Neurotransmitters and synapses

1. Neurotransmitters and synapses Option E.4

2. Assessment Statements • E.4.1 State that some presynaptic neurons excite postsynaptic transmission and others inhibit postsynaptic transmission. • E.4.2 Explain how decision-making in the CNS can result from the interaction between the activities of excitatory and inhibitory presynaptic neurons at synapses. • E.4.3 Explain how psychoactive drugs affect the brain and personality by either increasing or decreasing postsynaptic transmission. • E.4.4 List three examples of excitatory and three examples of inhibitory psychoactive drugs. • E.4.5 Explain the effects of THC and cocaine in terms of their action at synapses in the brain. • E.4.6 Discuss the causes of addiction, including genetic predisposition, social factors and dopamine secretion.

3. Synaptic transmission Neurons communicate with each other chemically across a space called a synapse One side of the synapse is the presynaptic membrane of the sending neuron and on the other side of the synapse is the postsynaptic membrane of the receiving neuron Molecule which moves across the space (synaptic cleft) between the two membranes is called a neurotransmitter Specific neurotransmitter is received by a specific receptor

4. Excitation and Inhibition • Some neurotransmitters are excitatory and stimulate the next neuron to forward the message • Do this by increasing the permeability of the postsynaptic membrane to positive ions, making it easier for positive ions to move in • Some neurotransmitters are inhibitory and cause the positive ions to move out of the postsynaptic cell • Positive ions move back in to the synaptic cleft chemically depressing the postsynaptic cell and makes it much harder to excite

5. Decision making in the CNS Impulse which moves down the presynaptic neuron is called the action potential As action potential reaches axon bulb, calcium ions rush into the end of the neuron Vesicles containing neurotransmitters fuse with the presynaptic membrane Neurotransmitter released into the synaptic cleft Neurotransmitter binds to specific receptors on the postsynaptic membrane Receptors let ions enter or leave when the neurotransmitter binds to them

6. Excitatory neurotransmitters • One example: acetylcholine • Generates action potential • Increases permeability of the postsynaptic membrane to positive ions • Causes positive sodium ions to diffuse into the postsynaptic neuron • Localized depolarization occurs • Inside of neuron develops a net positive charge compared to the outside • Depolarization continues as sodium ions diffuse to the next area of the neuron • Impulse is carried along the nerve • If threshold is not met, the neuron does not carry the impulse to the next neuron

8. Inhibitory neurotransmitters • Example: GABA • Inhibit action potentials • Causes hyperpolarization of the neuron • Inside of the neuron becomes more negative making it difficult for an action potential to be generated • GABA binds to specific receptor • Causes negatively charged chloride ions to move across the postsynaptic membrane into the postsynaptic cell OR it can cause positively charged K+ ions to move out of the postsynaptic neuron • Movement of Cl- into the neuron or K+ out causes hyperpolarization

10. Putting it together • A neuron is always on the receiving end of many excitatory and inhibitory stimuli • Neuron sums up the signals • If the sum of the signals is inhibitory then the axon does not fire • If the sum of the signals is excitatory, the axon fires • Summation of the messages is the way that decisions are made by the CNS

11. Cholinergic synapses • Acetylcholine is released by all motor neurons and activates skeletal muscle • If it remained in the synapse, the postsynaptic membrane would go on firing indefinitely • Acetylcholinesterase breaks it down • Acetylcholine is involved in the parasympathetic nervous system • Causes relaxation rather than flight

12. Nicotine stimulates transmission in cholinergic synapses which is why it has a calming effect on the body and personality • People addicted to nicotine become very agitated if they cannot have a cigarette

13. Adrenergic synapses • Noradrenaline depolarizes the postsynaptic neuron • Noradrenaline is involved in the sympathetic sysem • It causes a “fight or flight” reaction • Cocaine and amphetamines both cause increased alertness, energy and euphoria

15. Effect of drugs on the brain Can alter your mood or your emotional state Excitatory drugs (nicotine, coaaine, amphetamine) increase nerve transmission Inhibitory drugs (benzodiazepines, alcohol, and THC) decrease the likelihood of nerve transmission Drugs can change synaptic transmission in the following ways: Block a receptor for a neurotransmitter (structure similar to the transmitter) Block release of neurotransmitter from the presynaptic membrane Enhance neurotransmission by mimicking a neurotransmitter Block removal of neurotransmitter from the synapse and prolong the effect of the neurotransmitter

