1. Spread of tau protein measured in brains of Alzheimer’s patients

    May 25, 2017 by Ashley

    From the Karolinska Institutet press release:

    In a new study presented in Molecular Psychiatry, researchers at Karolinska Institutet have measured how deposits of the pathological protein tau spread through the brain over the course of Alzheimer’s disease. Their results show that the size of the deposit and the speed of its spread differ from one individual to the next, and that large amounts of tau in the brain can be linked to episodic memory impairment.

    Already in a very early phase of Alzheimer’s disease there is an accumulation of tau in the brain cells, where its adverse effect on cell function causes memory impairment. It is therefore an attractive target for vaccine researchers. For the present study, Professor Agneta Nordberg at Karolinska Institutet’s Department of Neurobiology, Care Sciences and Society and her doctoral student Konstantinos Chiotis along with the rest of her team used PET brain imaging to measure the spread of tau deposits as well as the amyloid plaque associated with Alzheimer’s disease, and charted the energy metabolism of the brain cells. They then examined how these three parameters changed over the course of the disease.

    “There’s been an international race to measure tau spread, and we probably got there first,” says Professor Nordberg. “There are no previous reports on how tau deposits spread after 17 months into the disease. Our results can improve understanding of tau accumulation in Alzheimer’s disease, help ongoing research to quantify the effect of tau vaccines, and enable early diagnosis.”

    The study included 16 patients at different stages of Alzheimer’s disease from the memory unit at Karolinska Hospital in Huddinge. The patients were given a series of neurological memory tests and underwent PET scans at 17-month intervals. While all 16 participants had abundant amyloid plaque deposition in the brain, the size and speed of spread of their tau deposits differed significantly between individuals.

    “We also saw a strong direct correlation between size of deposit and episodic memory impairment,” continues Professor Nordberg. “This could explain why the disease progresses at such a varying rate from one patient to the other. That said, tau doesn’t seem to have much of an effect on the global general memory, which is more reasonably related to brain metabolism.”

    The study was conducted in collaboration with Uppsala University, where the PET scans were performed.


  2. Study finds ‘moral enhancement’ technologies neither feasible nor wise

    by Ashley

    From the North Carolina State University press release:

    A recent study by researchers at North Carolina State University and the Montreal Clinical Research Institute (IRCM) finds that “moral enhancement technologies” — which are discussed as ways of improving human behavior — are neither feasible nor wise, based on an assessment of existing research into these technologies.

    The idea behind moral enhancement technologies is to use biomedical techniques to make people more moral. For example, using drugs or surgical techniques to treat criminals who have exhibited moral defects.

    “There are existing ways that people have explored to manipulate morality, but the question we address in this paper is whether manipulating morality actually improves it,” says Veljko Dubljevic, lead author of the paper and an assistant professor of philosophy at NC State who studies the ethics of neuroscience and technology.

    Dubljevic and co-author Eric Racine of the IRCM reviewed the existing research on moral enhancement technologies that have been used in humans to assess the effects of these technologies and how they may apply in real-world circumstances.

    Specifically, the researchers looked at four types of pharmaceutical interventions and three neurostimulation techniques:

    • Oxytocin is a neuropeptide that plays a critical role in social cognition, bonding and affiliative behaviors, sometimes called “the moral molecule”;
    • Selective serotonin reuptake inhibitors (SSRIs) are often prescribed for depression, but have also been found to make people less aggressive;
    • Amphetamines, which some have argued can be used to enhance motivation to take action;
    • Beta blockers are often prescribed to treat high blood pressure, but have also been found to decrease implicit racist responses;
    • Transcranial magnetic stimulation (TMS) is a type of neurostimulation that has been used to treat depression, but has also been reported as changing the way people respond to moral dilemmas;
    • Transcranial direct current stimulation (TDCS) is an experimental form of neurostimulation that has also been reported as making people more utilitarian; and
    • Deep brain stimulation is a neurosurgical intervention that some have hypothesized as having the potential to enhance motivation.

