A guide to the BRAIN Initiative Cell Census Network data ecosystem.

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization.

Functional MRI reveals brain-wide actions of thalamically-initiated oscillatory activities on associative memory consolidation.

As a key oscillatory activity in the brain, thalamic spindle activities are long believed to support memory consolidation. However, their propagation characteristics and causal actions at systems level remain unclear. Using functional MRI (fMRI) and electrophysiology recordings in male rats, we found that optogenetically-evoked somatosensory thalamic spindle-like activities targeted numerous sensorimotor (cortex, thalamus, brainstem and basal ganglia) and non-sensorimotor limbic regions (cortex, amygdala, and hippocampus) in a stimulation frequency- and length-dependent manner.

Brain Data Standards - A method for building data-driven cell-type ontologies.

Large-scale single-cell 'omics profiling is being used to define a complete catalogue of brain cell types, something that traditional methods struggle with due to the diversity and complexity of the brain. But this poses a problem: How do we organise such a catalogue - providing a standard way to refer to the cell types discovered, linking their classification and properties to supporting data? Cell ontologies provide a partial solution to these problems, but no existing ontology schemas support the definition of cell types by direct reference to supporting data, classification of cell types using classifications derived directly from data, or links from cell types to marker sets along with confidence scores. Here we describe a generally applicable schema that solves these problems and its application in a semi-automated pipeline to build a data-linked extension to the Cell Ontology representing cell types in the Primary Motor Cortex of humans, mice and marmosets.

Ontology Development Kit: a toolkit for building, maintaining and standardizing biomedical ontologies.

Similar to managing software packages, managing the ontology life cycle involves multiple complex workflows such as preparing releases, continuous quality control checking and dependency management. To manage these processes, a diverse set of tools is required, from command-line utilities to powerful ontology-engineering environmentsr. Particularly in the biomedical domain, which has developed a set of highly diverse yet inter-dependent ontologies, standardizing release practices and metadata and establishing shared quality standards are crucial to enable interoperability.

Antidepressant-like effects of transcorneal electrical stimulation in rat models.

Background: Given that visual impairment is bi-directionally associated with depression, we examined whether transcorneal electrical stimulation (TES), a non-invasive treatment for visual disorders, can ameliorate depressive symptoms.

Objective: The putative antidepressant-like effects of TES and the underlying mechanisms were investigated in an S334ter-line-3 rat model of retinal degeneration and a rat model of chronic unpredictable stress (CUS).

Methods: TES was administered daily for 1 week in S334ter-line-3 and CUS rats.

Sex-Specific ADHD-like Behaviour, Altered Metabolic Functions, and Altered EEG Activity in Sialyltransferase ST3GAL5-Deficient Mice.

A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-alpha-2,3-sialyltransferase (ST3GAL5), leads to severe neuropathology, including epilepsy and metabolic abnormalities. Disruption of ganglioside production by this enzyme may also have a role in the development of neuropsychiatric disorders. ST3Gal5 knock-out () mice lack a-, b-, and c-series gangliosides, but exhibit no overt neuropathology, possibly owing to the production of compensatory 0-series glycosphingolipids.

A Brief Comparative Look at Experimental Memory Editing Techniques for Cognitive Dysfunction.

Neuroscience has long sought to develop methods that can "edit" or even "erase" memories, with the aim to provide treatments for memory-related neurological and psychiatric diseases such as anxiety and addiction. Current efforts are heavily focused on modifying cognitive behavioral therapy protocols or pharmacological treatments, but the efficacy and safety of these methods have been called into question by several studies. Advances in modern technology and the rapid emergence of techniques that can directly stimulate/alter neuronal activity, such as neuromodulation, have great potential in achieving the goal of memory modification for treating dementia such as Alzheimer's disease.

An existentialist approach to authentic science.

The pressures of the ethos of "publish or perish" in academia has led to a multitude of issues for science and scientists. In this paper, we argue that the existentialist philosophy concept of authenticity would be useful for scientists to prevent issues of reproducibility, data manipulation, fraud, and mentorship. We highlight some major caveats and call for policies to prevent them.

Prelimbic cortical stimulation disrupts fear memory consolidation through ventral hippocampal dopamine D receptors.

Background And Purpose: Anxiety disorders pose one of the biggest threats to mental health worldwide, yet current therapeutics have been mostly ineffective due to issues with relapse, efficacy and toxicity of the medications. Deep brain stimulation (DBS) is a promising therapy for treatment-resistant psychiatric disorders including anxiety, but very little is known about the effects of deep brain stimulation on fear memories.

Experimental Approach: In this study, we employed a standard tone-footshock fear conditioning paradigm and modified plus maze discriminative avoidance task to probe the effects of prelimbic cortex deep brain stimulation on various stages of memory.

Interdisciplinary Research in Alzheimer's Disease and the Roles International Societies Can Play.

