Posts tagged neuroplasticity
Articles and news from the latest research reports.
A turbocharger for nerve cells
Locating a car that’s blowing its horn in heavy traffic, channel-hopping between football and a thriller on TV without losing the plot, and not forgetting the start of a sentence by the time we have read to the end – we consider all of these to be normal everyday functions. They enable us to react to fast-changing circumstances and to carry out even complex activities correctly. For this to work, the neuron circuits in our brain have to be very flexible. Scientists working under the leadership of neurobiologists Nils Brose and Erwin Neher at the Max Planck Institutes of Experimental Medicine and Biophysical Chemistry in Göttingen have now discovered an important molecular mechanism that turns neurons into true masters of adaptation.
Neurons communicate with each other by means of specialised cell-to-cell contacts called synapses. First, an emitting neuron is excited and discharges chemical messengers known as neurotransmitters. These signal molecules then reach the receiving cell and influence its activation state. The transmitter discharge process is highly complex and strongly regulated. Its protagonists are synaptic vesicles, small blisters surrounded by a membrane, which are loaded with neurotransmitters and release them by fusing with the cell membrane. In order to be able to respond to stimulation at any time by releasing transmitters, a neuron must have a certain amount of vesicles ready to go at each of its synapses. Brose has been studying the molecular foundations of this stockpiling for years.
The problem is not merely academic. “The number of immediately releasable vesicles at a synapse determines its reliability,” explains Brose. “If there are too few and they are replenished too slowly, the corresponding synapse becomes tired very quickly in conditions of repeated activation. The opposite applies when a synapse can quickly top up its immediately available vesicles under pressure. In fact, such a synapse may even improve with constant activation.”
This synaptic adaptability can be observed in practically all neurons. It is known as short-term plasticity and is indispensable for a large number of extremely important brain processes. Without it, we would not be able to localise sounds, mental maths would be impossible, and the speed and flexibility with which we can alter our behaviour and turn our attention to new goals would be lost.
Some years ago, Brose and his team discovered a protein with the cryptic name of Munc13. Not only is this protein indispensable for the replenishment of vesicles for immediate release at synapses; neuron activity regulates it in such a way that the fresh supply of vesicles can be adjusted in line with demand. This regulation occurs by means of a complex consisting of the signal protein calmodulin and calcium ions that build up in the synapses during intense neuron activity.
“Our earlier work on individual neurons in culture dishes showed that the calcium-calmodulin complex activates Munc13 and consequently ensures that immediately releasable vesicles are replenished faster,” says Noa Lipstein, an Israeli guest scientist in Brose’s lab. “But many colleagues were not convinced that this process also played a role in neurons in the intact brain.”
So Lipstein and her Japanese colleague Takeshi Sakaba created a mutant mouse with genetically altered Munc13 proteins that could not be activated by calcium-calmodulin complexes. The two neurophysiologists first studied the effects of this genetic manipulation on synapses involved in the localisation of sound, which are typically activated several hundred times every second. “Our study shows that the sustained efficiency of synapses in intact neuron networks is critically dependent on the activation of Munc13 by calcium-calmodulin complexes,” explains Lipstein.
The Göttingen-based scientists are convinced of the significance of their study. After all, leading neuroscientists of the past described the calcium sensor responsible for synaptic short-term plasticity and its target protein as the Holy Grail. “I am confident that we have discovered a key molecular mechanism of short-term plasticity that plays a role in all synapses in the brain, and not only in cultivated neurons, as many colleagues believed,” affirms Lipstein. And if she is, in fact, proved right about the interpretation of her findings, Munc13 could even be an ideal pharmacological target for drugs that influence brain function.
Posttraumatic Stress Disorder Treatment: Genetic Predictor of Response to Exposure Therapy
There is growing evidence that a gene variant that reduces the plasticity of the nervous system also modulates responses to treatments for mood and anxiety disorders. In this case, patients with posttraumatic stress disorder, or PTSD, with a less functional variant of the gene coding for brain-derived neurotrophic factor (BDNF), responded less well to exposure therapy.
This gene has been implicated previously in treatment response. Basic science studies have convincingly shown that BDNF levels are an important modifier of the therapeutic effects of antidepressants in animal models. Other researchers have made similar findings in a small group of depressed patients treated with the rapid-acting antidepressant ketamine. Low BDNF plasma levels also have been linked to poorer effects of cognitive rehabilitation in schizophrenia. BDNF infused directly into the infralimbic prefrontal cortex in rats was found to extinguish conditioned fear, and BDNF levels were found to modulate the amount of fear extinction.
"Findings are accumulating to suggest that BDNF is an important modifier of the responses to a number of clinical interventions, presumably because BDNF is such an important regulator of neuroplasticity, i.e., the ability of the brain to adapt," said Dr. John Krystal, Editor of Biological Psychiatry.
In this study, researchers from Australia and Puerto Rico teamed up to investigate the influence of the BDNF Val66Met genotype on response to exposure therapy in patients with PTSD. They recruited 55 patients, all of whom participated in an 8-week exposure-based cognitive behavior therapy program.
