Fate of Cajal–Retzius Neurons in the Postnatal Mouse Neocortex

Cajal–Retzius (CR) neurons play a critical role in cortical neuronal migration, but their exact fate after the completion of neocortical lamination remains a mystery. Histological evidence has been unable to unequivocally determine whether these cells die or undergo a phenotypic transformation to become resident interneurons of Layer 1 in the adult neocortex. To determine their ultimate fate, we performed chronic in vivo two-photon imaging of identified CR neurons during postnatal development in mice that express the green fluorescent protein (GFP) under the control of the early B-cell factor 2 (Ebf2) promoter. We find that, after birth, virtually all CR neurons in mouse neocortex express Ebf2. Although postnatal CR neurons undergo dramatic morphological transformations, they do not migrate to deeper layers. Instead, their gradual disappearance from the cortex is due to apoptotic death during the second postnatal week. A small fraction of CR neurons present at birth survive into adulthood. We conclude that, in addition to orchestrating cortical layering, a subset of CR neurons must play other roles beyond the third postnatal week

Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders

A leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this one-dimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here, we combined computational simulations with analysis of in vivo two-photon Ca2+ imaging data from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: (1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; (2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; (3) The direction of circuit alterations in Fmr1 KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher dimensional models that can better capture the multidimensional computational functions of neural circuits

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

The population tracking model:a simple, scalable statistical model for neural population data

Our understanding of neural population coding has been limited by a lack of analysis methods to characterize spiking data from large populations. The biggest challenge comes from the fact that the number of possible network activity patterns scales exponentially with the number of neurons recorded ([Formula: see text]). Here we introduce a new statistical method for characterizing neural population activity that requires semi-independent fitting of only as many parameters as the square of the number of neurons, requiring drastically smaller data sets and minimal computation time. The model works by matching the population rate (the number of neurons synchronously active) and the probability that each individual neuron fires given the population rate. We found that this model can accurately fit synthetic data from up to 1000 neurons. We also found that the model could rapidly decode visual stimuli from neural population data from macaque primary visual cortex about 65 ms after stimulus onset. Finally, we used the model to estimate the entropy of neural population activity in developing mouse somatosensory cortex and, surprisingly, found that it first increases, and then decreases during development. This statistical model opens new options for interrogating neural population data and can bolster the use of modern large-scale in vivo Ca[Formula: see text] and voltage imaging tools

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

Two-photon axotomy and time-lapse confocal imaging in live zebrafish embryos

Zebrafish have long been utilized to study the cellular and molecular mechanisms of development by time-lapse imaging of the living transparent embryo. Here we describe a method to mount zebrafish embryos for long-term imaging and demonstrate how to automate the capture of time-lapse images using a confocal microscope. We also describe a method to create controlled, precise damage to individual branches of peripheral sensory axons in zebrafish using the focused power of a femtosecond laser mounted on a two-photon microscope. The parameters for successful two-photon axotomy must be optimized for each microscope. We will demonstrate two-photon axotomy on both a custom built two-photon microscope and a Zeiss 510 confocal/two-photon to provide two examples

The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning.

Neuronal ApoE receptors are linked to learning and memory, but the pathways governing their abundance, and the mechanisms by which they affect the function of neural circuits are incompletely understood. Here we demonstrate that the E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis and plasticity. IDOL-dependent changes in ApoER2 abundance modulate dendritic filopodia initiation and synapse maturation. Loss of IDOL in neurons results in constitutive overexpression of ApoER2 and is associated with impaired activity-dependent structural remodeling of spines and defective LTP in primary neuron cultures and hippocampal slices. IDOL-deficient mice show profound impairment in experience-dependent reorganization of synaptic circuits in the barrel cortex, as well as diminished spatial and associative learning. These results identify control of lipoprotein receptor abundance by IDOL as a post-transcriptional mechanism underlying the structural and functional plasticity of synapses and neural circuits