Intrinsic and Synaptic Contributions to Repetitive Spiking in Dentate Granule Cells.

Repetitive firing of granule cells (GCs) in the dentate gyrus (DG) facilitates synaptic transmission to the CA3 region. This facilitation can gate and amplify the flow of information through the hippocampus. High-frequency bursts in the DG are linked to behavior and plasticity, but GCs do not readily burst. Under normal conditions, a single shock to the perforant path in a hippocampal slice typically drives a GC to fire a single spike, and only occasionally more than one spike is seen. Repetitive spiking in GCs is not robust, and the mechanisms are poorly understood. Here, we used a hybrid genetically encoded voltage sensor to image voltage changes evoked by cortical inputs in many mature GCs simultaneously in hippocampal slices from male and female mice. This enabled us to study relatively infrequent double and triple spikes. We found GCs are relatively homogeneous and their double spiking behavior is cell autonomous. Blockade of GABA type A receptors increased multiple spikes and prolonged the interspike interval, indicating inhibitory interneurons limit repetitive spiking and set the time window for successive spikes. Inhibiting synaptic glutamate release showed that recurrent excitation mediated by hilar mossy cells contributes to, but is not necessary for, multiple spiking. Blockade of T-type Ca2+ channels did not reduce multiple spiking but prolonged interspike intervals. Imaging voltage changes in different GC compartments revealed that second spikes can be initiated in either dendrites or somata. Thus, pharmacological and biophysical experiments reveal roles for both synaptic circuitry and intrinsic excitability in GC repetitive spiking.

Insights from a Multicenter Study on Adult H3 K27M-Mutated Glioma: Surgical Resection's Limited Influence on Overall Survival, ATRX as Molecular Prognosticator.

BACKGROUND: H3 K27M-mutated gliomas were first described as a new grade 4 entity in the 2016 WHO classification. Current studies have focused on its typical appearance in children and young adults, increasing the need to better understand the prognostic factors and impact of surgery on adults. Here, we report a multicentric study of this entity in adults. METHODS: We included molecularly confirmed H3 K27M-mutated glioma cases in patients >18 years diagnosed between 2016 and 2022. Clinical, radiological, and surgical features were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Among 70 patients with a mean age of 36.1 years, the median overall survival (OS) was 13.6 + 14 months. Gross-total resection was achieved in 14.3% of patients, whereas 30% had a subtotal resection and 54.3% a biopsy.Tumors located in telencephalon/diencephalon/myelencephalon were associated with a poorer OS, while a location in the mesencephalon/metencephalon showed a significantly longer OS (8.7 vs. 25.0 months, p=0.007). Preoperative Karnofsky Performance Score (KPS) < 80 showed a reduced OS (4.2 vs. 18 months, p=0.02). Furthermore, ATRX loss, found in 25.7%, was independently associated with an increased OS (31 vs. 8.3 months, p=0.0029). Notably, patients undergoing resection showed no survival benefit over biopsy (12 vs. 11 months, p=0.4006). CONCLUSION: The present study describes surgical features of H3 K27M-mutated glioma in adulthood in a large multicentric study. Our data reveal that ATRX status, location and KPS significantly impact OS in H3 K27M-mutated glioma. Importantly, our dataset indicates that resection does not offer a survival advantage over biopsy.

Multi-omics for studying and understanding polar life.

Polar ecosystems are experiencing amongst the most rapid rates of regional warming on Earth. Here, we discuss 'omics' approaches to investigate polar biodiversity, including the current state of the art, future perspectives and recommendations. We propose a community road map to generate and more fully exploit multi-omics data from polar organisms. These data are needed for the comprehensive evaluation of polar biodiversity and to reveal how life evolved and adapted to permanently cold environments with extreme seasonality. We argue that concerted action is required to mitigate the impact of warming on polar ecosystems via conservation efforts, to sustainably manage these unique habitats and their ecosystem services, and for the sustainable bioprospecting of novel genes and compounds for societal gain.

Inter and Intralaminar Excitation of Parvalbumin Interneurons in Mouse Barrel Cortex.