Exposure therapy is currently the most effective treatment for PTSD, although it does not work for everyone. This type of therapy is delivered over multiple one-on-one sessions with a trained therapist, with a goal of reducing patients’ fear and anxiety.
They found that patients with the Met-66 allele of BDNF, compared with patients with the Val/Val allele, showed poorer response to exposure therapy.
"This paper reflects an important and significant advance, in translating recent ground-breaking findings in animal and human neuroscience into clinically anxious populations," said first author Dr. Kim Felmingham.
She added, “Findings from this study support a widely held, but largely untested, hypothesis that extinction is necessary for exposure therapy. It also provides evidence that genotypes influence response to cognitive behavior therapy.”
This finding supports prior evidence and highlights the importance of considering genotypes as potential predictor variables in clinical trials of exposure therapy.
(Source: alphagalileo.org)
Rewired visual input to sound-processing part of the brain leads to compromised hearing
Scientists at Georgia State University have found that the ability to hear is lessened when, as a result of injury, a region of the brain responsible for processing sounds receives both visual and auditory inputs.
Yu-Ting Mao, a former graduate student under Sarah L. Pallas, professor of neuroscience, explored how the brain’s ability to change, or neuroplasticity, affected the brain’s ability to process sounds when both visual and auditory information is sent to the auditory thalamus.
The study was published in the Journal of Neuroscience.
The auditory thalamus is the region of the brain responsible for carrying sound information to the auditory cortex, where sound is processed in detail.
When a person or animal loses input from one of the senses, such as hearing, the region of the brain that processes that information does not become inactive, but instead gets rewired with input from other sensory systems.
In the case of this study, early brain injury resulted in visual inputs into the auditory thalamus, which altered how the auditory cortex processes sounds.
The cortical “map” for discriminating different sound frequencies was significantly disrupted, she explained.
“One of the possible reasons the sound frequency map is so disrupted is that visual responsive neurons are sprinkled here and there, and we also have a lot of single neurons that respond to both light and sound,” Pallas said. “So those strange neurons sprinkled there probably keeps the map from forming properly.”
Mao also discovered reduced sensitivity and slower responses of neurons in the auditory cortex to sound.
Finally, the neurons in the auditory cortex were less sharply tuned to different frequencies of sound.
“Generally, individual neurons will be pretty sensitive to one sound frequency that we call their ‘best frequency,’” Pallas said. “We found that they would respond to a broader range of frequencies after the rewiring with visual inputs.”
While Pallas’ research seeks to create a basic understanding of brain development, knowledge gained from her lab’s studies may help to give persons who are deaf, blind, or have suffered brain injuries ways to keep visual and auditory functions from being compromised.
“Usually we think of plasticity as a good thing, but in this case, it’s a bad thing,” she said. “We would like to limit the plasticity so that we can keep the function that’s supposed to be there.”
Source: Georgia State University
![How digital culture is rewiring our brains
Our brains are superlatively evolved to adapt to our environment: a process known as neuroplasticity. The connections between our brain cells will be shaped, strengthened and refined by our individual experiences. It is this personalisation of the physical brain, driven by unique interactions with the external world, that arguably constitutes the biological basis of each mind, so what will happen to that mind if the external world changes in unprecedented ways, for example, with an all-pervasive digital technology?
A recent survey in the US showed that more than half of teenagers aged 13 to 17 spend more than 30 hours a week, outside school, using computers and other web-connected devices. If their environment is being transformed for so much of the time into a fast-paced and highly interactive two-dimensional space, the brain will adapt, for good or ill. Professor Michael Merzenich, of the University of California, San Francisco, gives a typical neuroscientific perspective.
”There is a massive and unprecedented difference in how [digital natives’] brains are plastically engaged in life compared with those of average individuals from earlier generations and there is little question that the operational characteristics of the average modern brain substantially differ,” he says.](http://41.media.tumblr.com/tumblr_m8ft5jgs2V1rog5d1o1_400.jpg)
How digital culture is rewiring our brains
Our brains are superlatively evolved to adapt to our environment: a process known as neuroplasticity. The connections between our brain cells will be shaped, strengthened and refined by our individual experiences. It is this personalisation of the physical brain, driven by unique interactions with the external world, that arguably constitutes the biological basis of each mind, so what will happen to that mind if the external world changes in unprecedented ways, for example, with an all-pervasive digital technology?
A recent survey in the US showed that more than half of teenagers aged 13 to 17 spend more than 30 hours a week, outside school, using computers and other web-connected devices. If their environment is being transformed for so much of the time into a fast-paced and highly interactive two-dimensional space, the brain will adapt, for good or ill. Professor Michael Merzenich, of the University of California, San Francisco, gives a typical neuroscientific perspective.
”There is a massive and unprecedented difference in how [digital natives’] brains are plastically engaged in life compared with those of average individuals from earlier generations and there is little question that the operational characteristics of the average modern brain substantially differ,” he says.