The Neuron (II): Synaptic Transmission Psychopharmacology PDF

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Summary

Communication Between Neurons
-Structure of Synapses
-Synaptic Transmission
-Integration of Signals at Synapse

Psychopharmacology
-Classes of Neurotransmitters
-Drug actions
-Drugs: Stimulants, Opiates, Marijuana, Hallucinogens

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LECTURE 3: PS1005 Biological psychology The Neuron II: Synaptic Transmission Psychopharmacology

THE NEURON (II): SYNAPTIC TRANSMISSION & PSYCHOPHARMACOLOGY COMMUNICATION BETWEEN NEURONS Transmission at synapse is different to transmission along an axon Reflex Arc  sensory neuron excites a second neurons which then excites a motor neuron, activating a muscle Sherrington’s Evidence for Synaptic Delay (1906)

SYNAPSES  Neurons are not physically connected  Info is transmitted chemically at junctions called “synapses”

Structure of Synapses A synapse consists of a presynaptic and postsynaptic membrane

1) Presynaptic membrane Located in presynaptic terminal of axon Contains vesicles filled with neurotransmitters Membrane with high concentration of Ca++channels Synaptic cleft: Gap of 20-40 nm that separates pre- and post- synaptic membranes Contains extra-cellular fluid, through which neurotransmitters diffuse 2) Postsynaptic membrane Located on postsynaptic spine of dendrite or cell body Contains specialised proteins (receptors) that respond to neurotransmitters Neurotransmitters receptors vary widely in function; often control ion channels (e.g. Na +, Cl-)

LECTURE 3: PS1005 Biological psychology The Neuron II: Synaptic Transmission Psychopharmacology

Integration of Signals at Synapse The sum of all postsynaptic effects determines what happens.

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Spatial summation: overall sum of all potentials (EPSPs and IPSPs) in space

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Temporal summation: overall sum of all potentials in time (closer in time, greater probability of generating an action potential)

Graded potentials: -Within dendrites (and cell body) membrane potentials are graded and do not follow the all-or-none law. -Thus, no individual synapse determines whether the neuron will be excited or inhibited. -A given neuron has many synaptic connections, so it receives signals from many other neurons. -These signals (local potentials) are integrated to determine whether the neuron will generate an action potential.

Types of signals: Signals may be excitatory or inhibitory: Excitatory postsynaptic potential (EPSP): - Graded potential which depolarises postsynaptic membrane - Occurs when Na+ ions enter cell - Decays over time and space Inhibitory postsynaptic potential (IPSP): - Graded potential which hyperpolarises postsynaptic membrane - Occurs when K+ ions leave cell or Cl- ions enter cell - Decays over time and space - Suppresses excitation  Probability of an action potential depends on ratio of EPSPs and IPSPs at any given moment  The neuron generates an action potential ONLY IF the graded potential depolarises the axon hillox enough to reach threshold.

LECTURE 3: PS1005 Biological psychology The Neuron II: Synaptic Transmission Psychopharmacology

Synaptic Transmission 1) An action potential arrives at the presynaptic axon terminal. 2) Voltage-gated calcium channels in axon terminal open, Ca ++ enters axon terminal. 3) Ca++ causes vesicles to bind to presynaptic membrane and burst, releasing neurotransmitter into the synaptic cleft (exocytosis). 4) Neurotransmitter diffuses across the cleft & binds to receptors in postsynaptic membrane. -If receptor opens Na+ channels, postsynaptic neuron depolarises (EPSP). -If receptor opens K+ or Cl- channels, postsynaptic neuron hyperpolarises (IPSP). 5) The IPSPs & EPSPs in post-synaptic cell spread towards axon hillock. If depolarisation there is enough to reach threshold, neuron fires an AP.

6) The neurotransmitters separate from the receptors. 7) The neurotransmitters are taken back into the presynaptic neuron (reuptake), diffuse away, or are inactivated by chemicals. 8) The postsynaptic cell may send negative feedback to presynaptic autoreceptors, to slow the release of further neurotransmitters.