Parvalbumin (PV) interneurons are inhibitory fast-spiking cells with essential roles in directing the flow of information through cortical circuits. These neurons set the balance between excitation and inhibition, control rhythmic activity, and have been linked to disorders including autism spectrum and schizophrenia. PV interneurons differ between cortical layers in their morphology, circuitry, and function, but how their electrophysiological properties vary has received little attention. Here we investigate responses of PV interneurons in different layers of primary somatosensory barrel cortex (BC) to different excitatory inputs. With the genetically-encoded hybrid voltage sensor, hVOS, we recorded voltage changes simultaneously in many L2/3 and L4 PV interneurons to stimulation in either L2/3 or L4. Decay-times were consistent across L2/3 and L4. Amplitude, half-width, and rise-time were greater for PV interneurons residing in L2/3 compared to L4. Stimulation in L2/3 elicited responses in both L2/3 and L4 with longer latency compared to stimulation in L4. These differences in latency between layers could influence their windows for temporal integration. Thus PV interneurons in different cortical layers of BC show differences in response properties with potential roles in cortical computations.

Velocity of conduction between columns and layers in barrel cortex reported by parvalbumin interneurons.

Inhibitory interneurons expressing parvalbumin (PV) play critical roles throughout the brain. Their rapid spiking enables them to control circuit dynamics on a millisecond time scale, and the timing of their activation by different excitatory pathways is critical to these functions. We used a genetically encoded hybrid voltage sensor to image PV interneuron voltage changes with sub-millisecond precision in primary somatosensory barrel cortex (BC) of adult mice. Electrical stimulation evoked depolarizations with a latency that increased with distance from the stimulating electrode, allowing us to determine conduction velocity. Spread of responses between cortical layers yielded an interlaminar conduction velocity and spread within layers yielded intralaminar conduction velocities in different layers. Velocities ranged from 74 to 473 µm/ms depending on trajectory; interlaminar conduction was 71% faster than intralaminar conduction. Thus, computations within columns are more rapid than between columns. The BC integrates thalamic and intracortical input for functions such as texture discrimination and sensory tuning. Timing differences between intra- and interlaminar PV interneuron activation could impact these functions. Imaging of voltage in PV interneurons reveals differences in signaling dynamics within cortical circuitry. This approach offers a unique opportunity to investigate conduction in populations of axons based on their targeting specificity.

Comparing confocal and two-photon Ca2+ imaging of thin low-scattering preparations.

Ca2+ imaging provides insight into biological processes ranging from subcellular dynamics to neural network activity. Two-photon microscopy has assumed a dominant role in Ca2+ imaging. The longer wavelength infra-red illumination undergoes less scattering, and absorption is confined to the focal plane. Two-photon imaging can thus penetrate thick tissue ∼10-fold more deeply than single-photon visible imaging to make two-photon microscopy an exceptionally powerful method for probing function in intact brain. However, two-photon excitation produces photobleaching and photodamage that increase very steeply with light intensity, limiting how strongly one can illuminate. In thin samples, illumination intensity can assume a dominant role in determining signal quality, raising the possibility that single-photon microscopy may be preferable. We therefore tested laser scanning single-photon and two-photon microscopy side by side with Ca2+ imaging in neuronal compartments at the surface of a brain slice. We optimized illumination intensity for each light source to obtain the brightest signal without photobleaching. Intracellular Ca2+ rises elicited by one action potential had twice the signal/noise ratio with confocal as with two-photon imaging in axons, were 31% higher in dendrites, and about the same in cell bodies. The superior performance of confocal imaging in finer neuronal processes likely reflects the dominance of shot noise when fluorescence is dim. Thus, when out-of-focus absorption and scattering are not issues, single-photon confocal imaging can yield better quality signals than two-photon microscopy.

Imaging Voltage Globally and in Isofrequency Lamina in Slices of Mouse Ventral Cochlear Nucleus.

