Alcohol Effects : Brain, Long-Term Potentiation

by National Institute of Health

(Page 3 of 6)

Alcohol's Effects on Long-Term Potentiation

In addition to interfering with the activity of CA1 cells, alcohol can impair other hippocampal functions. One of these, a process called long-term potentiation, is an experimentally induced adaptation of the nerve cell connections in response to repeated activation or stimulation of these connections. (Although there have been some demonstrations of "LTP-like phenomena" in the brain during certain types of learning, the term "LTP" itself refers to an experimentally induced change in brain function.) To illustrate, imagine two neurons in the hippocampus - a CA1 neuron and a neuron from a region called CA3 - that connect in the hippocampus, with the CA3 neuron sending signals to the CA1 neuron. To transmit the signals, the CA3 neuron releases a neurotransmitter, which then interacts with receptors on the surface of the CA1 neuron, resulting in the formation of a new nerve signal in the CA1 neuron. (In normal brain function, nerve signals during memory formation are passed from other areas of the cortex to a region known as dentate gyrus, then to CA3 cells, CA1 cells, and finally back to the cortex.) The intensity of this signal depends on various factors, including the number of receptors on the CA1 neuron. When the CA3 neuron first is exposed to a stimulus, it will emit a signal that leads to a certain level of response in the CA1 neuron. This is called the baseline response. The CA3 neuron then can be stimulated experimentally in a specific pattern, a process that resembles what happens during actual learning events. If the original stimulus subsequently is reapplied to the CA3 neuron, it will evoke a response in the CA1 neuron that is substantially greater than the response that occurred after the initial stimulation (i.e., the response is potentiated). In other words, as the result of the patterned stimulation, the CA1 cell becomes more responsive to signals emitted by the CA3 cell. This potentiated response often persists for a long period of time, hence the name "long-term" potentiation. There is accumulating evidence that something like LTP occurs naturally during learning and memory formation.

Alcohol has been shown to interfere with LTP during experiments using hippocampal brain slices from rats. In these experiments, alcohol concentrations corresponding to those achieved in humans after consuming only one or two drinks interfered with the establishment of LTP. The brain slices were kept in a special fluid, and two electrodes were introduced into the tissue, one that allowed stimulation of the CA3 cells and one that recorded the responses of the CA1 cells. If sufficient alcohol was present in the surrounding fluid during the repeated patterned stimulation of the CA3 cells, LTP was not detected in the CA1 cells - that is, their response remained at the baseline level. However, adding alcohol to the fluid after the patterned stimulation had no effect on LTP, which is consistent with the observation that alcohol consumption does not impair recall of previously established memories. Although experiments like this make it tempting to equate LTP with actual learning, it is important to remember that LTP really is a manifestation of neural plasticity that shares some common mechanisms with learning. Even though actual learning is certainly more complex than simple LTP induced in the lab, the LTP process represents an excellent opportunity to study the brain mechanisms underlying memory and the effects of drugs such as alcohol on these mechanisms.

One neurotransmitter system involved in the establishment of LTP is the excitatory neurotransmitter glutamate and its NMDA receptor. When this receptor is activated by glutamate, it allows calcium to enter the cells. Repeated calcium influx, in turn, sets off a chain reaction leading to long-lasting changes in the structure and/or function of the cells that cause LTP. Alcohol has been shown to interfere with activation of the NMDA receptor, thereby reducing calcium influx and, thus, the subsequent changes in cell function that result in LTP. Researchers think that this is the main mechanism through which alcohol prevents establishment of LTP, although other neurotransmitter systems also may play a role.

Differential Effects of Acute Alcohol on Memory in Adolescents and Adults

Some evidence suggests that alcohol's effects on memory and learning are much more severe in adolescents than in adults. Although difficult to assess in humans, age differences in alcohol's effects on memory can be studied in rodents. One approach uses a test called the Morris water maze task. In this type of experiment, animals are placed in a large circular tank filled with opaque water. The animals must then locate a platform, submerged about an inch beneath the surface, where they can rest. The ability to remember the location of the platform across repeated trials requires activity of the hippocampus; thus, changes in hippocampal function can be detected by measuring the animal's ability to learn the location of the platform.

To assess age-dependent effects of alcohol, Markwiese and colleagues compared the performance of alcohol-exposed adolescent and adult rats in the Morris water maze task. Each animal underwent 5 days of training to learn the location of the platform. Before each training session, one group of animals received no alcohol, and two other groups received one of two different alcohol doses. The investigators then compared how long it took the alcohol-exposed and control animals to remember the location of the platform. Among the adult animals, only those exposed to the highest alcohol concentration showed learning impairments compared with the control group. In contrast, adolescent animals also showed impairments after they had received the lower alcohol dose. This experiment demonstrates that adolescent rats are more vulnerable to alcohol's effects on memory and learning than are adult rats. It is not known if the same age-related difference exists in humans, as corresponding experiments in human adolescents cannot be done for obvious reasons. However, as mentioned previously, one study comparing people in their early twenties with people in their late twenties found that the younger age group seemed more vulnerable to alcohol-induced memory impairment.

About the Author

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