Posts tagged neuroscience
Articles and news from the latest research reports.
Episodic Memory and Appetite Regulation in Humans
Psychological and neurobiological evidence implicates hippocampal-dependent memory processes in the control of hunger and food intake. In humans, these have been revealed in the hyperphagia that is associated with amnesia. However, it remains unclear whether ‘memory for recent eating’ plays a significant role in neurologically intact humans. In this study we isolated the extent to which memory for a recently consumed meal influences hunger and fullness over a three-hour period. Before lunch, half of our volunteers were shown 300 ml of soup and half were shown 500 ml. Orthogonal to this, half consumed 300 ml and half consumed 500 ml. This process yielded four separate groups (25 volunteers in each). Independent manipulation of the ‘actual’ and ‘perceived’ soup portion was achieved using a computer-controlled peristaltic pump. This was designed to either refill or draw soup from a soup bowl in a covert manner. Immediately after lunch, self-reported hunger was influenced by the actual and not the perceived amount of soup consumed. However, two and three hours after meal termination this pattern was reversed - hunger was predicted by the perceived amount and not the actual amount. Participants who thought they had consumed the larger 500-ml portion reported significantly less hunger. This was also associated with an increase in the ‘expected satiation’ of the soup 24-hours later. For the first time, this manipulation exposes the independent and important contribution of memory processes to satiety. Opportunities exist to capitalise on this finding to reduce energy intake in humans.
Study of link between night eating and the peculiar internal clock of fat cells
When researchers at the University of Pennsylvania messed with the internal clocks of mouse fat cells, a surprising thing happened.
The mice got fat.
Figuring out why led to more surprises. Mice usually eat at night, but the altered mice ate more of their food during the day. They got fat even though they ate the same number of calories as regular, nocturnal-feeding mice.
And when the researchers gave altered mice two of the key ingredients in fish oil, the animals didn’t get fat.
That’s a lot to digest, but it has potential implications for humans as we enter the season of stuffed refrigerators that beckon some to eat when they should be resting.
Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness
General anesthesia involves rapidly inducing a reversible coma by administering a large dose of a fast-acting drug, such as propofol. Previous research has demonstrated that propofol enhances inhibitory input to neurons throughout the spinal cord, brainstem, thalamus, and cortex. However, how these effects in single cells translate to larger-scale neural circuits and cause unconsciousness is not well understood. We recorded spiking activity from ensembles of single neurons and intracranial electrical activity during the induction of propofol general anesthesia in human subjects undergoing surgery. We found that loss of consciousness (LOC) corresponds to the abrupt onset of a slow cortical oscillation that marks a fragmentation of neuronal networks. These results identify the slow oscillation as a dramatic neural correlate of LOC and demonstrate that slow oscillation marks the transition into a brain state in which local neuronal networks are isolated, impairing both temporal and spatial communication throughout the cortex.
Lithium rescues synaptic plasticity and memory in Down syndrome mice
Down syndrome (DS) patients exhibit abnormalities of hippocampal-dependent explicit memory, a feature that is replicated in relevant mouse models of the disease. Adult hippocampal neurogenesis, which is impaired in DS and other neuropsychiatric diseases, plays a key role in hippocampal circuit plasticity and has been implicated in learning and memory. However, it remains unknown whether increasing adult neurogenesis improves hippocampal plasticity and behavioral performance in the multifactorial context of DS. We report that, in the Ts65Dn mouse model of DS, chronic administration of lithium, a clinically used mood stabilizer, promoted the proliferation of neuronal precursor cells through the pharmacological activation of the Wnt/β-catenin pathway and restored adult neurogenesis in the hippocampal dentate gyrus (DG) to physiological levels. The restoration of adult neurogenesis completely rescued the synaptic plasticity of newborn neurons in the DG and led to the full recovery of behavioral performance in fear conditioning, object location, and novel object recognition tests. These findings indicate that reestablishing a functional population of hippocampal newborn neurons in adult DS mice rescues hippocampal plasticity and memory and implicate adult neurogenesis as a promising therapeutic target to alleviate cognitive deficits in DS patients.
A new promising approach in the therapy of pain
The treatment of inflammatory pain can be improved by endogenous opioid peptides acting directly in injured tissue. Scientists at the Charité – Universitätsmedizin Berlin and the Université Paris Descartes showed that pain can be successfully treated by targeting immune and nerve cells outside the brain or spinal cord. The study is published in the current issue of The FASEB Journal.
