Understanding the Brain: How Neurons Communicate

Summer 1999

Table of Contents

Introduction

Neurons

How Neurons Communicate

Regulation of Neurotransmitter and Receptor Interaction

Utilizing Neurotransmitter-Receptor Systems as Targets for Drugs

Profile of Mark Geyer, Ph.D.

Director's Letter

Introduction

During the "Decade of the Brain," great strides have been made in understanding how the brain works. Efforts to develop new drugs for treating psychosis have benefited from a greatly enhanced understanding of how neurons communicate with one another. This article will provide an introduction to basic concepts including neurotransmitters (chemical messengers, receptors), and how cells talk with one another. These concepts will provide the foundation for discussions of how psychotherapeutic drugs work.

Neurons

The body contains more than 100 billion neurons. Neurons are similar to other cells in the body in that they have a cell membrane, a nucleus containing genes, and organelles that carry out basic cellular functions such as energy production. One important difference is the presence of extensions that receive messages (dendrites) and transmit or send messages (axons). Although mostly concentrated in the brain, neurons are also important for communicating sensory information and also controlling body functions such as muscle activity.

^Top

How Neurons Communicate

Many neuronal functions are based on complex electrochemical processes. Various stimuli such as light, sound, temperature and pain interact with specific sensory receptors which transform the stimulus into a neural code that is carried by a chain of neurons to the brain. Systems of neurons in the brain are then responsible for interpreting this information -- information processing.

Information is carried along axons and dendrites by changes in electrical properties called action potential. An action potential is initiated when a chemical messenger attaches to a specific site called a receptor. This attachment triggers an electrical signal to be generated that travels through the neuron. Once the electrical signal reaches the end of the axon, a neurotransmitter is released into the synaptic cleft, the gap between neurons. As the neurotransmitter diffuses across the cleft, it binds with receptor sites on another neuron, initiating another action potential. This process is repeated and a chain reaction occurs exciting many neurons in the process.

^Top

Regulation of Neurotransmitter and Receptor Interaction

Once a neurotransmitter has fulfilled its function of stimulating a receptor, it is important that it is removed from the cleft. This accomplished primarily, by 2 processes. Enzymatic degradation (deactivation) occurs when a specific enzyme changes the neurotransmitter so that it will no longer be recognized by the receptor. MAO is one such enzyme. MAO inhibitors (MAOI), such as Nardil, are antidepressants that work by preventing MAO from deactivating the neurotransmitters. Another method is re-uptake, whereby a structure that functions as a pump recycles the neurotransmitter, removing it from the cleft. Most antidepressants work by blocking this re-uptake structure.

^Top

Utilizing Neurotransmitter-Receptor Systems as Targets for Drugs

Each of the components involved in neural functioning creates a potential target for therapeutic drugs. Our increasing knowledge has resulted in achievements that have benefited patients in two primary ways. Firstly, drugs have been developed that are much more specific in their actions. For example, drugs such as olanzapine and risperidone act more specifically on particular receptors therefore greatly minimizing the unpleasant side effects associated with conventional drugs such as haloperidol. The second benefit has resulted from developing drugs that precisely target newly identified receptors.

As discussed earlier, the re-uptake apparatus is a site of action for many antidepressants. Antipsychotic drugs act primarily at receptors. There are several receptor sites specifically for dopamine, which are classified into categories based on structural, pharmacological, and functional characteristics. The main target of the classic antipsychotic drugs is the D2 dopamine receptor. New research has identified the D4 dopamine receptor, which may have unique functions such as regulating the production of dopamine.

The D4 receptor is of interest because it may be a site of action of clozapine. It is important because of its ability to readily bind with this antipsychotic drug, compared with the other dopamine receptors, without producing extrapyramidal symptoms (EPS) such dystonia (severe muscle spasms), tremors, lethargy, etc. Although clozapine binds to many well known receptors (dopamine, serotonin, cholinergic, adrenergic), researchers have speculated that its D4 activity may impact its unique therapeutic characteristics.

Consequently, efforts have been made to identify drugs that act exclusively on the D4 receptor. Currently, several MIRECC researchers are studying new compounds that target the dopamine D4 receptor site specifically, using sophisticated animal experiments. Preliminary results suggest that they may be effective for both positive (i.e. hallucinations) and negative (i.e. withdrawal) symptoms of psychotic illnesses without the usual side effects such as movement disorders (tardive dyskinesia), seizures, and sedation. We look forward to reporting results as they become available.

^Top