LECTURE 3: PS1005 Biological psychology The Neuron II: Synaptic Transmission Psychopharmacology

PSYCHOPHARMACOLOGY Classes of Neurotransmitters Main classes of neurotransmitters Amino acids A modified amino acid Monoamines (also modified from amino acids)

Peptides (chains of amino acids) Purines Gases

Glutamate, GABA, glycine, aspartate, maybe others acetylcholine Indoleamines: serotonin Catecholamines: dopamine, norepinephrine, epinephrine Endorphins, substance P, neuropeptide Y, many others ATP, adenosine, maybe others NO (nitric oxide), maybe others  poisonous in large quantities, tells blood that a brain area has become more active  dilates nearby blood vessels thereby increasing blood flow in that area of the brain / and acts as messenger

Synthesis of neurotransmitters

 Neurotransmitters are synthesised from amino acids originating in food  Drugs can alter the way that NT’s are synthesised.

Release and Diffusion of Neurotransmitters

-the NT then diffuses across the synaptic cleft to the postsynaptic membrane -At the postsynaptic membrane, it attaches to a receptor -More than on type of NT can be released at the same time and it can have an effect on the other NT

LECTURE 3: PS1005 Biological psychology The Neuron II: Synaptic Transmission Psychopharmacology

The effect of a NT depends on its receptor at the postsynaptic cell where it will do one of TWO things: It will either cause:  Ionotropic effect: quick and fast, implicates visual and auditory processes -refers to when a neurotransmitter attaches to receptors and immediately opens ion channels -most of the brain’s excitatory ionotropic synapses use glutamate or acetylcholine as a neurotransmitter  Metabotropic effect: slower, longer lasting and implicate taste, smell, arousal, pleasure, attention -refers to when a neurotransmitter attaches to a receptor and initiates a sequence of metabolic reactions that are slower and longer-lasting -include behaviours such as: hunger, fear, thirst or anger

Inactivation and Reuptake: 1) Neurotransmitters released into the synapse do not remain and are subject to either inactivation or reuptake 2) Reuptake – when the presynaptic neuron takes up most of the neurotransmitter molecules intact and reuses them 3) Transporters are special membrane proteins that facilitate reuptake Examples: -serotonin & catecholamines are taken back up into the presynaptic terminal, some are also converted into inactive chemicals / COMT and MAO are enzymes that convert catecholamine transmitters into inactive chemicals -Acetylcholine is broken down by acetylcholinesterase into acetate – choline

NEUROTRANSMITTERS:  Acetylcholine (ACh) -first NT discovered -released by cholinergic synapses which project widely throughout the brain & peripheral nervous system -2 types of receptors: nicotinic (ionotropic) and muscarinic (metabotropic) -all muscular movement is achieved through the release of Ach -responsible for cortical arousal, processes occurring during REM sleep, learning & memory -widespread loss of cholinergic neurons in Alzheimer’s disease, suggesting they are crucial for learning and memory

LECTURE 3: PS1005 Biological psychology The Neuron II: Synaptic Transmission Psychopharmacology

MONOAMINES: CATECHOLAMINES  Dopamine (DA) -Several subtypes of DA receptors, D!, D2, D3, D4, D5 -Loss of dopaminergic neurons results in Parkinson’s disease  plays crucial role in motor control -overactivity linked with schizophrenia  Norepinephrine (NE) -active in maintaining emotional tone -Decrease in NE activity thought to be related to depression -Increase in NE thought to be related to mania (overexcited behaviour) -wide projections paths in brain  modulates many behavioural and physiological processes -4 subtypes of receptors (all metabotropic)

MONOAMINES: INDOLEAMINES  Serotonin (5-HT) -relatively few 5-HT cell bodies but exert widespread influence throughout rest of brain -at least 15 types of 5-HT receptors -controls sleep states, mood, anxiety, appetite, arousal, sexuality -low levels associated with: depressions, bipolar disorder, anxiety, migraine -anti-depressants increase 5-HT activity

LECTURE 3: PS1005 Biological psychology The Neuron II: Synaptic Transmission Psychopharmacology

Drugs: Psychopharmacology is the study of the effects of drugs on the nervous system A drug is a chemical substance, produced outside the body, that in relatively small doses alters the function of cells Drugs affect communication between neurons, through the synthesis of neurotransmitter, its release or reuptake Any point in the chain of events that comprises communication between neurons can be disrupted or changed by drugs