    “What we found is that, yes, many of these techniques do have some effects,” Dubljevic says. “But these techniques are all blunt instruments, rather than finely tuned technologies that could be helpful. So, moral enhancement is really a bad idea.

    “In short, moral enhancement is not feasible — and even if it were, history shows us that using science to in an attempt to manipulate morality is not wise,” Dubljevic says.

    The researchers found different problems for each of the pharmaceutical approaches.

    Oxytocin does promote trust, but only in the in-group,” Dubljevic notes. “And it can decrease cooperation with out-group members of society, such as racial minorities, and selectively promote ethnocentrism, favoritism, and parochialism.”

    The researchers also found that amphetamines boost motivation for all types of behavior, not just moral behavior. Moreover, there are significant risks of addiction associated with amphetamines. Beta blockers were found not only to decrease racism, but to blunt all emotional response which puts their usefulness into doubt. SSRIs reduce aggression, but have serious side-effects, including an increased risk of suicide.

    In addition to physical side effects, the researchers also found a common problem with using either TMS or TCDS technologies.

    “Even if we could find a way to make these technologies work consistently, there are significant questions about whether being more utilitarian in one’s decision-making actually makes one more moral,” Dubljevic says.

    Lastly, the researchers found no evidence that deep brain stimulation had any effect whatsoever on moral behavior.

    “Our goal here is to share a cautionary note with those who are discussing different techniques for moral enhancement,” Dubljevic says. “I am in favor of research that is done responsibly, but against dangerous social experiments.”


  3. Brain injury causes impulse control problems in rats

    May 24, 2017 by Ashley

    From the University of British Columbia press release:

    New research from the University of British Columbia confirms for the first time that even mild brain injury can result in impulse control problems in rats.

    The study, published in the Journal of Neurotrauma, also found that the impulsivity problems may be linked to levels of an inflammatory molecule in the brain, and suggest that targeting the molecule could be helpful for treatment.

    “Few studies have looked at whether traumatic brain injuries cause impulse control problems,” said the study’s lead author, Cole Vonder Haar, a former postdoctoral research fellow in the UBC department of psychology who is now an assistant professor at West Virginia University. “This is partly because people who experience a brain injury are sometimes risk-takers, making it difficult to know if impulsivity preceded the brain injury or was caused by it. But our study confirms for the first time that even a mild brain injury can cause impulse control problems.”

    For the study, researchers gave rats with brain injuries a reward test to measure impulsivity.

    Rats that were unable to wait for the delivery of a large reward, and instead preferred an immediate, but small reward, were considered more impulsive.

    The researchers found that impulsivity in the rats increased regardless of the severity of the brain injury. The impulsivity also persisted eight weeks after injury in animals with a mild injury, even after memory and motor function returned.

    “These findings have implications for how brain injury patients are treated and their progress is measured,” said Vonder Haar. “If physicians are only looking at memory or motor function, they wouldn’t notice that the patient is still being affected by the injury in terms of impulsivity.”

    After analyzing samples of frontal cortex brain tissue, the researchers also found a substantial increase in levels of an inflammatory molecule, known as interleukin-12, that correlated with levels of impulsivity. Interleukins are groups of proteins and molecules responsible for regulating the body’s immune system.

    The study builds on the researchers’ previous findings about the link between interleukin-12 and impulsivity.

    Catharine Winstanley, the study’s senior author and associate professor in the UBC department of psychology, said the findings are important because impulsivity is linked to addiction vulnerability.

    “Addiction can be a big problem for patients with traumatic brain injuries,” she said. “If we can target levels of interleukin-12, however, that could potentially provide a new treatment target to address impulsivity in these patients.”


  4. Study examines extent of neuronal loss in the brain during MS

    May 22, 2017 by Ashley

    From the Queen Mary University of London press release:

    A study by researchers from Queen Mary University of London establishes for the first time the extent of neuronal loss in the brain of a person with MS over their life, and finds that demyelination may not be as good an indicator of disease progression as previously thought.

