2019 Jan 10 – Cumulating data obtained in vivo as well as in intact preparations such as acute brain slices indicate that astrocytes – by means of bidirectional communications with neighboring cells including neurons – are active, integral elements of circuits. This view emerged already in 1999, when the tripartite synapse concept was proposed to the scientific community by Alfonso Araque and colleagues. Indeed, the advent of calcium imaging techniques in the ’90s and, more recently, advanced optical microscopy, have helped clarify how finely astrocytes may decode neuronal signaling [responding to 1) glutamate, acetylcholine, ATP, GABA and endocannabinoids, while evidence is scarce regarding other neurotransmitters; 2) neuromodulators and changes in the extracellular environment] and integrate this information into the release of gliotransmitters such as glutamate, ATP/adenosine, D-serine and GABA. In the review linked below, Alfonso Araque and the PhD student Caitlin Durkee take into account recent experiments highlighting the coordinated contribution of astrocytes to higher brain functions via highly specific modulation of synaptic transmission and neuronal excitability.
2018 Nov 26 – Brain-computer interfaces record, decode and translate brain electrical activity into useful control signals for external devices, aiming at providing assistance to people with severe motor disabilities. The latest publication from the clinical trial BrainGate2 illustrates one of the proceedings in the development of this technology: challenging but general control of a commercial tablet was achieved by three participants with tetraplegia (two of whom were diagnosed with amyotrophic lateral sclerosis and were dependent on ventilators, and a third with cervical spinal cord injury) who had either one or two multielectrode arrays implanted in the motor cortex (4×4 mm, electrode length 1.0-1.5 mm). This invasive technique allows precise recordings from single neurons.
2018 Ott 09 – Cryptochromes are a class of flavoproteins [i.e. they contain a photo-excitable FAD cofactor, although this is questionable for CRY2 in mammalians] which are key regulators of cellular functions, including the circadian clock in plants and animals. They have been proposed to serve as magnetosensors in different organisms: according to an influential model, the radical pair [FADH• + O2•–] is formed as an intermediate in cryptochromes following photoinduced reduction of FAD. External fields such as the geomagnetic field influence the conversion rate and the ratio of the radical pair in the singlet/triplet state, and in turn would alter the signalling properties of the molecule. Both this model and alternative biochemical pathways are compatible with the release of reactive oxigen species (ROS) – which has been already demonstrated in response to light – providing a means for signaling magnetoreception at the cellular level and ultimately for affecting animal sensitivity.
A novel study coordinated by Margaret Ahmad focuses on human CRY1 and ROS. The authors show that transgenic expression of human CRY1 in mutant larvae of Drosophila deficient in cryptochrome rescues the expected behavioral response to applied magnetic fields. In addition, cryptochrome-dependent increase in ROS is observed upon stimulation by low-flux pulsed electromagnetic fields in distinct cell lines derived from insects, mouse or humans. In human HEK293 cells, as expected, this increase was accompanied by overexpression of genes implicated in oxidoreductase reactions. Overall, the study highlights one possible mechanism of response to therapeutic PEMFs in humans and other animals, as well as to electromagnetic pollution.
2018 Sep 7 – “On 4 September 2018, 11 national research funding organisations, with the support of the European Commission including the European Research Council (ERC), announced the launch of cOAlition S, an initiative to make full and immediate Open Access to research publications a reality. It is built around Plan S, which consists of one target and 10 principles“.
On the same line, the Swedish Government set the goal of immediate open access by 2026. Agreements with the scientific publisher Elesevier have not been renewed after 30th of June on behalf of Swedish universities, university colleges, governmental agencies and research institutes.
