Note & Recensioni

Volumi e saggiJay Schulkin, Reflections on the Musical Mind. An Evolutionary Perspective, [Michele Gardini, p. 202] • Hans Belting, Faces. Eine Geschichte des Gesichts [Pietro Conte, p. 205] • Aby Warburg, Il primo Rinascimento italiano. Sette conferenze inedite [Alice Barale, p. 207] • Laura Anna Macor (a cura di), Reading Schiller: Ethics, Aesthetics and Religion [Lorenzo Leonardo Pizzichemi, p. 209] • Bernard Lafargue, Stéphanie Cardoso (a cura di), Figures de l’art n° 25, Philosophie du design [Claire Azéma, Anne Beyaert Geslin, Stéphanie Cardoso, Cécile Croce, p. 212] • Helmut Leder et al., What Makes an Art Expert? Emotion and Evaluation in Art Appreciation, “Cognition and Emotion”, 2013, 28, pp. 1-11; Enric Munar et al., Aesthetic Appreciation: Event-Related Field and Time-Frequency Analyses, “Frontiers in Human Neurosciences”, 2012, 5, pp. 1-11; Gerald C. Cupchik et al., Viewing Artworks: Contributions of Cognitive Control and Perceptual Facilitation to Aesthetic Experience, “Brain and Cognition”, 2009, 70, pp. 84-91 [Gianluca Consoli, p. 217

Note e Recensioni

Renaud Barbaras, La vie lacunaire [Thomas Vercruysse, p. 324] • Wolfram Hogrebe, Der implizite Mensch [Federica Ceranovi, p. 334] • Emmanuel Alloa, Das durchscheinende Bild [Maria Teresa Costa, p. 344] • Alexander R. Galloway, The Interface Effect [Angela Maiello, p. 346] • Francisco José Ramos, La significación del lenguaje poético [Michele Gardini, p. 348] • Alessandro Arbo, Entendre comme. Wittgenstein et l’esthétique musicale [Leonardo V. Distaso, p. 351

Kajian Keprihatinan Ahli Akademik Terhadap Tatacara Berpakaian, Sahsiah dan Rupa Diri Pelajar Universiti Malaysia Pahang

Tamadun adalah perkataan Arab “Maddana” yang bermaksud adab, akhlaq, moral dan mempunyai agama yang baik. Manakala hidup bertamadun bermaksud kehidupan yang penuh dengan adab sopan, moral dan berakhlak. Dalam konteks dunia pendidikan hari ini isu tatacara berpakaian, rupa diri, sahsiah dan akhlak pelajar pernah dibincangkan dan diketengahkan di peringkat institusi pengajian tinggi amnya, namun masih tidak menampakkan hasil positif. Kelihatan seolah-olah tiada keseriusan daripada pelbagai pihak untuk mengendalikan dan menjayakan isu ini sebaik mungkin sehingga ke akar umbinya dan secara tidak langsung untuk berusaha menyelesaikannya. Justeru, satu kajian berfokus telah dijalankan terhadap pelajar di Universiti Malaysia Pahang dari pelbagai fakulti. Kajian ini bertujuan meninjau sejauh mana komitmen pensyarah selaku aset penting yang berintegriti tinggi, bernilai dan berakhlak mulia dalam menjalankan amanah mereka mendidik anak bangsa khususnya dalam membangunkan akhlak dan sahsiah diri terpuji dalam kalangan mahasiswa. Kajian ini dilakukan secara tinjauan melalui aplikasi internet iaitu SurveyMonkey kepada lebih dari 100 orang pelajar. Melalui kajian ini terdapat enam perkara yang diperhatikan dan dikaji secara terperinci. Kajian ini berkisar komitmen pelajar dan pensyarah di kampus antaranya ialah komitmen pelajar terhadap pemakaian kad pelajar universiti (kad matrik), komitmen pensyarah memperuntukkan masa dalam kelas bagi menyatakan kepentingan tatacara berpakaian dan rupa diri di kampus, komitmen mengambil tindakan terhadap pelajar yang gagal mematuhi peraturan tatacara berpakaian dan rupa diri, komitmen mengambil tindakan terhadap pelajar yang lewat atau gagal hadir dalam kelas, dan amanah dalam mengisi ruang di slip kehadiran rakan sekuliah dalam kelas. Hasil kajian mendapati bahawa komitmen di kalangan pelajar dan pensyarah kurang memberangsangkan. Perkara ini harus dipandang serius dan sangat membimbangkan kerana penekanan terhadap isu-isu tersebut sangat penting dalam melahirkan pelajar bertamadun iaitu berpengetahuan luas, berkemahiran tinggi dan bersikap, berakhlak serta bersahsiah terpuji

