Essential Cell Biology 5th edition

Ion Channels and Nerve Cell Signaling
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stimulate the neuron, while others inhibit it. The motor neuron has to
combine all of the information it receives and react, either by stimulating
a muscle to contract or by remaining quiet.
This task of computing an appropriate output from a babble of inputs is
achieved by a complicated interplay between different types of ion channels
in the neuron’s plasma membrane. Each of the hundreds of types of
neurons in the brain has its own characteristic set of receptors and ion
channels that enables the cell to respond in a particular way to a certain
set of inputs and thus to perform its specialized task.
Ion channels are thus critical components of the machinery that enables
us to act, think, feel, speak, learn, and remember. Given that these
channels operate within neuronal circuits that are dauntingly complex,
will we ever be able to deeply understand the molecular mechanisms
that direct the complex behaviors of organisms such as ourselves?
Although cracking this problem in humans is still far in the future, we
now have increasingly powerful ways to study the neural circuits—and
molecules—that underlie behavior in experimental animals. One of the
most promising techniques makes use of a different type of ion channel,
a light-gated ion channel borrowed from unicellular algae, as we now
discuss.
Light-gated Ion Channels Can Be Used to Transiently
Activate or Inactivate Neurons in Living Animals
Photosynthetic green algae use light-gated channels to sense and navigate
toward sunlight. In response to blue light, one of these channels—called
channelrhodopsin—allows Na + to flow into the cell. This depolarizes the
plasma membrane and, ultimately, modulates the beating of the flagella
that the organism uses to swim. Although these channels are peculiar to
unicellular green algae, they function perfectly well when they are artificially
transferred into other cell types, thereby rendering the recipient
cells responsive to light.
Because nerve cells are also activated by a depolarizing influx of Na + , as
we have discussed (see Figure 12–38), channelrhodopsin can be used to
manipulate the activity of neurons and neural circuits—including those in
living animals. In one particularly stunning experiment, the channelrhodopsin
gene was introduced into a select subpopulation of neurons in the
mouse hypothalamus—a brain region involved in many functions, including
aggression. The activity of these neurons could then be controlled by
light that was provided by a thin, optic fiber implanted in the animal’s
brain. When the channels were illuminated, the mouse would launch an
attack on any object in its path—including other mice or, in one comical
instance, an inflated rubber glove. When the light was switched off, the
neurons once again fell silent, and the mouse’s behavior would immediately
return to normal (Figure 12–44 and Movie 12.14).
Because the approach relies on a light-gated channel that is introduced
into cells by genetic engineering techniques (discussed in Chapter 10),
the method has been dubbed optogenetics. This tool is revolutionizing
neurobiology, allowing investigators to dissect the neural circuits that
govern even the most complex behaviors in a variety of experimental
animals, from fruit flies to monkeys. But its implications extend beyond
the laboratory. As genetic studies continue to identify genes associated
with various human neurological and psychiatric disorders, the ability
to exploit light-gated ion channels to study where and how these genes
function in model organisms promises to greatly advance our understanding
of the molecular and cellular basis of our own behavior.