10 January 2013

How Nerve Cell Activity Between Neurons is Regulated Within the Brain's Hippocampus

Scientists have discovered the process on how the synapses regulate nerve cell activity when communicating with each other. Neuronal activity within the hippocampus must be maintained at a steady and optimal level since over activity can cause seizures while the opposite can cause degradation of neural cells as well as impair information.

The brain is made up of four major parts. The cerebrum, the cerebellum,the brain stem, and the limbic system which contains the hippocampus. These major parts are responsible for different functions of the brain from feeling emotion, decision making, and even breathing.

The cerebrum is responsible for memory, problem solving, thinking, movement, and feeling. It is located at the front part of the brain. The cerebellum, which can be found at the back is responsible for balance and coordination. The brain stem located at the bottom of the brain, is responsible for the autonomic nervous system. These are processes that are below the conscious level such as breathing, digestion, and even heart rate.

The limbic system which is the learning and emotional part of the brain is made up of the thalamus, hypothalamus, amygdala, and hippocampus. It can be found buried within the cerebrum.

Hippocampus is latin for seahorse since the organ resembles a seahorse (see image). The hippocampus is responsible for the consolidation of memory, both short term and long term. It is also part of the limbic system that primarily deals with emotion, behavior, motivation, long-term memory, and olfaction (sense of smell). It also plays a role in spatial thinking, which relates to determining location within the environment.

Humans have two hippocampi situated on the left and right side of the brain.

Regulating Neural Signals Within the Hippocampus

Scientists have long wondered how nerve cell activity in the brain's hippocampus, the epicenter for learning and memory, is controlled — too much synaptic communication between neurons can trigger a seizure, and too little impairs information processing, promoting neurodegeneration. Researchers at Georgetown University Medical Center say they now have an answer. In the January 10 issue of Neuron, they report that synapses that link two different groups of nerve cells in the hippocampus serve as a kind of "volume control," keeping neuronal activity throughout that region at a steady, optimal level.

"Think of these special synapses like the fingers of God and man touching in Michelangelo's famous fresco in the Sistine Chapel," says the study's senior investigator, Daniel Pak, PhD, an associate professor of pharmacology. "Now substitute the figures for two different groups of neurons that need to perform smoothly. The touching of the fingers, or synapses, controls activity levels of neurons within the hippocampus."

The hippocampus is a processing unit that receives input from the cortex and consolidates that information in terms of learning and memory. Neurons known as granule cells, located in the hippocampus' dentate gyrus, receive transmissions from the cortex. Those granule cells then pass that information to the other set of neurons (those in the CA3 region of the hippocampus, in this study) via the synaptic fingers.

Video: Hippocampus

Those fingers dial up, or dial down, the volume of neurotransmission from the granule cells to the CA3 region to keep neurotransmission in the learning and memory areas of the hippocampus at an optimal flow — a concept known as homeostatic plasticity. "If granule cells try to transmit too much activity, we found, the synaptic junction tamps down the volume of transmission by weakening their connections, allowing the proper amount of information to travel to CA3 neurons," says Pak. "If there is not enough activity being transmitted by the granule cells, the synapses become stronger, pumping up the volume to CA3 so that information flow remains constant."

There are many such touching fingers in the hippocampus, connecting the so-called "mossy fibers" of the granule cells to neurons in the CA3 region. But importantly, not every one of the billions of neurons in the hippocampus needs to set its own level of transmission from one nerve cell to the other, says Pak.

To explain, he uses another analogy. "It had previously been thought that neurons act separately like cars, each working to keep their speed at a constant level even though signal traffic may be fast or slow. But we wondered how these neurons could process learning and memory information efficiently, while also regulating the speed by which they process and communicate that information.

"We believe, based on our study, that only the mossy fiber synapses on the CA3 neurons control the level of activity for the hippocampus — they are like the engine on a train that sets the speed for all the other cars, or neurons, attached to it," Pak says. "That frees up the other neurons to do the job they are tasked with doing — processing and encoding information in the forms of learning and memory."

Not only does the study offer a new model for how homeostatic plasticity in the hippocampus can co-exist with learning and memory, it also suggests a new therapeutic avenue to help patients with uncontrollable seizures, he says.

"The CA3 region is highly susceptible to seizures, so if we understand how homeostasis is maintained in these neurons, we could potentially manipulate the system. When there is an excessive level of CA3 neuronal activity in a patient, we could learn how to therapeutically turn it down."


Georgetown University Medical Center
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