Tactile defensiveness and impaired adaptation of neuronal activity in the Fmr1 knockout mouse model of autism

Sensory hypersensitivity is a common symptom in autism spectrum disorders (ASDs), including Fragile X Syndrome (FXS), and frequently leads to tactile defensiveness. In mouse models of ASDs, there is mounting evidence of neuronal and circuit hyperexcitability in several brain regions, which could contribute to sensory hypersensitivity. However, it is not yet known whether or how sensory stimulation might trigger abnormal sensory processing at the circuit level or abnormal behavioral responses in ASD mouse models, especially during an early developmental time when experience-dependent plasticity shapes such circuits. Using a novel assay, we discovered exaggerated motor responses to whisker stimulation in young Fmr1 knockout (KO) mice (postnatal days (P) 14-16), a model of FXS. Adult Fmr1 KO mice actively avoided a stimulus that was innocuous to wild-type controls, a sign of tactile defensiveness. Using in vivo two-photon calcium imaging of Layer 2/3 barrel cortex neurons expressing GCaMP6s, we found no differences between wild-type and Fmr1 KO mice in overall whisker-evoked activity, though 45% fewer neurons in young Fmr1 KO mice responded in a time-locked manner. Notably, we identified a pronounced deficit in neuronal adaptation to repetitive whisker stimulation in both young and adult Fmr1 KO mice. Thus, impaired adaptation in cortical sensory circuits is a potential cause of tactile defensiveness in autism

Four cases of progressive multifocal leukoencephalopathy in iatrogenic immunocompromised patients

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by John Cunningham Virus (JCV). We report four PML cases in immunocompromised patients, respectively treated with (1) Natalizumab, (2) Rituximab, (3) autologous stem-cell transplantation, and (4) Tacrolimus. All patients underwent neurological examination, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), JCV-DNA research on biological samples, and lymphocytes subpopulation study. All cases presented with motor, behavioural, and cognitive disorders. Visual, sensitive, and cerebellar deficits developed in three cases. MRI revealed widespread progressive demyelinating areas with active borders; three patients presented contrast enhancement. One patient developed inflammatory reconstitution syndrome (IRIS). At MRS, all cases presented decreased N-acetyl-aspartate (NAA) and three cases showed increased choline (Cho). In one patient, plasma and urine tested positive for JCV-DNA, while cerebrospinal fluid (CSF) analysis confirmed JCV in two patients. The fourth patient had a low JCV-DNA blood titer and brain biopsy showed subacute necrosis. Two patients had abnormal lymphocyte subpopulations. Three patients underwent therapy with Mirtazapine, one of whom received Mefloquine in add-on. No clinical response was registered. Clinical onset, MRI and MRS were highly suggestive of PML in all patients, despite three cases presented contrast enhancement. In three cases JCV-DNA detection in biological samples confirmed the diagnosis. The fourth patient fulfilled diagnosis of “presumptive PML”. Our data confirm the importance to complete the diagnostic workup despite the presence of findings not completely consistent with classical PML. We hypothesize that atypical characteristics could due to the clinical conditions leading to PML

A Versatile Method for Viral Transfection of Calcium Indicators in the Neonatal Mouse Brain