    By dissecting and analysing brains from nine people with MS and seven healthy controls using gold standard techniques, they found that the mean number of neurons was 14.9 billion in MS versus 24.4 billion in controls — a 39% difference.

    The density of neurons in MS was smaller by 28%, and cortical volume by 26%, and they found that the whole brain was affected equally.

    Importantly, the number of neurons was strongly associated with the thickness of the cortex, which is something that can be measured by MRI. The decline in volume of the cortex could therefore be detected in vivo and be used to predict neuronal loss in patients or measure neurodegeneration during clinical trials.

    Lead researcher Klaus Schmierer said: “Given that we found no association between neuronal loss and demyelination, trying to detect demyelinating lesions in the cortex — an area of research strongly driven by the availability of high field MRI systems — may be of lesser importance than measuring cortical volume and getting on with early active treatment.”

    As cortical neuronal loss is responsible for cognitive and other functions, which occur early in MS, the researchers say that to avoid neurodegeneration, early treatment is key.


  5. Study links flower pesticides to neurobehavioral effects in children

    May 21, 2017 by Ashley

    From the University of California – San Diego press release:

    Ecuador is the third largest producer of cut flowers in the world, primarily roses, many of which are destined to be sold for Mother’s Day. The industry employs more than 103,000 people, and relies heavily on agricultural pesticides.

    In a paper published in the May 2017 issue of the journal NeuroToxicology, researchers at the University of California San Diego School of Medicine, with colleagues in Ecuador and Minnesota, have found altered short-term neurological behaviors in children associated with a peak pesticide spraying season linked to the Mother’s Day flower harvest. This study examined children who did not work in agriculture but who lived in agricultural communities in Ecuador.

    “Our findings are among the first in non-worker children to suggest that a peak pesticide use period (the Mother’s Day flower production) may transiently affect neurobehavioral performance,” said first author Jose R. Suarez-Lopez, MD, PhD, assistant professor in the Department of Family Medicine and Public Health at UC San Diego School of Medicine.

    “Children examined sooner after the flower harvest displayed lower performance on most measures, such as attention, self-control, visuospatial processing (the ability to perceive and interact with our visual world) and sensorimotor (eye-hand coordination) compared to children examined later in a time of lower flower production and pesticide use.”

    “This discovery is novel because it shows that pesticide spray seasons can produce short-term alterations in neurobehavioral performance in addition to the long-term alterations that have been previously described. This is troublesome because the altered mental functions observed are essential for children’s learning, and in May-July, students typically take their end-of-year exams. If their learning and performance abilities are affected in this period, they may graduate from high school with lower scores which may hinder their ability to access higher education or obtain a job.”

    Early exposure to commonly applied agricultural pesticides is associated with neurobehavioral delays in children, such as attention deficit hyperactivity disorder. Pesticide exposure has been linked to altered development of reflexes and psychomotor and mental function in newborns. Boys appear more susceptible than girls.

    Suarez-Lopez, who is principal investigator of the ESPINA study, an on-going, long-term study of environmental pollutants and child development in Ecuador, said past animal research had suggested that fluctuating levels of pesticide exposure might also produce corresponding, short-term neurobehavioral effects.

    He and colleagues tested 308 children, ages four to nine, living in floricultural communities in Ecuador (but who did not actually work in agriculture themselves) prior to peak Mother’s Day flower production and within 100 days after harvest. Behavior and blood tests were conducted.

    Organophosphate-based insecticides, commonly used to treat flowers for pests before export, inhibit an enzyme called acetylcholinesterase (AChE) that regulates acetylcholine, a neurotransmitter vital to promoting communications between nerve cells in the brain and body. The insecticides are also directly toxic to neurons and supporting cells called glia. In previous research, Suarez-Lopez and colleagues had shown that lower AChE activity is associated with lower attention, inhibitory control and memory scores, again affecting boys more than girls.

    The authors note that the study was cross-sectional, collecting and analyzing observational data on a representative population for a specific point in time. “Our findings need to be replicated in studies of children with assessments conducted before, during and after peak exposure periods,” said Suarez-Lopez. “But given the evidence thus far, and the potential for pesticide exposure to alter both short- and long-term learning abilities, cognition, social interactions and overall well-being, taking additional precautions to shield children from exposure is certainly advised.”

