Modern Neuroscience Research Articles

Reduced oriens-lacunosum/moleculare cell model identifies biophysical current balances for in vivo theta frequency spiking resonance.

Conductance-based models have played an important role in the development of modern neuroscience. These mathematical models are powerful "tools" that enable theoretical explorations in experimentally untenable situations, and can lead to the development of novel hypotheses and predictions. With advances in cell imaging and computational power, multi-compartment models with morphological accuracy are becoming common practice. However, as more biological details are added, they make extensive explorations and analyses more challenging largely due to their huge computational expense. Here, we focus on oriens-lacunosum/moleculare (OLM) cell models. OLM cells can contribute to functionally relevant theta rhythms in the hippocampus by virtue of their ability to express spiking resonance at theta frequencies, but what characteristics underlie this is far from clear. We converted a previously developed detailed multi-compartment OLM cell model into a reduced single compartment model that retained biophysical fidelity with its underlying ion currents. We showed that the reduced OLM cell model can capture complex output that includes spiking resonance in in vivo-like scenarios as previously obtained with the multi-compartment model. Using the reduced model, we were able to greatly expand our in vivo-like scenarios. Applying spike-triggered average analyses, we were able to to determine that it is a combination of hyperpolarization-activated cation and muscarinic type potassium currents that specifically allow OLM cells to exhibit spiking resonance at theta frequencies. Further, we developed a robust Kalman Filtering (KF) method to estimate parameters of the reduced model in real-time. We showed that it may be possible to directly estimate conductance parameters from experiments since this KF method can reliably extract parameter values from model voltage recordings. Overall, our work showcases how the contribution of cellular biophysical current details could be determined and assessed for spiking resonance. As well, our work shows that it may be possible to directly extract these parameters from current clamp voltage recordings.

Emerging Molecular Targets for Anti-Epileptogenic and Epilepsy Modifying Drugs.

The pharmacological treatment of epilepsy is purely symptomatic. Despite many decades of intensive research, causal treatment of this common neurologic disorder is still unavailable. Nevertheless, it is expected that advances in modern neuroscience and molecular biology tools, as well as improved animal models may accelerate designing antiepileptogenic and epilepsy-modifying drugs. Epileptogenesis triggers a vast array of genomic, epigenomic and transcriptomic changes, which ultimately lead to morphological and functional transformation of specific neuronal circuits resulting in the occurrence of spontaneous convulsive or nonconvulsive seizures. Recent decades unraveled molecular processes and biochemical signaling pathways involved in the proepileptic transformation of brain circuits including oxidative stress, apoptosis, neuroinflammatory and neurotrophic factors. The "omics" data derived from both human and animal epileptic tissues, as well as electrophysiological, imaging and neurochemical analysis identified a plethora of possible molecular targets for drugs, which could interfere with various stages of epileptogenetic cascade, including inflammatory processes and neuroplastic changes. In this narrative review, we briefly present contemporary views on the neurobiological background of epileptogenesis and discuss the advantages and disadvantages of some more promising molecular targets for antiepileptogenic pharmacotherapy.

Neurophilic herpesvirus: a powerful tool for neuroscience research

Viruses are powerful tools for the study of modern neurosciences. Most of the research on the connection and function of neurons were done by using recombinant viruses, among which neurotropic herpesvirus is one of the most important tools. With the continuous development of genetic engineering and molecular biology techniques, several recombinant neurophilic herpesviruses have been engineered into different viral tools for neuroscience research. This review describes and discusses several common and widely used neurophilic herpesviruses as nerve conduction tracers, viral vectors for neurological diseases, and lytic viruses for neuro-oncology applications, which provides a reference for further exploring the function of neurophilic herpesviruses.

Translational aspects of deep brain stimulation for chronic pain.

The use of deep brain stimulation (DBS) for the treatment of chronic pain was one of the first applications of this technique in functional neurosurgery. Established brain targets in the clinic include the periaqueductal (PAG)/periventricular gray matter (PVG) and sensory thalamic nuclei. More recently, the anterior cingulum (ACC) and the ventral striatum/anterior limb of the internal capsule (VS/ALIC) have been investigated for the treatment of emotional components of pain. In the clinic, most studies showed a response in 20%-70% of patients. In various applications of DBS, animal models either provided the rationale for the development of clinical trials or were utilized as a tool to study potential mechanisms of stimulation responses. Despite the complex nature of pain and the fact that animal models cannot reliably reflect the subjective nature of this condition, multiple preparations have emerged over the years. Overall, DBS was shown to produce an antinociceptive effect in rodents when delivered to targets known to induce analgesic effects in humans, suggesting a good predictive validity. Compared to the relatively high number of clinical trials in the field, however, the number of animal studies has been somewhat limited. Additional investigation using modern neuroscience techniques could unravel the mechanisms and neurocircuitry involved in the analgesic effects of DBS and help to optimize this therapy.

