Download Topic 7

Biology 463 - Neurobiology
Topic 7
A Continuation of
Neurotransmitter Systems
Lange
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.
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, Leber’s Disease.
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.
Overstimulation 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.
Neurogenerative diseases or conditions thought to be mediated (at least
partially) through excessive stimulation of glutamate receptors:
1. Alzheimer’s disease:
2. 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.
3. drug addiction, tolerance, and dependency
4. glaucoma – excessive pressures in the humors of the eye may lead to
excessive stimulation of glutamate receptors, leading to retinal failure.
5. Huntington’s disease – a mutated form of the Huntingtin gene
produces an abnormal protein that can cause glutamate toxicity.
6. Leber’s disease – a genetic condition where there is loss of visual
acuity due to the toxic overstimulation of the glutamate receptors
in the retina.
7. Parkinsonism – an atypical form of Parkinson’s 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).
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
The different receptor subtypes are located in different regions
of the brain and are associated with different glutamate related
neural disorders.
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.
A farmer harvesting opium poppies.
The drug opium, is an agonist of this
receptor class . The endogenous
opioids are:
dynorphins
Enkephalins
endorphins
endomorphins
nociceptin
These five compounds all affect pain
sensation and modulation.
•
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
•
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)
•
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.
•
Amino Acidergic Neurons
•
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
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.
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)
END.