TL;DR
- Researchers have developed a new method for simultaneous imaging brain activity from two people, allowing them to study social interaction.
- Implant-free optogenetics minimizes brain damage during neuronal stimulation.
- Researchers have been able to restore sensation to the hand of a research participant with a severe spinal cord injury using a brain-computer interface (BCI) system. The technology harnesses neural signals that are so minuscule they can’t be perceived and enhances them via artificial sensory feedback sent back to the participant, resulting in greatly enriched motor function.
- The NIH BRAIN initiative, research by Carnegie Mellon’s Biomedical Engineering Department Head Bin He advances high-density electroencephalography (EEG) as the future paradigm for dynamic functional neuroimaging.
- A team at the University of Massachusetts Amherst has discovered, while on their way to better understanding protein nanowires, how to use these biological, electricity conducting filaments to make a neuromorphic memristor, or “memory transistor,” device. It runs extremely efficiently on very low power, as brains do, to carry signals between neurons.
- Our short-term memory makes systematic mistakes; according to scientists, these mistakes help us to stabilize the continually changing impressions of our environment.
- Researchers have discovered that astrocytes, the most abundant cells in the brain, play a direct role in the regulation of adult neuronal circuits involved in learning and memory.
- Neuroscientists have examined what happens in the brain when hearing gradually deteriorates: key areas of the brain are reorganized, and this affects memory.
- Scientists estimate non-verbal learning disorder may affect up to 3 million children in the United States.
- Researchers have revealed how a commonly used general anesthetic, isoflurane, weakens the transmission of electrical signals between neurons.
- Biomedical engineers have successfully used deep brain stimulation based on light to treat motor dysfunction in an animal model of Parkinson’s disease.
- Single-nucleus transcriptomics reveal brain alterations associated with major depression. Deep layer excitatory cells and immature oligodendrocytes showed most changes, involving synaptic plasticity, immune function and steroid hormones.
- A new staining technique could allow detailed anatomical analysis and whole-organ comparisons between species at the cellular level.
- Using fNIRS hyperscanning in three-versus-three-person intergroup competitions, new study shows that in-group bonding and within-group synchronization of reduced dorsolateral prefrontal activity escalate intergroup conflict.
- A new subset of disease-associated astrocytes (DAAs) is identified in a mouse model of Alzheimer’s disease by single-nucleus RNA sequencing. DAAs are also found in aged wild-type mice, suggesting a link to genetic and age-related factors.
- Researchers have successfully rebuilt the bridge between experimental neuroscience and advanced artificial intelligence learning algorithms. Conducting new types of experiments on neuronal cultures, the researchers were able to demonstrate a new accelerated brain-inspired learning mechanism. When the mechanism was utilized on the artificial task of handwritten digit recognition, for instance, its success rates substantially outperformed commonly-used machine learning algorithms.
- Can staying up late make you fat? Researchers found the opposite to be true when they studied sleep in worms: It’s not the sleep loss that leads to obesity, but rather that excess weight can cause poor sleep.
- And more!
Neuroscience market
The global neuroscience market size was valued at USD 28.4 billion in 2016 and it is expected to reach USD 38.9 billion by 2027.
Articles
Imaging Real-Time Tactile Interaction With Two-Person Dual-Coil fMRI
by Ville Renvall, Jaakko Kauramäki, Sanna Malinen, Riitta Hari,and Lauri Nummenmaa in Frontiers in Psychiatry
Researchers at Aalto University and Turku PET Centre have developed a new method for simultaneous imaging brain activity from two people, allowing them to study social interaction
Studies of brain mechanisms supporting social interaction are demanding because real interaction only occurs when persons are in contact. Instead, most brain imaging studies scan subjects individually. Researchers present a proof-of-concept demonstration of two-person blood oxygenation dependent (BOLD) imaging of brain activity from two individuals interacting inside the bore of a single MRI scanner. They developed a custom 16-channel (8 + 8 channels) two-helmet coil with two separate receiver-coil pairs providing whole-brain coverage, while bringing participants into a shared physical space and realistic face-to-face contact. Ten subject pairs were scanned with the setup. During the experiment, subjects took turns in tapping each other’s lip versus observing and feeling the taps timed by auditory instructions. Networks of sensorimotor brain areas were engaged alternatingly in the subjects during executing motor actions as well as observing and feeling them; these responses were clearly distinguishable from the auditory responses occurring similarly in both participants. Even though the signal-to-noise ratio of our coil system was compromised compared with standard 32-channel head coils, our results show that the two-person fMRI scanning is feasible for studying the brain basis of social interaction.