2018 Sep 6 – A novel preclinical study shows mild improvements in the locomotor function of laboratory mice with spinal cord lesions not greater than 75%, upon engraftment of human neuroepithelial stem cells dissected post-mortem from spinal cord primordia of embryos (post-conceptional week 5 to 8), and maintained in vitro in active proliferation state. Improvements 1) depend on the formation of a relay system reconnecting supraspinal axons with denervated target neurons below the injury level, 2) require anatomical matching of graft with recipient tissue and 3) are accompanied by efficient differentiation of engrafted cells toward both neuronal and glial fate. The viability of this approach was confirmed in Sprague Dawley rats with a contusion of thoracic spinal cord – a clinically relevant model because contusion is the most common cause of lesion – receiving homospecific neuroepithelial stem cells derived from the embryonic spinal cord primordia.
2018 Jul 31 – Magnetic resonance-guided focused ultrasound stimulation (MRgFUS) in combination with intravenously injected microbubbles has been shown to transiently increase the permeability of the blood–brain barrier (BBB) in animal models of neuropathologies, including brain tumors, Parkinson’s and Alzheimer’s disease. Nir Lipsman and coworkers of the Sunnybrook Research Center in Toronto, Canada, have now published the outcomes of the first pilot phase I trial evaluating safety and technical feasibility of this procedure in the clinics, in order to assist in the targeted delivery of therapeutic agents to selective areas in the central nervous system. The procedure was administered twice (1 month interval) to the right frontal lobe of 4 patients with early to moderate Alzheimer’s disease. Reversible BBB opening was achieved with high spatial and temporal specificity at low frequency (220 kHz) and approximately 50% power required to generate cavitation, with less than 1% of the energy used in thermal ablation. No serious clinical or radiographic adverse events were observed (deaths, hemorrhages, swelling, neurologic deficits), nor group-wise changes in levels of deposited beta-amyloid resulted from the analysis of positron emission tomography/computed tomography scans at 7 days following each sonication. Psychometric scores did not differ significantly at up to 2 months. To further current research, a phase 2a study is scheduled to begin in September on a larger sample size, targeting a more eloquent brain area in Alzheimer’s.
2018 Jun 08 – Notwithstanding the necessity to gain a firm grasp on both its detailed mechanisms and long-term effects, focused ultrasound stimulation (FUS) guided by magnetic resonance imaging holds significant attention in trials for the treatment of selective neurological and psychiatric disorders. FUS is also assisting novel research in causal brain mapping, cognitive neuroscience and circuit plasticity. As a mechanical wave, FUS combines noninvasiveness with unprecedented sharp spatial focus (in the range of millimeters in diameter for the stimulated volume) and depth penetration. In addition to thermal ablation at high stimulus intensities (as early as 1954, Lindstrom and Fry et al. pioneered this application, and several protocols have been approved for use in a community setting), targeted drug delivery and neuromodulation induced by FUS are currently under investigation. Neuromodulatory effects are elicited at low intensities – lower or comparable to already adopted thresholds in ecography – by activation of ion channels sensitive to mechanic perturbations. Neural responses triggered by FUS have the exquisite capability of being either excitatory or inhibitory, transient or long-lasting, depending on specific parameter settings. Below is the link to the most recent review on ultrasonic neuromodulation, written by Jan Kubanek, Stanford University, California. It is worth noting that mechanosensation plays a significant role in the neurogenesis, maintenance, and repair of the central nervous system.
2018 May 30 – Even though familial amyotrophic lateral sclerosis (ALS) accounts for 5 to 10% of all cases, the identification of genes implicated in rare familial forms of the pathology has significant impact on the unraveling of the molecular mechanisms underlying sporadic ALS. Emerging findings indicate that ALS-causing mutations affect key regulators of RNA processing, and dysregulated RNA processing occurring during development could eventually contribute to the increased vulnerability of mature motor neurons that characterizes ALS progression.
Of note, intron retention (IR) is the predominant RNA splicing change during early motor neurogenesis. A novel study shows that both IR in the Splicing Factor Proline and Glutamine rich (SFPQ) transcript and nuclear loss of the SFPQ protein are common molecular hallmarks across diverse genetic and sporadic forms of ALS. Preliminary evidences were collected from RNA sequencing reads of spinal motor neurons differentiating in vitro , and carrying a rare ALS-causing mutation in the gene VCP. Results were subsequently confirmed and generalised in two mouse transgenic models of ALS (SOD1G93A and VCPA232E) as well as upon examination of spinal cord post-mortem tissue from sporadic human ALS cases.
