Class Notes (835,928)
Canada (509,506)
Psychology (2,075)
PSYCH 447 (25)


7 Pages
Unlock Document

Richard Ennis

Chapter 6- Neurotransmitter Systems Introduction: • Three major classes of neurotransmitters: amino acids, amines, and peptides • First molecule identified as a neurotransmitter was acetylcholine, Ach • Cholinergic- cells that produce and release Ach • Noradrenergic- neurons that use the amine neurotransmitter norepinephrine (NE) • Glutamatergic- synapses that use glutamate • GABAergic- synapses that use GABA • Peptidergic- synapses that use peptides • Ach and all the molecular machinery associated with it are collectively called cholinergic system Studying Neurotransmitter Systems: • Certain criteria must be met to distinguish a molecule as a neurotransmitter: o The molecule must be synthesized and stored in the presynaptic neuron o The molecule must be released by the presynaptic axon terminal upon stimulation o The molecule must produce a response in the postsynaptic cell Localization of Transmitters and Transmitter-Synthesizing Enzymes: • Hints that a particular molecule may be a neurotransmitter: o Molecule is concentrated in the brain tissue o Application of the molecule to certain neurons alters their action potential firing rate • To confirm the molecule is a neurotransmitter, the molecule must be localized in and synthesized by particular neurons • Two techniques used are immunocytochemistry and in situ hybridization Immunocytochemistry: • Immunocytochemistry- a method used to anatomically localize particular molecules to particular cells o Once the neurotransmitter candidate has been chemically purified, it is injected into the bloodstream of an animal, where it stimulates an immune response o The response is the generation of large proteins called antibodies  Antibodies can bind tightly to specific sites on the foreign molecule such as the transmitter candidate  Best antibodies for this method bind very tightly to the transmitter of interest, and bind very little or not at all to other chemicals in the brain o This method can be used to localize any molecule for which a specific antibody can be generated In Situ Hybridization: • Is also useful for confirming that a cell synthesizes a particular protein or peptide • Recall: proteins are assembled by the ribosomes according to instructions from specific mRNA molecules • A unique mRNA molecule for every polypeptide is synthesized by a neuron • If the sequence of nucleic acids in a strand of mRNA is known, it is possible to construct in the lab a complementary strand that will stick to the mRNA molecule o Complementary strand is called a probe o Process by which the probe bonds to the mRNA molecule is called hybridization • In order to see if the mRNA for a particular peptide is localized in a neuron, we chemically label the appropriate probe so it can be detected, apply it to a section of brain tissue, allow time for the probes to stick to any complementary mRNA strands, then wash away all the extra probes that have not stuck; finally we search for neurons that contain the label • In situ hybridization, probes are usually labelled by making them radioactive o Since we cannot see radioactivity, hybridized probes are detected by laying the brain tissue on a sheet of special film that is sensitive to radioactive emissions o After exposure to the tissue, the film is developed like a photograph, and negative images of the radioactive cells are visible as clusters of small dots  This technique for viewing the distribution of radioactivity is called autoradiography • Immunocytochemistry is a method for viewing the location of specific molecules, including proteins, in sections of brain tissue • In situ hybridization is a method for localizing specific mRNA transcripts for proteins • Both methods put together, enable us to see whether a neuron contains and synthesizes a transmitter candidate Studying Transmitter Release: • Most regions of the outer central nervous system (CNS) contain a diverse mixture of intermingled synapses using different neurotransmitters • Read Pg. 137-138! Studying Synaptic Mimicry: • Knowing that a molecule is localized in, synthesized by, and released from a neuron is still not sufficient to qualify it as a neurotransmitter • A 3 criterion must be met: o The molecule must evoke the same response as that produced by the release of naturally occurring neurotransmitter from the presynaptic neuron • To asses the postsynaptic actions of a transmitter candidate a method called microionophoresis is used o Microionophoresis- a method of applying drugs and neurotransmitters in very small quantities to cells • Read this section on Pg. 138 Studying Receptors: • Each neurotransmitter exerts its postsynaptic effects by binding to specific receptors o As a rule no two neurotransmitters bind to the same receptor; but one neurotransmitter can bind to many different receptors • Each of the different receptors a neurotransmitter binds to is called a receptor subtype • Ach acts on two different cholinergic receptor subtypes: one type is present in skeletal muscle and the other is in heart muscle o Both subtypes are also present in many other organs and within the CNS • 3 Approaches