New tool probes brain circuits

Researchers at the Picower Institute for Learning and Memory at MIT report in the Jan. 24 online edition of Science that they have created a way to see, for the first time, the effect of blocking and unblocking a single neural circuit in a living animal.

This revolutionary method allowed Susumu Tonegawa, Picower Professor of Biology and Neuroscience, and colleagues to see how bypassing a major memory-forming circuit in the brain affected learning and memory in mice.

“Our data strongly suggest that the hippocampal neural pathway called the tri-synaptic pathway, or TSP, plays a crucial role in quickly forming memories when encountering new events and episodes in day-to-day life,” Tonegawa said. “Our results indicate that the decline of these abilities, such as that which accompanies neurodegenerative diseases and normal aging in humans, is likely to be due, at least in part, to the malfunctioning of this circuit.”

Combining several cutting-edge genetic engineering techniques, Tonegawa's laboratory invented a method called doxycycline-inhibited circuit exocytosis-knockdown, or DICE-K-an acronym that also reflects Tonegawa's admiration of ace Boston Red Sox pitcher Daisuke Matsuzaka. DICE-K allows researchers for the first time to induce and reverse a blockade of synaptic transmission in specific neural circuits in the hippocampus.

“The brain is the most complex machine ever assembled on this planet,” Tonegawa said. “Our cognitive abilities and behaviors are based on tens of thousands of molecules that compose several billion neurons, as well as how those neurons are connected.

“One effective way to understand how this immensely complex cellular network works in a major form of cognition like memory is to intervene in the specific neural circuit suspected to be involved,” he said.

Computing memories

The hippocampus, a seahorse-shaped brain region, plays a part in memory and spatial navigation. In Alzheimer's disease, the hippocampus is one of the first regions to suffer damage; memory problems and disorientation are among the disease's first symptoms.

The hippocampus is made up of several regions--CA1, CA3 and the dentate gyrus--that are wired up with distinct pathways.

The MIT study sought to determine how the interactions between neural pathways and the hippocampal regions affect learning and memory tasks.

Imagine that the three hippocampal regions are computers, and neural pathways are the conduits through which the computers get data from all over the brain. The computers perform different tasks, so the types of data processing will depend on which conduits the data travels through.

The hippocampus has two major, parallel information-carrying routes: the tri-synaptic pathway (TSP) and the shorter monosynaptic pathway (MSP). The TSP includes data processing from all three hippocampal regions, whereas the MSP skips through most of them.

Uisng DICE-K, the researchers were surprised to find that mice in which the major TSP pathway was shut down could still learn to navigate a maze. The shorter MSP pathway was sufficient for the job.

However, the maze is a task that is slowly learned over many repeated trials. When the mice were tested with a different task in a new environment that required rapid learning and memory formation, the researchers found that the mice with TSP shut down could not perform the task. Thus, the TSP pathway is required for animals to quickly acquire memories in a new environment. “This kind of learning results in the most sophisticated form of memory that makes animals more intelligent and is known to decline with age,” Tonegawa said.

Source: Massachusetts Institute of Technology

Related stories:

Brain's reaction to self-administered cocaine differs
New research has uncovered a fundamental cellular mechanism that may drive pathological drug-seeking behavior. The study, published by Cell Press in the July 31 issue of the journal Neuron, examines the brain's reward circuitry and details strikingly distinct influences of self-administered cocaine compared to natural rewards or passive cocaine injection.
Probing Question: Fishhooks of addiction
When the American writer Theodore Roethke taught at Penn State from 1936 to 1943, he was known for three things: being a good poet, coaching the men’s tennis team, and falling down drunk, perhaps the latter more than the former. Roethke, a brilliant and tortured man, knew well the seduction of drink and the agony of addiction. In his poem “Journey Into the Interior,” Roethke writes, “In the long journey out of the self, / There are many detours, washed-out interrupted raw places / Where the shale slides dangerously / And the back wheels hang almost over the edge / At the sudden veering, the moment of turning.”
Neuroscientists show insulin receptor signaling regulates structure of brain circuits
Impact of the signaling upon synapses and dendrites is shown for the first time in living creatures
A team of neuroscientists at Cold Spring Harbor Laboratory (CSHL) has demonstrated for the first time in living animals that insulin receptors in the brain can initiate signaling that regulates both the structure and function of neural circuits.
Brain stem cells can be awakened, say scientists
Scientists at Schepens Eye Research Institute have identified specific molecules in the brain that are responsible for awakening and putting to sleep brain stem cells, which, when activated, can transform into neurons (nerve cells) and repair damaged brain tissue. Their findings are published online this week in the Proceedings of the National Academy of Science (PNAS).
At the synapse: Gene may shed light on neurological disorders
In our brains, where millions of signals move across a network of neurons like runners in a relay race, all the critical baton passes take place at synapses. These small gaps between nerve cell endings have to be just the right size for messages to transmit properly. Synapses that grow too large or too small are associated with motor and cognitive impairment, learning and memory difficulties, and other neurological disorders.
What gets a female's attention -- at least a songbird's
Male songbirds produce a subtly different tune when they are courting a female than when they are singing on their own. Now, new research offers a window into the effect this has on females, showing they have an ear for detail. The finding provides insights not only into the intricacies of songbird attraction and devotion but also into the way in which the brain develops and responds to social cues, in birds – and humans.
Drosophila drug screen for fragile X syndrome finds promising compounds and potential drug targets
Scientists using a new drug screening method in Drosophila (fruit flies), have identified several drugs and small molecules that reverse the features of fragile X syndrome -- a frequent form of mental retardation and one of the leading known causes of autism. The discovery sets the stage for developing new treatments for fragile X syndrome.
Deafness and seizures result when mysterious protein deleted in mice
Scientists have discovered that mice genetically engineered to lack a particular protein in the brain have profound deafness and seizures. The finding suggests a pathway, they say, for exploring the hereditary causes of deafness and epilepsy in humans.

News discussion:

Medicine & Health news