Ethoscopy and ethoscope-lab: a framework for behavioural analysis to lower entrance barrier and aid reproducibility.

High-throughput analysis of behaviour is a pivotal instrument in modern neuroscience, allowing researchers to combine modern genetics breakthrough to unbiased, objective, reproducible experimental approaches. To this extent, we recently created an open-source hardware platform (ethoscope; Geissmann Q, Garcia Rodriguez L, Beckwith EJ et al. Rethomics: an R framework to analyse high-throughput behavioural data. PLoS One 2019;14:e0209331) that allows for inexpensive, accessible, high-throughput analysis of behaviour in Drosophila or other animal models. Here we equip ethoscopes with a Python framework for data analysis, ethoscopy, designed to be a user-friendly yet powerful platform, meeting the requirements of researchers with limited coding expertise as well as experienced data scientists. Ethoscopy is best consumed in a prebaked Jupyter-based docker container, ethoscope-lab, to improve accessibility and to encourage the use of notebooks as a natural platform to share post-publication data analysis. Ethoscopy is a Python package available on GitHub and PyPi. Ethoscope-lab is a docker container available on DockerHub. A landing page aggregating all the code and documentation is available at https://lab.gilest.ro/ethoscopy.

Regulation of axonal regeneration after mammalian spinal cord injury.

One hundred years ago, Ramón y Cajal, considered by many as the founder of modern neuroscience, stated that neurons of the adult central nervous system (CNS) are incapable of regenerating. Yet, recent years have seen a tremendous expansion of knowledge in the molecular control of axon regeneration after CNS injury. We now understand that regeneration in the adult CNS is limited by (1) a failure to form cellular or molecular substrates for axon attachment and elongation through the lesion site; (2) environmental factors, including inhibitors of axon growth associated with myelin and the extracellular matrix; (3)astrocyte responses, which can both limit and support axon growth; and (4) intraneuronal mechanisms controlling the establishment of an active cellular growth programme. We discuss these topics together with newly emerging hypotheses, including the surprising finding from transcriptomic analyses of the corticospinal system in mice that neurons revert to an embryonic state after spinal cord injury, which can be sustained to promote regeneration with neural stem cell transplantation. These gains in knowledge are steadily advancing efforts to develop effective treatment strategies for spinal cord injury inhumans.

Steps towards neuro-excellence

Between September 28 and October 1, 2022, took place the 47th National Congress of the Romanian Society of Neurosurgery. It was organized in Iasi, at the Palace of Culture. On this occasion, the 26th Francophone Course and the 4th National Congress of Modern Neuroscience were held. These three events represent the quintessence of all current modern neurosurgical problems. Extremely important topics were disputed which helped to grow the passion in the hearts of young enthusiasts and their mentors.

Spatial Computing in Modular Spiking Neural Networks with a Robotic Embodiment

One of the challenges in modern neuroscience is creating a brain-on-a-chip. Such a semiartificial device based on neural networks grown in vitro should interact with the environment when embodied in a robot. A crucial point in this endeavor is developing a neural network architecture capable of associative learning. This work proposes a mathematical model of a midscale modular spiking neural network (SNN) to study learning mechanisms within the brain-on-a-chip context. We show that besides spike-timing-dependent plasticity (STDP), synaptic and neuronal competitions are critical factors for successful learning. Moreover, the shortest pathway rule can implement the synaptic competition responsible for processing conditional stimuli coming from the environment. This solution is ready for testing in neuronal cultures. The neuronal competition can be implemented by lateral inhibition actuating over the SNN modulus responsible for unconditional responses. Empirical testing of this approach is challenging and requires the development of a technique for growing cultures with a given ratio of excitatory and inhibitory neurons. We test the modular SNN embedded in a mobile robot and show that it can establish the association between touch (unconditional) and ultrasonic (conditional) sensors. Then, the robot can avoid obstacles without hitting them, relying on ultrasonic sensors only.

Gender morphology of Broca's motor speech area

To study the general patterns and differences in the macroscopic structure of Broca's motor speech area in the left and right hemispheres of male and female brains. The study was conducted on MRI images of the brains of 9 men and 9 women (36 hemispheres in total). All the people were between the ages of 20 and 30, without any mental or neurological disorders. The localization and structure of the main sulci and gyri of Broca's area, namely the pars triangularis and pars opercularis, were studied. In addition, the topography of the main sulci in Broca's motor speech area, namely their shape, length, and relative position to the other sulci, was analyzed. The features of the localization of the sulci in Broca's area, the differences in the number of additional sulci in the pars triangularis and pars opercularis of male and female brains, as well as the degree of asymmetry of Broca's area in the left and right hemispheres of the brains of men and women were established.In modern neuroscience a new scientific direction of genderology, which studies the behavior and cognitive functions of males and females, is rapidly developing. Broca's motor speech area of the brain of men and women differs in macroscopic structure.

