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Neuron
Synapse
Synapse Under Electron Microscope
Presynaptic
Terminal
Synapse
Postsynaptic membrane
Best Known Small Molecule
Neurotransmitter Groups
• http://www.youtube.com/watch?v=7irX53PZuAE go to 1:11
• (ignore the Vietnamese subtitles !  )
• Acetylcholine (ACh)
• Monoamines
• Norepinephrine (NE)
• Dopamine (DA)
These 3 are “catecholamines”
• Epinephrine (E)
• Serotonin (5HT) (an “indoleamine”)
• Amino Acids
•
•
•
•
Glutamate
GABA
Aspartate
Glycine
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Large molecules
Large Molecule Transmitters
Small transmitters synthesized
right in synaptic ending
• Neuropeptides (small proteins)
•
•
•
•
•
Pituitary peptides – like LH
Hypothalamic peptides – like oxytocin
Brain-gut peptides- like insulin
Opiate peptides – like endorphins
Miscellaneous others
Synapse
Unconventional Transmitters
Presynaptic
Terminal
• Unconventional in their chemistry, their release and
their effects
• Soluble Gases
• Nitric Oxide (NO) – causes blood vessels to dilate
• Carbon Monoxide (CO)
• Endocannabinoids
Synapse
• Anandamide
Postsynaptic membrane
Autoreceptors are presynaptic receptors!
• Neurons using different neurotransmitters as their
messenger are not evenly distributed throughout the
nervous system.
• Most neurotransmitters serve as messengers just in
particular areas or systems, and thus are related to
particular behaviors or functions.
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• ACh: parasympathetic neurons; motor neurons; many
cortical neurons
• NE: sympathetic n.s.; reticular formation;
hypothalamus; limbic system
• 5HT: limbic system; sleep system; pain suppression
system
• DA: basal ganglia; reward system; prefrontal cortex;
hypothalamus-pituitary
Transmitter
Precursor
Comes from:
Acetylcholine
Choline or lecithin Cauliflower, milk
Yolk, liver, soy,
peanuts, butter
Catecholamines
Phenylalanine or
tyrosine
Proteins, almonds,
avocados, bananas,
seeds
Serotonin
Tryptophan
Poultry, dairy, beef,
soy, peanuts, barley,
brown rice
Released Transmitter
Removed or Cleaned Up By:
• 1. Reuptake back into the presynaptic ending and/or
• 2. enzymatic breakdown
Presynaptic membrane contains proteins that
serve as transporters.
Excess transmitter inside neuron also broken down by enzymes.
The Action of Neurotransmitters
The effect produced at the synapse depends not only on the
type of neurotransmitter but also the type of receptor.
We now know each neurotransmitter fits multiple types of
receptors – e.g. at least 5 types of DA receptors and 6 types
of 5HT receptors have been discovered.
Example: ACh
• 2 types of ACh receptors:
• Nicotinic – e.g. motor neuron to muscle fibers
• Muscarinic – e.g. parasympathetic nerves to organs and
glands
• Different drugs bind to each type of receptor
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Drug Actions
Psychoactive drugs act by affecting 1 or more of the steps of chemical
transmission (synthesis, storage, release, receptor binding, breakdown or
reuptake)
Some drugs enhance transmitter action (“agonists”)
Some interfere with transmitter action (“antagonist”)
 AGONIST examples:
 Narcotic pain relievers fit and
activate opiate receptors
mimicking the action of
normal endorphin.
 Nicotine fits into & stimulates
ACh receptor sites, arousing
the cortex like ACh
 ANTAGONIST examples:
 Haldol blocks DA receptors
in schizos
 Naloxone blocks opiate
receptors
 Atropine blocks muscarinic
ACh receptors & curare or
botox block nicotinic ACh
receptors
L-dopa
MAOI
Reserpine
Amphet
• For example, the first drug we’ll encounter in our discussion of
Parkinson’s disease, l-dopa, affects the first step (synthesis of
neurotransmitter).
• L-dopa is a “precursor” or ingredient DA neurons can use to make DA.
Botox
Nicotine, endorphins
Cocaine
Parkinson’s Disease
THC
Antipsychoticsl
• About 1-2/100 of those over 50 have PD (about 1,000,000
total in US)
• Progressive loss of DA cells in substantia nigra which
normally send messages to basal ganglia
• We all gradually lose neurons but those with PD may have
accelerated loss (70% or more gone)
• Symptoms: Difficulty initiating movements, slow
movements, muscle rigidity & tremors-at-rest
• Also cognitive slowing & depression in many
Substantia nigra of midbrain contains the cell bodies of DA
neurons whose axons go to the basal ganglia & other forebrain
areas
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Basal Ganglia or “Striatum”
PD vs normal SN
Normal # of DA cells vs PD
Possible Causes
• Early Parkinson’s disease – strong genetic link (weak
association in late-life form of PD- identical twins not more
concordant than frats)
• Environmental toxin of some sort (herbicides, pesticides):
IA, MN, ND, SD, & NEB have highest rates in US!
• Head injury may be associated with up to 11 fold increase in
risk & earlier age of onset.
• Caffeine or nicotine use may decrease your risk
Or basal ganglia
In midbrain
Bundle of axons
from midbrain to
basal ganglia is
called the
nigrostriatal
pathway
Treatments
• Increase DA production with l-dopa
• L-dopa is having an “agonist” action
• Problems: l-dopa induced side effects & loss of
effectiveness over time
• Variety of new meds being tried
• DA agonists, antioxidants, nerve growth factors
•When Drug Therapy Fails
• When drug effectiveness declines, experimental
options include:
• Deep brain (thalamic or subthalamic) stimulation to block
activity in these same regions
• http://www.youtube.com/watch?v=WYDoHmg9ECI
• Lesion other parts of motor control system
• Pallidotomy ; thalamotomy (Michael J. Fox)
• Transplant of DA producing cells into brain
http://www.youtube.com/watch?v=puJCjUsgq7o
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