Drug effects: Drugs work by doing one or more of the following to neurotransmitters: Increasing the synthesis Causing vesicles to leak Increasing/Blocking release -Botulinum toxin (~Botox): blocks release of ACh  muscle paralysis -Black widow venom: triggers release of ACh Decreasing reuptake - Certain anti-depressants inhibit 5-HT reuptake Blocking the breakdown into inactive chemicals - Other anti-depressants inhibit enzymes which break down 5-HT, NE, DA Directly stimulating or blocking postsynaptic receptors - Nicotine activates ACh receptors - Curare: blocks ACh receptors  paralyses muscles

Drugs fit like keys into molecular locks: Ligand: substance that binds to a receptor Agonist: ligand that mimics or increases effect of a neurotransmitter Antagonist: ligand that blocks effects of a neurotransmitter A drug has an affinity for a particular type of receptor if it binds to that receptor. - Can vary from strong to weak. The efficacy of the drug is its tendency to activate the receptor. - Drugs can have a high affinity but low efficacy Drugs can be made to adhere to specific subtypes of receptors (e.g., antagonists of 5HT3 receptors produce specific anti-nausea effect).

drugs

that

are

selective

 Drug effects are changes we can observe in an organism’s physiological processes & behaviour E.g. pupil dilation, euphoria, paranoia, relaxation, etc.

LECTURE 3: PS1005 Biological psychology The Neuron II: Synaptic Transmission Psychopharmacology

Types of drugs: Stimulants • Increase excitement, alertness, motor activity and elevate mood. • E.g.: amphetamines, cocaine, MDMA (Ecstasy), nicotine, caffeine • Stimulant drugs directly stimulate dopamine receptor types D2, D3, and D4. 1)Amphetamine enhances NT activity in several ways, e.g., blocking reuptake of catecholamines into the presynaptic terminal - short-term: heightened alertness, euphoria, no need for sleep, lowered fatigue - tolerance leads to larger doses  sleeplessness, general physical & mental deterioration, paranoid schizophrenia - chronic use leads to symptoms of brain damage even after quitting drug 2)Cocaine blocks the reuptake of catecholamines  available for longer in synaptic cleft - Many of same effects as amphetamines - Overdose fatalities most likely after intravenous injection - Chronic use leads to lasting changes in brain metabolism & blood flow, can lead to psychotic symptoms - Highly addictive; Withdrawal symptoms – drug cravings, depression 3)Nicotine (active ingredient in tobacco). Stimulates one type of acetylcholine receptor known as the nicotinic receptor. - Nicotinic receptors are found in the central nervous system, the neuromuscular junctions of skeletal muscles and in the nucleus accumbens (part of brain’s reinforcement system). - Increases heart rate, blood pressure, secretion of hydrochloric acid in stomach, motor activity of bowel.

Opiates Drugs Examples: morphine, codeine, heroin, methadone. Derived from (or similar to those derived from) the opium poppy. • Decrease sensitivity to pain and increase relaxation. • They bind to the same receptors in the brain as endorphins • Opiates have a net effect of increasing the release of dopamine by stimulating endorphin receptors. • Opiates also decrease activity in the locus coeruleus which results in decreased response to stress and decreased memory storage. • Strong potential for addiction

Marijuana Cannabinoids dissolve in body’s fats and leave slowly  effects last hours Relieves pain or nausea, combats glaucoma, increases appetite Subjective experience quite variable: Relaxation, mood alteration, or stimulation, hallucination, paranoia Sustained use can cause addiction; heavy use causes respiratory diseases, impairs memory THC (Δ9-Tetrahydrocannabinol) is the active ingredient in marijuana.

LECTURE 3: PS1005 Biological psychology The Neuron II: Synaptic Transmission Psychopharmacology

-THC works by attaching to cannabinoid receptors esp. in the cerebral cortex, cerebellum, basal ganglia and hippocampus. Anandamide and 2-AG are the endogenous cannabinoids that attach to these receptors. -The cannabinoid receptors are located on the presynaptic neuron and inhibit the release of glutamate and GABA.

Hallucinogens Distort sensory perception Fantastic pictures with intense colours Chemically diverse – affect many different transmitter systems depending on particular drug Examples: (Lysergic acid diethylamide) LSD, psilocybin (magic mushrooms): Act as serotonin receptor agonists, esp. at 5HT2 receptors

Reading Kalat, J.W. Biological Psychology (11th Ed). Chapter 3....