What are inhibitory and excitatory impulses?

Quick Answer
Two types of processes occur in neurons: those that excite the cell to react to a stimulus and those that inhibit the cell. Cells receive many impulses of both types and must integrate the incoming messages to determine what response should be produced.
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Introduction

An unstimulated neuron —one that is neither receiving nor transmitting an impulse—maintains a difference in ions on either side of its cell membrane. While many positively charged potassium (K+) ions are present within the cytoplasm of a cell, proteins and other large molecules located there carry more numerous negative charges, making a negative net charge inside the membrane. Large numbers of positively charged sodium ions (Na+) are located on the outside of the cell in the intercellular space, giving it a net positive charge. Thus, in a resting neuron, there is a positive charge on the outside of the cell membrane and a negative charge on the inside. This charge difference is called the resting membrane potential. It is usually expressed as 70 millivolts, meaning that the inside of the cell is seventy thousandths of a volt more electrically negative than the outside.

The resting membrane potential is maintained by active transport of ions across the cell membrane. Sodium and potassium ions move across the membrane by diffusion, with sodium leaking into the cell and potassium leaking out. These ions are said to be moving down their concentration gradients, going from an area of higher concentration of each ion to an area of lower ion concentration. Such movement occurs passively, without the addition of energy by the cell. If this movement were allowed to continue uninterrupted, the resting potential would be lost fairly quickly, as the ions would reach equilibrium where they would be at the same concentration on both sides of the membrane. This is prevented from happening by the active transport process of the sodium-potassium pump. Active transport is a means of moving materials across the cell membrane from an area of lower concentration to an area of higher concentration. It cannot occur by diffusion, but requires the input of energy from the cell, released by breakage of a molecule by adenosine triphosphate (ATP), the energy currency of the cell. The sodium-potassium pump is a protein that spans the cell membrane and acts as a channel through which both sodium and potassium are pushed against their concentration gradients by the cell’s energy. Much of the ATP made by every cell is used to run this pump and maintain the resting potential, not only in neurons but in all other cells as well. The sodium-potassium pump moves two potassium ions into the cell and three sodium ions out of the cell for each ATP molecule broken.

Process of Information Transmission

The electrical difference between the sides of the cell membrane is particularly important in neurons, since it is through a change in this difference that a message is passed along the surface of a single neuron. In this information transmission, an electrical impulse passes down an excited, activated neuron’s axon (the single fiberlike extension of a neuron that carries information away from the cell body toward the next cell in a pathway) to the “output” end of the cell, the axon terminal. There the electrical impulse causes tiny vesicles or sacs filled with a chemical called a neurotransmitter to move to the cell membrane and fuse with it, emptying the contents of the vesicles into the space between cells, which is called a synapse. The cell that releases its chemical messengers at the synapse is the presynaptic neuron, and the cell that receives the message is the postysynaptic neuron. The message of the neurotransmitter is received by the second cell when the chemical binds to a protein receptor on the surface of the postsynaptic cell, usually on a dendrite (a branching extension of a neuron through which information enters the cell) or the cell body. This message may be interpreted as an excitatory stimulus or as an inhibitory stimulus. Either kind of stimulus causes a change in the properties of the receptor and of the postsynaptic cell to which it belongs, generally by changing the permeability of the cell’s membrane.

Excitatory Stimulation

When the stimulus is excitatory, the charge difference on the two sides of the membrane is at first lowered. A threshold level of electrical charge is reached, about 55 millivolts, and an action potential—a rapid change in electrical charges on a neuron’s cell membrane, with depolarization followed by repolarization, leading to a nerve impulse moving down an axon—is generated, followed by the firing of the neuron. A self-propagating wave of depolarization results from an excitatory stimulus that causes the neuron to reach threshold. Depolarization can be defined as a shift in ions and electrical charges across a cell membrane, causing loss of resting membrane potential and bringing the cell closer to the action potential. Special proteins called sodium gates open in the cell membrane, forming a channel that allows sodium ions from outside the cell to flow rapidly down their concentration gradient into the cell’s interior. As the net charge inside the cell becomes positive, the charge outside the cell becomes negative. There is a sharp rise, then a decline of the charge within the cell, called a spike, that reaches as high as 35 millivolts with the inflow of sodium ions. The action potential that results from this entry of ions acts according to the all-or-none law. A neuron will either reach the threshold and respond completely or will not reach the threshold and will not respond at all; there is no partial response. After sodium ions rush into the cell, the sodium gates close and the potassium gates open, allowing potassium ions to flow out of the cell, restoring the negative charge inside the cell. The sodium-potassium pump then must reestablish the relative ion concentrations across the membrane, necessitating a period in which the cell cannot respond to an excitatory impulse, called the absolute refractory period.