2018 May 17 – Birbaumer and colleagues published in 1999 a pivotal paper on brain-computer interfaces (BCIs), showing subjects suffering from advanced amyotrophic lateral sclerosis use slow cortical potentials of the electroencephalogram to drive a cursor on a video screen, thus operating a spelling software. Over the years, BCI studies have largely ignored the contribution of user-training strategies while focusing on machine learning. However, the prizewinning approach in the 2016 Cybathlon BCI race benefited from the refinement of a mutual, incremental interaction between user training and machine learning. From the users’ perspective, this co-adaptive system allowed typical motor outputs to occur, in that these became automatic with practice (i.e. based on implicit learning, not on explicit information such as motor imagery). The related case study analyzed the two participants involved in this specific experimental set-up, who were both severely impaired as a consequence of spinal cord lesions at level C5–C6. They were trained to control their avatar by modulating sensorimotor rhythms in the μ (8–12 Hz) and β (18–30 Hz) ranges. Recordings where acquired by means of a 16 electrodes electroencephalographic cap targeting sensorimotor cortices.
2018 May 8 – Tactile sensory feedback and proprioception are essential for the manipulation and feeling of body ownership of robotic prosthesis. Biomedical engineers at Shanghai Jiao Tong University, China, carried out psychophysical experiments to optimize phantom finger perceptions evoked in upper limb amputees by transcutaneous electrical nerve stimulation delivered at the skin of the residual limb.
2018 Mar 22 – Following their initial formation upon activation of discrete ensembles of hippocampal neurons, memories are unstable and subjected either to get lost or to further processing. In principle, the comparison of newly forming memories with stored ones during periods of memory instability would allow common features to be extracted; instability may thus provide one gateway to create/modulate generalized knowledge, consistent with the significant interplay observed between the prefrontal cortex and the hippocampus at this stage. Edwin Robertson from the University of Glasgow, UK, considers this hypothesis in a short essay published in Plos Biology.
2018 Mar 6 – “There is clearly a growing excitement around treating neurological diseases using neuromodulation, rather than pharmaceuticals”. We report below the full commentary recently published by Helen Thomson’s in Nature, introducing relevant questions and essential information on the subject.
2018 Feb 19 – Bayes’ law might fit the capacity of brain circuits to encode certain prior distributions of events and use them to derive posterior probabilities. In a work published in Nature Communications, authors hypothesized that the cerebellum would be best suited to learn sub-second to second prior temporal distributions of time intervals and support Bayesian estimates. To validate their hypothesis, they elaborated and tested a mathematical model called TRACE (Temporally Reinforced Acquisition of Cerebellar Engram) that synthesizes known anatomical and physiological mechanisms of the cerebellum. TRACE performed in a manner highly consistent with Bayesian estimation theory. When human subjects were tested in two established cerebellar timing tasks, the results were consistent with the predictions of the model. This work poses the prospect of a new implication for the cerebellum.
2018 Feb 7 – Among their heterogeneous and coordinating functions, astrocytes are implicated in the modulation of neuronal excitability and synaptic transmission. In particular, it has been suggested that astrocytes may influence the activity of local neural circuits controlling sleep, breathing and feeding via the vesicular release of signaling molecules called gliotransmitters. In a novel study, researchers collaborating across UK, US and the Russian Federation employed molecular approaches aimed at blocking or stimulating such release in the preBötzinger complex of adult conscious rats, where essential respiratory rhythm-generating circuits are located. The results show that astrocytes in the preBötzinger complex 1) modulate the respiratory rhythm-generating circuits, 2) critically mediate respiratory adaptive responses in conditions of increased metabolic demand and 3) contribute to determine the exercise capacity (i.e. the maximal oxygen uptake during exercise).
