Category Archives: Neuroscience

Neuroscience

Can Obesity and Stress Influence Appetite? – Neuroscience News

Summary: Stress impacts the brains response to food, researchers report. Additionally, both lean and obese people react to food cues in brain areas associated with reward and cognitive control.

Source: Johns Hopkins Medicine

In a series of experiments using functional magnetic resonance imaging (fMRI) to measure brain activity across networks in the brain, Johns Hopkins Medicine researchers looked at how stress might increase appetite in obese and lean adults.

The researchers found that stress impacts the brains responses to food, and that both lean and obese adults react to food cues in areas of the brain associated with reward and cognitive control.

The findings of the studywere published Sept. 28 inPLOS ONE.

For the study, the researchers analyzed data from 29 adults (16 women and 13 men), 17 of whom had obesity and 12 of whom were lean. Participants completed two fMRI scans, one following a combined social and physiological stress test.

Participants were given afood word reactivity testduring both scans. Thistestinvolved looking at how peoples brains reacted to food words, such as menu items on a chalkboard.

To maximize the appetitive response in the brain, the researchers asked participants to imagine how each food looked, smelled and tasted, and how it would feel to eat it at that moment.

They were also asked how much they wanted each food, and if they felt they should not eat that food, to see how they approached decision-making related to each food.

The experiments showed that obese and lean adults differ somewhat in their brain responses, with obese adults showing less activation of cognitive control regions to food words, especially to high-calorie foods, like for example, grilled cheese, says lead researcherSusan Carnell, Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

The study also showed that stress impacts brain responses to food. For example, obese individuals showed greater activation of the orbitofrontal cortex, a brain reward region, after the stress test.

We also found evidence for links between the subjective stress experienced and brain responses in both groups. For example, lean individuals who reported higher stress following the test showed lower activation of the dorsolateral prefrontal cortex, a key brain area for cognitive control, says Carnell.

Author: Marisol MartinezSource: Johns Hopkins MedicineContact: Marisol Martinez Johns Hopkins MedicineImage: The image is in the public domain

Original Research: Open access.Obesity and acute stress modulate appetite and neural responses in food word reactivity task byCarnell et al. PLOS ONE

Abstract

Obesity and acute stress modulate appetite and neural responses in food word reactivity task

Obesity can result from excess intake in response to environmental food cues, and stress can drive greater intake and body weight. We used a novel fMRI task to explore how obesity and stress influenced appetitive responses to relatively minimal food cues (words representing food items, presented similarly to a chalkboard menu).

Twenty-nine adults (16F, 13M), 17 of whom had obesity and 12 of whom were lean, completed two fMRI scans, one following a combined social and physiological stressor and the other following a control task. A food word reactivity task assessed subjective food approach (wanting) as well as food avoidant (restraint) responses, along with neural responses, to words denoting high energy-density (ED) foods, low-ED foods, and non-foods.

A multi-item ad-libitum meal followed each scan. The obese and lean groups demonstrated differences as well as similarities in activation of appetitive and attention/self-regulation systems in response to food vs. non-food, and to high-ED vs. low-ED food words.

Patterns of activation were largely similar across stress and non-stress conditions, with some evidence for differences between conditions within both obese and lean groups. The obese group ate more than the lean group in both conditions.

Our results suggest that neural responses to minimal food cues in stressed and non-stressed states may contribute to excess consumption and adiposity.

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Can Obesity and Stress Influence Appetite? - Neuroscience News

Neuroscience

Reductionism as a Dead End in Neuroscience Captured in an Essay – Walter Bradley Center for Natural and Artificial Intelligence

University of Sussex professor of cognitive and computational neuroscience Anil K. Seth, during a routine dismissal of Ren Descartes (15961650), assures us, It looks like scientists and philosophers might have made consciousness far more mysterious than it needs to be.

More mysterious than it needs to be?

As noted earlier, what makes understanding the human mind necessarily complex is that it is both the entity we are trying to perceive and the tool by which we hope to perceive it. Such a problem is like trying to imagine a five-dimensional box in relation to the real world. Unlike the five-dimensional box, consciousness is part of the life experience of every human being.

How would Dr. Seth unravel the problem? In a classic essay, he reassures us,

Once, biochemists doubted that biological mechanisms could ever explain the property of being alive. Today, although our understanding remains incomplete, this initial sense of mystery has largely dissolved. Biologists have simply gotten on with the business of explaining the various properties of living systems in terms of underlying mechanisms: metabolism, homeostasis, reproduction and so on. An important lesson here is that life is not one thing rather, it has many potentially separable aspects.

Well, wait. We know a great deal more than we did centuries ago about the circumstances that enable a life form to keep itself alive and pass on that state to a further generation. But we are still at a complete loss as to the origin of life.

This is despite hundreds of speculative papers published every year. Eminent chemist James Tour has often remarked on well, expostulated about this problem. Its fascinating. It is especially relevant to the search for life on other planets in our galaxy. But looking for evidence of lifes existence is quite different from explaining lifes origin.

Origin of consciousness is in roughly the same state as origin of life. We have vast amounts of useful information about being conscious but we have no idea how it comes about.

What does Dr. Seth say about consciousness (or selfhood)?

Of the many distinctive experiences within our inner universes, one is very special. This is the experience of being you. Its tempting to take experiences of selfhood for granted, since they always seem to be present, and we usually feel a sense of continuity in our subjective existence (except, of course, when emerging from general anaesthesia). But just as consciousness is not just one thing, conscious selfhood is also best understood as a complex construction generated by the brain.