Inflammatory pain is the most common form of painful diseases. Examples are acute pain after surgery, and chronic pain as in the case of rheumatoid arthritis. However, the treatment of inflammatory pain is often difficult because it rarely responds to conventional therapies. Furthermore, opiates, such as morphine, produce serious side effects including addiction mediated in the brain, while drugs, such as ibuprofen, may cause stomach ulcers, internal bleeding, and cardiovascular complications. The activation of opiate receptors in nerve cells outside the brain or spinal cord can alleviate pain without serious side effects. This can be achieved by synthetic opiates or endogenous opioid peptides, e.g. enkephalins and endorphins. However, these peptides are rapidly inactivated by two major enzymes, aminopeptidase N (APN) and neutral endopeptidase (NEP), which limit their analgesic effects.
The aim of the research group of Prof. Halina Machelska-Stein from the Klinik für Anästhesiologie at Campus Benjamin Franklin was to prevent the breakdown of endogenous opioid peptides directly in the inflamed tissue. In an animal model, the group has shown that inflammatory pain can be alleviated if the two enzymes (APN and NEP), responsible for the inactivation of the opioid peptides, were blocked by the selective inhibitors. In preparations from immune or nerve cells, which express these enzymes, the opioid peptides were quickly broken down. This was prevented by the enzyme inhibitors, bestatin, thiorpan and P8B. As a result, the sensation of pain was either markedly reduced or completely disappeared. “Targeting of endogenous opioid peptides directly in injured tissues might be a promising strategy to treat inflammatory pain without serious side effects,” states Prof. Machelska-Stein, explaining the results of the investigation. Furthermore, blocking pain at the site of its origin may prevent excitatory mechanisms in the nervous system, which lead to the development of chronic pain.
(Source: charite.de)
What howler monkeys can tell us about the role of interbreeding in human evolution
Did different species of early humans interbreed and produce offspring of mixed ancestry?
Recent genetic studies suggest that Neanderthals may have bred with anatomically modern humans tens of thousands of years ago in the Middle East, contributing to the modern human gene pool. But the findings are not universally accepted, and the fossil record has not helped to clarify the role of interbreeding, which is also known as hybridization.
Now a University of Michigan-led study of interbreeding between two species of modern-day howler monkeys in Mexico is shedding light on why it’s so difficult to confirm instances of hybridization among primates—including early humans—by relying on fossil remains.
The study, published online Dec. 7 in the American Journal of Physical Anthropology, is based on analyses of genetic and morphological data collected from live-captured monkeys over the past decade. Morphology is the branch of biology that deals with the form and structure of animals and plants.
The two primate species in the study, mantled howler monkeys and black howler monkeys, diverged about 3 million years ago and differ in many respects, including behavior, appearance and the number of chromosomes they possess. Each occupies a unique geographical distribution except for the state of Tabasco in southeastern Mexico, where they coexist and interbreed in what’s known as a hybrid zone.
New understanding of how we see colors
Scientists have until now not fully understood how animals see in color, since visual pigments in eyes contain exactly the same chromophore (light absorbing segment of the molecule) and yet can absorb different wavelengths of light.
The chromophore retinal (Vitamin A aldehyde or retinaldehyde) is used by all animals but, depending on the photoreceptor proteins (opsins) associated with it, the same molecule can absorb a spectrum of colors from blues or even ultraviolet to reds. How a single molecule can do this has until now been uncertain.
Now researchers, led by Prof. Babak Borhan of Michigan State University at East Lansing, set out to try to understand the mechanism by which the opsins change the light absorption spectrum of the chromophore retinal. They concentrated their efforts on a pigment found in human retinal photoreceptor cells, rhodopsin, which consists of opsin and chromophore components.
One of the major theories about how retinal works is that because it is strongly positively charged at one end it could distribute this electrostatic charge across the chromophore molecule, and this would enable it to absorb the longer wavelengths at the red end of the spectrum. Another theory held that a change in shape of the chromophore-opsin complex could alter the absorption capabilities.
The problem with testing the theories, Borhan said, is that the visual pigments have proved difficult to work with. So instead, Borhan and colleagues used human cellular retinol binding protein II, (hCRBPII), a gut protein that binds retinol, which is closely related to retinal but which tolerates mutations more readily.