2017 Nov 10 – Stroke lesions with substantial unilateral cortex destruction allow very limited regaining of lost functions through plastic remodeling of neuronal networks, whereas assistive experimental approaches such as pharmacological treatments and transcranial stimulation are burdened with variability in cell targeting. To selectively activate intact corticospinal-projecting neurons contralateral to an ischemic lesion of the premotor and sensorimotor cortices corresponding to the preferred paw in adult rats, neurobiologists from Zurich, Switzerland, combined daily optogenetic stimulation starting early after stroke with subsequent intensive rehabilitative training. This led to the restoration of impaired forelimb movement patterns in a single pellet grasping task, as assessed by an unsupervised computer vision analysis of posture and kinematics developed at the Interdisciplinary Center for Scientific Computing, University of Heidelberg, Germany. Stimulated animals – with or without training – additionally performed significantly better than controls in two unfamiliar tasks of skilled forelimb usage. Functional rehabilitation positively correlated with fiber sprouting across the midline to the denervated cervical hemi-cord, together with fiber growth in the ipsilesional ventral corticospinal tract, as previosuly described in rats undergoing sequential treatment with anti-Nogo-A immunotherapy and intensive training.
In animals fully recovered under the latter protocol, optogenetically silencing neurons of the intact main motor forelimb area (M1) caused a significant drop in performance, suggesting their causal role.
Even though optogenetics requires invasive viral vector injections and implants of optic fibers, this study strongly encourages further research on high-resolution interventions to promote corticospinal rewiring for future stroke therapies.
2017 June 29 – There is rising interest in the neurobiology of forgetting (transience). Richards and Frankland from Toronto, Canada, made an original contribution to the field by outlining parallels between the mechanisms of transience at synapses and principles from machine learning and computational neuroscience. In this light, they reviewed the literature on the role of transience in 1) “enhancing behavioral flexibility by eliminating outdated information” and 2) “promoting generalization by preventing overfitting memories to specific instances from the past that may not accurately predict the future”.
Apr 12 2017 – A novel work published in Plos Biology underlies the importance of whole transcriptome analysis and pharmacogenomics. Azim, Angonin and colleagues identified in silico specific bioactive molecules that can direct the differentiation of neural stem cells (NSCs) in the dorsal subventricular zone (dSVZ) of the lateral ventricle of mice, based on their transcriptional signature. Transcriptional changes that promoted oligodendrogenesis were induced in the postnatal dSVZ, along with changes promoting both the generation of glutamatergic neuronal progenitors and increased oligodendrogenesis in the adult mouse. Moreover, consistent preliminary results were yielded in a mouse model of postnatal hypoxic brain injury. If the hypothesis is correct that endogenous NSCs might be harnessed to assist brain repair following neurodegeneration or demyelination, this approach is of potential therapeutic interest.
2016 Dec 16 – A five-year open science initiative (open data, open materials such as informatic resources and biosamples, no patenting) has been launched at the Montreal Neurological Institute. The institution aims at 1) having researchers from across Canada and the world collaborate more effectively and 2) attracting commercial entities as well as patient organizations, in order to build a local hub for knowledge-based economic development.
2016 Apr 19 – “For two decades now, the UNESCO Science Report series has been mapping science, technology and innovation (STI) governance around the world on a regular basis. Since STI do not evolve in a vacuum, this latest edition summarizes the evolution since 2010 against the backdrop of socio-economic, geopolitical and environmental trends that have helped to shape contemporary STI policy and governance”.
2014 Dec 16 – Conversion of nonneuronal cells into induced neurons has been proposed as an innovative strategy towards neural repair in the cerebral cortex. Retroviral expression of the transcription factor Sox2 – alone or in combination with Ascl1 – can induce the conversion of reactive NG2 glia into doublecortin (DCX)+ neurons in vivo, as shown in a mouse model of traumatic cerebral cortex injury. NG2 glia were readily targeted by retroviruses at the injury site. However, only a small fraction of induced DCX+ neurons appeared to develop into more mature state.