Biomedical Engineering Reference
In-Depth Information
Alpha Function
2
1
0
0
2
4
6
8
10
12
Bi−exponential
2
1
0
0
2
4
6
8
10
12
time (msec)
Figure 6.2:
Alpha function and bi-exponential model for synaptic conductance.
6.7 THEMANYMECHANISMS OF DISEASES ANDDRUGS
The effect of many drugs and diseases in the brain can be generalized as either decreasing or increasing
the effect that the pre-synaptic potential has on the post-synaptic potential. There are, however, many
methods by which these effects may be achieved. Below are five different mechanisms.
1. If the neurotransmitter uptake mechanism is not present due to a mutation or is blocked by a drug,
the neurotransmitter will not be cleared and continue to have an impact. Alternatively, the uptake
could be too effective and the neurotransmitter will be cleared before it can have its full effect.
2. If drugs or mutations either block
Ca
2
+
channels or bind to
Ca
2
+
ions (a buffer) in the pre-synapse,
the mechanism for vesicle release will be compromised. The impact is that no neurotransmitter
will be released into the cleft.
3. The structure of the neurotransmitter itself could be compromised either by a mutation or by a
drug that binds to the neurotransmitter before it can reach the post-synapse.
4. The post-synaptic channel could be compromised either by disallowing neurotransmitter binding
(e.g., docking proteins on the
I
syn
channel are mutated) or by a change in the channel itself that
limits the passage of ions. A more complicated target for drugs or diseases is to alter a second
messenger which relays the message of neurotransmitter binding.
5. Diseases and drugs can induce long-term changes on the number of vesicles available, number of
neurotransmitters per vesicle, or number of post-synaptic binding sites.These changes may impact
availability and saturation.
Most drugs have more than one effect because the same drug can impact different regions of the brain in
different ways. Furthermore, the most powerful drugs often act throughmore than one of the mechanisms
on the list above.
6.8 SYNAPTIC PLASTICITY ANDMEMORY
In 1949, Donald Hebb published a topic,
The Organization of Behavior
, which introduced the idea that
the “strength” of a synapse could change over time in response to external factors. His idea was that
local