The cochlear nuclei (CNs) receive sensory information from the ear and perform fundamental computations before relaying this information to higher processing centers. These computations are performed by distinct types of neurons interconnected in circuits dedicated to the specialized roles of the auditory system. In the present study, we explored the use of voltage imaging to investigate CN circuitry. We tested two approaches based on fundamentally different voltage sensing technologies. Using a voltage-sensitive dye we recorded glutamate receptor-independent signals arising predominantly from axons. The mean conduction velocity of these fibers of 0.27 m/s was rapid but in range with other unmyelinated axons. We then used a genetically-encoded hybrid voltage sensor (hVOS) to image voltage from a specific population of neurons. Probe expression was controlled using Cre recombinase linked to c-fos activation. This activity-induced gene enabled targeting of neurons that are activated when a mouse hears a pure 15-kHz tone. In CN slices from these animals auditory nerve fiber stimulation elicited a glutamate receptor-dependent depolarization in hVOS probe-labeled neurons. These cells resided within a band corresponding to an isofrequency lamina, and responded with a high degree of synchrony. In contrast to the axonal origin of voltage-sensitive dye signals, hVOS signals represent predominantly postsynaptic responses. The introduction of voltage imaging to the CN creates the opportunity to investigate auditory processing circuitry in populations of neurons targeted on the basis of their genetic identity and their roles in sensory processing.

Viz.ai Implementation of Stroke Augmented Intelligence and Communications Platform to Improve Indicators and Outcomes for a Comprehensive Stroke Center and Network.

BACKGROUND AND PURPOSE: Comprehensive stroke centers continually strive to narrow neurointerventional time metrics. Although process improvements have been put in place to streamline workflows, complex pathways, disparate imaging locations, and fragmented communications all highlight the need for continued improvement. MATERIALS AND METHODS: This Quality Improvement Initiative (VISIION) was implemented to assess our transition to the Viz.ai platform for immediate image review and centralized communication and their effect on key performance indicators in our comprehensive stroke center. We compared periods before and following deployment. Sequential patients having undergone stroke thrombectomy were included. Both direct arriving large-vessel occlusion and Brain Emergency Management Initiative telemedicine transfer large-vessel occlusion cases were assessed as were subgroups of OnHours and OffHours. Text messaging thread counts were compared between time periods to assess communications. Mann-Whitney U and Student t tests were used. RESULTS: Eighty-two neurointerventional cases were analyzed pre vs. post time periods: (DALVO-OnHours 7 versus 7, DALVO-OffHours 10 versus 5, BEMI-OnHours 13 versus 6, BEMI-OffHours 17 versus 17). DALVO-OffHours had a 39% door-to-groin reduction (157 versus 95 minutes, P = .009). DALVO-All showed a 32% reduction (127 versus 86 minutes, P = .006). BEMI-All improved 33% (42 versus 28 minutes, P = .036). Text messaging thread counts improved 30% (39 versus 27, P = .04). CONCLUSIONS: There was an immediate improvement following Viz.ai implementation for both direct arriving and telemedicine transfer thrombectomy cases. In the greatest opportunity subset (direct arriving large-vessel occlusion-OffHours: direct arriving cases requiring team mobilization off-hours), we noted a 39% improvement. With Viz.ai, we noted that immediate access to images and streamlined communications improved door-to-groin time metrics for thrombectomy. These results have implications for future care processes and can be a model for centers striving to optimize workflow and improve thrombectomy timeliness.

Unitary synaptic responses of parvalbumin interneurons evoked by excitatory neurons in the mouse barrel cortex.

The mammalian cortex integrates and processes information to transform sensory inputs into perceptions and motor outputs. These operations are performed by networks of excitatory and inhibitory neurons distributed through the cortical layers. Parvalbumin interneurons (PVIs) are the most abundant type of inhibitory cortical neuron. With axons projecting within and between layers, PVIs supply feedforward and feedback inhibition to control and modulate circuit function. Distinct populations of excitatory neurons recruit different PVI populations, but the specializations of these synapses are poorly understood. Here, we targeted a genetically encoded hybrid voltage sensor to PVIs and used fluorescence imaging in mouse somatosensory cortex slices to record their voltage changes. Stimulating a single visually identified excitatory neuron with small-tipped theta-glass electrodes depolarized multiple PVIs, and a common threshold suggested that stimulation elicited unitary synaptic potentials in response to a single excitatory neuron. Excitatory neurons depolarized PVIs in multiple layers, with the most residing in the layer of the stimulated neuron. Spiny stellate cells depolarized PVIs more strongly than pyramidal cells by up to 77%, suggesting a greater role for stellate cells in recruiting PVI inhibition and controlling cortical computations. Response half-width also varied between different excitatory inputs. These results demonstrate functional differences between excitatory synapses on PVIs.