“During social interaction, people’s brains are literally synchronised. The associated mental imitation of other people’s movements is probably one of the basic mechanisms of social interaction. The new technology now developed will provide totally new opportunities for studying the brain mechanisms of social interaction,” says Professor Lauri Nummenmaa from Turku PET Centre.
“For example, during a conversation or problem solving, people’s brain functions become flexibly linked with each other. However, we cannot understand the brain basis of real-time social interaction if we cannot simultaneously scan the brain functions of both persons involved in social interaction,” Hari says.
Restoring the Sense of Touch Using a Sensorimotor Demultiplexing Neural Interface
by Patrick D. Ganzer, Samuel C. Colachis 4th, Michael A. Schwemmer, David A. Friedenberg, Collin F. Dunlap,Carly E. Swiftney, Adam F. Jacobowitz, Doug J. Weber, Marcia A. Bockbrader, and Gaurav Sharma in Cell
Researchers have been able to restore sensation to the hand of a research participant with a severe spinal cord injury using a brain-computer interface (BCI) system. The technology harnesses neural signals that are so minuscule they can’t be perceived and enhances them via artificial sensory feedback sent back to the participant, resulting in greatly enriched motor function.
- Following spinal cord injury, subperceptual touch signals affect the human motor cortex
- A brain-computer interface uses subperceptual signals to restore the sense of touch
- Sensorimotor function is further enhanced using demultiplexed sensorimotor signals
- Touch-regulated grip force can automate movement cascades and grip reanimation
Paralyzed muscles can be reanimated following spinal cord injury (SCI) using a brain-computer interface (BCI) to enhance motor function alone. Importantly, the sense of touch is a key component of motor function. Researchers demonstrate that a human participant with a clinically complete SCI can use a BCI to simultaneously reanimate both motor function and the sense of touch, leveraging residual touch signaling from his own hand. In the primary motor cortex (M1), residual subperceptual hand touch signals are simultaneously demultiplexed from ongoing efferent motor intention, enabling intracortically controlled closed-loop sensory feedback. Using the closedloop demultiplexing BCI almost fully restored the ability to detect object touch and significantly improved several sensorimotor functions. Afferent grip-intensity levels are also decoded from M1, enabling grip reanimation regulated by touch signaling. These results demonstrate that subperceptual neural signals can be decoded from the cortex and transformed into conscious perception, significantly augmenting function.
“It has been amazing to see the possibilities of sensory information coming from a device that was originally created to only allow me to control my hand in a one-way direction,” says first author Patrick Ganzer, a principal research scientist at Battelle.
Context information supports serial dependence of multiple visual objects across memory episodes
by Cora Fischer, Stefan Czoschke, Benjamin Peters, Benjamin Rahm, Jochen Kaiser & Christoph Bledowski in Nature Communications
Our short-term memory makes systematic mistakes; according to scientists, these mistakes help us to stabilize the continually changing impressions of our environment.
Serial dependence is thought to promote perceptual stability by compensating for small changes of an object’s appearance across memory episodes. So far, it has been studied in situations that comprised only a single object. The question of how we selectively create temporal stability of several objects remains unsolved. In a memory task, objects can be differentiated by their to-be-memorized feature (content) as well as accompanying discriminative features (context). Researchers test whether congruent context features, in addition to content similarity, support serial dependence. In four experiments, they observe a stronger serial dependence between objects that share the same context features across trials. Apparently, the binding of content and context features is not erased but rather carried over to the subsequent memory episode. As this reflects temporal dependencies in natural settings, their findings reveal a mechanism that integrates corresponding content and context features to support stable representations of individualized objects over time.
