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Memory and Acetylcholine
by Brad Chase
Acetylcholine, an important neurotransmitter in the brain is also important to our ability to form
new memories. Find out how acetylcholine helps the brain to hold on to new memories.
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What is Acetylcholine?
Acetylcholine is an important neurotransmitter in the nervous system. It is found in both
peripheral and central nervous systems as well as in the cardiovascular and neuromuscular
systems.
While acetylcholine activates muscles and seems to produce predominantly excitatory responses
in the peripheral nervous system, it is mainly a neuromodulator in the central nervous system. As
a neuromodulator, acetylcholine helps sustain attention by enhancing sensory perception while
we are awake. While we are asleep, it promotes the REM (rapid eye movement) stage of sleep.
The acetylcholine pathways in the brain represents areas where there are high concentrations of
the neurotransmitters as well as the cholinergic nerves that help transmits signals mediated by it.
These pathways involved usually terminate at or pass through the cortex and hippocampus, areas
of the brain involved in attention, learning and memory…
Acetylcholine is synthesized in nerve cells making up the cholinergic pathway especially those
found in the basal forebrain. The neurotransmitter is produced from choline and acetyl CoA in a
reactive step catalyzed by the enzyme, choline acetyltransferase.
Another enzyme, acetylcholinesterase, found in the synapses between nerve cells is responsible
for breaking down acetylcholine into choline and acetate.
Some neurodegenerative diseases including Alzheimer’s disease involve damage to the
acetylcholine-producing cells in the basal forebrain. The resulting reduction in acetylcholine
production is believed to contribute to memory impairments.
To improve acetylcholine activity in that area of the brain, a group of drugs known as
cholinesterase inhibitors are usually prescribed. These drugs act by blocking the actions of the
enzyme, acetylcholinesterase, thus allowing acetylcholine to act longer at the synapses between
cells.
Cholinesterase inhibitors are commonly used to improve memory in people suffering from mild
dementia.
How Acetylcholine Affects Memory
The Paradoxical Effects of Acetylcholine on Cholinergic Neurons
For a long while, scientists have known that the cholinergic pathway is involved in the memory
and learning. The prime example of this involvement is seen with scopolamine which is known
to block muscarinic subtype of acetylcholine receptors.
Those given scopolamine often have short-term memory loss and cannot recall events while they
are under the influence of the drug.
Other experiments have demonstrated the flip side of this observation: that acetylcholine and
drugs that bind to its receptors to mimic its effect in the cortical neurons can enhance
memory.(One of these types of drugs is called physostigmine).
Once bound to these receptors, acetylcholine and cholinergic agonists that mimic it cause
membrane depolarization by reducing the potassium ion potential of membranes. This causes an
effect known as “suppression of adaptation” in the neurons and it can improve memory
functions…
Why does this work? Acetylcholine suppresses signal transmission in the hippocampus, and
actually prevents the retrieval of old memories from interfering with the making of new
memories.
Therefore, acetylcholine serves a very important function by clearly separating the encoding and
retrieval of memories. This allows for no interference between memories, and for the separation
of memories into clear segments that can be easily retrieved later.
Acetylcholine and SK Channels
In a study published in the journal, Neuron, researchers from the University of Bristol were able
to find a missing link which provides a deeper insight into our acetylcholine improves memory
and slows down cognitive decline.
One of the ways acetylcholine contributes to learning and memory is through increasing the
activity of NMDA (N-methyl-D-aspartate) receptors in the brain.
Acetylcholine does this by blocking proteins of the SK channels which normally inhibit NMDA
receptors.
There are 4 SK channels (small conductance calcium-activated potassium channels) and they are
known to regulate the hyperpolarization of neurons in the brain. Because they also influence
synaptic plasticity, SK channels affect memory and learning.
SK channels block the normal functioning of NMDA receptors and, therefore, interfere with the
ability of neurons to modulate signal transmission. This action limits the encoding of memories
in the brain.
The Bristol study found out that acetylcholine can lift this blockade caused by SK channels.
By developing drugs that target and block the SK channels, it is possible to improve memory and
learning without directly increasing acetylcholine production in the brain.
Drugs that target cholinergic pathway may increase acetylcholine synthesis, activate
acetylcholine receptors and/or block SK channels.
Studies on Acetylcholine and Memory
Martinez and Kesner, 1991
On Acetylcholine and its Role on Memory Formation
Abstract
This study was performed in the biological perspective, where lab rats were used to test the role
that a neurotransmitter has in the formation of memory.
Aim
To see the role that acetylcholine has on memory formation.
Method
The lab rats were put under three different controls:
1. Rats were injected with scopolamine (drug), which is known to block acetylcholine
receptor proteins on the post-synaptic neurones. This means that acetylcholine, a hormone
expected to help form memories cannot travel from one neuron to another, i.e. no nerve impulse
is sent across neurones.
2. Rats were injected with physostigmine, a drug that is antagonistic towards
acetylcholinesterase. Cholinesterase (or acetylcholinesterase) is what cleans up the acetylcholine
from receptor proteins on the post-synaptic neurones, returning the neurones to their "resting
potential", where no nerve impulse is being sent. Physostigmine blocks cholinesterase which
prevents this "cleaning-up" of acetylcholine.
3. Rats were not injected or altered in any form at all.
Procedure:
1. All rats were placed in the maze individually and completed the maze (maze had reward of
food at the end)
2. Rats were given their respective treatments (see 3 groups above)
3. Rats were placed in maze individually and time taken to complete maze was measured
Results
- Condition 1 (rats that were injected with scopolamine) took the longest to complete the maze
- Condition 2 (rats that were injected with physostigmine) took the shorted amount of time to
complete the maze
- Condition 3 (rats with no treatment) had maze-completion times between the condition 1 and
condition 2 rats
Discussion
- Scopolamine has the effect of preventing or slowing down the process of memory formation.
This can be concluded because the rats given scopolamine took the longest to complete their
mazes. Acetylcholine is involved in memory formation because scopolamine is what blocks
acetylcholine receptors.
- Acetylcholine is involved in memory formation because the condition 2 rats were quickest in
completing the maze: their injection of physostigmine prevented the removal of acetylcholine
from the receptor proteins of the post-synaptic neurons.
- The more acetylcholine is available, the more productive memory formation is. This can be
concluded because condition 3 rats were in-between the other two conditions in terms of mazecompletion time.
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Acetylcholine and Memory
Directions: Read the article, and then answer the questions which follow. Question number 9
will require you to answer on a separate sheet of paper.
1.
What are the primary functions of the neurotransmitter Acetylcholine?
2.
What disease may a lack of Acetylcholine production cause? Why?
3.
How can memory in dementia patients be improved?
4.
Scopolamine is a drug which blocks Acetylcholine receptor sites. Why would this have
an effect on memory?
5.
What effect would physostigmine have on memory? Why?
6.
What role dose Acetylcholine play in memory functioning?
7.
Why was Martinez and Kesner’s study conducted on rats and not humans? What
principle of biological analysis states that we can apply these results to humans?
8.
What are the strengths and limitations of this study (Think CEGM)
9.
Write a ½ - 1 page (font 12, double spaced) response to the following question:
Using evidence from the article, discuss how Martinez and Kesner’s findings support
the idea that acetylcholine effects memory formation. Be sure to define all of your
psychology words (IE: Neurotransmission, Acetylcholine, etc).
Be sure to cite evidence from the article and from the studies.
Answers should be written in the format of an 8-mark question. (Three Paragraphs)