There is the bodily self, which is the experience of being a body and of having a particular body. There is the perspectival self, which is the experience of perceiving the world from a particular first-person point of view. The volitional self involves experiences of intention and of agency of urges to do this or that, and of being the causes of things that happen. At higher levels, we encounter narrative and social selves. The narrative self is where the I comes in, as the experience of being a continuous and distinctive person over time, built from a rich set of autobiographical memories. And the social self is that aspect of self-experience that is refracted through the perceived minds of others, shaped by our unique social milieu.

In daily life, it can be hard to differentiate these dimensions of selfhood.

The problem isnt so much that it is hard to differentiate these dimensions of selfhood as that it is hard to believe that a simple, reductionist approach to the question will provide much insight.

For example, Dr. Seth writes, The specific experience of being you (or me) is nothing more than the brains best guess of the causes of self-related sensory signals. That seems inconsistent with the council of selves that Dr. Seth himself sketches out in the paragraph quoted above. If he is right, your local town council votes may be less frenetic at any given time than what is going on in your own mind but that is not an argument for reductionism.

It becomes even more confusing when Dr. Seth tells us,

This returns us one last time to Descartes. In dissociating mind from body, he argued that non-human animals were nothing more than beast machines without any inner universe. In his view, basic processes of physiological regulation had little or nothing to do with mind or consciousness. Ive come to think the opposite. It now seems to me that fundamental aspects of our experiences of conscious selfhood might depend on control-oriented predictive perception of our messy physiology, of our animal blood and guts. We are conscious selves because we too are beast machines self-sustaining flesh-bags that care about their own persistence.

So, contemplating the vast mystery as well as complexity of consciousness, Dr. Seth asserts that it shows that we too are beast machines.

Actually, it provides a convincing demonstration of how reductionism does not work well in neuroscience. At most, it would mean that animal consciousness is more complex than we have earlier supposed. For that, at least, we have a growing body of evidence.

You may also wish to read: Psychiatry has always been difficult but its unclear how trashing almost every philosophical tradition from which it is approached will really help. Understanding the human mind is necessarily complex because it is both what we are trying to perceive and the tool by which we hope to perceive it.

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Reductionism as a Dead End in Neuroscience Captured in an Essay - Walter Bradley Center for Natural and Artificial Intelligence

Neuroscience

How I used my background in neuroscience to make it as a lawyer – Legal Cheek

Bristows Gregory Bacon on his transition from academia to IP and what STEM students can offer law firms

Gregory Bacon, partner and patent litigation specialist at Bristows, is well-placed to discuss a career change from science to law. He completed a PhD in neuroscience at Oxford University and spent time as postdoctoral researcher at Kings College London.

Intellectual property is often considered one of the areas of law most accessible to those with a background in science, technology, engineering and mathematics (STEM). The highly technical nature of projects in this area offers an array of challenges for those with puzzle-oriented minds.

Bristows represents huge clients at the cutting-edge of the science and technology sector, working with mega-brands like Google, Facebook and Samsung. They also have an impressive life sciences client base and the firm worked with AstraZeneca and Oxford University on their Covid jab during the pandemic. Bringing new products and technologies to the commercial market can be a difficult process and Bacon specialises in helping clients navigate disputes over their patents.

He describes a case he is currently working on for a drug developed and licensed to treat multiple sclerosis, a lifelong condition affecting the brain and spinal cord. Treatments available still dont cure the disease, but they can significantly reduce underlying autoimmune reactions and slow disease progression, he explains. My client, a pharmaceutical company, developed and sells one of these treatments. Earlier this year, we made some new case law in relation to patent rights in the UK for that product, and whether these can be asserted before the patent is granted. Being an effective lawyer means coming up with solutions for your client, including sometimes ones that have not been tried before. Another case Bacon is working on involves a dispute between two pharmaceutical companies as to whether contractual royalties are payable in relation to a product that is licensed and sold by one of them for the treatment of rare forms of childhood epilepsy.

Whilst a STEM background is not a requirement to be a good patent lawyer, Bacon continues, it helps to have a basic grounding of scientific knowledge. He is quick to point out that the niche knowledge from his PhD is often not as helpful as the ability to interpret evidence. Being able to take data and understand it is key. For example, you need to be able to read scientific literature and understand how the information in that article can support your case or maybe actually supports the other sides case! Bacon says.

Enthusiasm for learning about technology is also an important quality for this kind of work, which is often something that STEM students develop through their studies. He says:

You need to want to keep learning about the technology as well as about the law. So when you get a new project on a chemical youve never heard of before or an interaction with an organ that youve never dealt with before, you think this sounds really interesting I want to get to know more!

Bacon acknowledges that his transition from science into law is made more unusual by his direct route. Strangely, I didnt go for a vacation scheme, I went straight for a training contract. I was offered an interview here at Bristows 20 years ago, and the interview went well. After accepting their offer of a job and completing his conversion course, Bacon started his training contract with the firm. I just loved every aspect of it, every seat! he reveals. But his interest in patent law had already taken root and after qualifying, he was offered a permanent position in their patents team.

