Scientists now have a better understanding of how precise memories are formed thanks to research led by Prof. Jean-Claude Lacaille of the University of Montreal’s Department of Physiology. “In terms of human applications, these findings could help us to better understand memory impairments in neurodegenerative disorders like Alzheimer’s disease,” Lacaille said. The study looks at the cells in our brains, or neurons, and how they work together as a group to form memories.
Chemical receptors at neuron interconnections called synapses enable these cells to form electrical networks that encode memories, and neurons are classified into two groups according to the type of chemical they produce: excitatory, who produce chemicals that increase communication between neurons, and inhibitory, who have the opposite effect, decreasing communication. “Scientists knew that inhibitory cells enable us to refine our memories, to make them specific to a precise set of information,” Lacaille explained. “Our findings explain for the first time how this happens at the molecular and cell levels.”
Many studies have been undertaken on excitatory neurons, but very little research has been done on inhibitory neurons, partly because they are very difficult to study. The scientists found that a factor called “CREB” plays a key role in adjusting gene expression and the strength of synapses in inhibitory neurons. Proteins are biochemical compounds encoded in our genes that enable cells to perform their various functions, and new proteins are necessary for memory formation. “We were able to study how synapses of inhibitory neurons taken from rats are modified in the 24 hours following the formation of a memory,” Lacaille said. “In the laboratory, we simulated the formation of a new memory by using chemicals. We then measured the electrical activity within the network of cells. In cells where we had removed CREB, we saw that the strength of the electrical connections was much weaker. Conversely, when we increased the presence of CREB, the connections were stronger.”
This new understanding of the chemical functioning of the brain may one day lead to new treatments for disorders like Alzheimer’s, as researchers will be able to look at these synaptic mechanisms and design drugs that target the chemicals involved. “We knew that problems with synapse modifications are amongst the roots of the cognitive symptoms suffered by the victims of neurodegenerative diseases,” Lacaille said. “These findings shine light on the neurobiological basis of their memory problems. However, we are unfortunately many years away from developing new treatments from this information.”
Photo: Memory (1896). Olin Warner (completed by Herbert Adams). Bronze door at main entrance of the Library of Congress Thomas Jefferson Building, Washington DC.
Researchers at the University of Montreal’s Sainte-Justine Hospital have identified how neural cells are able to build up resistance to opioid pain drugs within hours. “A better understanding of these mechanisms will enable us to design drugs that avoid body resistance to these drugs and produce longer therapeutic responses, including longer-acting opioid analgesics”, lead author Dr. Graciela Pineyro said.
Humans have known about the usefulness of opioids, which are often harvested from poppy plants, for centuries, but we have very little insight into how they lose their effectiveness in the hours, days and weeks following the first dose. “Our study revealed cellular and molecular mechanisms within our bodies that enable us to develop resistance to this medication, or what scientists call drug tolerance,” she added.
The research team looked at how drug molecules would interact with molecules called “receptors” that exist in every cell in our body. Receptors, as the name would suggest, receive “signals” from the chemicals that they come into contact with, and the signals then cause the various cells to react in different ways. They sit on the cell wall, and wait for corresponding chemicals known as receptor ligands to interact with them. Ligands can be produced by our bodies or introduced, for example, as medication.
"Until now, scientists have believed that ligands acted as ‘on-off’ switches for these receptors, all of them producing the same kind of effect with variations in the magnitude of the response they elicit," Pineyro explained. "We now know that drugs that activate the same receptor do not always produce the same kind of effects in the body, as receptors do not always recognize drugs in the same way. Receptors will configure different drugs into specific signals that each will have different effects on the body."
Once activated by a drug, receptors move from the surface of the cell to its interior, and once they have completed this ‘journey’, they can either be destroyed or return to the surface and used again through a process known as “receptor recycling.” By comparing two types of opioids – DPDPE and SNC-80 – the researchers found that the ligands (chemicals that enable interaction with the cell) that encouraged recycling produced less analgesic tolerance than those that didn’t. “We propose that the development of opioid ligands that favour recycling could be a way of producing longer-acting opioid analgesics,” Pineyro said.
Pineyro is attempting to tease the “painkilling” function of opioids from the part that triggers mechanisms that enable tolerance build up. “My laboratory and my work are mostly structured around rational drug design, and trying to define how drugs produce their desired and non-desired effects, so as to avoid the second, Pineyro said. “If we can understand the chemical mechanisms by which drugs produce therapeutic and undesired side effects, we will be able to design better drugs.”
The study “Differential association of receptor-Gβγ complexes with β-arrestin2 determines recycling bias and potential for tolerance of delta opioid receptor (DOR) agonists" was published in The Journal of Neuroscience on April 3, 2012. The research was funded by the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research. Dr. Graciela Pineyro, MD, PhD is affiliated with the Departments of Psychiatry and Pharmacology at the University of Montreal and the Sainte-Justine University Hospital Center (UHC)’ Research Center. The University of Montreal and the Sainte-Justine UHC’s Research Centre are officially known as Université de Montréal and Centre de recherche du Centre hospitalier universitaire Sainte-Justine, respectively.
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I just got back from a mega road trip from Montréal to San Diego (between my favourite and second-favourite North American cities, respectively). While I was away visiting Grizzlepuss and my other nephews and nieces, the embargo lifted on some awesome new neuroscience research that I promoted - click through for the full press release.
Researchers at uMontreal’s Rivière-des-Prairies Hospital have been looking at the brains of people with autism for a long time. By using brain scans, they discovered that their neurological functions are completely reorganized, which explains why some people with autism have special visual abilities.
Jane Hughes at the BBC explains it this way:
[The study] suggests that the brains of autistic people are organised differently from those of other people; the area at the back of the brain, which processes visual information, is more highly developed.
That leaves less brain capacity in areas which deal with decision-making and planning. That may be why people with autism can be better than others at carrying out some types of visual tasks. For example, some are able to draw highly accurate and detailed images from memory. However, they can find it difficult to interpret things like facial expressions.
The condition varies in severity, with some people functioning well, but others completely unable to take part in normal society.
The American Museum of Natural Science in New York City also picked up on the research, and provided this extraordinarily eloquent slide show to explain the findings.
Image: This image shows areas in the brain where autistics show more activity than non-autistics when processing visual information: “faces” in red, “objects” in green, and “words” in blue. Credit: Human Brain Mapping, Wiley-Blackwell Inc.