Synaptophysin transmembrane domain III controls fusion pore dynamics in Ca2+-triggered exocytosis.

Synaptophysin (syp) is a major protein of secretory vesicles with four transmembrane domains (TMDs) and a large cytoplasmic C-terminus. Syp has been shown to regulate exocytosis, vesicle cycling, and synaptic plasticity through its C-terminus. However, the roles of its TMDs remain unclear. The TMDs of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are thought to line initial fusion pores, and structural work together with sequence analysis suggest that TMD III of syp may play a similar role. To test this hypothesis, we performed tryptophan scanning experiments of TMD III in chromaffin cells and used amperometry to evaluate fusion pores. In contrast to SNARE TMDs, tryptophan substitutions in syp TMD III had no effect on the flux through initial fusion pores. However, a number of these mutants increased the fraction of kiss-and-run events and decreased the initial fusion pore lifetime. These results indicate that TMD III stabilizes the initial fusion pore and controls the initial choice between kiss and run and full fusion. Late-stage fusion pores were not impacted by TMD III mutations. These results indicate that syp TMD III does not line the initial fusion pore. However, its impact on pore dynamics suggests that it interacts with a SNARE protein implicated as a part of the fusion pore that forms at the onset of exocytosis.

Methylation subgroup and molecular heterogeneity is a hallmark of glioblastoma: implications for biopsy targeting, classification and therapy.

BACKGROUND: Intratumoral heterogeneity at the cellular and molecular level is a hallmark of glioblastoma (GB) that contributes to treatment resistance and poor clinical outcome. Little is known regarding epigenetic heterogeneity and intratumoral phylogeny and their implication for molecular classification and targeted therapies. PATIENTS AND METHODS: Multiple tissue biopsies (238 in total) were sampled from 56 newly-diagnosed, treatment-naive GB patients from a prospective in-house cohort and publicly available data and profiled for DNA methylation using the Illumina MethylationEPIC array. Methylation-based classification using the glioma classifier developed by Ceccarelli et al. and estimation of the MGMT promoter methylation status via the MGMT-STP27 model were carried out. In addition, copy number variations (CNVs) and phylogeny were analyzed. RESULTS: Almost half of the patients (22/56, 39%) harbored tumors composed of heterogeneous methylation subtypes. We found two predominant subtype combinations: classic-/mesenchymal-like, and mesenchymal-/pilocytic astrocytoma-like. Nine patients (16%) had tumors composed of subvolumes with and without MGMT promoter methylation, whereas 20 patients (36%) were homogeneously methylated, and 27 patients (48%) were homogeneously unmethylated. CNV analysis revealed high variations in many genes, including CDKN2A/B, EGFR, and PTEN. Phylogenetic analysis correspondingly showed a general pattern of CDKN2A/B loss and gain of EGFR, PDGFRA, and CDK4 during early stages of tumor development. CONCLUSIONS: (Epi)genetic intratumoral heterogeneity is a hallmark of GB, both at DNA methylation and CNV level. This intratumoral heterogeneity is of utmost importance for molecular classification as well as for defining therapeutic targets in this disease, as single biopsies might underestimate the true molecular diversity in a tumor.

Obesity and perioperative adverse events in patients undergoing complex revision surgery for the thoracolumbar spine.