    Co-authors include: Harvey Checkoway, Wael K. Al-Delaimy, Sheila Gahagan, UC San Diego; and David R. Jacobs, Jr., University of Minnesota.


  6. Study suggests human sense of smell is stronger than we think

    May 19, 2017 by Ashley

    From the Rutgers University press release:

    When it comes to our sense of smell, we have been led to believe that animals win out over humans: No way can we compete with dogs and rodents, some of the best sniffers in the animal kingdom.

    But guess what? It’s a big myth. One that has survived for the last 150 years with no scientific proof, according to Rutgers University-New Brunswick neuroscientist John McGann, associate professor in the Department of Psychology, School of Arts and Sciences, in a paper published on May 12 in Science.

    McGann, who has been studying the olfactory system, or sense of smell, for the past 14 years, spent part of the last year reviewing existing research, examining data and delving into the historical writings that helped create the long-held misconception that human sense of smell was inferior because of the size of the olfactory bulb.

    “For so long people failed to stop and question this claim, even people who study the sense of smell for a living,” says McGann, who studies how the brain understands sensory stimuli using information gleaned from prior experience.

    “The fact is the sense of smell is just as good in humans as in other mammals, like rodents and dogs.” Humans can discriminate maybe one trillion different odors, he says, which is far more, than the claim by “folk wisdom and poorly sourced introductory psychology textbooks,” that insist humans could only detect about 10,000 different odors.

    McGann points to Paul Broca, a 19th century brain surgeon and anthropologist as the culprit for the falsehood that humans have an impoverished olfactory system — an assertion that, McGann says, even influenced Sigmund Freud to insist that this deficiency made humans susceptible to mental illness.

    “It has been a long cultural belief that in order to be a reasonable or rational person you could not be dominated by a sense of smell,” says McGann. “Smell was linked to earthly animalistic tendencies.” The truth about smell, McGann says, is that the human olfactory bulb, which sends signals to other areas of a very powerful human brain to help identify scents, is quite large and similar in the number of neurons to other mammals.

    The olfactory receptor neurons in the nose work by making physical contact with the molecules composing the odor, and they send this information back to that region of the brain.

    “We can detect and discriminate an extraordinary range of odors; we are more sensitive than rodents and dogs for some odors; we are capable of tracking odor trails; and our behavioral and affective states are influenced by our sense of smell,” McGann writes in Science.

    In Broco’s 1879 writings, he claimed that the smaller volume of the olfactory area compared to the rest of the brain meant that humans had free will and didn’t have to rely on smell to survive and stay alive like dogs and other mammals.

    In reality, McGann says, there is no support for the notion that a larger olfactory bulb increases sense of smell based solely on size and insists that the human sense of smell is just as good and that of animals.

    “Dogs may be better than humans at discriminating the urines on a fire hydrant and humans may be better than dogs at discriminating the odors of fine wine, but few such comparisons have actual experimental support,” McGann writes in Science.

    The idea that humans don’t have the same sense of smell abilities as animals flourished over the years based on some genetic studies which discovered that rats and mice have genes for about 1000 different kinds of receptors that are activated by odors, compared to humans, who only have about 400.

    “I think it has been too easy to get caught up in numbers,” says McGann. “We’ve created a confirmation bias by working off a held belief that humans have a poor sense of smell because of these lower numbers of receptors, which in reality is still an awful lot.”

    The problem with this continuing myth, McGann says, is that smell is much more important than we think. It strongly influences human behavior, elicits memories and emotions, and shapes perceptions.

    Our sense of smell plays a major, sometimes unconscious, role in how we perceive and interact with others, select a mate, and helps us decide what we like to eat. And when it comes to handling traumatic experiences, smell can be a trigger in activating PTSD.