After twenty years with Bristows, Bacons enthusiasm for what he does has in no way diminished. He describes finding an unexpected source of enjoyment in the management responsibilities that come with being a partner. It is quite an unusual step to go from not having any management responsibilities to having almost the full suite of management responsibilities, he explains. It brings with it a whole host of extra skills that you have to have to develop to be a partner. After eight or ten years of your post-qualification career, you take on all these new responsibilities: training junior colleagues, recruitment, winning client pitches and keeping clients happy. I think I enjoy this almost as much as doing the fee-earning work for the clients.

This split between his responsibilities as a fee earner and as a partner is also something that characterises his daily work. My day is split around 70:30. Seventy percent of my time is spent doing legal work, calls with clients, deciding on strategy, drafting documents, preparing cases for court, reading technical documents and speaking with international lawyers. Then the remainder of my time is involved in the management of the group, my department, and the wider firm. This includes ensuring my junior colleagues have enough work and theyre getting enough exposure to the right levels of work. And some general admin of course!

Considering his own career journey, what advice would he give to students looking at making the transition from STEM to law?

Do your research, Bacon stresses. Try and go to an open day or a law fair. If you can really get to see the firm as it operates behind the scenes, youll get a better feel for what the job looks like. Thats important because if youre a STEM student, youre looking at around a four-year process before youre qualified as a solicitor, and youve got something to show for all that work. So do the research and make sure it is something you want to invest four years of your time into.

Gregory Bacon will be speaking at STEM Focus: Life as an intellectual property lawyer with Bristows, a virtual student event taking place on Thursday 20 October. You can apply to attend the event, which is free, now.

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How I used my background in neuroscience to make it as a lawyer - Legal Cheek

Neuroscience

Research Paves Way for Innovative Theory of Cognitive Processing – Neuroscience News

Summary: A new theory suggests glial cells, specifically astrocytes, play a key role in cognitive processing.

Source: University Health Network

A team of scientists from the Krembil Brain Institute, part of the University Health Network in Toronto, and Duke University in Durham, North Carolina, has developed the first computer model predicting the role of cortical glial cells in cognition.

The paper was published today in the prestigious journalProceedings of the National Academy of Sciences(PNAS).

The role of neurons is well documented, but neurons are interspersed with glial cells and many synapses in the brain have glia nearby, says Dr. Maurizio De Pitt, a scientist at the Krembil Brain Institute and the first author of the study. We currently do not understand how neurons and glia work together, or how glial dysfunction contributes to cognitive deficits.

Glial cells are abundant throughout the brain and play several important roles. These cells have long been thought to be passive bystandersphysically supporting neurons and synapses, bringing nutrients to neurons, and removing toxins and waste products. However, scientists have recently discovered that glia interact with neurons in a fashion similar to the way that neurons communicate with one another through chemical signals.

This paper presents the first theory of the role glia play in cognitive processing, in the brain. The type of glial cells that we studyknown as astrocytescan modify the activity of our brain circuits and influence the way we behave, says Dr. De Pitt.

The study looked at the role of astrocytes in working memory, which is the ability to store information for ongoing tasks, such as following the storyline of a movie or counting to ten.

We know that astrocytes release specialized chemical signals and we have shown that this signalling could mediate different readouts of working memory, says Dr. De Pitt.

Revealing that chemical interactions between neurons and astrocytes could be at the core of working memory, also tells us what could go wrong when we have working memory deficits, which are often warning signs of major brain disorders.

He adds, If we want to truly understand dysfunction in working memory, we need to consider the interaction between glial cells and neurons.

Also noted in the article:

Like radio systems, synapses have been traditionally thought to transmit on a single frequency band. Taking astrocytes into account, we now know there can be multiple frequency bands.

It is generally believed that different forms of working memory rely on a variety of circuits; however, this study shows that the same neuron-glial circuits could encode for various forms of working memory.

The way that astrocytes are arranged with respect to neurons could control our working memory capacity, or how many things we can keep in mind simultaneously.

Currently, there are no effective techniques to record glial activity in the human brain. The researchers hope to eventually create a high-fidelity modela digital twinof the brains neuron-glia circuits, from genes to cells.

Such a model can help to uncover markers of neuron-glial interactions and improve the diagnosis and treatment of various brain diseases, such as Alzheimers, Parkinsons and epilepsy.

With our new theory, we are not just looking at the brain in black and whitethat is, whether given neuron populations are active or inactive. Rather, we are viewing the brain in technicolour, gaining a deeper understanding of cellular communication by including glia and their signalling, says Dr. De Pitt.

This gives us a much more comprehensive and realistic picture of the complexity of the brain.

As technology advances, De Pitt and his team at the Krembil will use their models to develop techniques to modify neuron-glial circuit activity to treat disease. Our ultimate goal is to study neuron-glial interactions to uncover new therapeutic targets for brain disorders.

Funding: This work was funded by an FP7 Marie Skodowska-Curie International Outgoing Fellowship.Research at Dr. De Pitts lab is supported by operating grants from the Krembil Research Institute, the European Research Commission, the Krembil Foundation and UHN Foundation.

Author: Ana FernandesSource: University Health NetworkContact: Ana Fernandes University Health NetworkImage: The image is in the public domain

Original Research: Closed access.Multiple forms of working memory emerge from synapseastrocyte interactions in a neuronglia network model by Maurizio De Pitt et al. PNAS

Abstract

Multiple forms of working memory emerge from synapseastrocyte interactions in a neuronglia network model

Persistent activity in populations of neurons, time-varying activity across a neural population, or activity-silent mechanisms carried out by hidden internal states of the neural population have been proposed as different mechanisms of working memory (WM).