Noninvasive electromagnetic source imaging of spatiotemporally distributed epileptogenic brain sources
by Abbas Sohrabpour, Zhengxiang Cai, Shuai Ye, Benjamin Brinkmann, Gregory Worrell & Bin He in Nature Communications
Marking a major milestone on the path to meeting the objectives of the NIH BRAIN initiative, research by Carnegie Mellon’s Biomedical Engineering Department Head Bin He advances high-density electroencephalography (EEG) as the future paradigm for dynamic functional neuroimaging.
Brain networks are spatiotemporal phenomena that dynamically vary over time. Functional imaging approaches strive to noninvasively estimate these underlying processes. Researchers propose a novel source imaging approach that uses high-density EEG recordings to map brain networks. This approach objectively addresses the long-standing limitations of conventional source imaging techniques, namely, difficulty in objectively estimating the spatial extent, as well as the temporal evolution of underlying brain sources. They validate our approach by directly comparing source imaging results with the intracranial EEG (iEEG) findings and surgical resection outcomes in a cohort of 36 patients with focal epilepsy. To this end, we analyzed a total of 1,027 spikes and 86 seizures. They demonstrate the capability of our approach in imaging both the location and spatial extent of brain networks from noninvasive electrophysiological measurements, specifically for ictal and interictal brain networks. Researchers’ approach is a powerful tool for noninvasively investigating large-scale dynamic brain networks.
Frequency-Specific Optogenetic Deep Brain Stimulation of Subthalamic Nucleus Improves Parkinsonian Motor Behaviors
by Chunxiu Yu, Isaac R. Cassar, Jaydeep Sambangi and Warren M. Grill in Journal of Neuroscience
Biomedical engineers have successfully used deep brain stimulation based on light to treat motor dysfunction in an animal model of Parkinson’s disease
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapy for the motor symptoms of Parkinson’s disease (PD). However, the neural elements mediating symptom relief are unclear. A previous study concluded that direct optogenetic activation of STN neurons was neither necessary nor sufficient for relief of parkinsonian symptoms. However, the kinetics of the ChR2 used for cell-specific activation are too slow to follow the high rates required for effective DBS, and thus the contribution of activation of STN neurons to the therapeutic effects of DBS remains unclear. Researchers quantified the behavioral and neuronal effects of optogenetic STN DBS in female rats following unilateral 6-hydroxydopamine lesion using an ultrafast opsin (Chronos). Optogenetic STN DBS at 130 pulses per second reduced pathological circling and ameliorated deficits in forelimb stepping similarly to electrical DBS, while optogenetic STN DBS with ChR2 did not produce behavioral effects. As with electrical DBS, optogenetic STN DBS exhibited a strong dependence on stimulation rate; high rates produced symptom relief while low rates were ineffective. High rate optogenetic DBS generated both increases and decreases in firing rates of single neurons in STN, globus pallidus externa and substantia nigra pars reticular (SNr), and disrupted beta band oscillatory activity in STN and SNr. High rate optogenetic STN DBS can indeed ameliorate parkinsonian motor symptoms through reduction of abnormal oscillatory activity in the STN-associated neural circuit, and these results highlight that the kinetic properties of opsins have a strong influence on the effects of optogenetic stimulation.
Whether STN local cells contribute to the therapeutic effects of STN DBS in PD remains unclear. Scientists re-examined the role of STN local cells in mediating the symptom-relieving effects of STN DBS using cell type specific optogenetic stimulation with a much faster opsin, Chronos. Direct optogenetic stimulation of STN neurons was effective in treating the symptoms of parkinsonism in the 6-OHDA lesion rat. These results highlight that the kinetic properties of opsins can have a strong influence on the effects of optogenetic activation/inhibition and must be considered when employing optogenetic to study high rate neural stimulation.