The first three postnatal weeks in rodents are a time when sensory experience drives the maturation of brain circuits, an important process that is not yet well understood. Alterations in this critical period of experience-dependent circuit assembly and plasticity contribute to several neurodevelopmental disorders, such as autism, epilepsy, and schizophrenia. Therefore, techniques for recording network activity and tracing neuronal connectivity over this time period are necessary for delineating circuit refinement in typical development and how it deviates in disease. Calcium imaging with GCaMP6 and other genetically encoded indicators is rapidly becoming the preferred method for recording network activity at the single-synapse and single-cell level in vivo, especially in genetically identified neuronal populations. We describe a protocol for intracortical injection of recombinant adeno-associated viruses in P1 neonatal mice and demonstrate its use for longitudinal imaging of GCaMP6s in the same neurons over several weeks to characterize the developmental desynchronization of cortical network activity. Our approach is ideally suited for chronic in vivo two-photon calcium imaging of neuronal activity from synapses to entire networks during the early postnatal period

Glutamate Induces the Elongation of Early Dendritic Protrusions via mGluRs in Wild Type Mice, but Not in Fragile X Mice

Fragile X syndrome (FXS), the most common inherited from of autism and mental impairment, is caused by transcriptional silencing of the Fmr1 gene, resulting in the loss of the RNA-binding protein FMRP. Dendritic spines of cortical pyramidal neurons in affected individuals are abnormally immature and in Fmr1 knockout (KO) mice they are also abnormally unstable. This could result in defects in synaptogenesis, because spine dynamics are critical for synapse formation. We have previously shown that the earliest dendritic protrusions, which are highly dynamic and might serve an exploratory role to reach out for axons, elongate in response to glutamate. Here, we tested the hypothesis that this process is mediated by metabotropic glutamate receptors (mGluRs) and that it is defective in Fmr1 KO mice. Using time-lapse imaging with two-photon microscopy in acute brain slices from early postnatal mice, we find that early dendritic protrusions in layer 2/3 neurons become longer in response to application of glutamate or DHPG, a Group 1 mGluR agonist. Blockade of mGluR5 signaling, which reverses some adult phenotypes of KO mice, prevented the glutamate-mediated elongation of early protrusions. In contrast, dendritic protrusions from KO mice failed to respond to glutamate. Thus, absence of FMRP may impair the ability of cortical pyramidal neurons to respond to glutamate released from nearby pre-synaptic terminals, which may be a critical step to initiate synaptogenesis and stabilize spines

EZcalcium: Open-Source Toolbox for Analysis of Calcium Imaging Data

Fluorescence calcium imaging using a range of microscopy approaches, such as two-photon excitation or head-mounted “miniscopes,” is one of the preferred methods to record neuronal activity and glial signals in various experimental settings, including acute brain slices, brain organoids, and behaving animals. Because changes in the fluorescence intensity of genetically encoded or chemical calcium indicators correlate with action potential firing in neurons, data analysis is based on inferring such spiking from changes in pixel intensity values across time within different regions of interest. However, the algorithms necessary to extract biologically relevant information from these fluorescent signals are complex and require significant expertise in programming to develop robust analysis pipelines. For decades, the only way to perform these analyses was for individual laboratories to write their custom code. These routines were typically not well annotated and lacked intuitive graphical user interfaces (GUIs), which made it difficult for scientists in other laboratories to adopt them. Although the panorama is changing with recent tools like CaImAn, Suite2P, and others, there is still a barrier for many laboratories to adopt these packages, especially for potential users without sophisticated programming skills. As two-photon microscopes are becoming increasingly affordable, the bottleneck is no longer the hardware, but the software used to analyze the calcium data optimally and consistently across different groups. We addressed this unmet need by incorporating recent software solutions, namely NoRMCorre and CaImAn, for motion correction, segmentation, signal extraction, and deconvolution of calcium imaging data into an open-source, easy to use, GUI-based, intuitive and automated data analysis software package, which we named EZcalcium

Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome