E4: Neurotransmitters and Synapses DnlNjuguna ~ DAIS

Excitatory and Inhibitory synapses

Some Pre-synaptic neurons excite postsynaptic transmission (excitatory pre-synaptic neurons) and others inhibit postsynaptic transmission (inhibitory pre-synaptic neurons )

Excitatory Pre- synaptic neurons Inhibitory Pre- synaptic neurons Depolarises the postsynaptic membrane Influx of Na + ions Possibly reaching threshold Generation of new action potential E.g. Acetylcholine Hyperpolarises the postsynaptic membrane Influx of Cl - or loss of K + ions Makes it more difficult to reach threshold Lowers the resting potential E.g. Gama-aminobutryic acid (GABA)

Decision-making in the CNS can result from the interaction between the activities of excitatory and inhibitory pre-synaptic neurons at synapses. Neurones form synaptic junctions with the cell body of other neurones A post synaptic neurone can have many pre- synaptic neurones forming synaptic junctions with it. Pre synaptic neurones depolarise (excitatory) or hyperpolarise (inhibitory) the post synaptic membrane locally. The sum of their effects takes place at the axon hillock Synapse Pre- Post-

Post-Synaptic Potentials (PSPs) can be: Excitatory (EPSP)(+); or Inhibitory (IPSP) (-). Post-synaptic Pre-synaptic Synapse

The EPSP must build up in the postsynaptic neuron to the threshold level to allow the formation of an action potential. Synapse E.g. this Neuron needs a 2 more “+” than “-” before it can generate an action potential.

Neurons can integrate signals from other neurons: 1) through spatial summation (different pre-synaptic neurones ‘add together’ their local depolarisation's to reach threshold at the axon hillock) Synapse

Summation of the depolarising effects of three different excitatory pre- synaptic neurones i.e. a+b+c Having reached the threshold (T), a new action potential is generated in the post synaptic neurone If the summation of the 3 is below threshold there would be no action potential or response from the central nervous system

+ Synapse ) through temporal summation where a number of waves neurotransmitter from the same pre- synaptic neurone depolarises the post synaptic membrane (i.e. waves of depolarisation are added together to reach threshold).

The same pre-synaptic neurone(a)has a high frequency of action potentials arriving at the synapse. This sends a number of waves of neurotransmitter to depolarise the post synaptic membrane. Waves of depolarisation (from one neurone) are added together to reach threshold Pre-synaptic neurones depolarises the post synaptic membrane with a number of rapid stimulations.

Decision-making in the CNS synapses are the sites of decision-making in the brain a post-synaptic neuron's membrane potential is the summation of input from pre-synaptic neurons EPSPs depolarize post-synaptic neurons while IPSPs hyper-polarize post-synaptic neurons if the post-synaptic neuron reaches threshold potential at its axon hillock, it will produce an action potential pre-synaptic neurons can vary in the frequency, but not intensity of their input, since action potentials are "all-or-none“ rule

Psychoactive drug: Is chemical substances that acts upon the CNS altering the state of mind by changing (stopping or enhancing) the activity at the post synaptic neurone. It result in changes in perception, mood, consciousness, cognition, and behaviour. Alcohol Amphetamine Marijuana

How psychoactive drugs affect the brain and personality: Psychoactive drugs affect the brain and personality by either increasing or decreasing post-synaptic transmission. The post-synaptic membrane contains receptors for the normal neurotransmitters. Normally when the neurotransmitter attaches to these receptors it either: Depolarise the post synaptic neurone resulting in an action potential Hyperpolarise the post synaptic neurone resulting in no action potential A drug can therefore change post synaptic output by: Blocking or enhancing the depolarising neurotransmitter Blocking or enhancing the hyperpolarise neurotransmitter

Major Neurotransmitters in the Body NeurotransmitterRole in the Body Acetylcholine (excitatory) Dopamine (inhibitory) Gamma-aminobutyric acid (GABA) (inihibitory) used by the spinal cord neurons to control muscles and by many neurons in the brain to regulate memory. produces feelings of pleasure when released by the brain, it has multiple functions depending on where in the brain it acts. The most common inhibitory neurotransmitter in the brain.