Superiority and stigma in modern psychology and neuroscience.

Bias in early psychological and neuroscientific research distorted conclusions about women and people of color. Unintentional biases persisting today in studies of older adults and people with stigmatized conditions may perpetuate stigma and hinder scientific discovery. We can combat these biases by changing how we analyze, interpret, and describe differences.

Neurodireito e neurociência do livre-arbítrio: uma revisão crítica e apontamentos para o Direito Penal

Due to the advent of modern neurosciences, several scientific disciplines have developed entirely new theories, perspectives, and methodologies. The substantial advances and discoveries made in this field over the last decades, especially those concerned with human cog-nition and behavior, have steered the course of many traditional research areas and given rise to others, like neuroethics and neurolaw. Here we take a look at some of the general characteristics of the growing field of neurolaw, an interdisciplinary field that dwells on the intersection of law and neuroscience. We then discuss the neuroscience of free will, one of the most impacting and pressing topics in the neurolaw debate, with special attention to Libet’s paradigm, recent scientific developments, and novel interpretations that question customary assumptions about it. This debate has many implications for criminal law, especially because the notion free will plays a foundational role in many traditional legal theories in the field.

Quantitative Super-resolution of Synaptic Proteins

Single molecule localization microscopy (SMLM) recently became more and more popular for studying the synaptic architecture, providing substantial advances in modern neuroscience. Recently developed methods based on DNA origami calibration transformed SML into an effective quantitative tool able to estimate the oligomeric states of macromolecular complexes. In this work, we apply a recently developed quantitative method based on stochastic optical reconstruction microscopy (qSTORM) to study the distribution of the synaptic proteins Homer in hippocampal neurons. Our experiments prove qSTORM as a suitable tool for novel quantitative insights into the nanoscale organization of excitatory synapses.

Place cells are nonrandomly clustered by field location in CA1 hippocampus.

A challenge in both modern and historic neuroscience has been achieving an understanding of neuron circuits, and determining the computational and organizational principles that underlie these circuits. Deeper understanding of the organization of brain circuits and cell types, including in the hippocampus, is required for advances in behavioral and cognitive neuroscience, as well as for understanding principles governing brain development and evolution. In this manuscript, we pioneer a new method to analyze the spatial clustering of active neurons in the hippocampus. We use calcium imaging and a rewarded navigation task to record from 100 s of place cells in the CA1 of freely moving rats. We then use statistical techniques developed for and in widespread use in geographic mapping studies, global Moran's I, and local Moran's I to demonstrate that cells that code for similar spatial locations tend to form small spatial clusters. We present evidence that this clustering is not the result of artifacts from calcium imaging, and show that these clusters are primarily formed by cells that have place fields around previously rewarded locations. We go on to show that, although cells with similar place fields tend to form clusters, there is no obvious topographic mapping of environmental location onto the hippocampus, such as seen in the visual cortex. Insights into hippocampal organization, as in this study, can elucidate mechanisms underlying motivational behaviors, spatial navigation, and memory formation.

Taking subjectivity seriously: towards a unification of phenomenology, psychiatry, and neuroscience.

Nearly all psychiatric diseases involve alterations in subjective, lived experience. The scientific study of the biological basis of mental illness has generally focused on objective measures and observable behaviors, limiting the potential for our understanding of brain mechanisms of disease states and possible treatments. However, applying methods designed principally to interpret objective behavioral measures to the measurement and extrapolation of subjective states presents a number of challenges. In order to help bridge this gap, we draw on the tradition of phenomenology, a philosophical movement concerned with elucidating the structure of lived experience, which emerged in the early 20th century and influenced philosophy of mind, cognitive science, and psychiatry. A number of early phenomenologically-oriented psychiatrists made influential contributions to the field, but this approach retreated to the background as psychiatry moved towards more operationalized disease classifications. Recently, clinical-phenomenological research and viewpoints have re-emerged in the field. We argue that the potential for phenomenological research and methods to generate productive hypotheses about the neurobiological basis of psychiatric diseases has thus far been underappreciated. Using specific examples drawing on the subjective experience of mania and psychosis, we demonstrate that phenomenologically-oriented clinical studies can generate novel and fruitful propositions for neuroscientific investigation. Additionally, we outline a proposal for more rigorously integrating phenomenological investigations of subjective experience with the methods of modern neuroscience research, advocating a cross-species approach with a key role for human subjects research. Collaborative interaction between phenomenology, psychiatry, and neuroscience has the potential to move these fields towards a unified understanding of the biological basis of mental illness.

