PSYCHOLOGY 0505 LECTURE OBJECTIVES AND OUTLINE Spring 2014 LECTURE NEUROPHARMACOLOGY OF THE NERVOUS SYSTEM Objectives Terms and concepts to learn Neurotransmitter typically used when talking about a more private type of communication of neurons talking to one another in close proximity and are chemical messengers released by neurons job to be direct communicator Two Types of Synapse Directed Synapse where communication between terminal and dendritic membrane and neurotransmitter stays within this particular location and does not diffuse anywhere else one on one private communication Non Directed Synapse neurotransmitters leak into surrounding area string of beads synapse where little bulges along length of membrane neurotransmitter released into extracellular fluid but still relatively close within that same area of Neuromodulator can also be a neurotransmitter but often travels further disperses more widely and some may be released by neurons and some by endocrine glands function to modulate activity of other neurons and neurotransmitters job of regulator Hormones substances that are released by endocrine glands that impact other organs and glands in the body and some of them also impact neurons so even if same substance as neurotransmitter but is released by endocrine gland and not neurons then is a hormone epinephrine can be released from nervous system as neurotransmitter and as hormone form adrenal glands in response to stress same substance but released form two different places and has two different functions Two Key Types Neurotransmitters both amino acids found in fast acting directed synapses Glutamate common in proteins that we eat consumed as amino acid and serves as precursor for glutamate in neurons and is likely the most common prevalent excitatory neurotransmitter helps modulate and enhance activity in central nervous system GABA synthesized by making a small molecular change to glutamate and is most prevalent inhibitory neurotransmitter in central nervous system big for the regulation of sleep may be so important that if we were to deplete someone of GABA we can get uncontrollable seizures so though to be in deficiency in certain seizure disorders overstimulation of brain is what lead to seizure release receptor and binding site acetylcholine acetylcholine synthesis acetyl coenzyme A aetyl CoA and a choline molecule which comes primarily from the diet come together to move acetate ion by the enzyme choline actyl transferase chAT to then produce a coenzyme A CoA and an acetylcholine ACh which is later bound in vesicles and is available for release when neurons are stimulated once released it is released along with degradation enzyme to be used in synapse to start degradation and reuptake so enzyme that then separates acetate ion form choline molecule is called acetylcholine esterase AChE and choline recycled again via reuptake used to make new acetylcholine acetyl coenzyme A choline epinephrine adrenergic choline acetyltransferase acetylcholinesterase seven steps in neurotransmitter action agonistic drug effects and examples antagonistic drug effects and examples atropine botulinium toxin neuromodulator neurotransmitter functions and effects monoamines monoamine synthesis catecholamines monoamine oxidase MAO epinephrine adrenergic norepinephrine noradrenergic dopamine serotonin tyrosine L dopa tryptophan and 5 hydroxytryptophan blood brain barrier I NEUROTRANSMITTERS particular classes or groups exist like how amino acid ones are a group A Acetylcholine found in a group of its own class by itself and is the first neurotransmitter that was discovered by accident when Lowi wanted to investigate the vagus nerve which regulated heart rate and breathing rate and innervates other internal organs and comes form brain as wandering nerve studied frogs would remove heart from frog which kept beating for 5 min after out of body and put it in a saline solution to maintain cells and electrically stimulated vagus nerve to initiate action potential artificially heart slowed the rate of beating when put second heart in same saline water it slows to rate of previous rate before even stimulated so perhaps when vagus nerve stimulated whatever was producing the change in the first heart produced changes in the saline bath that then stimulated the second heart when this compound was isolated it was acetylcholine and as soon as this found the hunt was on for further chemicals must have acetylcholine receptors on heart muscle and acetylcholine is inhibitory to heart hyperpolarizing some of neurons that are responsible for heart rate typically neurotransmitters are either excitatory or inhibitory BUT acetylcholine has both excitatory and inhibitory functions as controls the opening of sodium channels on skeletal muscles depolarizes neurons excitatory other functions besides being major for all muscles like heart and skeletal and one of the things released in hippocampus that has to do with learning and memory internal structure thought critical for memory consolidation and formation hippocampus stores memories information temporarily though day and becomes active again in sleep to hold these memories long term potentiation or consolidation and make associations to other things too also has to do with Alzheimer s when new information not remembered etc so this must be a depletion in the levels of acetylcholine and areas associated with this chemical are smaller acetylcholine is part of failing mechanism that lead to the memory loss also important in initialing sleep and REM sleep dream phase of sleep when it increases in REM after a general decrease in activity in early sleep pathways stimulated in dreaming associated with frontal cortex that pull our produce bits of memories and are randomly activated are due to acetylcholine activity brain making sense of these random bits of images are then what we know as a dream in day acetylcholine levels rise again when we are very active B Monoamines another category of neurotransmitters that are synthesized form a single amino acid and are also then further categorized 1 Catecholamines all chemically similar and derived from one another in a particular order originally stemming from tyrosine as a precursor molecule tyrosine acted on by enzyme tyrosine hydroxylase to form L dopa which is acted on my enzyme DOPA decarboxylase to form dopamine which is acted on by enzyme dopamine beta hydrocylase to form norepinephrine which is acted on my