapt to prolonged stimulation by decreasing their response to continuous stimuli. Whereas visual motion adaptation has traditionally been studied in immobilized animals, recent work indicates that the animal's behavioral state influences the response properties of higher-order motion vision-sensitive neurons. During insect flight octopamine is released, and pharmacological octopaminergic activation can induce a fictive locomotor state. In the insect optic ganglia, lobula plate tangential cells (LPTCs) spatially pool input from local elementary motion detectors (EMDs) that correlate luminosity changes from two spatially discrete inputs after delaying the signal from one. The LPTC velocity optimum thereby depends on the spatial separation of the inputs and on the EMD's delay properties. Recently it was shown that behavioral activity increases the LPTC velocity optimum, with modeling suggesting this to originate in the EMD's temporal delay filters. However, behavior induces an additional post-EMD effect: the LPTC membrane conductance increases in flying flies. To physiologically investigate the degree to which activity causes presynaptic and postsynaptic effects, we conducted intracellular recordings of Eristalis horizontal system (HS) neurons. We constructed contrast response functions before and after adaptation at different temporal frequencies, with and without the octopamine receptor agonist chlordimeform (CDM). We extracted three motion adaptation components, where two are likely to be generated presynaptically of the LPTCs, and one within them. We found that CDM affected the early, EMD-associated contrast gain reduction, temporal frequency dependently. However, a CDM-induced change of the HS membrane conductance disappeared during and after visual stimulation. This suggests that physical activity mainly affects motion adaptation presynaptically of LPTCs, whereas post-EMD effects have a minimal effect.

Case report: Infrapatellar bursitis caused by Prototheca wickerhamii.

A 54-year-old immunocompetent man presented with an infrapatellar bursitis caused by Prototheca wickerhamii. Because of clinical and microbiological relapse two weeks after bursectomy, six weekly injections of 5 mg of conventional amphotericin B were chosen for intrabursal treatment. Four months after completion of the treatment, the patient remains cured.

Complications encountered with the use of constrained acetabular prostheses in total hip arthroplasty.

At our department, 46 constrained acetabular components in 38 patients were placed successively for a period of 4 years. Indications included recurrent dislocation, septic and aseptic loosening with extensive bone loss, tumor surgery with extensive bone resection, and instability due to neurologic impairment. Because 2 cup failures and 10 dislocations were observed with the constrained devices at 4 to 7 years of follow-up, the authors started to use large-diameter metal-on-metal bearings for similar indications. A series of 36 such bearings in 38 patients revealed only one cup failure and one dislocation at 2 to 4 years of follow-up. Although the 2 series are different and therefore difficult to compare, the authors recommend judicious use of constrained devices because of the high failure rate (26%) and consideration of alternative options such as the use of large-diameter metal-on-metal bearings.

Does intraoperative cell salvage remove cobalt and chromium from reinfused blood?

In 12 patients undergoing a revision hip arthroplasty after a failed metal-on-metal primary hip arthroplasty, the effectiveness of intraoperative cell salvage (ICS) in removing metal ions was investigated. Samples of blood collected during surgery were filtered using 2 ICS devices. The samples had the concentrations of cobalt (Co) and chromium (Cr) measured before and after filtration. There was an average reduction of 76.3% for Cr concentration and 78.6% for Co concentration after ICS filtering. The Co-to-Cr ratio before and after filtration was similar. At the present time, these salvage systems should be used with caution in the patient undergoing revision of metal-on-metal bearing surfaces.

Dexamethasone transforms lipopolysaccharide-stimulated human blood myeloid dendritic cells into myeloid dendritic cells that prime interleukin-10 production in T cells.

Myeloid dendritic cells (MDC) play an important role in antigen-specific immunity and tolerance. In transplantation setting donor-derived MDC are a promising tool to realize donor-specific tolerance. Current protocols enable generation of tolerogenic donor MDC from human monocytes during 1-week cultures. However, for clinical application in transplantation medicine, a rapidly available source of tolerogenic MDC is desired. In this study we investigated whether primary human blood MDC could be transformed into tolerogenic MDC using dexamethasone (dex) and lipopolysaccharide (LPS). Human blood MDC were cultured with dex and subsequently matured with LPS in the presence or absence of dex. Activation of MDC with LPS after pretreatment with dex did not prevent maturation into immunostimulatory MDC. In contrast, simultaneous treatment with dex and LPS yielded tolerogenic MDC, that had a reduced expression of CD86 and CD83, that poorly stimulated allogeneic T-cell proliferation and production of T helper 1 (Th1) cytokines, and primed production of the immunoregulatory cytokine interleukin-10 (IL-10) in T cells. In vitro, however, these tolerogenic MDC did not induce permanent donor-specific hyporesponsiveness in T cells. Importantly, tolerogenic MDC obtained by LPS stimulation in the presence of dex did not convert into immunostimulatory MDC after subsequent activation with different maturation stimuli. In conclusion, these findings demonstrate that combined treatment with dex and LPS transforms primary human blood MDC into tolerogenic MDC that are impaired to stimulate Th1 cytokines, but strongly prime the production of the immunoregulatory cytokine IL-10 in T cells, and are resistant to maturation stimuli. This strategy enables rapid generation of tolerogenic donor-derived MDC for immunotherapy in clinical transplantation.