Results for "axon"

Filters

Flashcards

# Synaptic transmission and the vesicle cycle ILO: - the two fundamental synaptic mechanisms by which excitable cells and in particular neurones can affect one another's function: electrical or chemical synaptic communication - how a neurotransmitter supporting chemical synaptic communication is defined and the diversity of types of small molecules that can be defined as being a neurotransmitter - how these are stored in small membranous vesicles, what constitutes the classical vesicle cycle and full collapse vesicle fusion during release - the experimental evidence for this full collapse fusion release model and how the vesicle membrane is recycled - further experimental evidence for an alternative to this model: the "kiss and run" model of vesicle cycling - the proteins that make up the release machinery and how they are readied for release during "docking" and "priming" - what happens to these proteins during the release process and the subsequent retrieval of vesicle membrane following full collapse fusion # Types of synapse - **chemical synapse** - molecules stored in vesicles - molecules diffuse across a gap - relatively slow - unidirectional - majority of synaptic transmission in the nervous system - **electrical synapse** - holes in adjoining cell membranes - linked by channels - gap junctions or connexons - signalling is very fast - bidirectional - direct electrical coupling between cells - electrical synchronisation in the heart - relatively rare in the nervous system - inhibitory interneurons or local networks # Chemical synapse Key functional roles - Neural computation - integration of many input +/- - Exhibit plasticity - development, learning and memory - Act as targets for drug action - neurotransmitter synthesis, release, receptors, uptake, degradation to produce a broad range or complex series of effects - inc functional flexibility ## Neurotransmitter 6 criteria : ![image.png](attachment:0898b027-b327-4d45-8d77-72d04923e833:image.png) ### Types ![image.png](attachment:498ab7fd-6e68-4048-bd85-c72fd719f49c:image.png) - amino acids - amines - purines - peptides - **dales principle** - neurons release just one transmitter at all of its synapses - how is dales principle challenged? - challenged by co existence and co release of small molecule transmitter and peptides by interneurons eg GABA and enkephalins - and more than one small molecule transmitter in some projection pathways eg L glutamate and dopamine ## Vesicles - neurotransmitters are likely to be stored in one type of vesicle ### Types ![image.png](attachment:5da914ec-93bf-4d3d-aff9-336319d6f003:image.png) For LDCVs - concentration is lower because of the relatively proximity to the voltage gated channels - only seen when there is sustained AP in a more global manner rather than restricted to synaptic active zone ### Cycling ![image.png](attachment:b2fd1be7-2c19-4a45-abfa-44ea522eb3c3:image.png) 1. vesicle is filled with neurotransmitter with appropriate transporter which uses ATP as an energy source to drive against conc gradient and fill the vesicle 2. vesicle collected in to reserve pool, mobilised to active zone for docking 1. atp dependent process 3. primed to be sensitive to calc conc to initiate membrane fusion 1. also atp dependent 4. exocytosis following inc in intracellular conc of calcium 5. vesicle membrane fully collapses into the membrane 6. loss of membrane recovered with endocytosis, calcium dependent with coated pits 1. uncoating requires atp 7. small vesicles become part of endosome, all recycled 8. then pinched off again to start the cycle ### Evidence for full fusion/collapse - slam freezing - rapidly cooling of the neuromuscular junction on a metal block after electrical stimulation of motor neurone axon fibres to initiate acetylcholine release - sections of the presynaptic membrane were visualised at different types after electrical stimulation to follow any changes in presynaptic membrane - activity led to increase in membrane surface area - therefore vesicle recycling ### Step 1 - docking - close association with plasma membrane - synaptic vesicles only dock at active zone - presynaptic area adjacent to signal transduction machinery - active zones differ between neurons by vesicle number ### Step 2 - priming - ready for release - maturation of synaptic vesicle - made competent to release transmitter - requires ATP - conformational change in proteins that drive release ### Step 3 fusion/exocytosis - full fusion of synaptic vesicle and presynaptic terminal membrane - requires calcium - calcium sensor protein - fusion induces exocytosis - takes 1ms ### Step 4 endocytosis - recovery of fused membrane - triggered by inc intracellular calcium - involves cytoskeletal protein lattice formation from clathrin monomers - this helps to pinch off membrane with clathrin coated pits - takes about 5 seconds - ATP dependent ### Step 5 - recycling - mechanism to conserve synaptic vesicle membrane via endosome - decoating of clathrin coated pits is also atp dependent - vesicles refill with transmitter - atp dependent ### Kiss and Run Model? - fast recycling and low capacity, favoured at low frequency stimulation - may be majority of glutamate release in hippocampus - whereas classical is slow, high capacity, favoured at high frequency stimulation - full vesicle fusion may not be required - neurotransmitter leaks out of small fusion pores - SSVs recycled intact - and not recycled as clathrin coated vesicles via the endosome Functional evidence - flickering capacitance changes instead of up stepping capacitance - capacitance dependent on surface area ### Targeting vesicles Vesicle associated proteins - synaptobrevins VAMP - synaptotagmins Plasma membrane associated proteins - SNAP-25 - syntaxins ### Snares for release - synaptobrevin - single transmembrane spanning - t snare - syntaxin - single transmembrane spanning - SNAP-25 - anchored to membrane by S-acylation ### Release machinery in the different steps ![image.png](attachment:ffc3a410-82b8-4045-82d5-4ff0aee440ac:image.png) ![image.png](attachment:6af1a3d7-86c4-412d-8a08-b63468b5bccc:image.png) ![image.png](attachment:90f59e60-5b40-47bd-a977-0e8f2405a504:image.png) ![image.png](attachment:a14859d2-5b34-4505-a332-3088a31257da:image.png) Syntaxin regulatory domain is important in maintaining a tight connection to the cell membrane Snares form a tighter complex during priming - atp dependent - Habc domains binding assisted by Munc18 - zippering - formation of the SNARE pins What is the Ca2+ sensor? - synaptotagmin - found on vesciles - binds to SNARE pins in absence of Ca2+ - during priming - binds to phospholipids in C region in presence of Ca2+ - Ca2+ binding may cause synaptotagmin to pull vesicle into membrane Why must SNAREs disassociate? - to allow internalisation of empty vesicles - re docking of another vesicle - involves NSF - ATPase which binds to the SNARE-pin complex to facilitate disassociation
Updated 5h ago
flashcards Flashcards (28)
Axonal Specificity
Updated 5d ago
flashcards Flashcards (59)
Axon miroscope
Updated 29d ago
flashcards Flashcards (8)
Axon
Updated 29d ago
flashcards Flashcards (9)
axonopathies
Updated 33d ago
flashcards Flashcards (19)
Chapter 7:6 Study Guide NERVOUS SYSTEM P179-187 Nervous System-complex, highly organized system that coordinates all the activities of the body. *The basic structural unit of the nervous system is the neuron, or nerve cell. It consists of a cell body containing:  Nucleus  Nerve fibers called dendrites (carry impulses toward the cell body)  Single nerve fiber called axon (carry impulses away from the cell body) Many axons have a lipid covering called a myelin sheath, which increases the rate of impulse transmission and insulates and maintains the axon. The axon of one neuron lies close to the dendrites of many other neurons. The spaces between them are known as synapses. Special chemicals, called neurotransmitters, located at the end of each axon allow the nerve impulses to pass from one neuron to another. Nerves are a combination of many nerve fibers located outside the brain and spinal cord. Meninges are membranes or protective lining that covers the brain and spinal cord. Afferent, or sensory, nerves carry messages from all parts of the body to the brain and spinal cord. Efferent, or motor, nerves carry messages from the brain and spinal cord to the muscles and glands. Associative, or internuncial, nerves carry both sensory and motor messages. There are two main divisions to the nervous system: 1. 2. Central nervous system: consists of the brain and spinal cord Peripheral nervous system: consists of the nerves. A separate division of the peripheral nervous system is the autonomic nervous system. This system controls involuntary body functions. *Brain-mass of nerve tissue well protected by membranes and the cranium, or skull. The main sections include:  Cerebrum-the largest and highest section of the brain. Responsible for: reasoning, thought, memory, speech, sensation, sight, smell, hearing, and voluntary body movement.  Cerebellum-section below the back of the cerebrum. Responsible for: muscle coordination, balance and posture, muscle tone.  