“If you think of the area of the brain being treated in deep brain stimulation as a plate of spaghetti, with the meatballs representing nerve cell bodies and the spaghetti representing nerve cell axons, there’s a longstanding debate about whether the treatment is affecting the spaghetti, the meatballs or some combination of the two,” said Warren Grill, the Edmund T. Pratt, Jr. School Distinguished Professor of Biomedical Engineering at Duke.
Disease-associated astrocytes in Alzheimer’s disease and aging
by Naomi Habib, Cristin McCabe, Sedi Medina, Miriam Varshavsky, Daniel Kitsberg, Raz Dvir-Szternfeld, Gilad Green, Danielle Dionne, Lan Nguyen, Jamie L. Marshall, Fei Chen, Feng Zhang, Tommy Kaplan, Aviv Regev & Michal Schwartz in Nature Neuroscience
A new subset of disease-associated astrocytes (DAAs) is identified in a mouse model of Alzheimer’s disease by single-nucleus RNA sequencing. DAAs are also found in aged wild-type mice, suggesting a link to genetic and age-related factors.
The role of non-neuronal cells in Alzheimer’s disease progression has not been fully elucidated. Using single-nucleus RNA sequencing, we identified a population of disease-associated astrocytes in an Alzheimer’s disease mouse model. These disease-associated astrocytes appeared at early disease stages and increased in abundance with disease progression. Scientists discovered that similar astrocytes appeared in aged wild-type mice and in aging human brains, suggesting their linkage to genetic and age-related factors.
Within-group synchronization in the prefrontal cortex associates with intergroup conflict
by Jiaxin Yang, Hejing Zhang, Jun Ni, Carsten K. W. De Dreu & Yina Ma in Nature Neuroscience
Using fNIRS hyperscanning in three-versus-three-person intergroup competitions, this study shows that in-group bonding and within-group synchronization of reduced dorsolateral prefrontal activity escalate intergroup conflict.
Individuals immersed in groups sometimes lose their individuality, take risks they would normally avoid and approach outsiders with unprovoked hostility. In this study, researchers identified within-group neural synchronization in the right dorsolateral prefrontal cortex (rDLPFC) and the right temporoparietal junction (rTPJ) as a candidate mechanism underlying intergroup hostility. They organized 546 individuals into 91 three-versus-three-person intergroup competitions, induced in-group bonding or no-bonding control manipulation and measured neural activity and within-group synchronization using functional near-infrared spectroscopy. After in-group bonding (versus control), individuals gave more money to in-group members than to out-group members and contributed more money to outcompete their rivals. In-group bonding decreased rDLPFC activity and increased functional connectivity between the rDLPFC and the rTPJ. Especially during the out-group attack, in-group bonding also increased within-group synchronization in both the rDLPFC and the rTPJ, and within-group rDLPFC synchronization positively correlated with intergroup hostility. Within-group synchronized reduction in prefrontal activity might explain how in-group bonding leads to impulsive and collective hostility toward outsiders.
Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons
by Corina Nagy, Malosree Maitra, Arnaud Tanti, Matthew Suderman, Jean-Francois Théroux, Maria Antonietta Davoli, Kelly Perlman, Volodymyr Yerko, Yu Chang Wang, Shreejoy J. Tripathy, Paul Pavlidis, Naguib Mechawar, Jiannis Ragoussis & Gustavo Turecki in Nature Neuroscience
Single-nucleus transcriptomics reveal brain alterations associated with major depression. Deep layer excitatory cells and immature oligodendrocytes showed most changes, involving synaptic plasticity, immune function and steroid hormones
Major depressive disorder (MDD) has an enormous impact on global disease burden, affecting millions of people worldwide and ranking as a leading cause of disability for almost three decades. Past molecular studies of MDD employed bulk homogenates of postmortem brain tissue, which obscures gene expression changes within individual cell types. Scientists used single-nucleus transcriptomics to examine ~80,000 nuclei from the dorsolateral prefrontal cortex of male individuals with MDD (n = 17) and of healthy controls (n = 17). They identified 26 cellular clusters, and over 60% of these showed differential gene expression between groups. They found that the greatest dysregulation occurred in deep layer excitatory neurons and immature oligodendrocyte precursor cells (OPCs), and these contributed almost half (47%) of all changes in gene expression. These results highlight the importance of dissecting cell-type-specific contributions to the disease and offer opportunities to identify new avenues of research and novel targets for treatment.
