A Continuation of Neurotransmitter Systems

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Biology 463 - Neurobiology

• Topic 7
• A Continuation of Neurotransmitter Systems
• Lange

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Dale's Principle (or Dale's Law) is a rule
attributed to the English neuroscientist Henry
Hallett Dale (We first mentioned him in the first
section of this chapter.). The principle states
that a neuron does the same thing at all of its
synaptic connections to other cells, regardless
of the identity of the target cell. The concept
is generally true, but there are exceptions in
many cells that have peptide neurotransmitters.
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Theodor Karl Gustav von Leber was a German
ophthalmologist who studied the neurology of the
eye. He also identified the disease now named
after him, Lebers Disease.
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Glutamate Receptors - synaptic receptors located
primarily on the membranes of neuronal cells.
Glutamate is one of the 20 amino acids used to
assemble proteins and as a result is abundant in
many areas of the body. Glutamate receptors are
responsible for the glutamate-mediated
post-synaptic excitation of neural cells, and are
important for neural communication, memory
formation, learning, and regulation. Glutamate
receptors are implicated in the pathologies of
several neurodegenerative diseases. It is
believed their relationship to these disesases is
due to their role in excitotoxicity. Overstimulat
ion of glutamate receptors causes
neurodegeneration and neuronal damage through the
process of excitotoxicity. Excessive glutamate,
or exogenous excitotoxins acting on the same
glutamate receptors, overactivate glutamate
receptors, causing high calcium ions influx into
the postsynaptic cell.
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• Neurogenerative diseases or conditions thought to
  be mediated (at least partially) through
  excessive stimulation of glutamate receptors
• Alzheimers disease
• amyotrophic lateral sclerosis (ALS) Lou
  Gehrig's Disease - the degeneration of motor
  neurons, the nerve cells in the central nervous
  system that control voluntary muscle movement.
• drug addiction, tolerance, and dependency
• glaucoma excessive pressures in the humors of
  the eye may lead to excessive stimulation of
  glutamate receptors, leading to retinal failure.

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1. Huntingtons disease a mutated form of the
   Huntingtin gene produces an abnormal protein that
   can cause glutamate toxicity.
2. Lebers disease a genetic condition where there
   is loss of visual acuity due to the toxic
   overstimulation of the glutamate receptors in the
   retina.
3. Parkinsonism an atypical form of Parkinsons
   Disease that is often the result of exogenous
   neurotoxicity.

Parkinsonism was shown in the 1990 film
Awakenings which dramatized the efforts of
neuroscientist Oliver Sachs (played by Robin
Williams).
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There are three known types of glutamate
receptors. Each type responds to glutamate, but
differentially responds to their specific
exogenous molecule as well AMPA NMDA Kainate Th
e different receptor subtypes are located in
different regions of the brain and are associated
with different glutamate related neural
disorders.
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Top Image A farmer harvesting opium resin from
cut opium poppies. Lower Image A fellow
smoking opium in a water pipe.
Opioid receptors a group of G protein-coupled
receptors with opioids as ligand molecules. The
drug opium, is an agonist of this receptor class
. The endogenous opioids are
dynorphins Enkephalins endorphins endomorphins noc
iceptin These five compounds all affect pain
sensation and modulation.
A farmer harvesting opium poppies.
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• Cholinergic (ACh) Neurons
• - synthesis involves the enzyme (ChAT)
  (choline acetyletransferase)
• - the rate limiting step in synthesis is
  the amount of uptake of choline in the axon
  terminal
• - Acetylcholinesterase (AchE) is an enzyme
  used to degrade Ach in the synapse for reuse

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• Catecholaminergic Neurons
• Involved in movement, mood, attention, and
  visceral function
• Tyrosine is the precursor for the three most
  prevelant catecholamines
• Dopamine (DA)
• Norepinephrine (NE)
• Epinephrine (E, adrenaline)

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• Serotonergic (5-HT) Neurons
• Derived from tryptophan
• Regulates mood, emotional behavior, sleep
• Selective serotonin reuptake inhibitors (SSRIs)
  Antidepressants
• Synthesis of serotonin is via the enzyme
  tryptophan hydroxylase.

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• Amino Acidergic Neurons

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• Other Neurotransmitter Candidates and
  Intercellular Messengers
• ATP Excites neurons
• Endocannabinoids
• Other retrograde messengers
• lipid molecules that may function to allow the
  postsynaptic neuron to decrease release of
  neurotransmitter from the presynaptic neuron

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Consumption of Cannabis Effect is due to its
ability to alter neural activity most notably in
slowing the release of neurotransmitters that
interact with the cannabinoid receptors
associated with the endocannabanoids. Function
is still largely not understood and is a very
active avenue of research.
Endocannabainoids are endogenously produced
neurotransmitters or retrograde neurotransmitter
agents. Cannabis (marijuana) is a plant that
produces structurally similar compounds to the
endocannabinoids.
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Conclusion

• Neurotransmitters
• Transmit information between neurons
• Essential link between neurons and effector cells
• Signaling pathways
• Inputs vary temporally and spatially to increase
  and/or decrease drive (first part of Chapter 6)
• Delicately balanced
• Signals regulate signals- drugs can shift the
  balance of signaling power (first part of
  Chatper 6)

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END.