16. Excitatory drugs and how they act Nicotine mimics acetylcholine (Ach) Acts on the cholinergic synapses of the body and the brain to cause a calming effect After Ach is received by the receptors, it is broken down by acetylcholinesterase but it cannot break down nicotine This excites the postsynaptic neuron and it begins to fire, releasing a molecule called dopamine Dopamine gives you a feeling of pleasure Cocaine stimulates transmission at adrenergic synapses and causes alertness and euphoria Causes dopamine release Cocaine blocks removal of dopamine from the synapse so that it builds up Leads to overstimulation of the postsynaptic neuron Leads to euphoria Both of these drugs causes addiction

17. Amphetamine stimulates transmission at adrenergic synapses and gives increased energy and alertness Amphetamine acts by passing directly into the nerve cells which carry dopamine and noradrenaline It moves directly into the vesicles of the presynaptic neuron and causes their release into the synaptic cleft Normally these would be broken down, but amphetamines interfere with breakdown High concentrations of dopamine cause euphoria and high concentrations of noradrenaline may be responsible for the alertness and high energy effect

18. Inhibitory drugs and how they act Benzodiaizepine reduces anxiety Can be used against epileptic seizures Modulates the activity of GABA which is the main inhibitory neurotransmitter When GABA binds to the postsynaptic membrane, it causes Cl-to enter the neuron Causes hyperpolarization and resists firing B increases the binding of GABA to the receptor and therefore greater hyperpolarization

19. Alcohol acts similarly to B in that it increases the binding of GABA to the postsynaptic membrane Decreases activity of glutamate, an excitatory neurotransmitter Alcohol helps to increase the release of dopamine by a process which is not well understood Appears to stop the activity of the enzyme which breaks down dopamine in the synaptic cleft

20. Tetrahydrocannabinol (THC) is the main pschoactive chemical in marijuana THC mimics the neurotransmitter, anandamide THC binds to the same receptor and cause the postsynaptic neuron to be hyperpolarized Anandamide may play a role in memory functions, such as eliminating information from our memory that is not needed Marijuana disrupts short-term memory in humans

21. THC effects Feelings of relaxation, lightheadedness, haziness Decrease in learning, coordination, problem-solving, and short-term memory Stays in synapse longer than anandamide High concentrations of receptors found in hippocampus (short-term memory); cerebellum (coordination)

22. Cocaine effects Euphoria, talkativeness, increase in mental alertness Temporary decrease in the need for food and sleep Large amts. Cause erratic and violent behavior Sustains level of dopamine in the synapse

23. Causes of addiction Body develops a tolerance and needs more of the drug to produce the same result Chemical dependency is caused by drug “rewiring the brain” and becoming an essential biochemical in the body Role of abused drugs is to stimulate the reward pathway located in the brain

24. Withdrawal symptoms Anxiety, depression, craving Seizures, severe shaking Continued addiction Lung damage Risk of contracting HIV, hepatitis B and C Kidney disease

25. Genetic predisposition Studies in male twins find that when one twin suffers an addiction to alcohol or drugs, the rate of addiction in the second twin is 50% greater among identical twins than among fraternal twins Other experiments indicate that a genetically determined deficiency of dopamine receptors predisposes certain people to addiction Persons who become addicted to drugs that increase dopamine levels do so to compensate for that deficiency

26. Social factors of addiction • Family addiction, family parenting skills, mental health problems of family or child • Often related to peer group; users teach new users what effects to expect and what altered state is desirable • Alcohol at social gatherings fosters the paradigm that it must be available to have a party • Alcohol very rare in Saudi Arabia since it is prohibited

27. Dopamine secretion • Neurotransmitter which activates the reward pathway and gives us a sense of pleasure or satisfaction • During cocaine use, dopamine builds up in the synapse • Over-stimulation decreases the number of receptors and the remaining receptors become less sensitive to dopamine (desensitization or tolerance)

28. With tolerance, exposure to the drug causes less response that it previously caused • More and more of the drug is needed to have even the normal sense of well-being • Type of neuroadaptive change

29. Knockout mice • Genetically manipulated mice addicted to cocaine • Studies show that glutamate may oversee the learning and memories which lead to cocaine-seeking • Mouse party