An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques
by Xin Gong, Diego Mendoza-Halliday, Jonathan T. Ting, Guoqiang Bi, Robert Desimone, Guoping Feng et al. in Neuron
A minimally invasive optogenetic technique that does not require brain implants successfully manipulated the activity of neurons in mice and monkeys, researchers report. The researchers first genetically engineered neurons to produce a newly developed, extremely light-sensitive protein called SOUL. They then demonstrated that it is possible to shine light through the skull to alter neuronal responses throughout the entire mouse brain, and to reach superficial regions of the macaque brain.
- Researchers introduce SOUL, a new step-function opsin with ultrahigh light sensitivity
- SOUL activates deep mouse brain and change behaviors via transcranial illumination
- SOUL activates macaque cortical neurons via illumination through the dura
- Transdural activation of SOUL in macaques induces oscillatory activity reversibly
Optogenetics is among the most widely employed techniques to manipulate neuronal activity. However, a major drawback is the need for invasive implantation of optical fibers. To develop a minimally invasive optogenetic method that overcomes this challenge, researchers engineered a new step-function opsin with ultra-high light sensitivity (SOUL). They show that SOUL can activate neurons located in deep mouse brain regions via transcranial optical stimulation and elicit behavioral changes in SOUL knock-in mice. Moreover, SOUL can be used to modulate neuronal spiking and induce oscillations reversibly in macaque cortex via optical stimulation from outside the dura. By enabling external light delivery, our new opsin offers a minimally invasive tool for manipulating neuronal activity in rodent and primate models with fewer limitations on the depth and size of target brain regions and may further facilitate the development of minimally invasive optogenetic tools for the treatment of neurological disorders.
(A) Schematic of in vivo recording and transcranial stimulation of MD with SOUL (left) or SSFO (right) in awake mice. Scale bar, 1 mm. Gray bar, optical fiber; blue region, illumination.
(B) Raster plot of the representative recording of the neuron from SSFO- (top panel) or SOUL-expressing (bottom panel) MD during blue and orange light illumination (colored bars).
(C ) Mean (±SEM) firing rate (normalized to baseline) across neurons in SOUL- (dark green circle) or SSFO-expressing (brown circle) MD transcranially stimulated with blue light of different intensities (*p < 0.05; **p < 0.01; ***p < 0.001; two-tailed Wilcoxon signed rank tests). SOUL, n = 36; SSFO, n = 31 neurons from 2 mice.
(D) Schematic of transcranial optical stimulation (blue) of SOUL-expressing lateral hypothalamus (LH, red) through the intact skull (gray) of awake mice.
(E) Coronal section of mice injected with SOUL-P2A-tdTomato in LH, expressing tdTomato (red) in LH and stained for DAPI (blue). Scale bar, 1 mm.
(F) Representative confocal images of LH sections from mice expressing mCherry (red, top panel) or SOUL-P2A-tdTomato (red, bottom panel) and stained for cFos (green). Scale bar, 20 mm.
(G) Mean cell counts of c-Fos+ cells in LH of mice injected with AAVs coding SOUL or mCherry (Ctrl.) as in (E) (unpaired t test; *p < 0.05, p = 0.035). SOUL, n = 3 mice; mCherry, n = 3 mice.
Bioinspired bio-voltage memristors
by Tianda Fu, Xiaomeng Liu, Hongyan Gao, Joy E. Ward, Xiaorong Liu, Bing Yin, Zhongrui Wang, Ye Zhuo, David J. F. Walker, J. Joshua Yang, Jianhan Chen, Derek R. Lovley & Jun Yao in Nature Communications
Only 10 years ago, scientists working on what they hoped would open a new frontier of neuromorphic computing could only dream of a device using miniature tools called memristors that would function/operate like real brain synapses. A team at the University of Massachusetts Amherst has discovered, while on their way to better understanding protein nanowires, how to use these biological, electricity conducting filaments to make a neuromorphic memristor, or “memory transistor,” device. It runs extremely efficiently on very low power, as brains do, to carry signals between neurons.
