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In a discovery that challenges conventional wisdom on the mechanisms of learning, UCLA neuro-physicists have found there is an optimal brain "rhythm," or frequency, for changing synap strength. And, like stations on a radio dial, each synapse is tuned to a different frequency.
The findings provide a grand-unified theory of the mechanisms that underlie learning in the brain and may lead to possible new therapies for treating learning disabilities.
The study appears in the current issue of the journal Frontiers in Computational Neuroscience.
"Many people have learning and memory disorders, and beyond that group, most of us are not Einstein or Mozart," said Mayank R. Mehta, the paper's senior author and an associate professor in UCLA's departments of neurology, neurobiology, physics and astronomy. "Our work suggests that some problems with learning and memory are caused by synapses not being tuned to the right frequency."
A change in the strength of a synapse in response to stimuli is known as synaptic plasticity, and is induced through "spike trains" which are neural signals occurring at the synapse with varying frequency and timing.
Previous experiments demonstrated that stimulating neurons at a very high frequency (such as 100 spikes per second) strengthened the connecting synapse, while low-frequency stimulation (one spike per second) reduced synaptic strength.
These earlier experiments used hundreds of consecutive spikes in the very high-frequency range to induce plasticity. Yet when the brain is activated through real-life behavioral tasks, neurons fire only about 10 consecutive spikes, not several hundred. And they do so at a much lower frequency -- typically in the 50 spikes-per-second range.
Explains Mehta: "spike frequency refers to how fast the spikes come. Ten spikes could be delivered at a frequency of 100 spikes a second or at a frequency of one spike per second."
Prior research had been unable to conduct experiments that simulated more naturally occurring levels. But Mehta and co-author Arvind Kumar were able to obtain their measurements using a mathematical model they developed and validated.
Contrary to a previous assumption that stimulating neurons at the highest frequencies was the best way to increase synaptic strength, Mehta and Kumar found that stimulating synapses with naturally occurring spike patterns improved synaptic strength. For example, a synapse stimulated with just 10 spikes at a frequency of 30 spikes per second, induced a far greater increase in strength than stimulating that synapse with 10 spikes at 100 times per second.
"The expectation, based on previous studies, was that if you drove the synapse at a higher frequency, the effect on synaptic strengthening, or learning, would be at least as good as, if not better than, the naturally occurring lower frequency," Mehta said.
"To our surprise, we found that beyond the optimal frequency, synaptic strengthening actually declined as the frequencies got higher."
The knowledge that a synapse has a preferred frequency for maximal strengthening/learning led the researchers to compare optimal frequencies based on the location of the synapse on a neuron tree. Neurons trees are shaped with the nucleus as the base of the tree, dendrites resembling the extensive branches and the synapses as the leaves on those branches.
Comparing synaptic learning based on where synapses are located, Mehta and Kumar found: the optimal frequency for inducing synaptic learning changed depending on where the synapse was located. The farther the synapse was from the neuron's cell body, the higher its optimal frequency.
"Incredibly, when it comes to learning, the neuron behaves like a giant antenna, with different branches of dendrites tuned to different frequencies for maximal learning," Mehta said.
Not only does each synapse have a preferred frequency for achieving optimal learning, but the frequency needs to be perfectly rhythmic - timed at exact intervals. Even at optimal frequency, if the rhythm was thrown off, synaptic learning was substantially diminished.
Also, once a synapse learns, its optimal frequency changes. If the optimal frequency for a naïve synapse - one without any input - was perhaps 30 spikes per second, after input, that very same synapse would receive optimally at a lower frequency, say 24 spikes per second.
Thus, learning itself changes the optimal frequency for a synapse.
This learning-induced "detuning" process has important implications for treating disorders related to forgetting, such as post-traumatic stress disorder, the researchers believe.
Although much more research is needed, the findings raise the possibility that drugs could be developed to "retune" the brain rhythms of people with learning or memory disorders, or that many more of us could become Einstein or Mozart if the optimal brain rhythm was delivered to each synapse.
"We already know there are drugs and electrical stimuli that can alter brain rhythms," Mehta said. "Our findings suggest that we can use these tools to deliver the optimal brain rhythm to targeted connections to enhance learning."
Funding for the study was provided by the National Science Foundation, the National Institutes of Health, the Whitehall Foundation, and the W.M. Keck Foundation. The authors report no conflict of interest.
Article publication and related materials: http://www.physics.ucla.edu/~mayank/.
The UCLA Department of Neurology, with over 100 faculty members, encompasses more than 20 disease-related research programs, along with large clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks first among its peers nationwide in National Institutes of Health funding.
Original article: http://newsroom.ucla.edu/portal/ucla/how-the-brain-makes-memories-rhythmically-215953.aspx