Tutorial 3-Synapse And neurotransmission
What are the receptors of Dopamine?
D1, D2,D3,D4 and D5
What are neuropeptides?
A type of neurotransmitter that is bigger -I don't. Know of we have to know about it
Tell me something about glutamate
Amino acid that functions as a neurotransmitter Involved in memory and learning (memory neurotransmitter) Principal excitatory neurotransmitter in the brain : makes that neuron more likely to fire an AP Produces EPSP Mainly interacts with ionotropic NMDA and AMPA receptors Found everywhere in the CNS
What are the major classes of neurotransmitters?
Amino acids (Glutamate, GABA) Monoamines: catecholamines : dopamine, epinephrine, norepinephrine AND indolamines : serotonin Acetylcholine NeuroPeptides
What can happen it a neurotransmitter being released into the synaptic cleft it binds to an ionotropic receptor?
An EPSPs or IPSPs start occurring inside the neutron => an AP can occur or not
Who causes the release of a neurotransmitter?
An action potential
Tell me something about GABA
An inhibitory neurotransmitter=if a neuron interacts with GABA it is less likely that an AP will fire or release neurotransmitters; widespread distribution throughout the brain and spinal cord Binds to GABAa(ionotropic) and GABAb (metabotropic) It contributes to motor control, vision and cortical functions
Definition drugs
Any substance or product that is used to modify or explore physiological systems or pathological states for the benefit of the recipient -drugs mimic the actions of a neurotransmitter -can affect both ionotropic and metabotropic receptors
What are the two types of receptors for neurotransmitters?
Ionotropic and metabotropic
What is kiss and run?
Is when a vasicle after release fuses with Presynaptic membrane, releases neurotransmitter, reveals, leaves and becomes refilled with neurotransmitter, mixes with other vesicles in terminal button
What is Glycine?
It is an amino acid that appears to be inhibitory neurotransmitter -produces rapid =, long lasting postsynaptic potentials
Definition of a synapse?
Junction between the terminal buttons or ends of the axonal branches of a neuron and the membrane of another
What are the three stages that vesicles can take after release?
Kiss and run; merge and recycle and bulk endocytosis
Tell me something about Acetylcholine (ACh)
Learning neurotransmitter -excitatory neurotransmitter : activates muscle contraction in the body and also stimulates hormone secretion Involved in thought, learning and memory with the brain -in CNS implicated in awakening, attention, anger, aggression, sexuality and thirst -VERY RESPONSIBLE FOR MOTOR ACTIONS -found in motor neurons
What is the process of bulk endocytosis for the vesicles after release?
Membranes of vesicles in reserve pool are recycled; basically bubbles of membranes have to go back; constant back and forth, fusing and then leaving again
Tell me something about dopamine
Monoamine neurotransmitter catechalomine Pleasure neurotransmitter +involved in movement and reward, arousal Catecholamine(slow speed of neurotransmission) Can be inhibitory or excitatory A lot in the substantia nigra and in the midbrain or hypathalamus, olfactory bulb or retina Receptors: D1, D2, D3, D4 and D5
Describe the postsynaptic side of a synapse
Postsynaptic side is either at the dendrites, on the soma or on other axons
What are the components of a synapse?
Presynaptic membrane, synaptic cleft, specialised postsynaptic membrane Inside the axon we have synaptic vesicles
What are the two sides of a synapse?
Presynaptic side and the postsynaptic side. ,
Describe de Presynaptic side of a synapse
Presynaptic side is at the axon terminal and forms a synapse on a neutron or other targets cells
What is reuptake?
Process where simply an extremely rapid removal of neurotramitter from the synaptic cleft by the terminal button. The neurotransmitter does not return in the vesicles. When an action potential arrives, the terminal button releases a small amount of neurotransmitter into the synaptic cleft and then takes it back, giving the postsynaptic receptors only a brief exposure to the neurotransmitter
What are synaptic vesicles?
Small rounded structures made of membrane and filled with molecules -are found in greater numbers around the part of the Presynaptic membrane -they are filled with neurotransmitters!!
What causes the effects of neurotransmitters?