BACKGROUND: There are no previous studies that evaluate the effect of obesity on patients undergoing complex revision thoracolumbar spine surgery. The primary objective was to determine the relationship between obesity and perioperative adverse events (AEs) with patients undergoing complex revision thoracolumbar spine surgery while controlling for psoas muscle index (PMI) as a confounding variable. The secondary objective was to determine the relationship between obesity and 30-day readmission rates, 30-day re-operation rates, rate of discharge to a facility, and post-operative length of stay (LOS). METHODS: Between May 2016 and February 2020, a retrospective analysis of individuals undergoing complex revision surgery of the thoracolumbar spine was performed at a single institution. Obesity was defined as BMI ≥ 30.0 kg/m2. PMI < 500 mm2/m2 for males and < 412 mm2/m2 for females were used to define low muscle mass. A Spine Surgical Invasiveness Index (SSII) > 10 was used to define complex revision surgery. A multivariable logistic regression model was used to ascertain the effects of low muscle mass, obesity, age, and gender on the likelihood of the occurrence of any AE. RESULTS: A total of 114 consecutive patients were included in the study. Fifty-four patients were in the obese cohort and 60 patients in the non-obese cohort. There was not a significant difference in perioperative outcomes of both the obese and non-obese patients. There were 22 obese patients (40.7%) and 33 non-obese patients (55.0%) that experienced any AE (p = 0.130). Multivariable analysis demonstrated that individuals with low muscle mass had a significantly higher likelihood for an AE than individuals with normal or high muscle mass (OR: 7.53, 95% CI: 3.05-18.60). Obesity did not have a significant effect in predicting AEs. CONCLUSIONS: Obesity is not associated with perioperative AEs, 30-day readmission rates, 30-day re-operation rates, rate of discharge to a facility, or post-operative length of stay (LOS) among patients undergoing complex revision thoracolumbar spine surgery. LEVEL OF EVIDENCE: III.

Full-fusion and kiss-and-run in chromaffin cells controlled by irreversible vesicle size-dependent fusion pore transitions.

Exocytosis operates through two distinct modes. Full-fusion leads to rapid expulsion of the entire content of a vesicle; kiss-and-run leads to slow and partial expulsion. These two modes have important biological consequences for endocrine regulation and synaptic transmission. Amperometry recordings of catecholamine release from chromaffin cells reveal single-vesicle fusion events corresponding to both of these modes, but classification is often difficult. This study introduces a new method of analyzing amperometry data to improve this classification. The ratio of the average amplitude to the peak amplitude differs between full-fusion and kiss-and-run, and the probability distribution of this ratio is well fitted by a double-Gaussian. Kiss-and-run events identified by this method have fusion pores with kinetic properties different from pores associated with full-fusion. They have slower transition rates and lifetime distributions indicative of irreversible transitions. The total-charge of an amperometric spike is expected to scale with vesicle volume during a full-fusion event. The cube root of this quantity should therefore scale with diameter, but the distribution of this quantity differs from the distribution of vesicle diameter seen in the electron microscope. Fusion pore lifetimes associated with full-fusion depend on vesicle size, and this makes the choice of mode size dependent. The fusion pore thus bifurcates after opening, and vesicle size influences this choice. The secretory vesicle protein synaptophysin influences the size dependence of fusion pore lifetime and the choice of release mode. Incorporating vesicle size into an analysis of release mode reconciled the kinetics of fusion pores, as well as the distributions of vesicle diameter and catecholamine content. Thus, the initial fusion pore emerges as a critical focus in endocrine regulation. By modulating the size-dependence of the mode of exocytosis, changes in the molecular makeup of the exocytotic apparatus can impact the shape and size of an amperometric event, and the speed and composition of secretion.

Percutaneous Transsplenic Balloon-Assisted Transjugular Intrahepatic Portosystemic Shunt Placement in Patients with Portal Vein Obliteration for Portal Vein Recanalization: Feasibility, Safety and Effectiveness.

PURPOSE: To assess the feasibility, safety and effectiveness of portal vein recanalization (PVR)-transjugular portosystemic shunt (TIPS) placement via splenic access using a balloon puncture technique. MATERIALS AND METHODS: In a single-center retrospective study from March 2017 to February 2021, 14 consecutive patients with portal hypertension, chronic liver disease and portal vein occlusion or near-complete (> 95%) occlusion were referred for PVR-TIPS placement. Feasibility, safety and effectiveness including procedural characteristics such as technical success, complication profile and splenic access time (SAT), balloon positioning time (BPT), conventional portal vein entry time (CPVET), overall procedure time (OPT), fluoroscopy time (FT), dose-area product (DAP) and air kerma (AK) were evaluated. RESULTS: Transsplenic PVR-TIPS using balloon puncture technique was technically feasible in 12 of 14 patients (8 men, 49 ± 13 years). In two patients without detectable intrahepatic portal vein branches, TIPS placement was not feasible and both patients were referred for further treatment with nonselective beta blockers and endoscopic variceal ligation. No complications grade > 3 of the Cardiovascular and Interventional Radiological Society of Europe classification system occurred. The SAT was 25 ± 21 min, CPVET was 33 ± 26 min, the OPT was 158 ± 54 min, the FT was 42 ± 22 min, the DAP was 167.84 ± 129.23 Gy*cm2 and the AK was 1150.70 ± 910.73 mGy. CONCLUSIONS: Transsplenic PVR-TIPS using a balloon puncture technique is feasible and appears to be safe in our series of patients with obliteration of the portal vein. It expands the interventional options in patients with chronic PVT.

