Memories, Magic, & a Major Addiction

What causes memory loss in patients with Alzheimer’s disease? Why did witches once believe that they
could fl y? Why is it so hard to stop smoking? The answers to
these questions can be found by understanding the function of
acetylcholine, a neurotransmitter chemical that exists almost
everywhere in nature. It has been found in both uni- and multicellular organisms, including in a strain of Pseudomonas fl uorescens
isolated from the juice of fermenting cucumbers, as well as in
the blue-green algae, Oscillatoria agardhii, where it may be involved
with photosynthesis. Acetylcholine stimulates silk production
in spiders and limb regeneration in salamanders. In humans,
acetylcholine enables movement by stimulating the muscles to
contract, and it plays an important role in the action of the
parasympathetic and sympathetic nervous systems, which are
part of the autonomic nervous system (ANS). The ANS maintains homeostasis, or a balance of forces or equilibrium, for
your entire body. Among other functions, it controls the rate at
which your heart beats, how fast you breathe, how much saliva
your mouth is making, the rate of movement of material in
your gut, your ability to initiate urination, how much you are
perspiring, the size of your pupils, and the degree of visible
sexual excitation you might experience. Within the human brain
are numerous acetylcholine pathways that infl uence the function of the cortex, hippocampus, and many other regions (see
Fig. 2–1). Within these various regions, the actions of acetylcholine allow you to learn and remember, to regulate your attention and mood, and to control how well you can move. Thus,
anything that affects the function of acetylcholine neurons has
the potential to affect all of these brain and body functions.
That “anything” could be a certain drug or a disease.
Sometimes we can learn much about the role of a particular
neurotransmitter system by investigating what happens when it
is injured or diseased. In the brains of people with Alzheimer’s
disease, for example, acetylcholine neurons that project into the
hippocampus and cortex very slowly die. The effects of this
neuronal death have been the subject of research in my laboratory for more than 25 years. The loss of normal acetylcholine
function in the cortex may be why patients with Alzheimer’s
M E M O R I E S , M A G I C , & A M A J O R A D D I C T I O N s 2 5
Corpus collosum
Figure 2–1. Schematic anatomy of neurotransmitter systems. A. Acetylcholine
neurons mostly originate within the basal forebrain region and project to the
cortex, hippocampus, amygdala, and olfactory bulbs. Ad. Adenosine can be released
by virtually every cell in the brain. CB. Cannabinoid neurons are scattered
throughout the brain and cerebellum. D. Dopamine neurons originate within the
midbrain project into the basal ganglia and frontal lobes. G. GABA neurons are
found throughout the brain as small inter-neurons and also project from one brain
region to another. H. Histamine neurons mostly lie near the bottom of the brain
and project diffusely into most brain regions. N. Norepinephrine neurons originate
within the locus coeruleus in the floor of the 4th ventricle, under the cerebellum,
and project virtually everywhere in the brain. O. Orexin neurons that project onto
acetylcholine, dopamine, histamine, serotonin, and norepinephrine neurons to
promote wakefulness. P. Peptide-containing neurons tend to be diffusely scattered
although there are notable exceptions. S. Serotonin neurons originate with a scattered group of nuclei that lie along the midline of the brainstem and projectdownward into the spinal cord and upward into all regions of the brain. Glutamate
neurons are found everywhere in the brain; they are not represented in the fi gure.
disease have diffi culty paying attention to their environment.
The loss of acetylcholine projections to the amygdala, part of
the brain’s limbic system, may underlie the emotional instability,
such as irritability and paranoia, that is sometimes observed in
these patients. And the loss of acetylcholine projections into
the hippocampus may underlie the profoundly debilitating
memory loss that is the major hallmark of this disease.
Let me illustrate the effect of at least one of these losses by
fi rst describing the role of acetylcholine in the cortex of a
normal brain (yours). Imagine that, using an electroencephalogram or EEG, I have attached some electrodes to the front half
of your head to record the electrical activity occurring inside
your brain. Next, I calmly inform you that as soon as I ring a
bell (at the point in time shown by the number 1 in Fig. 2–2) a
1 2 3 4
Bell rings
Bell rings
Figure 2–2. Electroencephalogram recorded over the frontal lobes showing the
presence of an “anticipation wave” with an intact acetylcholine system (labeled pre)
and without a functioning acetylcholine system (labeled post). The sharp vertical
spikes are associated with a bell ringing at the beginning and end of the recording,masked gunman will enter the room and start shooting. [You
must also believe that I’m telling the truth for this to work.]
Okay, now I ring the bell. Take a look at the EEG recording
labeled “pre” in the fi gure. It shows that an electrical wave
quickly appears within the frontal lobes of your brain that
began as soon as I rang the bell. The bell ringing causes those
sharp spikes prior to the formation of the wave. This electrical
pattern, also known as an EEG wave, will continue to live in
your brain until one of two things happens: either someone
runs into the room with a gun (at the point in time shown by
the number 3) or the bell rings again and you decide nothing is
going to happen after all. At that point, the EEG wave will
disappear. This pre wave indicates that you were paying close
attention to what you thought was about to happen. It is an
expression of your brain experiencing anticipation .

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