to study the different receptor subtypes have been useful: o Neuropharmacological analysis of synaptic transmission o Ligand-binding methods o Molecular analysis of receptor proteins Neuropharmacological Analysis: • Skeletal muscle and heart muscle respond differently to various cholinergic drugs • Nicotine (derived from tobacco plant), is a receptor agonist in skeletal muscle but has no effect in the heart o The receptor is called nicotinic ACh receptors in skeletal muscle • Muscarine (derived from poisonous species of mushroom), has little or no effect on skeletal muscle but is an agonist at the cholinergic receptor subtype in the heart o The receptor is called muscarine ACh receptors in the heart • ACh slows the heart rate • Muscarine is poisonous because it causes a precipitous drop in heart rate and blood pressure • Nicotinic and muscarinic receptors also exist in the brain • Glutamate receptors mediate much of the synaptic excitation in the CNS o 3 subtypes of glutamate receptors are:  AMPA receptors  NMDA receptors  Kainite receptors • Each named for a diff. chemical agonist o The neurotransmitter glutamate activates all 3 receptor subtypes  But AMPA acts only at the AMPA receptor, NMDA acts only at the NMDA receptor and so on • Pharmacological analyses were used to split the receptors into two subtypes: o NE receptors into alpha and beta o GABA receptors into GABA anA GABA B Ligand-Binding Methods: • Any chemical compound that binds to a specific site on a receptor is called a ligand for that receptor • Ligand-binding method- technique of studying receptors using radioactively labelled ligands o A ligand for a receptor can be an agonist, an antagonist, or the chemical neurotransmitter itself Molecular Analysis: • Read Pg. 141 Neurotransmitter Chemistry • Most of the known neurotransmitter molecules are either: o Amino acids o Amines derived from amino acids o Peptides constructed from amino acids • ACh is an exception; but it is derived from acetyl CoA, • Choline which is important for fat metabolism throughout the body • Amino acid and amine transmitters are generally each stored in and released by separate sets of neurons • Dale’s principle- idea that a neuron has only one neurotransmitter • Many peptide containing neurons violate Dale’s principle because these cells usually release more than one neurotransmitter: an amino acid or amine and a peptide • Co-transmitters- two or more transmitters released from one nerve terminal • But still most neurons release only a single amino acid or amine neurotransmitters Cholinergic Neurons: • Acetylcholine (ACh)- is the neurotransmitter at the neuromuscular junction and therefore is synthesized by all the motor neurons in the spinal cord and brain stem • ACh synthesis requires a specific enzyme, choline acetyltransferase (ChAT) • ChAT is manufactured in the soma and transported to the axon terminal like all presynaptic proteins • Only cholinergic neurons contain ChAT, therefore this enzyme is a good marker to identify cells that use ACh as it’s neurotransmitter • ChAT synthesizes ACh in the cytosol of the axon terminal, and the neurotransmitter is concentrated in synaptic vesicles by the actions of an ACh transporter o ChAT transfers an acetyl group from acetyl CoA to choline o Source of choline is the extracellular fluid, where it exists in low micromolar concentrations o Choline is taken up by the cholinergic axon terminals via specific transporter o Because the availability of choline limits how much ACh can be synthesized in the axon terminal, transport of choline into the neuron is said to be the rate-limiting step in ACh synthesis • Rate-limiting Step- in a biochemical reaction that leads to the production of a chemical, the one step that limits the rate of synthesis. • Cholinergic neurons also manufacture the ACh degradative enzyme acetylcholinesterase (AChE) o AChE is secreted into the synaptic cleft and is associated with cholinergic axon terminal membranes o AChE is also manufactured by some noncholinergic neurons, so this enzyme is not as useful a marker for cholinergic synapses as ChAT • AChE degrades ACh into choline and acetic acid o This happens very quickly because AChE has one of the fastest catalytic rates among all known enzymes • Inhibition of AChE prevents the breakdown of ACh, disrupting transmission at cholinergic synapses on skeletal muscle and heart muscle o Deaths from the irreversible inhibition of AChE is typically a result of respiratory paralysis Catecholaminergic Neurons • Amino acid tyrosine is the precursor for three different amine neurotransmitters that contain a chemical structure called a catechol • These neurotransmitters are called catecholamines o Catecholamine neurotransmitters are:  Dopamine (DA)  Norepinephrine (NE)  Epinephrine (Adrenaline) • Catecholaminergic neurons are found in regions of the nervous system involved in the regulation of movement, mood, attention, and visceral function • All catecholaminergic neurons contain the enzyme tyrosine hydroxylase (TH), which catalyzes the first step in catecholamine synthesis, the conversion of tyrosine to a comp
More Less

Related notes for PSYCH 447

Log In


Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.