Os 100 anos de “Além do Princípio do Prazer” e as novas concepções sobre a pulsão de morte / 100th year of the text “Beyond the Pleasure Principle” and the new conceptions on death drive

O interesse teórico e clínico acerca dos desdobramentos da noção freudiana de pulsão de morte ressurge com intensidade em razão do advento dos 100 anos do texto Além do Princípio do Prazer, sobretudo para aqueles que se dedicam à escuta de sofrimentos relacionados ao vazio psíquico, ao tédio e à apatia. No presente artigo, a autora dedica-se a apreciar as construções metapsicológicas derivadas desse texto freudiano, dando ênfase ao pensamento de Sándor Ferenczi, Donald Winnicott, André Green e Michael Balint, assim como aos aspectos clínicos referentes à posição do analista na escuta de tais casos em que predomina a circulação do mortífero.(AU)

The theoretical and clinical interest regarding the development of the Freudian notion of death drive reappears with intensity due to the advent of the 100th year of the text Beyond the Pleasure Principle, especially for those who work in psychoanalytical clinic with patients suffering from boredom, apathy and psychic void. In this article, the author appreciates the metapsychological constructions derived from this Freudian text, emphasizing the theories of Sándor Ferenczi, Donald Winnicott, André Green and Michael Balint, as well as the clinical aspects regarding the analyst’s position in listening to such cases in which predominates the circulation of the death drive.(AU)

Outcomes after stereotactic radiosurgery of brain metastases in patients with malignant melanoma and validation of the melanoma molGPA

Malignant melanoma is the third most common primary in the diagnosis of brain metastases. Stereotactic radiosurgery (SRS) is a well-established treatment option in limited brain disease. We analyzed outcomes of SRS with a particular focus on the graded prognostic assessment (GPA, melanoma molGPA), prognostic factors, and toxicity. Methods We evaluated 173 brain metastases in 83 patients with malignant melanoma. All were treated with SRS median dose of 20 Gy prescribed to the 80 or 100% isodose line between 2002 and 2019. All patients were followed-up regularly, including contrast‐enhanced brain imaging as well as clinical examination, initially 6 weeks after treatment, then in quarterly follow-up. Results The median age was 61 years (range 27–80); 36 female and 47 male patients were treated. After a median follow-up of 5.7 months, median OS (overall survival) was 9.7 months 95%-KI 4.7–14.7). LC (local control) at 6 months, 12, 24 months was 89%, 86%, and 72%, respectively (median was not reached). Median DBC (distant brain control) was 8.2 months (95%-KI 4.7–11.7). For OS, a KPS ≥ 80%, a positive BRAF mutation status, a small PTV (planning target volume), the absence of extracranial metastases, as well as a GPA and melanoma molGPA > 2 were prognostic factors. In the MVA, a small PTV and a melanoma molGPA > 2 remained significant. Conclusion The present survival outcomes support the use of the disease-specific melanoma molGPA as reliable prognostic score. Favorable outcomes for SRS compared to other studies were observed. In the treatment of brain metastases of malignant melanoma patients, a multidisciplinary approach consisting of surgery, SRS, chemotherapy, and immunotherapy should be considered (AU)

Disrupted relationship between blood glucose and brain dopamine D2/3 receptor binding in patients with first-episode schizophrenia.