Whether these mechanisms could be mutually exclusive or occur in the same neuronal circuit remains, however, elusive, and so do their biophysical underpinnings.

While WM is traditionally regarded to depend purely on neuronal mechanisms, cortical networks also include astrocytes that can modulate neural activity.

We propose and investigate a network model that includes both neurons and glia and show that gliasynapse interactions can lead to multiple stable states of synaptic transmission.

Depending on parameters, these interactions can lead in turn to distinct patterns of network activity that can serve as substrates for WM.

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Research Paves Way for Innovative Theory of Cognitive Processing - Neuroscience News

Neuroscience

Pain Relief Without Side Effects and Addiction – Neuroscience News

Summary: Researchers have developed a new substance that activates adrenalin receptors rather than opioid receptors to help relieve chronic pain. The new compounds have similar pain-relieving qualities as opioids but do not appear to induce respiratory depression or addiction.

Source: Friedrich-Alexander-Universitt Erlangen-Nrnberg

New substances that activate adrenalin receptors instead of opioid receptors have a similar pain-relieving effect to opiates, but without the negative aspects such as respiratory depression and addiction.

This is the result of research carried out by an international team of researchers led by the Chair of Pharmaceutical Chemistry at Friedrich-Alexander-Universitt Erlangen-Nrnberg (FAU).

Their findings,which have now been published in the renowned scientific journalScience, are a milestone in the development of non-opioid pain relief.

Opiates cause addiction, new substances do not

They are a blessing for patients suffering from severe pain, but they also have serious side effects: Opioids, and above all morphine, can cause nausea, dizziness and constipation and can also often cause slowed breathing that can even result in respiratory failure.

In addition, opiates are addictive a high percentage of the drug problem in the USA is caused by pain medication, for example.

In order to tackle the unwanted medical and social effects of opioids, researchers all over the world are searching for alternative analgesics.

Prof. Dr. Peter Gmeiner, Chair of Pharmaceutical Chemistry is one of these researchers. We are focusing particularly on the molecular structures of the receptors that dock onto the pharmaceutical substances, says Gmeiner.

It is only when we understand these on the atomic level that we can develop effective and safe active substances.

Collaborating with an international team of researchers, Prof. Gmeiner discovered an active substance in 2016 that bonds to known opioid receptors and that offers the same level of pain relief as morphine, even though it has no chemical similarity to opiates.

New approach: Adrenaline receptors instead of opioid receptors

Peter Gmeiner is currently following a lead that seems very promising: Many non-opioid receptors are involved in pain processing, but only a small number of these alternatives have as yet been validated for use in therapies, he explains.

Gmeiner and a team of researchers from Erlangen, China, Canada and the USA have now turned their attention to a new receptor that is responsible for binding adrenaline the alpha 2A adrenergic receptor. There are already some analgesics that target this receptor such as brimonidine, clonidine and dexmedetomidine.

Gmeiner: Dexmedetomidine relieves pain, but has a strong sedative effect, which means its use is restricted to intensive care in hospital settings and is not suitable for broader patient groups.

The aim of the research consortium is to find a chemical compound that activates the receptor in the central nervous system without a sedative effect. In a virtual library of more than 300 million different and easily accessible molecules, the researchers looked for compounds that physically match the receptor but are not chemically related to known medication.

After a series of complex virtual docking simulations, around 50 molecules were selected for synthesis and testing and two of these fulfilled the desired criteria. They had good bonding characteristics, activated only certain protein sub-types and thus a very selective set of cellular signal pathways, whereas dexmedetomidine responds to a significantly wider range of proteins.

Pain relief without sedation in animal models

By further optimizing the identified molecules, for which extremely high-resolution cryo-electron microscopic imaging was used, the researchers were able to synthesize agonists that produced high concentrations in the brain and reduced the sensation of pain effectively in investigations with animal models.

Various tests confirmed that docking on the receptor was responsible for the analgesic effect, explains Gmeiner. We are particularly pleased about the fact that none of the new compounds caused sedation, even at considerably higher doses than those that would be required for pain relief.

The successful separation of analgesic properties and sedation is a milestone in the development of non-opioid pain medication, especially as the newly-identified agonists are comparatively easy to manufacture and administer orally to patients.

However, Prof. Gmeiner has to dampen any hopes of rapid widespread use in human medicine: We are currently still talking about basic research. The development of medication is subject to strict controls and in addition to significant amounts of funding, it takes a long time. However, these results still make us very optimistic.

Author: Katrin PiechaSource: Friedrich-Alexander-Universitt Erlangen-NrnbergContact: Katrin Piecha Friedrich-Alexander-Universitt Erlangen-NrnbergImage: The image is in the public domain

Original Research: Closed access.Structure-based discovery of nonopioid analgesics acting through the 2A-adrenergic receptor by Peter Gmeiner et al. Science

Abstract

Structure-based discovery of nonopioid analgesics acting through the 2A-adrenergic receptor

Because nonopioid analgesics are much sought after, we computationally docked more than 301 million virtual molecules against a validated pain target, the 2A-adrenergic receptor (2AAR), seeking new 2AAR agonists chemotypes that lack the sedation conferred by known 2AAR drugs, such as dexmedetomidine.

We identified 17 ligands with potencies as low as 12 nanomolar, many with partial agonism and preferential Giand Gosignaling. Experimental structures of 2AAR complexed with two of these agonists confirmed the docking predictions and templated further optimization.

Several compounds, including the initial docking hit 9087 [mean effective concentration (EC50) of 52 nanomolar] and two analogs, 7075 and PS75 (EC504.1 and 4.8 nanomolar), exerted on-target analgesic activity in multiple in vivo pain models without sedation.

These newly discovered agonists are interesting as therapeutic leads that lack the liabilities of opioids and the sedation of dexmedetomidine.

Original post:
Pain Relief Without Side Effects and Addiction - Neuroscience News

Neuroscience

Secret Structure in the Wiring Diagram of the Brain – Neuroscience News

Summary: Study reveals a hidden order in seemingly random connections between neurons.

Source: University Hospital Bonn

In the brain, our perception arises from a complex interplay of neurons that are connected via synapses. But the number and strength of connections between certain types of neurons can vary.

Researchers from the University Hospital Bonn (UKB), the University Medical Center Mainz and the Ludwig-Maximilians-University Munich (LMU), together with a research team from the Max Planck Institute for Brain Research in Frankfurt, as part of the DFG-funded Priority Program Computational Connectomics (SPP2041), have now discovered that the structure of the seemingly irregular neuronal connection strengths contains a hidden order. This is essential for the stability of the neuronal network.

The study has now been published in the journal PNAS.

Ten years ago, connectomics, that is the creation of a map of the connections between the approximately 86 billion neurons in the brain, was declared a future milestone of science. This is because in complex neuronal networks, neurons are connected to each other by thousands of synapses. Here, the strength of the connections between individual neurons is important because it is crucial for learning and cognitive performance.

However, each synapse is unique and its strength can vary over time. Even experiments that measured the same type of synapse in the same brain region yielded different values for synaptic strength. However, this experimentally observed variability makes it difficult to find general principles underlying the robust function of neuronal networks, says Prof. Tatjana Tchumatchenko, research group leader at the Institute of Experimental Epileptology and Cognitive Research of the UKB and at the Institute of Physiological Chemistry of the University Medical Center Mainz, explaining the motivation to conduct the study.

Mathematics and laboratory combined purposefully

In the primary visual cortex (V1), the visual stimuli transmitted by the eye via the thalamus, a switching point for sensory impressions in the diencephalon, are first recorded.

The researchers took a closer look at the connections between the neurons that are active during this process.

To do this, the researchers measured experimentally the joint response of two classes of neurons to different visual stimuli in the mouse model. At the same time, they used mathematical models to predict the strength of synaptic connections.

To explain their lab-recorded activities of such network connections in the primary visual cortex, they used the so-called stabilized supralinear network (SSN).

It is one of the few nonlinear mathematical models that offers the unique possibility to compare theoretically simulated activity with actually observed activity, says Prof. Laura Busse, research group leader at LMU Neurobiology.

We were able to show that combining SSN with experimental recordings of visual responses in the mouse thalamus and cortex allows us to determine different sets of connection strengths that lead to the recorded visual responses in the visual cortex.

Sequence between the connection strengths is the key

The researchers found that there was an order behind the observed variability in synapse strength.

For example, the connections from excitatory to inhibitory neurons were always the strongest, while the reverse connections in the visual cortex were weaker. This is because the absolute values of synaptic strengths varied in the modeling as they had in the earlier experimental studies but nevertheless always maintained a certain order.

Thus, the relative ratios are crucial for the course and strength of the measured activity, rather than the absolute values.

It is remarkable that analysis of earlier direct measurements of synaptic connections revealed the same order of synaptic strengths as our model prediction based on measured neuronal responses alone, says Simon Renner, Ph.D., of LMU Neurobiology, whose experimental recordings of cortical and thalamic activity allowed characterization of the connections between cortical neurons.

Our results show that neuronal activity contains much information about the underlying structure of neuronal networks that is not immediately apparent from direct measurements of synapse strengths.

Thus, our method opens a promising perspective for the study of network structures that are difficult to access experimentally, explains Nataliya Kraynyukova, Ph.D., from the Institute of Experimental Epileptology and Cognitive Research of the UKB and Max Planck Institute for Brain Research in Frankfurt.

This study is the result of an interdisciplinary collaboration between the lab of Prof. Busse and Prof. Tchumatchenko, who worked closely together, building on the computational and experimental expertise of their labs.

Author: Inka VthSource: University Hospital BonnContact: Inka Vth University Hospital BonnImage: The image is in the public domain

Original Research: Open access.In vivo extracellular recordings of thalamic and cortical visual responses reveal V1 connectivity rules by Simon Renner et al. PNAS

Abstract

In vivo extracellular recordings of thalamic and cortical visual responses reveal V1 connectivity rules

The brains connectome provides the scaffold for canonical neural computations. However, a comparison of connectivity studies in the mouse primary visual cortex (V1) reveals that the average number and strength of connections between specific neuron types can vary. Can variability in V1 connectivity measurements coexist with canonical neural computations?

We developed a theory-driven approach to deduce V1 network connectivity from visual responses in mouse V1 and visual thalamus (dLGN). Our method revealed that the same recorded visual responses were captured by multiple connectivity configurations.

Remarkably, the magnitude and selectivity of connectivity weights followed a specific order across most of the inferred connectivity configurations. We argue that this order stems from the specific shapes of the recorded contrast response functions and contrast invariance of orientation tuning.

Remarkably, despite variability across connectivity studies, connectivity weights computed from individual published connectivity reports followed the order we identified with our method, suggesting that the relations between the weights, rather than their magnitudes, represent a connectivity motif supporting canonical V1 computations.

Originally posted here:
Secret Structure in the Wiring Diagram of the Brain - Neuroscience News

Neuroscience

Yale Study Revises Understanding of How the Brain Processes and Responds to Rewards – Yale School of Medicine

A new Yale study of neuron activity in the brain has revised scientists understanding of how the brain processes and responds to rewards.

Researchers have located a set of GABA neurons in the brains ventral tegmental area (VTA) that consistently respond to a primary reward. This response differs from the response of dopamine neurons, which previously have been thought to be the principal cells responsible for mediating reward-related behaviors.

Unlike the activity of dopamine neurons, the response in the GABA pathway does not change as animals learn that a cue predicts reward availability, scientists found. Instead, the GABA cells continue to provide a highly stable signal of the size of the primary reward. In reward learning tasks, stimulating this pathway improved the behavior and motivation of animals as they worked to receive rewards across multiple days.

These findings are exciting because they identify a brain pathway that stably signals the size and intensity of a reward and does not shift during learning, revising our understanding of how reward is encoded in the brain, said Marina Picciotto, PhD, Charles B. G. Murphy Professor of Psychiatry and professor in the Child Study Center, of neuroscience, and of pharmacology, and the studys senior author. This finding also provides a new way to think about how cells in the VTA calculate rewarded outcomes in learning tasks.

The findings were published in the journal Science Advances. They appear to clarify the role of dopamine and GAPA neurons in the VTA, located in the midbrain.

Dopamine neurons were thought to be principally responsible for mediating reward-related behaviors, however researchers now believe the neurons fire in response to cues that predict reward, and not to the presentation of the reward itself.

In contrast, GABA neurons in the VTA have been thought to primarily be local cells that inhibit dopamine neurons, but the study shows these neurons project out of the VTA to the ventral pallidum, the major output nucleus of the mesolimbic reward system. Importantly, the researchers found that these neurons respond consistently to a primary reward, and that the response of these neurons scales with the size of the reward.

Other Yale researchers involved in the study are Wenliang Zhou, PhD, associate research scientist; Kristen Kim, neuroscience graduate student; and Yann S. Mineur, PhD, research scientist.

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Yale Study Revises Understanding of How the Brain Processes and Responds to Rewards - Yale School of Medicine

Neuroscience

Cerevel Therapeutics to Report Third Quarter 2022 Financial Results and Pipeline Update on Tuesday, November 8, 2022 – Yahoo Finance

Cerevel Therapeutics

CAMBRIDGE, Mass., Oct. 19, 2022 (GLOBE NEWSWIRE) -- Cerevel Therapeutics (Nasdaq: CERE), a company dedicated to unraveling the mysteries of the brain totreatneurosciencediseases, today announced it will report third quarter 2022 financial results on Tuesday, November 8, 2022, before the U.S. financial markets open.

Management will host a conference call to discuss third quarter 2022 financial results and recent business updates on Tuesday, November 8, 2022, at 8:00 a.m. ET. To access the call, please register at this link. Once registered, you will receive the dial-in information and a unique PIN number.

A live webcast of the call, along with supporting slides, will be available on the investors section of Cerevels website at investors.cerevel.com. Following the live webcast, an archived version of the call will be available on the website.

About Cerevel TherapeuticsCerevel Therapeutics is dedicated to unraveling the mysteries of the brain to treat neuroscience diseases. The company is tackling diseases with a targeted approach to neuroscience that combines expertise in neurocircuitry with a focus on receptor selectivity. Cerevel Therapeutics has a diversified pipeline comprising five clinical-stage investigational therapies and several preclinical compounds with the potential to treat a range of neuroscience diseases, including Parkinsons, epilepsy, schizophrenia, and dementia-related apathy. Headquartered in Cambridge, Mass., Cerevel Therapeutics is advancing its current research and development programs while exploring new modalities through internal research efforts, external collaborations, or potential acquisitions. For more information, visit http://www.cerevel.com.

Special Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements that are based on managements beliefs and assumptions and on information currently available to management. In some cases, you can identify forward-looking statements by the following words: may, will, could, would, should, expect, intend, plan, anticipate, believe, estimate, predict, project, potential, continue, ongoing or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. These statements involve risks, uncertainties and other factors that may cause actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. Although we believe that we have a reasonable basis for each forward-looking statement contained in this press release, we caution you that these statements are based on a combination of facts and factors currently known by us and our projections of the future, about which we cannot be certain. Forward-looking statements in this press release include, but are not limited to, statements about our upcoming financial results and pipeline update announcement and the potential attributes and benefits of our product candidates. We cannot assure you that the forward-looking statements in this press release will prove to be accurate. Furthermore, if the forward-looking statements prove to be inaccurate, the inaccuracy may be material. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties, including, among others: clinical trial results may not be favorable; uncertainties inherent in the product development process (including with respect to the timing of results and whether such results will be predictive of future results); the impact of COVID-19 on the timing, progress and results of ongoing or planned clinical trials; other impacts of COVID-19, including operational disruptions or delays or to our ability to raise additional capital; whether and when, if at all, our product candidates will receive approval from the FDA or other regulatory authorities, and for which, if any, indications; competition from other biotechnology companies; uncertainties regarding intellectual property protection; and other risks identified in our SEC filings, including those under the heading Risk Factors in our Quarterly Report on Form 10-Q filed with the SEC on August 1, 2022 and our subsequent SEC filings. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. The forward-looking statements in this press release represent our views as of the date of this press release. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release.

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Media Contact:Anna RobinsonCerevel Therapeutics anna.robinson@cerevel.com

Investor Contact:Matthew CalistriCerevel Therapeuticsmatthew.calistri@cerevel.com

Original post:
Cerevel Therapeutics to Report Third Quarter 2022 Financial Results and Pipeline Update on Tuesday, November 8, 2022 - Yahoo Finance

Neuroscience

One in Two Thousand: Grace Reynolds ‘22.5 The Williams Record – The Williams record

(Luke Chinman/The Williams Record)

Each week, the Record (using a script in R) randomly selects a student at the College for our One in Two Thousand feature, excluding current Record board members. This week, Grace Reynolds 22.5 discussed her neuroscience thesis, her plans after graduation, and how she likes to spend her time outside in Williamstown. This interview has been edited for length and clarity.

Luke Chinman (LC): Youre in the Class of 2022.5, which means that this is your last semester. How does it feel to be so close to the end of your college experience?

Grace Reynolds (GR): Its definitely really exciting. I feel like Im very close and also very far, because I am finishing up my thesis right now, so theres a lot going on with that.

LC: What is your thesis on?

GR: Im doing a neuroscience thesis with [Assistant] Professor [of Psychology Shivon] Robinson. Were studying the developmental effects of early-life exposure to opioids and neonatal opioid withdrawal syndrome.

LC: What is your major?

GR: I am a biology and psychology double major with a neuroscience concentration.

LC: Did you always know that would be your track?

GR: Ive always been interested in neuroscience. I was also [considering] public health for a little bit, but then I did a public health internship, which I didnt really like. So I kind of moved back to neuroscience.

LC: Because this is your last semester, do you have any advice that youd give to your first-year self?

GR: Although I love both my majors, I kind of wish I had taken some other classes outside of the classes Im comfortable with. Right now, for example, Im taking a history class which I really like, but its one of the few classes Ive taken thats very much outside of my comfort zone.

LC: Do you have a favorite class that youve taken?

GR: I think one of my highlights is a neuroethics class. It was such an interesting class and we talked about a lot of different things. I also took a class with my thesis advisor Professor Robinson about the opioid crisis, which is a psychology, public health, [and] neuroscience kind of class, and that was really interesting, too.

LC: How do you feel being a super senior on campus?

GR: I actually dont mind it. I was on campus this summer, so I feel like I kind of never left. So I dont feel like I had to come back for only one more semester. I really have liked doing an off-cycle thesis and having a summer in between. And also, it worked out well for my plans post-grad.

LC: What are your plans post-grad?

GR: I got a job at the Dana-Farber Cancer Institute in Boston, so Ill be working in a pediatric brain cancer lab.

LC: Is that the kind of career that you want to pursue?

GR: I think eventually I want to go to medical school. But I came into Williams very hardcore pre-med. I was interested in research more as something that would help me get into medical school but not really something I actually wanted to do. But working in labs has made me more interested in eventually doing more research, so I think itll be cool working in a lab outside of Williams.

LC: Okay, switching away from academics. Are you involved in any student organizations on campus?

GR: Ive been a part of WRAPS, which is Williams Recovery of All Perishable Surplus. We package leftover dining hall food and deliver it to local communities. Its a really fun way to get involved in the community! I also like teaching, so I worked in the elementary school with second graders.

LC: Id love to hear more about your work at the elementary school!

GR: I was a math tutor at Williamstown Elementary School and worked with second graders. A few times a week, Id go and help them with their math and sometimes teach a lesson. It was fun, because the way that they approached math was just so interesting to see.

LC: Do you have any aspirations for teaching?

GR: Ive always liked teaching, but I never really thought Id be a teacher especially an elementary school teacher. But I hope that in whatever I do, medicine or research, I get to teach in some capacity. But Im not sure I have the patience to teach all day.

LC: You previously mentioned to me that you like to spend time outside. What are some of your favorite outdoor activities?

GR: I grew up swimming, and I ran cross country in high school. If I dont get outside, I usually feel antsy. Most days I run outside or go for a bike ride. I just really love the Williamstown mountains.

LC: Whats your favorite outdoor spot?

GR: I really like going up Bee Hill. I love the view up there. I also just love running in Hopkins Forest.

LC: Okay, I have some rapid fire questions. Goodrich or Tunnel City if youre a coffee drinker?

GR: I definitely drink lots of coffee. I think Tunnel.

LC: Schow or Sawyer?

GR: I always worked in Schow my freshman year, but now I never go to Schow anymore. But I also never really go to Sawyer anymore. You can always find me in Wachenheim thats my preferred spot.

LC: Whats your favorite dining hall?

GR: Probably Driscoll.

LC: Whats your milk of choice?

GR: Oat milk, definitely.

Excerpt from:
One in Two Thousand: Grace Reynolds '22.5 The Williams Record - The Williams record

Neuroscience

Supercharging Brain Stimulation by Repurposing an Antibiotic – Neuroscience News

Summary: D-Cycloserine, an antibiotic used for the treatment of tuberculosis, increases the effectiveness of transcranial magnetic stimulation for those with major depressive disorder.