    While smell can begin to deteriorate as part of the aging process, McGann says, physicians should be more concerned when a patient begins to lose the ability to detect odors and not just retreat back to the misconception that humans’ sense of smell is inferior.

    “Some research suggests that losing the sense of smell may be the start of memory problems and diseases like Alzheimer’s and Parkinson’s,” says McGann. “One hope is that the medical world will begin to understand the importance of smell and that losing it is a big deal.”


  7. Study expands understanding of how the brain encodes fear memory

    by Ashley

    From the UC Riverside press release:

    Research published by scientists at the University of California, Riverside on “fear memory” could lead to the development of therapies that reduce the effects of post-traumatic stress disorder (PTSD).

    To survive in a dynamic environment, animals develop adaptive fear responses to dangerous situations, requiring coordinated neural activity in the hippocampus, medial prefrontal cortex (mPFC), and amygdala – three brain areas connected to one another. A disruption of this process leads to maladaptive generalized fear in PTSD, which affects 7 percent of the U.S. population.

    Jun-Hyeong Cho, an assistant professor of cell biology and neuroscience and Woong Bin Kim, a postdoctoral researcher in Cho’s lab, have now found that a population of hippocampal neurons project to both the amygdala and the mPFC, and that it is these neurons that efficiently convey information to these two brain areas to encode and retrieve fear memory for a context associated with an aversive event.

    The study, which appeared in the May 10 print issue of the Journal of Neuroscience, is the first to quantify these “double-projecting” hippocampal neurons and explain how they convey contextual information more efficiently for fear responses, compared to hippocampal neurons that project only to either the mPFC or the amygdala.

    “This study, done using a mouse model, expands our understanding of how associative fear memory for a relevant context is encoded in the brain,” said Cho, the lead author of the study and a member of the UCR School of Medicine’s Center for Glial-Neuronal Interactions, “and could inform the development of novel therapeutics to reduce pathological fear in PTSD.”

    To visualize the double-projecting hippocampal neurons, Cho and Kim used a tracing method in which hippocampal neurons that project to different brain areas were labeled with fluorescence proteins with different colors. The pair also developed a novel approach of electrophysiological recordings and optogenetics to examine how exactly the double-projecting neurons connected to the mPFC and amygdala. (These experimental approaches can be used to examine other brain areas that project to multiple targets.)

    “We were surprised to find that as much as 17 percent of hippocampal neurons that projected to the amygdala or the mPFC were, in fact, double-projecting neurons,” Cho said. “Although previous studies demonstrated the existence of double-projecting hippocampal neurons, neuroscientists largely ignored them when studying the role of neural pathways between the hippocampus, amygdala and mPFC in contextual fear learning.”

    Cho explained that the acquisition (encoding) and retrieval of contextual fear memory requires coordinated neural activity in the hippocampus, amygdala and mPFC. The hippocampus encodes context cues, the amygdala stores associations between a context and an aversive event, and the mPFC signals whether a defensive response is appropriate in the present context.

    Context is broadly defined as the set of circumstances around an event. In contextual fear conditioning, experimental subjects are placed in an emotionally neutral context (such as a room) and presented an aversive stimulus (such as an electrical shock). Then, they learn to associate the context with the aversive event, and show fear responses (such as freezing behavior) when placed subsequently in that context.

    “Our study suggests that double-projecting hippocampal neurons can facilitate synchronized neural activity in the mPFC and amygdala that is implicated in learned fear,” he said. “It is by modulating the activity of the mPFC and basal amygdala that these double-projecting hippocampal neurons contribute to the acquisition and retrieval of fear memory for a context associated with an aversive event.”

    Cho also explained that multiple projections from single neurons appear to be a general feature of the neural circuits in the brain and could promote synchronized neural activity and long-term changes in the efficiency of neural communication.

    The study came about when, a few years ago, Cho and Kim were selectively labeling and stimulating hippocampal neurons that project to the mPFC, and examining how this manipulation affects fear memory formation in mice. When they carefully examined the brain tissue, they found that labeled hippocampal neurons also projected to the amygdala.

