Cambridge, MA, USA. Researchers for the first time have created a way to see the effect of blocking and unblocking a single neural circuit in a living animal. 

This method allowed researchers to learn how bypassing a major memory-forming circuit in the brain affected learning and memory.

The specific area, the hippocampus, has been impicated in a variety of neurological disorders. It is also suspected as involved in the early expression of transsexuality.

According to Susumu Tonegawa, "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, of the Picower Institute for Learning and Memory, and his colleagues reported their findings in the journal Science.

The hippocampus is part of the limbic system and plays a part in memory and spatial navigation. It is located inside the medial temporal lobe of the brain.

The illustration shows the underside of the brain, with the frontal lobe at the top and the occipital lobe at the bottom.

The name hippocampus derives from its curved shape in coronal sections of the brain, which resembles a seahorse (Greek: hippos = horse, kampi = curve). Recent research shows the hippocampus is important for stress and learning interactions. It is necessary for modifying learning in males and females after acute stressful experience. (Bangasser & Tracey J Shors, 2007).   It is one of a number of brain regions that differ significantly in size between men and women. This has led many people to think that such variations result in sex differences in function and behavior, such as memory and emotionality.    For example, part of the hippocampus at the center of the brain and other areas at the front of the brain contribute to short-term memory. They are larger in women. Does this mean they have better working memories?   Other areas, thought to be seats of mating and arousal, grow larger in males, leading to conclusions that men are more aggressive. However, this is not always the case since size alone does not drive function.   Tests show that female and male brains can take different actions to arrive at the same behavioral response.  While brain activity differs between sexes, short-term memory performance is the same.

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

DICE-K Technique. Blocking the neural-signal transmission in one of the hippocampal circuits of the brain.

Click Pic for Details

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.

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

He says "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." Tonegawa, Picower Professor of Biology and Neuroscience at MIT. 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.

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TS-Si is dedicated to the acceptance, medical treatment, and legal protection of individuals correcting the misalignment of their brains and their anatomical sex, while supporting their transition into society as hormonally reconstituted and surgically corrected citizens.

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Comment deleted, Violation of the TS-Si.org Terms of Use

06 February 2008     

Violation of the TS-Si.org Terms of Use: commercial solicitation.
Sharon S. Gaughan

New Tool Probes Neural Circuits In The Hippocampus, What

21 March 2010     

What a well written article for the layperson. Congratulations on your important discoveries. Your research and experiments greatly interest me. My particularly interest is how neural circuits operate in the brains of survivors of sexual trauma. Apparently the right hippocampus is considerably diminished by trauma. Are the neural circuits within the hippocampus also damaged? Or is it a reduction in the size of the hippocampus? Any information you may have available would be greatly appreciated. Sincerely, Pamela Clute

Pamela Clute

Pamela Clute, Hi Pam, thank you for your kind comments.

21 March 2010     

Hi Pam, thank you for your kind comments. Work on neural circuit degradation has accelerated in recent years, mainly because we know more now about neural pathways and neural signaling. You can Google either of those phrases for meaningful results. You asked some specific questions about trauma, neural circuits, and the hippocampus. You asked: Are the neural circuits within the hippocampus also damaged? It appears beyond question that functional changes can occur within the hippocampus/amydala complex. However, the specific mechanisms are a bit more subtle than commonly assumed. For instance, a neural pathway (or neural tract) is the circuit that transports long haul communications between different parts of the nervous system, as compared to grey matter, which handles local communication (there are highly specialized exceptions). The pathway usually consists of white matter, bundles of elongated, myelin-insulated neurons. In effect, the hippocampus connects to other parts of the nervous system. The white matter and neural pathways are areas that bear closer examination to assess the effects of trauma. Here are two papers conveying well-vetted research. Both are available at TS-Si. (1) Posttraumatic Stress Disorder: A State-of-the-Science Review. Charles B. Nemeroff, J. Douglas Bremner, Edna B. Foa, Helen S. Mayberg, Carol S. North, and Murray B. Stein. Journal of Psychiatric Research 2006; 40: 1–21). doi:10.1016/j.jpsychires.2005.07.005. Click this link for the PDF. (2) Stress Psychobiology and molecular genetics of resilience. Adriana Feder, Eric J. Nestler amd Dennis S. Charney. Nature Reviews Neuroscience 2009; 10: 446-457. doi:10.1038/nrn2649. Click this link for the PDF.

Sharon S. Gaughan

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