An elemental function of brain dopamine is to coordinate cognitive and motor resources for successful exploitation of environmental energy sources. Dopamine transmission, goal-directed behavior, and glucose homeostasis are altered in schizophrenia patients prior to and after initiation of pharmacological treatment. Thus, we investigated the relationship between blood glucose levels and brain dopamine signaling in drug-naïve patients with first-episode psychosis. We quantified blood glucose levels and binding of the dopamine D2/3 receptor agonist radioligand (+)-[11C]-PHNO in 15 medication-naïve patients and 27 healthy volunteers employing positron emission tomography. Whole-brain voxel-wise linear model analysis identified two clusters of significant interaction between blood glucose levels and diagnosis on (+)-[11C]-PHNO binding-potential values. We observed positive relationships between blood glucose levels and binding-potential values in healthy volunteers but negative ones in patients with first episode psychosis in a cluster surviving rigorous multiple testing correction located in the in the right ventral tegmental area. Another cluster of homologous behavior, however at a lower level of statistical significance, comprised the ventral striatum and pallidum. Extracellular dopamine levels are a major determinant of (+)-[11C]-PHNO binding in the brain. In line with the concept that increased dopamine signaling occurs when goal-directed behavior is needed for restoring energy supply, our data indicate that in healthy volunteers, extracellular dopamine levels are high when blood glucose levels are low and vice-versa. This relationship is reversed in patients with first-episode psychosis, possibly reflecting an underlying pathogenic alteration that links two seemingly unrelated aspects of the illness: altered dopamine signaling and dysfunctional glucose homeostasis.

Direct synaptic excitation between hilar mossy cells revealed with a targeted voltage sensor.

The dentate gyrus not only gates the flow of information into the hippocampus, it also integrates and processes this information. Mossy cells (MCs) are a major type of excitatory neuron strategically located in the hilus of the dentate gyrus where they can contribute to this processing through networks of synapses with inhibitory neurons and dentate granule cells. Some prior work has suggested that MCs can form excitatory synapses with other MCs, but the role of these synapses in the network activity of the dentate gyrus has received little attention. Here, we investigated synaptic inputs to MCs in mouse hippocampal slices using a genetically encoded hybrid voltage sensor (hVOS) targeted to MCs by Cre-lox technology. This enabled optical recording of voltage changes from multiple MCs simultaneously. Stimulating granule cells and CA3 pyramidal cells activated well-established inputs to MCs and elicited synaptic responses as expected. However, the weak blockade of MC responses to granule cell layer stimulation by DCG-IV raised the possibility of another source of excitation. To evaluate synapses between MCs as this source, single MCs were stimulated focally. Stimulation of one MC above its action potential threshold evoked depolarizing responses in neighboring MCs that depended on glutamate receptors. Short latency responses of MCs to other MCs did not depend on release from granule cell axons. However, granule cells did contribute to the longer latency responses of MCs to stimulation of other MCs. Thus, MCs transmit their activity to other MCs both through direct synaptic coupling and through polysynaptic coupling with dentate granule cells. MC-MC synapses can redistribute information entering the dentate gyrus and thus shape and modulate the electrical activity underlying hippocampal functions such as navigation and memory, as well as excessive excitation during seizures.

Sobre reveries, quimeras e pensamentos paradoxais: impasses no setting analítico e o trabalho criativo do analista / On reveries, chimeras and paradoxal thoughts: the deadlocks in the analytical setting and the analyst’s creative work

Neste artigo, busca a autora garimpar subsídios sobre o tema da reverie, a fim de aprofundar a compreensão sobre os elementos motivadores do surgimento de imagens estranhas na mente do analista no curso de processos de análise, como pictogramas afetivos (ROCHA BARROS, 2000), quimeras e pensamentos paradoxais (M’UZAN, 1976). Sustenta-se que tais imagens surgem para atender a uma demanda de trabalho criativo quando são vivenciadas ameaças aos processos de simbolização, assim como a esterilidade do campo analítico em razão de impasses decorrentes de traumas primitivos, desvitalizações ou movimentos resistenciais da dupla analítica. O processo analítico, nesses casos, assume a natureza de “incubadora de símbolos” (HARTKE, 2005).(AU)

In this article, the author seeks to find subsidies on the theme of reverie, in order to deepen the understanding of the motivating elements that result in the appearance of strange images in the analyst’s mind during analysis, such as affective pictograms (ROCHA BARROS, 2000), chimeras and paradoxical thoughts (M’UZAN, 1976). It is sustained that such images appear to meet a demand for creative work when threats to the symbolization processes are experienced, as well as the sterility of the analytical field due to impasses resulting from primitive traumas, devitalizations or resistive movements of the analytical duo. The analytical process, in these cases, assumes the nature of a “symbol incubator” (HARTKE, 2005).(AU)