Inhibitory Stimulation

When the message imparted by the neurotransmitter is inhibitory, a different response occurs in the postsynaptic neuron. Instead of depolarizing the membrane by changing the membrane potential from 70 to 55 millivolts, the inhibitory message causes hyperpolarization, raising the difference in charge between the inside and outside of the membrane. The interior of the cell becomes more negative, reaching 80 millivolts or more, thus inhibiting the generation of an action potential in that cell. The inhibitory impulses help prevent the chaos that would result if excitatory impulses were firing with nothing to regulate the chain of stimulation. They also help fine-tune sensory perceptions; they can make sensations more exact and sensitive by blocking the firing of neurons around a specific point, such as the precise place on the skin that a touch is felt.

Role of Neurotransmitters

Transmission of information in the form of electrochemical messages is the job of the entire nervous system. This information movement can be understood through the study of neurotransmitters. Different parts of the nervous system show the action of many different chemicals that either excite or inhibit the passage of information by means of generation of an action potential in a postsynaptic neuron. The response of the postsynaptic neuron that leads to firing of an action potential is called an excitatory postsynaptic potential (EPSP). If such firing is instead prevented, the response is called an inhibitory postsynaptic potential (IPSP). Together these are referred to as postsynaptic potentials (PSPs).

An important aspect of the generation of these excitatory and inhibitory postsynaptic potentials is that they may be cumulative, with numerous different presynaptic cells sending different messages to the same postsynaptic cell. The messages may all be the same, leading to summation of the information. This would allow a neuron to fire even if each individual excitatory PSP is unable to reach threshold by itself, since the effect can be additive over time (temporal summation, with several messages received from the same cell in a short time) or over space (spatial summation, with several axons sending impulses at the same time). Inhibitory PSPs also have a cumulative effect, but the result of several of these would be to make it harder for the neuron to reach threshold and the development of an action potential. Alternatively, the messages coming into a neuron from several different presynaptic cells might be conflicting, some excitatory and others inhibitory. In this case, the postsynaptic cell would act like a computer and integrate the information from all presynaptic cells to determine whether the net result allows threshold to be reached. If threshold is achieved, the cell fires and a nerve impulse is generated. If threshold is not achieved, the cell does not fire, but it will be brought closer to the action potential by reduction of the voltage difference across the membrane. Since development of an action potential is an all-or-none response, no matter how the threshold is reached the same level of information passage will result. Behavior of an individual organism thus results from the actions of each separate neuron in determining the net balance of incoming information and determining whether an action potential is reached.

Four Types of Neurotransmitters

Neurotransmitters are the chemical messengers that act in the nervous system to excite or inhibit the postsynaptic neurons. At least four neurotransmitters have been studied in detail: acetylcholine, norepinephrine, dopamine, and serotonin. Other transmitter substances have also been examined, such as the amino acids glutamate, aspartate, gamma-aminobutyric acid (GABA), and glucine. From these studies it has been shown that the interpretation of the message lies within the postsynaptic neuron, since the same neurotransmitter may be either inhibitory or excitatory, depending on the tissues in which it is found.

Acetylcholine, for example, is found in both the brain and the peripheral nervous system. Since the peripheral nerves are more accessible to study, more is known about the activities of acetylcholine there than in the brain. Two types of cholinergic receptors (those for acetylcholine) are found in the peripheral nervous system, called muscarinic and nicotinic receptors. Acetylcholine has an excitatory effect on nicotinic receptors, as in causing the contraction of skeletal muscles, but an inhibitory effect on the muscarinic receptors, as in slowing the heartbeat. This neurotransmitter is also believed to cause excitation of tissues in the brain and in autonomic ganglia. In the cerebral cortex, acetylcholine is thought to be involved in cognitive processes, while in the hippocampus it appears to be linked to memory; in the amygdala, it seems to help control emotions.

Norepinephrine, dopamine, and serotonin are monoamines, neurotransmitters that act by means of a second messenger system to produce a postsynaptic response. In this system, cyclic adenosine monophosphate (cAMP) is produced within the cell when a neurotransmitter binds to its receptor, and the cAMP opens the ion channels (a pathway through the cell membrane, controlled by gates and used for passage of ions during electrical impulse generation) that cause excitation or inhibition to be produced. This causes a longer-lasting effect on the postsynaptic neuron, and the neurotransmitters that use this system are apparently involved in long-term behaviors that include memory, emotion, and motivation.