Examples of excitatory & inhibitory psychoactive drugs: Excitatory psychoactive drugs; Inhibitory psychoactive drugs; nicotine, cocaine, amphetamines. benzodiazepines, alcohol, tetrahydrocannabinol (THC).

Effects of THC in terms of its action at synapses in the brain. Marijuana/ganja is the buds and leaves of the Cannabis sativa plant. Marijuana contains more than 400 chemicals, including tetrahydrocannabinol (THC), the plant's main psychoactive chemical.

Cannabinoid receptors are activated by a neurotransmitter called anandamide. Anandamide belongs to a group of chemicals called cannabinoids. THC is also a cannabinoid chemical. THC mimics the actions of anandamide, meaning that THC binds with cannabinoid receptors and activates neurons, which causes adverse effects on the mind and body.

Effects of Tetrahydrocannabinol (THC) THC affects brain’s short-term memory THC affects motor coordination & appetite THC increases heart rate and raises levels of anxiety THC contains cancer-causing chemicals similar to those in tobaco THC affects higher order thinking THC users report feeling mellow and calm THC mimics the neuro-receptor anandamide THC binds to the post synaptic membrane receptor s for anandamide called Cannabinoid Receptor THC effect is to hyperpolarise the post synaptic neurone inhibiting generation of an action potential

Effects of Cocaine in terms of its action at synapses in the brain: Cocaine:- a powdered drug that is made from the leaves of the coca plant grown primarily in South America. Cocaine has been in use for centuries, many generations of South American Indians have chewed its leaves to give them strength and energy. The drug is nowadays taken in by either snorting, injecting or smoking.

Dopamine is released by cells of the nervous system during pleasurable activities such as eating or having sex. Once released, dopamine travels across a synapse, and binds to a receptor on a post- synaptic neurone. This sends a signal to that nerve cell, which produces a good feeling. Under normal conditions, once the dopamine sends that signal it is reabsorbed by the neuron that released it Cocaine interferes with a chemical messenger in the brain called dopamine, which is involved in the body's pleasure response.

Effects of Cocaine: cocaine is an excitatory psychoactive drugs that increases synaptic transmission; on post synaptic membrane receptor, it prevents the removal of acetylcholine; on pre-synaptic membrane, it prevents the recycling of acetylcholine; both effects maintain the stimulation of the post synaptic membrane ; cocaine also blocks the recycling of Dopamine at the Pre-synaptic membrane, making dopamine to remain active in the synapse; dopamine is associated with a feeling of pleasure, thus cocaine creates a mood of euphoria.

Drug addiction: Psychoactive drugs often cause addictive behaviour i.e. an individual persists in use of drugs despite problems related to their use habitual behaviour associated with addiction includes: craving for the use of the drug; lack of self control in limiting the taking of the drug; increasing quantities must be taken to achieve the same mental conditions; development of withdrawal behaviour if unable to satisfy the craving for the drug.

Causes of addiction: (i) Genetic predisposition ; Some people are more vulnerable to drug addiction than others, studies indicates that genetic factors have some influence on addiction, alcoholism, especially, tends to run in certain families

(ii) Social factors; various social factors correlate positively with addiction, including: cultural traditions; peer pressure; Poverty; social deprivation; traumatic life experiences; mental health problems; etc

(iii) Dopamine secretion; many addictive drugs are excitatory at dopaminergic synapses “reward pathway” giving a feel good effect/pleasure addiction results from dopaminergic synapses responding to regular drug use tolerance to a drug, leads to increased dosage to produce the desired effect withdrawal is caused by normal levels of dopamine failing to produce pleasure hence craving for drugs

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