Memristive devices are promising candidates to emulate biological computing. However, the typical switching voltages (0.2–2 V) in previously described devices are much higher than the amplitude in biological counterparts. Researchers demonstrate a type of diffusive memristor, fabricated from the protein nanowires harvested from the bacterium Geobacter sulfurreducens, that functions at the biological voltages of 40–100 mV. Memristive function at biological voltages is possible because the protein nanowires catalyze metallization. Artificial neurons built from these memristors not only function at biological action potentials (e.g., 100 mV, 1 ms) but also exhibit temporal integration close to that in biological neurons. The potential of using the memristor to directly process biosensing signals is also demonstrated.
A salt-induced kinase is required for the metabolic regulation of sleep
by Jeremy J. Grubbs, Lindsey E. Lopes, Alexander M. van der Linden, David M. Raizen in PLOS Biology
Can staying up late make you fat? Researchers found the opposite to be true when they studied sleep in worms: It’s not the sleep loss that leads to obesity, but rather that excess weight can cause poor sleep.
Many lines of evidence point to links between sleep regulation and energy homeostasis, but mechanisms underlying these connections are unknown. During Caenorhabditis elegans sleep, energetic stores are allocated to nonneural tasks with a resultant drop in the overall fat stores and energy charge. Mutants lacking KIN-29, the C. elegans homolog of a mammalian Salt-Inducible Kinase (SIK) that signals sleep pressure, have low ATP levels despite high-fat stores, indicating a defective response to cellular energy deficits. Liberating energy stores corrects adiposity and sleep defects of kin-29 mutants. kin-29 sleep and energy homeostasis roles map to a set of sensory neurons that act upstream of fat regulation as well as of central sleep-controlling neurons, suggesting hierarchical somatic/neural interactions regulating sleep and energy homeostasis. Genetic interaction between kin-29 and the histone deacetylase hda-4 coupled with subcellular localization studies indicate that KIN-29 acts in the nucleus to regulate sleep. We propose that KIN-29/SIK acts in nuclei of sensory neuroendocrine cells to transduce low cellular energy charge into the mobilization of energy stores, which in turn promotes sleep.
Hippocampal Synaptic Plasticity, Spatial Memory, and Neurotransmitter Receptor Expression Are Profoundly Altered by Gradual Loss of Hearing Ability
by Daniela Beckmann, Mirko Feldmann, Olena Shchyglo, Denise Manahan-Vaughan in Cerebral Cortex
Neuroscientists have examined what happens in the brain when hearing gradually deteriorates: key areas of the brain are reorganized, and this affects memory
Sensory information comprises the substrate from which memories are created. Memories of spatial sensory experience are encoded by means of synaptic plasticity in the hippocampus. Hippocampal dependency on sensory information is highlighted by the fact that sudden and complete loss of a sensory modality results in an impairment of hippocampal function that persists for months. Effects are accompanied by extensive changes in the expression of neurotransmitter receptors in cortex and hippocampus, consistent with a substantial adaptive reorganization of cortical function. Whether gradual sensory loss affects hippocampal function is unclear. Progressive age-dependent hearing loss (presbycusis) is a risk factor for cognitive decline. Researchers scrutinized C57BL/6 mice that experience hereditary and cumulative deafness starting in young adulthood. They observed that 2–4 months postnatally, increases in the cortical and hippocampal expression of GluN2A and GluN2B subunits of the N-methyl-D-aspartate receptor occurred compared to control mice that lack sensory deficits. Furthermore, GABA and metabotropic glutamate receptor expression were significantly altered. Hippocampal synaptic plasticity was profoundly impaired and mice exhibited significant deficits in spatial memory. These data show that during cortical adaptation to cumulative loss of hearing, plasticity-related neurotransmitter expression is extensively altered in the cortex and hippocampus. Furthermore, cumulative sensory loss compromises hippocampal function.