    “We initially thought there was something wrong with our experiments,” Kim, the postdoctoral researcher, said. “But, when we repeated the experiments, the same pattern was observed consistently. We realized that this could be an exciting finding that may account for how contextual information is processed and conveyed between brain areas for the formation of fear memory for the context associated with an aversive event.”

    Next, to better understand the role of double-projecting hippocampal neurons in fear learning and memory, Cho and Kim plan to selectively silence these neurons and examine how this manipulation impacts the formation of fear memory for a context associated with an aversive event.


  8. New hope for patients with primary progressive aphasia

    May 18, 2017 by Ashley

    From the Baycrest Centre for Geriatric Care press release:

    A Baycrest Health Sciences researcher and clinician has developed the first group language intervention that helps individuals losing the ability to speak due to a rare form of dementia, and could help patients maintain their communication abilities for longer.

    Primary Progressive Aphasia (PPA) is a unique language disorder that involves struggles with incorrect word substitutions, mispronounced words and/or difficulty understanding simple words and forgetting names of familiar objects and people. With PPA, language function declines before the memory systems, which is the opposite of Alzheimer’s disease.

    Dr. Regina Jokel, a speech-language pathologist at Baycrest’s Sam and Ida Ross Memory Clinic and a clinician-scientist with the Rotman Research Institute (RRI), has developed the first structured group intervention for PPA patients and their caregivers. This intervention could also help treat patients with other communication problems, such as mild cognitive impairment (a condition that is likely to develop into Alzheimer’s). The results of her pilot program were published in the Journal of Communication Disorders on April 14, 2017.

    “This research aims to address the needs of one of the most underserviced populations in language disorders,” says Dr. Jokel. “Individuals with PPA are often referred to either Alzheimer’s programs or aphasia centres. Neither option is appropriate in this case, which often leaves individuals with PPA adrift in our health care system. Our group intervention has the potential to fill the existing void and reduce demands on numerous other health services.”

    Language rehabilitation has made headway in managing the disorder, but there are limited PPA treatment options, adds Dr. Jokel.

    Dr. Jokel is one of the few researchers in the world studying this disease. She was motivated to acquire her PhD. and devise the intervention after encountering her first PPA patient more than 25 years ago.

    “When I realized the patient had PPA, I ran to the rehabilitation literature thinking that he needed to start some sort of therapy. I ran a search and came up with nothing. Absolutely nothing,” says Jokel. “That’s when I thought, ‘It’s time to design something.'”

    The 10-week intervention included working on language activities, learning communication strategies and receiving counselling and education for both patients and their caregivers. During the pilot program, patients either improved or remained unchanged on communication assessments for adults with communication disorders. Their caregivers also reported being better prepared to manage psychosocial issues and communication challenges and had more knowledge of PPA and the disease’s progression.

    “In progressive disorders, any sign of maintaining current level of function should be interpreted as success,” says Dr. Jokel. “Slowing the progression and maintenance of communication abilities should be the most important goal.”

    For the study’s next steps, Dr. Jokel has received support from a Brain Canada-Alzheimer’s Association partnership grant to assess the therapy’s impact on the language skills of PPA patients. With support from the Ontario Brain Institute, she is also collaborating with RRI brain rehabilitation scientist, Dr. Jed Meltzer, to explore the effect of brain stimulation on patients also undergoing language therapy.


  9. How shifts in excitation-inhibition balance may lead to psychiatric disorders

    by Ashley

    From the Elsevier press release:

    In a special issue of Biological Psychiatry titled “Cortical Excitation-Inhibition Balance and Dysfunction in Psychiatric Disorders,” guest editors Dr. Alan Anticevic and Dr. John Murray, both of Yale University, bring together seven reviews that highlight advancements in understanding the balance of excitatory and inhibitory signaling in the brain, and what might happen when it goes awry.

    Alterations in excitation/inhibition (E/I) balance constitute an emerging theme in clinical neuroscience, wrote Anticevic and Dr. John Lisman of Brandeis University in a commentary accompanying the special issue. The effects of E/I imbalance stretch across diagnostic boundaries, as indicated by the variety of psychiatric disorders addressed in the reviews, including schizophrenia, autism spectrum disorder, major depressive disorder, and bipolar disorder.