The receptor: one neurotransmitter can have completely different functions depending on the receptor E.g. adrenaline= usually excitatory but in fight-flight situation can be inhibitory
postsynaptic density
area in the postsynaptic cell membrane that contains neurotransmitter receptors and structural proteins important for synapse function
What are the four monoamine neurotransmitters? And what are the 2 subdivisions for them
catecholamines(slow speed of neurotransmission): dopamine, epinephrine and norepinephrine indolamines:serotonine
Transduction
conversion of one form of energy into another. In sensation, the transforming of stimulus energies, such as sights, sounds, and smells, into neural impulses our brains can interpret.
Tell me something about serotonin
-monoamine indolamine , derived from AA -found in the brain stem -mostly inhibitory but it can be excitatory -binds to 5-HT receptors -contributes to feelings of wellbeing and feelings of pleasure -affected by exercise, light exposure, plays a role in sleep cycle, digestive system regulation
How does an action potential cause synaptic vesicles to release the neurotransmitter? All the events
1. Ap travels down the axon and arrives at the axon terminal 2.this depolarisation opens voltage-gated calcium channels in the membrane of the axon terminal and allows Ca2+ ions to enter the terminal 3.Ca2+ causes the vesicles (filled with neurotransmitters) to fuse with the Presynaptic membrane and release the transmitter molecules into the synaptic cleft 4.transmitter molecules cross the clef and they bind to a special receptor molecules in the postsynaptic membrane 5. Step 4 leads to the opening of ion channels in the postsynaptic membrane 6. This ion flow creates local EPSPs or IPSPs in the postsynaptic neuron 7.Synaptic transmitter is either (a) degraded by enzymes or (b)go back into the presynapse or (c) bind to the receptor again
What are some of the agonistic drug effects?
1. Drug increses the synthesis of neurotransmitter molecules 2. Drug increases the number of neurotransmitter molecules by destroying enzymes 3. Drug increases the release of neurotransmitter molecules from terminal buttons 4.drug binds to autoreceptors and blocks their inhibitory effect on neurotransmitter release 5.drug blocks the deactivation of neurotransmitter molecules by blocking degradation or reuptake
What are the steps for a neurotransmitter to link to a metabotropic receptor?
1. Neurotransmitter molecules bin the receptor proteins in the postsynaptic membrane 2.receptor proteins activate small proteins -G-proteins- inside the membrane next to the receptor 3. The activated G-protein activate 'effector proteins or ion channel directly 4.intermediate steps lead to a messenger that can open or close a ion channel
How drugs influence synaptic transmission? What are the seven steps in neurotransmitter action?
1. Synthesis of the neurotransmitter from its precursors under the influence of enzymes 2.neurotransmitter molecules are stored in vesicles 3.breakdown in the cytoplasm of any neurotransmitter that leaks from the vesicles 4. AP cause vesicles to fuse with the Presynaptic membranes and release their neurotransmitter molecules into the synapse 5. Inhibitory feedback via auto receptors 6. Released neurotransmitter molecules bind to postsynaptic receptors 7. Deactivation
functions of postsynaptic density
1. to anchor receptors or neurotransmitters in the postsynaptic membrane 2.transduction=converting intracellular chemical signal (neurotransmitter)into intracellular signal(change in memberane potential) in the postsynaptic cell
What is the life cycle of a vesicle?
1.Vesicle is being produced-neurotramitters are in the vesicle 2. Vesicle docks with the membrane 3.vesicles are diffusing with the membrane 4.After the fusion, Calcium enters the Presynaptic membrane 5. Molecules of the neurotransmitter begin to leave the synaptic vesicle (vesicle empty) 6. At some point is taken back inside the neuron 7.Then it is filled again with neurotransmitters
What are some of the antagonistic drug effects?
1.drug blocks the synthesis of neurotransmitter molecules 2. Drug causes the neurotransmitter molecules to leak from the vesicles and then be destroyed by enzymes 3. Drug blocks the release of the neurotransmițători moleculei from terminal buttons 4. Drug activates autoreceptors and inhibits neurotransmitter release
Tell me something about adrenaline/ epinephrine
A fight or flight neurotransmitter -catechilamine -excitatory -release and by the adrenal gland but also by other neurons -increses heart rate and blood flow -produced during stressful or exciting situations
What is enzymatic deactivation (degradation)?
Accomplished by an enzyme that destroys molecules of the neurotransmitter
What are the two general categories that classify drugs?
