Neurochemistry refers to the chemical processes that occur in the brain and nervous system. The fact that one can read this text, remember what has been read, and even breathe during the entire time that these events take place relies on the amazing chemistry that occurs in the human brain and the nerve cells with which it communicates. There are two broad categories of chemistry in nerve systems that are important. The first is the chemistry that generates electrical signals which propagate along nerve cells. The key chemicals involved in these signals are sodium and potassium ions. To see how they give rise to a signal, one must first look at a nerve cell that is at rest.

Like any other cell, a nerve cell has a membrane as its outer “wall.” On the outside of the membrane, the concentration of sodium ions will be relatively high and that of potassium ions will be relatively low. The membrane maintains this concentration gradient by using channels and enzymes. The channels are pores that may be opened or closed by enzymes which are associated with them. Some ion channels allow the movement of sodium ions and others allow potassium ions to cross the membrane. They are also called “gated” channels because they can open and close much like a gate in a fence. The voltage they experience dictates whether the gate is open or closed. Thus, for example, a gated sodium ion channel in a membrane opens at certain voltages to allow sodium ions to pass from regions of high concentration to regions of low concentration.

Active transport mechanisms are also present. Enzymes that span the membrane can actively pump sodium and potassium ions from one side of the membrane to another. When the nerve cell is at rest, these mechanisms maintain a high potassium and low sodium environment inside the cell. Even when it is at rest, a nerve cell is in contact with many other nerve cells. When a neighboring cell passes on a signal to the resting cell, a dramatic change occurs in the ion concentrations. Once the resting nerve cell has received a sufficient signal from a neighbor to surpass a threshold level some of the sodium ion channels near the connection point open and sodium ions flow into the cell. This flow of charge results in an electrical potential that is called the action potential. The action potential does not stay localized, however. Farther down the nerve cell, more sodium ion channels surpass their threshold and open so that the sodium ions flow into them as well. Thus, the action potential moves down the nerve. After the sodium ion gates open, the potassium ion gates also open and potassium ions flow out of the cell. This flow of ions offsets the charge from sodium ions flowing into the cell and the signal has receded in that region (and has moved on).

Once the cell propagates a signal, how does that cell send its signal to a neighbor? This question leads to the second broad category of neurochemistry: the chemistry at the synapse. Nerve cells do not actually touch their neighbors, but rather form a small gap called the synapse. The signal is transferred across this gap by chemicals called neurotransmitters. The communication that occurs across the synapse may either excite or inhibit the action of the neighboring nerve cell. Thus, synapses are further categorized as either excitatory synapses or inhibitory synapses. The cell that is propagating the signal is called the presynaptic cell, and the cell that receives the signal is the postsynaptic cell.

The end of the presynaptic cell contains small vesicles, spherical collections of the same lipid molecules that make up the cell membrane. Inside these vesicles, neurotransmitters exist in high concentrations. When the action potential reaches the end of the presynaptic cell, some of the vesicles merge with the cell membrane and release their contents (a process called exocytosis). The released neurotransmitters experience an immediate concentration gradient. They diffuse away from the release point to counteract the gradient, and in doing this, they cross the synapse and arrive at the neighboring cell. On the postsynaptic cell, there are receptors that are capable of interacting with the neurotransmitters. Once these messenger molecules cross the synapse, they connect with the receptors and the two cells have successfully communicated. The proteins of the receptors are capable of opening sodium gated ion channels, and a new action potential is engaged in the postsynaptic cell.

The remaining step in the process is also a critical one. Somehow the action of the neurotransmitters must cease. If they continue to cross the synapse, or are not removed from the receptors of the postsynaptic cell, they will continue to activate that cell. An overexcited or inhibited nerve cell is not capable of proper function. For example, schizophrenia is a mental disease that is caused by the brain’s inability to eliminate excitatory neurotransmitters. The nerve cells continue firing, even when they need not, and the incorrect brain chemistry results in debilitating symptoms such as auditory hallucinations—hearing voices that are not actually there.

 

Many chemical compounds, some natural and some made by humans, show toxic effects in humans or other animals. Every toxin is harmful, but toxins that target the nervous system have been developed into chemical warfare agents, so the public concern about them is enhanced. Despite the connection with weapons of mass destruction, the most common neurotoxin in society is ethanol, found in alcoholic beverages. Neurons convey signals by manipulating ion concentrations, and neurotoxins reduce their ability to do so. Alcohol does this by essentially overloading the entire cell and hindering its ability to function. Many of the characteristics of alcohol intoxication, such as slurred speech and erratic motion, are the result of improper function of neurons in the brain. As the body metabolizes the alcohol and removes it from the blood, the neurotoxic effects wear off. With large overdoses of alcohol, however, the effects do not wear off, and death due to alcohol poisoning is a dramatic and unfortunately too common manifestation of neurotoxins.

The neurotoxins that are associated with chemical warfare typically operate in a different fashion. A neuron carries a signal as a miniature electric current. Ions carry charges, and when they move across the cell membrane in a specific region of a neuron at a rapid rate they change the electrical potential in that region. The rapid movement of ions migrates along the neuron and propagates an electrical signal. When this signal reaches the end of the neuron, it must somehow trigger a response in the next neuron. In a few cases, neurons are packed closely enough so that the charge associated with the moving action potential directly excites the next neuron. In most cases, the first neuron releases small molecules called neurotransmitters that diffuse across a small gap and interact with the next neuron, triggering its response. Many neurotoxins, including both human-made agents of chemical warfare and natural agents found in venoms and other natural toxins, work by disrupting this communication process.

There are two common mechanisms by which nerve signaling is disrupted. The cell that receives the signal does so when receptors within its membrane interact with the neurotransmitters. Some neurotoxins act by blocking these receptors, making it impossible for them to receive signals. When signaling stops, nerve function is impaired or eliminated and, the neurotoxin has caused its damage. The other key component of interneuron communication is that the neurotransmitters, once they have carried a signal across a synaptic cleft, must be removed. If a “receiving” neuron is continually stimulated because neurotransmitters continue to activate it, the neuron’s function will be impaired, and the neuron may even be killed. There are special enzymes in the synaptic cleft that break down certain neurotransmitters, such as acetylcholine, to end the signaling. Some neurotoxins block the actions of these hydrolytic enzymes, thereby preventing the removal of acetylcholine (or other neurotransmitters), leading to continuous stimulation of the neurons and, ultimately, cell death.