Region-Specific Transcriptional Control of Astrocyte Function Oversees Local Circuit Activities
by Anna Yu-Szu Huang, Junsung Woo, Debosmita Sardar, Antrix Jain, Adriana Paulucci-Holthauzen, Benjamin Deneen in Neuron
Researchers have discovered that astrocytes, the most abundant cells in the brain, play a direct role in the regulation of adult neuronal circuits involved in learning and memory
•NFIA is required to maintain astrocyte function in a brain-region-specific manner
•Brain-region-specific DNA binding by NFIA is inhibited by its association with NFIB
•Astrocyte-neuron communication in the hippocampus is disrupted
•Synaptic plasticity and memory are impaired in mice lacking astrocytic NFIA
Astrocytes play essential roles in brain function by supporting synaptic connectivity and associated circuits. How these roles are regulated by transcription factors is unknown. Moreover, there is emerging evidence that astrocytes exhibit regional heterogeneity, and the mechanisms controlling this diversity remain nascent. Researchers show that conditional deletion of the transcription factor nuclear factor I-A (NFIA) in astrocytes in the adult brain results in region-specific alterations in morphology and physiology that are mediated by selective DNA binding. Disruptions in astrocyte function following loss of NFIA are most pronounced in the hippocampus, manifested by impaired interactions with neurons, coupled with diminution of learning and memory behaviors. These changes in hippocampal astrocytes did not affect basal neuronal properties but specifically inhibited synaptic plasticity, which is regulated by NFIA in astrocytes through calcium-dependent mechanisms. Together, their studies reveal region-specific transcriptional dependencies for astrocytes and identify astrocytic NFIA as a key transcriptional regulator of hippocampal circuits.
Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms
by Han-Ying Wang, Kohgaku Eguchi, Takayuki Yamashita and Tomoyuki Takahashi in Journal of Neuroscience
Researchers have revealed how a commonly used general anesthetic, isoflurane, weakens the transmission of electrical signals between neurons
Volatile anesthetics are widely used for surgery, but neuronal mechanisms of anesthesia remain unidentified. At the calyx of Held in brainstem slices from rats of either sex, isoflurane at clinical doses attenuated excitatory post-synaptic currents by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca2+ currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca2+ currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca2+ influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending upon input frequencies. In simultaneous pre- and postsynaptic action potential recordings, isoflurane impaired the fidelity of repetitive spike transmission, more strongly at higher frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited monosynaptic cortico-cortical spike transmission, preferentially at a higher frequency. Theyconclude that dual presynaptic mechanisms operate for the anesthetic action of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass filtering role in spike transmission at central excitatory synapses.
Brain experiments imply adaptation mechanisms which outperform common AI learning algorithms
by Shira Sardi, Roni Vardi, Yuval Meir, Yael Tugendhaft, Shiri Hodassman, Amir Goldental & Ido Kanter in Scientific Reports
Researchers have successfully rebuilt the bridge between experimental neuroscience and advanced artificial intelligence learning algorithms. Conducting new types of experiments on neuronal cultures, the researchers were able to demonstrate a new accelerated brain-inspired learning mechanism. When the mechanism was utilized on the artificial task of handwritten digit recognition, for instance, its success rates substantially outperformed commonly-used machine learning algorithms.
Attempting to imitate the brain’s functionalities, researchers have bridged between neuroscience and artificial intelligence for decades; however, experimental neuroscience has not directly advanced the field of machine learning (ML). Here, using neuronal cultures, scientists demonstrate that increased training frequency accelerates the neuronal adaptation processes. This mechanism was implemented on artificial neural networks, where a local learning step-size increases for coherent consecutive learning steps, and tested on a simple dataset of handwritten digits, MNIST. Based on their on-line learning results with a few handwriting examples, success rates for brain-inspired algorithms substantially outperform the commonly used ML algorithms. They speculate this emerging bridge from slow brain function to ML will promote ultrafast decision making under limited examples, which is the reality in many aspects of human activity, robotic control, and network optimization.
Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues
by Etsuo A. Susaki, Chika Shimizu, Hiroki R. Ueda in Nature Communications
A new staining technique could allow detailed anatomical analysis and whole-organ comparisons between species at the cellular level
Whole-organ/body three-dimensional (3D) staining and imaging have been enduring challenges in histology. By dissecting the complex physicochemical environment of the staining system, researchers developed a highly optimized 3D staining imaging pipeline based on CUBIC. Based on our precise characterization of biological tissues as an electrolyte gel, they experimentally evaluated broad 3D staining conditions by using an artificial tissue-mimicking material. The combination of optimized conditions allows a bottom-up design of a superior 3D staining protocol that can uniformly label whole adult mouse brains, an adult marmoset brain hemisphere, an ~1 cm3 tissue block of a postmortem adult human cerebellum, and an entire infant marmoset body with dozens of antibodies and cell-impermeant nuclear stains. The whole-organ 3D images collected by light-sheet microscopy are used for computational analyses and whole-organ comparison analysis between species. This pipeline, named CUBIC-HistoVIsion, thus offers advanced opportunities for organ- and organism-scale histological analysis of multicellular systems.
Estimated Prevalence of Nonverbal Learning Disability Among North American Children and Adolescents
by Amy E. Margolis; Jessica Broitman; John M. Davis; et al in JAMA Network Open
Nonverbal learning disability (NVLD), a poorly understood and often-overlooked disorder that causes problems with visual-spatial processing, may affect nearly 3 million children in the United States, making it one of the most common learning disorders, according to a new study by led by Columbia University Irving Medical Center.
Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial processing but not in reading or verbal ability; in addition, problems in math calculation, visual executive functioning, fine-motor skills, and social skills are often present. To our knowledge, there are no population-based estimates of the prevalence of NVLD in community samples.To estimate the prevalence of the NVLD cognitive profile in 3 independent samples of children and adolescents from studies centered around brain imaging in the US and Canada.This cross-sectional study used data from 2 samples recruited from the community and overselected for children with psychiatric disorders (Healthy Brain Network [HBN], January 1, 2015, to December 31, 2019, and Nathan Kline Institute–Rockland Sample [NKI], January 1, 2011, to December 31, 2018) and 1 community-ascertained population sample (Saguenay Youth Study [SYS], January 1, 2003, to December 31, 2012) overselected for active maternal smoking during pregnancy. Criteria for NVLD were based on clinical records of deficits in visual-spatial reasoning and impairment in 2 of 4 domains of function (fine-motor skills, math calculation, visual executive functioning, and social skills). Sample weighting procedures adjusted for demographic differences in sample frequencies compared with underlying target populations. Inflation factor weights accounted for overrepresentation of psychiatric disorders (HBN and NKI samples). Across 3 independent samples, the prevalence of NVLD was estimated among 2596 children and adolescents aged 6 to 19 years (mean [SD] age, 12.5 [3.4] years; 1449 male [55.8%]). After sample and inflation weights were applied, the prevalence of NVLD was 2.78% (95% CI, 2.03%-3.52%) in the HBN sample and 3.9% (95% CI, 1.96%-5.78%) in the NKI sample. In the SYS sample, the prevalence of NVLD was 3.10% (95% CI, 1.93%-4.27%) after applying the sample weight. Across samples and estimation strategies, the population prevalence of NVLD was estimated to range from 3% to 4%. When applied to the US population younger than 18 years, 2.2 million to 2.9 million children and adolescents were estimated to have NVLD. The findings suggest that the prevalence of NVLD in children and adolescents may be 3% to 4%. Given that few youths are diagnosed with NVLD and receive treatment, increased awareness, identification of the underlying neurobiological mechanisms, and development and testing interventions for the disorder are needed.
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