Agonist: really mimics the neurotransmitter ; facilitates the effects of a particular neurotransmitter on the postsynaptic cell ; e.g. nicotine Antagonist: the channels can't do anything anymore; opposes or inhibits the effects of a particular neurotransmitter on the postsynaptic cell: receptor blockers
Describe a ionotropic receptor
Also known as ligand gated ion channels Direct gating they open channels through which ions can flow in and out Usually closed until a neurotransmitter binds itself to specific sites -fast, chemical synaptic transmission -short lasting effect -can be excitatory and inhibitory (produces EPSPs or IPSPs)
What are the types of chemical synapses in the central nervous system?
Axodendritic synapses=Presynaptic membrane is on axon; postsynaptic membrane is on dendrite Axosomatic synapses=Presynaptic membrane is on axon; postsynaptic membrane is soma Axoaxonic synapse=Presynaptic membrane is on axon;
What are different kinds of synapses?
Axodendritic, axoaxonic and axosomatic
Definition neurotransmitters
Chemical messengers released into the synaptic cleft by neurons that allow signals to pass between neuron and another cell
What does an Axodendritic synapse and a axoaxonic one?
Chemicals are released by the Presynaptic neurons at Axodendritic and axoaxonic synapse excite or inhibit dendrites and cell body type of the postsynaptic neuron ; if sufficiently excited it can lead to an action potential
What is the difference between directed or non-directed synapses?
Directed synapses: synapses at which the presynapse and the post synapse are in close proximity Indirect: synapses at which the site of release is at some distance from the site of reception
Tell me something about noradrenaline/norepinephrine
Excitatory -secreted by all the other sympathetic nerve endings throughout the body -contribute to diverse behavioural and physiological processes, mood, overall arousal, sexual behaviour
How can neurotransmitters be classified?
Excitatory or inhibitory Excitatory: activates receptors on the postsynaptic membrane that enhances the effects of the AP-> triggers depolarisation and increases likelihood of a response (Glutamate) Inhibitory: reverse mechanism-> triggers hyperpolarization and decreases the likelihood of a response (GABA)
What are the receptors of GABA
GABAa -ionotropic , when activated they open a CL-channel, this hypolarizes the neuron and make it less likely that an AP will fire GABAb-metabotropic -coupled to a G protein, when activated they frequently open K+channels which allow K+ions to flow out of the neuron, making the neuron jyperpolarized and make it less likely to fire and AP
What can happen if we have too less or too much Dopamine?
Low levels: Parkinson High levels: Schizophrenia
What are metabotropic receptors?
Movements of ions depend on the G-protein receptors -indirect gating -long lasting effects -slow transmission -can lead to the activation of DNA
What are the receptors of the glutamate
NMDA (only opens if glutamate is preset) and AMPA (produces EPSPs) When activated they let NA+ ions to flow into the postsynaptic neuron ->depolarising the neuron ->more likely to fire an AP
What can do an axoaxonic synapse?
On or near the terminal button can facilitate or inhibit the effects of that button on the postsynaptic neuron; Presynaptic facilitation and inhibition can selectively influence one particular synapse rather than the entire Presynaptic neuron
........ unbalanced secretion can lead to depression, suicide
Serotonin
What is the speed of neurotransmission?
Some neurrotransmitters have fast action(activation/deactivation) of a neuron : glutamate and GABA Some of them have slow action: all the others
What is synaptic transmission?
The transfer of information at the synapse from one neutron to another
What is the process of merge and recycle for the vesicles after release?
The vesicle after release fuses with postsynaptic membrane, loses identity; extra membrane from fused vesicles pinches off into the cytoplasm and forms vesicles, which are filled with neurotransmitter
What is the role and functions of monoamine neurotransmitters?
They are derived from amino acids. Their effects tend to be more diffused
What are amino acids and what are our examples in neurotransmission?
They are like building blocks of proteins Glutamate and GABA and Glycine
How can the actions of GABA be terminated?
They are terminated by proteins called GABA transporters which trasnport GABA into the synaptic cleft where they are destroyed by enzymes
What are neuromodulators?
They can change the action of the neuron and this could lead to more glutamate or more GABA -all the others neurotransmitters influence how GABA or glutamate do their work ( all the others being serotonin acetylcholine, dopamine and noradrenaline)
What can happen if we have too much or too little of Glutamate?
Too much: overstimulation of the brain: migraines or seizures Too less: memory impairment: Alzheimer's disease