Like acetylcholine, norepinephrine is formed in both the brain and the peripheral nervous tissues, while dopamine and serotonin have been localized to brain tissues only. In the peripheral nervous system, norepinephrine interacts with two kinds of adrenergic receptors on muscle cells, the alpha and beta receptors. Alpha receptors are found on blood-vessel cells, where an excitatory effect results from binding norepinephrine. Beta receptors are seen in the lungs, heart, and intestines, tissues in which norepinephrine has different effects. Binding of the neurotransmitter to beta receptors in cardiac tissue causes excitation, while binding to lung and intestinal receptors inhibits their activities. It is still unclear how the same kind of beta receptor can have different responses in different tissues to the same chemical message. In the brain, a diffuse system of neurons produces norepinephrine, so its effects are widespread, affecting emotion, learning, memory, and wakefulness.

Dopamine is produced by cells found in the substantia nigra, the hypothalamus, and the ventral tegmental areas of the brain, where abnormal levels cause profound behavioral disorders. The related monoamine, serotonin, has distribution and behavioral effects similar to those of norepinephrine. In the upper regions of the brain, the presence of serotonin stimulates higher sensory states and sleep, while reduced levels are associated with severe depression. Since most of the effects of raised or lowered quantities of these mood-altering neurotransmitters seem to cause depression and psychoses, their study has been of great interest. Many of the drugs that have been found to elevate mood clinically act by enhancing or interfering with the action of these neurotransmitters. Through their control of excitation and inhibition of the neural impulse, neurotransmitters control an incredibly complex system of neural interconnections and neuroneffector cell interactions. If this system were under less strict control, behavioral chaos would result, as it does in certain psychiatric and psychological disorders. Applications of knowledge in this area of behavioral research may eventually lead to the ability to control such disorders chemically.

Research on Squid Axons

Studies on the mechanisms of action of the neuron have been ongoing since the 1930s in giant axons of the squid nervous system. Discovered by J. Z. Young, these axons are so large that a single cell can be dissected out and examined in the laboratory. Much of what is known about the human nervous system’s response to excitatory and inhibitory stimuli comes from pioneering work done on these marine mollusks. K. C. Cole and coworkers developed a voltage clamp system of electronic feedback to maintain a constant membrane potential at a chosen voltage level. The axons are penetrated by tiny electrodes and used to measure how electrical transmission occurs in different areas of the neuron across the cell membrane. A later development is the whole cell patch recording, used to examine a small area of the neuron’s cell membrane with ion channels more or less intact. A classic series of papers published by Andrew Huxley and Alan Hodgkin in 1952 explained the regulation of electrical conductance along the neural membrane, including movement of ions across the sodium and potassium channels after excitatory stimulation. Huxley and Hodgkin received a Nobel Prize in 1963 for their work on squid axons.

Effect of Drugs and Transmitter Substances

Another way that excitatory and inhibitory responses are studied is with the muscarinic and nicotinic cholinergic receptors, which are inhibited from working by the actions of the drugs muscarine (from poisonous mushrooms) and nicotine (from tobacco). The drugs mimic the action of acetylcholine on these different kinds of molecules on target tissues. Less is known about the effects of acetylcholine on brain tissues, but this area of research is getting widespread attention because of the evidence that the neurotransmitter appears to be related to the development of Alzheimer’s disease. Acetylcholine deficiency in the nucleus basilis is a general finding at autopsy in patients with this disease of aging, which is accompanied by loss of memory and intellectual ability and by profound personality changes.

Behavioral disturbances, including depression and mania, are also caused by abnormally high or low concentrations of norepinephrine in the brain. Some of the drugs used to treat depression are able to do so by controlling the levels of norepinephrine and thus the stimulation of excitatory and inhibitory pathways in the brain. Dopamine is associated with Parkinson’s disease, in which there is an abnormally low level in the substantia nigra of the brain, and the condition can be treated by increasing the amount of dopamine and by slowing its breakdown in this region. In addition, an abnormally high level of dopamine in other parts of the brain has been associated with causing schizophrenia, suggested by the fact that drugs which block the actions of dopamine also reduce the behavioral aberrations seen in this disease. Since brains of patients with these diseases are studied at autopsy and not during the actions that cause the behaviors, it is difficult to tell what actually occurs at the synapses and whether actions are attributable to inhibition or excitation of particular neurons.

Other transmitter substances include amino acids and neuropeptides, but less information has been gathered on these chemicals, and less is known about their activities in the nervous system and behavior. Glutamate and aspartate are amino acids that are thought to be the main excitatory chemicals in use in the brain, while GABA and glycine are inhibitory. GABA is thought to be the most widespread neurotransmitter in the brain, particularly in functions involving movement. Neuropeptides include endorphins, but the mechanisms by which they act are less well known. It is thought that certain cells are able to produce and release both a neurotransmitter such as dopamine and a neuropeptide, giving the nervous system more versatility and complexity in its decision-making capabilities. Perhaps both excitation and inhibition may be handled by the same cell at different times in its regulation of behavioral activities.

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