The team first created a mutation of hCRPBII that could bind retinal. They then changed the distribution of the electrostatic charge on the retinal molecule by replacing amino acids at the binding site retinal uses on hCRPBII in various ways, and in so doing created a range of pigment proteins.
The team then used spectrophotometry to compare the light entering and leaving the proteins to determine which wavelengths were being absorbed. Using this approach they were able to prove the charge distribution theory was correct and that no change in shape was necessary.
A by-product of the new research is the production of the 11 new artificial pigments, which could be used in tracking proteins or cell types being studied, as well as other possible applications such as in food dyes. One of the new pigments could absorb a red wavelength of 644 nanometers (nm), which is above the theoretical maximum wavelength retinal can absorb (560 nm) and is close to infrared (750 nm +).
The paper was published in the journal Science.
(Source: medicalxpress.com)
The Meaning of Pupil Dilation
For more than a century, scientists have known that our pupils respond to more than changes in light. They also betray mental and emotional commotion within. In fact, pupil dilation correlates with arousal so consistently that researchers use pupil size, or pupillometry, to investigate a wide range of psychological phenomena. And they do this without knowing exactly why our eyes behave this way. “Nobody really knows for sure what these changes do,” said Stuart Steinhauer, who directs the Biometrics Research Lab at the University of Pittsburgh School of Medicine.
While the visual cortex in the back of the brain assembles the images we see, a different, older part of our nervous system manages the continuous tuning of our pupil size, alongside other functions—like heart rate and perspiration—that operate mostly outside our conscious control. This autonomic nervous system dictates the movement of the iris, like the lens of a camera, to regulate the amount of light that enters the pupil.
The iris is made of two types of muscle: in a brightly lit environment, a ring of sphincter muscles that encircle and constrict the pupil down to as little as a couple of millimeters across; in the dark, a set of dilator muscles laid out like bicycle spokes, which can expand the pupil up to 8 millimeters—approximately the diameter of a chickpea.
Cognitive and emotional events can also dictate pupil constriction and expansion, though such events occur on a smaller scale than the light reflex, causing changes generally less than half a millimeter. But that’s enough. By recording subjects’ eyes with infrared cameras and controlling for other factors that might affect pupil size, like brightness, color, and distance, scientists can use pupil movements as a proxy for other processes, like mental strain.
(Image: Wikimedia Commons)
A direct line through the brain to avoid rotten food
Consuming putrid food can be lethal as it allows bacterial pathogens to enter the digestive system. To detect signs of decay and thus allowing us and other animals to avoid such food poisoning is one of the main tasks of the sense of smell. Behavioural scientists and neurobiologists at the Max Planck Institute for Chemical Ecology in Jena, Germany, have now for the first time decoded the neural mechanisms underlying an escape reflex in fruit flies (Drosophila) activated in order to avoid eating and laying eggs in food infected by toxic microorganisms. A super-sensitive and completely dedicated neural line, from olfactory receptor, via sensory neuron and primary brain neurons, is activated as soon as the tiniest amount of geosmin is in the air. Geosmin is a substance released by bacteria and mold fungi toxic to the fly. This stimulus overrides all other food odour signals, irrespective of how attractive they are on their own. Consequently, geosmin is a full STOP signal that prevents flies from eating and laying eggs in toxic food, similar to when we open the fridge and smell last week’s forgotten dinner.
Drug fights hard-to-treat depression by targeting brain receptors in a new way
A first-of-its-kind antidepressant drug discovered by a Northwestern University professor and now tested on adults who have failed other antidepressant therapies has been shown to alleviate symptoms within hours, have good safety and produce positive effects that last for about seven days from a single dose.
The novel therapeutic targets brain receptors responsible for learning and memory — a very different approach from existing antidepressants. The new drug and others like it also could be helpful in treating other neurological conditions, including schizophrenia, bipolar disorder, anxiety and Alzheimer’s disease.
The results of the phase IIa clinical trial were presented (Dec. 6) at the 51st Annual Meeting of the American College of Neuropsychopharmacology in Hollywood, Fla.
Also this week a paper reporting some of the background scientific research that provided the foundation for the clinical development of GLYX-13 was published by the journal Neuropsychopharmacology.
The compound, called GLYX-13, is the result of more than two decades of work by Joseph Moskal, research professor of biomedical engineering at Northwestern’s McCormick School of Engineering and Applied Science and director of the University’s Falk Center for Molecular Therapeutics.
(Image: Shutterstock)