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Chapter 5

PSYC62 - Chapter Five.docx

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University of Toronto Scarborough
Suzanne Erb

Chapter Five – Page 1 of 7 Chapter 5: Synaptic Transmission, Drugs, and Chemical Neuroanatomy Neurotransmitters and Chemical Signaling in the Nervous System  Neurotransmitters are commonly viewed as chemicals that are located In specific regions of neurons, are released under specific stimulation, act on a specific set of receptors and induce some type of postsynaptic action such as a change in membrane potentials or metabolic activity  Neurohormone refers to substances that are synthesized and released from neurons, but act as hormones; these substances include hormones such as corticotrophin releasing factor, which is released from hypothalamic neurons and act on the anterior pituitary gland, and also includes oxytocin and vasopressin, which are synthesized in the hypothalamus and released into systemic circulation in the posterior pituitary  Neuromodulator includes any substance that alters neurotransmission in some way o Neurotransmission is a specific subclass of neuromodulation o However, neuromodulation is sometimes used to describe the condition in which a substance modifies neural transmission but isn’t itself the means of transmission (ie. It doesn’t show any direct shifts in membrane potential or conductance when tested for actions on its own  The same substance can meet the definition of a neurohormone, neuromodulator, and neurotransmitter (eg. DA)  Most substances that are neurotransmitters also act as neuromodulator  Dale’s Law or Dale’s Principal – a given neuron uses the same neurotransmitter at all its synapses. Thus, a given neuron can be identified in terms of which transmitter it uses (ie. A GABAergic neuron). This observation was first formulated based upon early studies of classical studies of classical transmittesr, but it sometimes has been misinterpreted to mean that one neuron uses only one transmitter. We now know that a given neuron can co-localize multiple transmitters - often a combo of a classical transmitter and a neuropeptide. It’s not true that any given neuron can have any combo of transmitters Neurotransmitter Groups  Monoamines (MA) – includes the catecholamines DA, NE, and EPI, as well as the indolamine 5- HT o The neurons that utilize MA share biochemical features and this also means that some drugs act broadly on all MA o The catecholamines DA, NE, and EPI are structurally related to each other. Also share common synthesis and enzymatic breakdown pathways. They’re closely related in their neurochemistry o All catecholamines are siblings and 5-HT neurons are their cousin o 5-HT – indolamine because of structure  Synthetic pathway resembles that of catecholamines, and one of the metabolizing enzymes (MAO) Chapter Five – Page 2 of 7  Acetylcholine (Ach) – released by electrical stimulation of the vagus nerve because the fluid surrounding the stimulated nerve terminals was shown to slow the heart rate o Involved in motor control, sleep, emotional/cognitive processes, and many drugs that treat Parkinson’s and Alzheimer’s act on ACh  Histamine (H) – promotes secretion in tissues o Drugs that block H receptors are used to treat colds, allergies, ulcers o Involved in regulating sleep and wakefulness  Amino Acids – important compounds for metabolism and are the basic building blocks for proteins and peptides, but some amino acids also act as neurotransmitters o GLU and aspartate (ASP) – excitatory amino acids  Induce excitation in neurons  GLU – most common excitatory transmitter in the NS, and glutamatergic pathways form much of the basic excitatory wiring of the neural circuitry of the brain  Excitatory amino acids are important for neural plasticity and the plastic changes in synaptic function that are regulated by GLU are important for learning and memory  Long term Potentiation (LTP) – widely studied model of synaptic plasticity – studies indicates that GLU is involved in LTP  Overstimulation of excitatory amino acid receptors can cause brain damage (excitotoxicity)  Factor in the secondary brain damage induced by cerebral strokes/hypoxia, because when GLU neurons die, they dump their GLU into the extracellular space  Drugs that block excitatory amino acid transmission can act as neuroprotective agents  GLU, ASP, and GLY (glycine) – alpha amino acids  Group of amino acids that are the building block units for peptides and proteins  GABA – most common inhibitory neurotransmitter but can be excitatory early in development  Induces inhibitory postsynaptic potentials  GABAa subtype – very heterogeneous – made up of five subunits that can combine into a wide variety of configurations o Combination of subunits determine what effects it will have  AN – endogenous cannaboid o Fatty acid derivative that acts as a neural signaling molecule o Delta 9 THC acts to mimic the effects of AN on its receptors  Adenosine – purine neurotransmitter/neuromodulator o Synthesized from cell energy pathways that use AMP-ADP-ATP o Widespread through body and brain Chapter Five – Page 3 of 7 o Typically described as a neurotransmitter but not stored in vesicles, nor is it released in a calcium dependent process o Minor stimulants (caffeine, etc) are adenosine antagonists  Peptides – small strings of amino acids o Endogenous opiates – morphine and codeine are two active ingredients from the opium poppy o Substance P – transmitter of info related to pain in the spinal cord  Central transmitter involved in motor control and other functions  Five Stages of Neurotransmission o Synthesis: neurotransmitters are made from a starting material known as a precursor o Storage: transmitters are stored in membranous vesicles, most concentrated in terminals o Release: release is usually stimulated by an influx of calcium into terminal o Postsynaptic Action: transmitter binds to receptors, and as a result of binding stimulates intrinsic biological activity o Inactivation: enzymes break down transmitter, or transporters take transmitter back into the terminal  See Figure 5.2  A drug can be said to block the inactivation of 5-HT by blocking uptake (eg. Prozac), block monoamine storage (antipsychotic reserpine) or stimulate release of DA and NE (stimulant amphetamine) Synthesis of Neurotransmitters  NT molecules are synthesized from a starting material known as a precursor  Precursors – very common metabolites or nutrients, or both  Enzymatic reactions convert the precursor into the NT  NT synthesis is a common sit of drug action  If one consumes carbohydrates a few hours before/after a protein-containing meal, brain concentrations of tryptophan and 5-HT synthesis may increase  Foods rich in GLU and ASP have no effect on the level of amino acids in the brain because they don’t have ready access to it  The brain isn’t affected by ingestion of aspartame and is affected by GLU only when it’s administered alone in very large doses Storage of Neurotransmitters  Once synthesized, most transmitters are stored in vesicles  Vesicle membranes are made of a phospholipid bilayer and transmembrane proteins  Vesicles - can vary in size, shape and appearance  Three major functions of storing NT molecules inside a vesicle: Chapter Five – Page 4 of 7 o Protection o Allows for more NT – means that there’s always a ready supply o There’s a subset of vesicles that maintains a pool of NT in a pre-release state. Thse vesicles are in close association with release sites on the terminal membrane and represent a readily releasable pool of transmitter molecules  Inhibition of vesicular storage provides a locus for the action of some drugs Release of Neurotransmitters  Most common mode of release – calcium dependent process o When an action potential arrives at the ter
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