An ever-increasing ageing population has elevated Alzheimer's disease to be one of the biggest challenges in modern medicine. Alzheimer's disease is highly complex, and we are still no closer to understanding the causes, let alone an effective treatment. The lack of good experimental models and lack of critical understanding has led to high failure rates of clinical trials with high associated costs, as well as difficulties in implementing treatments.

Dropout in Neural Networks Simulates the Paradoxical Effects of Deep Brain Stimulation on Memory.

Neuromodulation techniques such as deep brain stimulation (DBS) are a promising treatment for memory-related disorders including anxiety, addiction, and dementia. However, the outcomes of such treatments appear to be somewhat paradoxical, in that these techniques can both disrupt and enhance memory even when applied to the same brain target. In this article, we hypothesize that disruption and enhancement of memory through neuromodulation can be explained by the dropout of engram nodes.

A practical approach to the ethical use of memory modulating technologies.

Background: Recent advancements in neuroscientific techniques have allowed us to make huge progress in our understanding of memories, and in turn has paved the way for new memory modification technologies (MMTs) that can modulate memories with a degree of precision, which was not previously possible. With advancements in such techniques, new and critical ethical questions have emerged. Understanding and framing these ethical questions within the current philosophical theories is crucial in order to systematically examine them as we translate these techniques to the clinic.

Prelimbic Cortical Stimulation Improves Spatial Memory Through Distinct Patterns of Hippocampal Gene Expression in Aged Rats.

Dementia poses major health challenges worldwide, yet current treatments are faced with issues of efficacy and toxicity. Deep brain stimulation (DBS) is a promising non-pharmacological treatment for dementia, but most DBS studies use young healthy animals, which may not be aetiologically relevant. In this study, we used an aged rat model in which cognitive decline occurs through a natural ageing process.

Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation.

Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful as an unconditioned stimulus for modelling anticipatory fear and agoraphobia in a contextual fear conditioning paradigm. In this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then attempted to unravel some of the interactions with dopamine signalling using tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons.

The Paradoxical Effect of Deep Brain Stimulation on Memory.

Deep brain stimulation (DBS) is a promising treatment for many memory-related disorders including dementia, anxiety, and addiction. However, the use of DBS can be a paradoxical conundrum-dementia treatments aim to improve memory, whereas anxiety or addiction treatments aim to suppress maladaptive memory. In this review, the key hypotheses on how DBS affects memory are highlighted.

Eternal sunshine of the neuromodulated mind: Altering fear memories through neuromodulation.

Anxiety disorders pose one of the greatest threats to mental health. Modern treatment methods exist but are hindered by relapse, toxicity, and low efficacy. The use of neuromodulation to treat anxiety disorders has shown promising results, yet its underpinning mechanisms remain poorly understood.

Immunohistochemical insights into Saffold virus infection of the brain of juvenile AG129 mice.

Background: Saffold Virus (SAFV) is a human cardiovirus that is suspected of causing infection of the central nervous system (CNS) in children. While recent animal studies have started to elucidate the pathogenesis of SAFV, very little is known about the mechanisms behind it.

Method: In this study, we attempted to elucidate some of the mechanisms of the pathogenesis of SAFV in the brain of a juvenile mouse model by using immunohistochemical methods.

Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice.

Tetratricopeptide repeat domain 9A (TTC9A) expression is abundantly expressed in the brain. Previous studies in TTC9A knockout (TTC9A) mice have indicated that TTC9A negatively regulates the action of estrogen. In this study we investigated the role of TTC9A on anxiety-like behavior through its functional interaction with estrogen using the TTC9A mice model.

Saffold virus, an emerging human cardiovirus.

Saffold virus (SAFV) is an emerging human cardiovirus that has been shown to be ubiquitous. Initial studies of SAFV focused on respiratory and gastrointestinal infection; however, it has also recently been associated with diverse clinical symptoms including the endocrine, cardiovascular, and neurological systems. Given the systemic nature of SAFV, and its high prevalence, understanding its pathogenicity and clinical impact is of utmost importance.

The Pathogenesis of Saffold Virus in AG129 Mice and the Effects of Its Truncated L Protein in the Central Nervous System.

Saffold Virus (SAFV) is a human cardiovirus that has been suggested to cause severe infection of the central nervous system (CNS). Compared to a similar virus, Theiler's murine encephalomyelitis virus (TMEV), SAFV has a truncated Leader (L) protein, a protein essential in the establishment of persistent CNS infections. In this study, we generated a chimeric SAFV by replacing the L protein of SAFV with that of TMEV.

Spatial Learning Requires mGlu5 Signalling in the Dorsal Hippocampus.

We examined the role of hippocampal metabotropic glutamate receptor 5 (mGlu5) in spatial learning and memory. Although it has been shown that mGlu5 signalling is required for certain forms of learning and memory, its role in spatial learning is unclear since studies using pharmacological or knockout mice models provide inconsistent findings. Additionally, the location in the brain where mGlu5 signalling may modulate such learning is yet to be precisely delineated.