The importance of Cajal contribution to the knowledge of the visual system

AbstractThe Spanish neurohistologist Santiago Ramón y Cajal is universally considered as the founder of modern Neuroscience. His works were fundamental to unravel the structure of the nervous system, coining concepts that transformed the scientific society, opening the door for the scientific exploration of the brain. In his titannic labour, Cajal focused a significant number of his studies on the retina and the visual system, in general, of different species. Maybe the most known among these were the one that he wrote on the retina of the vertebrates (originally published in French, in 1893, which also includes some fundamental discoveries beyond the visual system, like the first description axonal growth cones), or the collaboration with his disciple Domingo Sánchez devoted to the retina and optic centers of the insects (published in Spanish, in 1915). In the present communication, I will try to put these studies in their historical and scientific context, as well as to emphasize the relevance of the visual system for the overall conception of the CNS structure that Cajal gifted to Humanity.

Leadership Coaching: Are We Missing the Alchemy?

In an era characterized by fear, uncertainty and doubt Leadership Coaches now find themselves operating on more difficult and unfamiliar terrain. Enabling their clients to cope, survive and thrive in such tenuous conditions offers a significant professional challenge. This paper offers an unusual supplemental approach to more conventional and traditional coaching methods. Utilizing principles derived from the ancient field of alchemy, as well as from modern neuroscience, this article provides both new ideas and guidance to the practitioner of leadership coaching. Beginning with a guided imagery, this piece will then cover the connection between alchemy and leadership, followed by alchemy’s relationship to leadership coaching. The article will next review some relevant findings from contemporary brain science focusing, in particular, on the role of the unconscious mind. The ensuing section provides some ideas for what Leadership Coaches might consider doing differently to be more effective in working with their clients. The article concludes with a short summary and discussion of future implications.

Anterior-posterior gradient in the integrated processing of forelimb movement direction and distance in macaque parietal cortex.

A major issue in modern neuroscience is to understand how cell populations present multiple spatial and motor features during goal-directed movements. The direction and distance (depth) of arm movements often appear to be controlled independently during behavior, but it is unknown whether they share neural resources or not. Using information theory, singular value decomposition, and dimensionality reduction methods, we compare direction and depth effects and their convergence across three parietal areas during an arm movement task. All methods show a stronger direction effect during early movement preparation, whereas depth signals prevail during movement execution. Going from anterior to posterior sectors, we report an increased number of cells processing both signals and stronger depth effects. These findings suggest a serial direction and depth processing consistent with behavioral evidence and reveal a gradient of joint versus independent control of these features in parietal cortex that supports its role in sensorimotor transformations.

Towards the Simulation of a Realistic Large-Scale Spiking Network on a Desktop Multi-GPU System.

The reproduction of the brain ’sactivity and its functionality is the main goal of modern neuroscience. To this aim, several models have been proposed to describe the activity of single neurons at different levels of detail. Then, single neurons are linked together to build a network, in order to reproduce complex behaviors. In the literature, different network-building rules and models have been described, targeting realistic distributions and connections of the neurons. In particular, the Granular layEr Simulator (GES) performs the granular layer network reconstruction considering biologically realistic rules to connect the neurons. Moreover, it simulates the network considering the Hodgkin–Huxley model. The work proposed in this paper adopts the network reconstruction model of GES and proposes a simulation module based on Leaky Integrate and Fire (LIF) model. This simulator targets the reproduction of the activity of large scale networks, exploiting the GPU technology to reduce the processing times. Experimental results show that a multi-GPU system reduces the simulation of a network with more than 1.8 million neurons from approximately 54 to 13 h.

Spatial cognition in birds

Finding the kitchen refrigerator in the middle of a sleepless night or arriving at the home parking lot at the end of a daily drive are things that we mostly take for granted. However, such feats rely on complex brain computations that integrate multiple environmental and internal cues. Together these computations mediate the process referred to as spatial cognition, the study of which has been one of the most active research fields in modern neuroscience. In the early 1970s, John O'Keefe recorded the activity of individual cells in the hippocampus of a freely moving rat: he found cells that fired action potentials when the rat passed through a specific place in the environment. Examining the activity pattern of such 'place cells', he concluded that the hippocampus may contain a 'cognitive map' that represents the animal's location in its proximate environment. Since O'Keefe's seminal discovery about half a century ago, extensive research has led to a detailed characterization of hippocampal space processing in rats and other mammalian species.

Winner Takes All! What Are Race Models, and Why and How Should Psychologists Use Them?

Interest in the processes that mediate between stimuli and responses is at the heart of most modern psychology and neuroscience. These processes cannot be directly measured but instead must be inferred from observed responses. Race models, through their ability to account for both response choices and response times, have been a key enabler of such inferences. Examples of such models appeared contemporaneously with the cognitive revolution, and since then have become increasingly prominent and elaborated, so that psychologists now have a powerful array of race models at their disposal. We showcase the state of the art for race models and describe why and how they are used.