Source: University of Calgary

University of Calgary researchers have shown that the antibiotic D-Cycloserine (DCS) increases the effectiveness of transcranial magnetic stimulation (TMS) for people with major depressive disorder (MDD).

TMS is a non-invasive, well-recognized therapy for people who have treatment resistant depression. Even so, it doesnt work for everyone. Researchers suspect the problem may be connected to a process in the brain essential for learning and memory.

We think TMS works by driving the brain to adapt to stimulation through a process called synaptic plasticity, explainsDr. AlexanderMcGirr, MD, PhD, principal investigator on the study.

One of the challenges, however, is that major depression is associated with reduced synaptic plasticity, and so TMS may be asking the depressed brain to adapt to stimulation in a way that it can not readily do. Adding D-Cycloserine to the TMS treatment appears to enhance TMSs ability to drive synaptic plasticity and treat depression.

All participants in the study underwent TMS every day for four weeks. Half of those also received DCS while the other half received a placebo. Results, published inJAMA Psychiatry, show that almost 75 percent of participants treated with DCS and TMS benefitted, compared to only 30 percent of those treated with TMS and a placebo. Depressive symptom severity was measured using the gold standardMontgomery Asberg Depression Rating Scale.

The combination treatment seemed to have benefits beyond depressive symptoms. The participants in this study that received DCS and TMS also had greater improvements in their symptoms of anxiety and overall well-being, says study first author Jaeden Cole a member of theMcGirr lab.

The clinical trial involved 50 people. McGirrs team plans to duplicate the research method with a larger group to be sure of the clinical efficacy and safety of this experimental treatment.

It is hard to convey how important this work could be for patients or the level of excitement that has been brewing since Dr. McGirr first presented these results, says Dr. Valerie Taylor, MD, PhD, head of the Department of Psychiatry at the Cumming School of Medicine.

If confirmed, this could change practice and have a very significant impact on patients treatment outcomes.

DCS is still used in the treatment of multidrug resistant tuberculosis and has been researched in other psychiatric applications such as trauma, and anxiety-related disorders. While the drug is not currently available in Canada, McGirr believes additional research proving the benefit of this combined therapy could pave the way for the drugs reintroduction here.

Alexander McGirr has a provisional patent filing for the combination of DCS and TMS in the treatment of depression.

Author: Kelly JohnstonSource: University of CalgaryContact: Kelly Johnston University of CalgaryImage: The image is in the public domain

Original Research: Closed access.Efficacy of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation for Major Depressive Disorder A Randomized Clinical Trial by McGirr et al. JAMA Psychiatry

Abstract

Efficacy of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation for Major Depressive Disorder A Randomized Clinical Trial

Importance

The antidepressant effects of transcranial magnetic stimulation protocols for major depressive disorder (MDD) are thought to depend on synaptic plasticity. The theta-burst stimulation (TBS) protocol synaptic plasticity is known to beN-methyl-D-aspartate (NMDA)receptor dependent, yet it is unknown whether enhancing NMDA-receptor signaling improves treatment outcomes in MDD.

Objective

To test whether low doses of the NMDA-receptor partial-agonist,D-cycloserine, would enhance intermittent TBS (iTBS) treatment outcomes in MDD.

Design, Setting, and Participants

This was a single-site 4-week, double-blind, placebo-controlled, randomized clinical trial conducted from November 6, 2019, to December 24, 2020, including 50 participants with MDD. Participants were recruited via advertisements and referral. Inclusion criteria were as follows: age 18 to 65 years with a primary diagnosis of MDD, a major depressive episode with score of 18 or more on the 17-item Hamilton Depression Rating Scale, a Young Mania Rating Scale score of 8 or less, and normal blood work (including complete blood cell count, electrolytes, liver function tests, and creatinine level).

Interventions

Participants were randomly assigned 1:1 to either iTBS plus placebo or iTBS plusD-cycloserine (100 mg) for the first 2 weeks followed by iTBS without an adjunct for weeks 3 and 4.

Main Outcomes and Measures

The primary outcome was change in depressive symptoms as measured by the Montgomery-sberg Depression Rating Scale (MADRS) at the conclusion of treatment. Secondary outcomes included clinical response, clinical remission, and Clinical Global Impression (CGI) scores.

Results

A total of 50 participants (mean [SD] age, 40.8 [13.4] years; 31 female [62%]) were randomly assigned to treatment groups: iTBS plus placebo (mean [SD] baseline score, 30.3 [4.2]) and iTBS plusD-cycloserine (mean [SD] baseline score, 30.4 [4.5]). The iTBS plusD-cycloserine group had greater improvements in MADRS scores compared with the iTBS plus placebo group (mean difference, 6.15; 95% CI, 2.43 to 9.88; Hedgesg=0.99; 95% CI, 0.34-1.62). Rates of clinical response were higher in the iTBS plusD-cycloserine group than in the iTBS plus placebo group (73.9% vs 29.3%), as were rates of clinical remission (39.1% vs 4.2%). This was reflected in lower CGI-severity ratings and greater CGI-improvement ratings. No serious adverse events occurred.

Conclusions and Relevance

Findings from this clinical trial indicate that adjunctiveD-cycloserine may be a promising strategy for enhancing transcranial magnetic stimulation treatment outcomes in MDD using iTBS requiring further investigation.

Trial Registration

ClinicalTrials.gov Identifier:NCT03937596

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Supercharging Brain Stimulation by Repurposing an Antibiotic - Neuroscience News