    Presenting both human and animal studies, the reviews summarize research on the developmental aspects of E/I regulation and how alterations in circuit stability and compensatory mechanisms with negative effects may emerge when the E/I balance tips. In particular, multiple reviews frame the disturbances in the E/I balance around altered glutamate synaptic development — the excitatory arm of the E/I balance — and present hypotheses for how those developmental alterations may lead to impaired structural and functional circuitry in the brain. A case is made for the need for a combination of approaches, including computational neuroscience, imaging, pharmacological, and genetic studies, in addition to consideration of the coregulation of excitation and inhibition (rather than focusing on the neurotransmitter systems independently) to explain the role of E/I imbalance in psychiatric disorders.

    The collection of reviews not only collate findings aimed at improving our understanding of how these developmental changes and potential negative consequences arise, but also explore how to restore E/I balance. Restoration aims to alleviate the subsequent dysfunctional neural activity that manifests as clinical symptoms, such as impaired working memory in schizophrenia. This is explored, for example, through pharmacological manipulation of glutamate modulation on E/I circuitry.

    The special issue is “Cortical Excitation-Inhibition Balance and Dysfunction in Psychiatric Disorders”, Biological Psychiatry, volume 81, issue 10 (May 2017), published by Elsevier.


  10. Neuronal targets to restore movement in Parkinson’s disease model

    by Ashley

    From the Carnegie Mellon University press release:

    Researchers working in the lab of Carnegie Mellon University neuroscientist Aryn Gittis, have identified two groups of neurons that can be turned on and off to alleviate the movement-related symptoms of Parkinson’s disease. The activation of these cells in the basal ganglia relieves symptoms for much longer than current therapies, like deep brain stimulation and pharmaceuticals.

    The study, completed in a mouse model of Parkinson’s, used optogenetics to better understand the neural circuitry involved in Parkinson’s disease, and could provide the basis for new experimental treatment protocols. The findings, published by researchers from Carnegie Mellon, the University of Pittsburgh and the joint CMU/Pitt Center for the Neural Basis of Cognition (CNBC) are available as an Advance Online Publication on Nature Neuroscience‘s website.

    Parkinson’s disease is caused when the dopamine neurons that feed into the brain’s basal ganglia die and cause the basal ganglia to stop working, preventing the body from initiating voluntary movement. The basal ganglia is the main clinical target for treating Parkinson’s disease, but currently used therapies do not offer long-term solutions.

    “A major limitation of Parkinson’s disease treatments is that they provide transient relief of symptoms. Symptoms can return rapidly if a drug dose is missed or if deep brain stimulation is discontinued,” said Gittis, assistant professor of biological sciences in the Mellon College of Science and member of Carnegie Mellon’s BrainHub neuroscience initiative and the CNBC. “There is no existing therapeutic strategy for long lasting relief of movement disorders associated with Parkinson’s.”

    To better understand how the neurons in the basal ganglia behave in Parkinson’s, Gittis and colleagues looked at the inner circuitry of the basal ganglia. They chose to study one of the structures that makes up that region of the brain, a nucleus called the external globus pallidus (GPe). The GPe is known to contribute to suppressing motor pathways in the basal ganglia, but little is known about the individual types of neurons present in the GPe, their role in Parkinson’s disease or their therapeutic potential.

    The research group used optogenetics, a technique that turns genetically tagged cells on and off with light. They targeted two cell types in a mouse model for Parkinson’s disease: PV-GPe neurons and Lhx6-GPe neurons. They found that by elevating the activity of PV-GPe neurons over the activity of the Lhx6-GPe neurons, they were able to stop aberrant neuronal behavior in the basal ganglia and restore movement in the mouse model for at least four hours — significantly longer than current treatments.

    While optogenetics is used only in animal models, Gittis said she believes their findings could create a new, more effective deep brain stimulation protocol.