Diencephalon-section between the cerebrum and midbrain. o Thalamus-acts as a relay center and directs sensory impulses to the cerebrum. o Hypothalamus-regulates and controls the autonomic nervous system, temperature, appetite, water balance sleep and blood vessel constriction and dilation. Also involved in emotions such as anger, fear, pleasure, pain and affection.  Midbrain-the section located below the cerebrum at the top of the brain stem. Responsible for conducting impulses between brain parts and for certain eye and auditory reflexes.  Pons-located below the midbrain and in the brain stem. Responsible for conducting messages to other parts of the brain; for certain reflex actions including chewing, tasting, and saliva production; and for assisting with respiration.  Medulla oblongata-the lowest part of the brain stem. Connects with the spinal cord and is responsible for regulating heartbeat, respiration, swallowing, coughing, and blood pressure. The spinal cord continues down from the medulla oblongata and ends at the first or second lumbar vertebrae. *The meninges are three membranes that cover and protect the brain and spinal cord. 1. 2. 3. Dura mater-thick, tough, outer layer Arachnoid membrane-delicate and web like Pia mater-closely attached to the brain and spinal cord and contains blood vessels that nourish the nerve tissue. The brain has four ventricles, hollow spaces that connect with each other and with the space under the arachnoid membrane. The ventricles are filled with a fluid called cerebrospinal fluid. This fluid circulates continually between the ventricles and through the subarachnoid space. It serves as a shock absorber to protect the brain and spinal cord. It also carries nutrients to some parts of the brain and spinal cord and helps remove metabolic products and wastes. After circulating, it is absorbed into the blood vessels of the dura mater and returned to the bloodstream through special structures called the arachnoid villi. The peripheral nervous system consists of the somatic and autonomic nervous systems. The somatic nervous system consists of 12 pairs of cranial nerves and their branches and 31 pairs of spinal nerves and their branches. Some of the cranial nerves are responsible for special senses such as sight, hearing, taste, and smell. The Autonomic nervous system is an important part of the peripheral nervous system. It helps maintain a balance in the involuntary functions of the body and allows the body to react in times of emergency. *There are two divisions to the autonomic nervous system: Sympathetic nervous system: prepares the body in times of emergencies. Prepares the body to act by increasing heart rate, respiration, and blood pressure and slowing activity in the digestive tract. This is known as the fight or flight response. Parasympathetic nervous system: After the emergency, this slows down the heart rate, decreases respirations, lowers blood pressure and increases activity in the digestive tract. Cerebral Palsy is a disturbance in voluntary muscle action and is caused by brain damage. Lack of oxygen to the brain, birth injuries, prenatal rubella, and infections can all cause cerebral palsy. Cerebrovascular Accident or CVA (stroke) occurs when the blood flow to the brain is impaired, resulting in a lack of oxygen and a destruction of brain tissue. CVA includes loss of consciousness; weakness or 1. 2. paralysis on one side of the body (hemiplegia); dizziness; dysphagia (difficulty swallowing); visual disturbances; mental confusion; aphasia (speech and language impairment); and incontinence. When a CVA occurs, immediate care within the first three hours can help prevent brain damage. Treatment with thrombolytic or “clot-busting” drugs such as TPA (tissue plasminogen activator) can dissolve the blood clot and restore blood flow to the brain. Aphasia is a speech or language impairment. There are different types. ALS is amyotrophic lateral sclerosis. Also called Lou Gehrig’s disease. This is a chronic degenerative neuromuscular disease. The cause is unknown. Carpal tunnel syndrome is a progressive, painful condition of the wrist and hand. It occurs when the median nurse is pinched or compressed. Concussions are traumatic brain injuries, usually from a blow to the head by an accident, injury or fall. The brain slides back/forward and forcefully hits against the skull. Think of it like a bruise on the brain. Encephalitis is an inflammation of the brain and is caused by a virus, bacterium, or chemical agent. Epilepsy or seizure syndrome is a brain disorder associated with abnormal electrical impulses in the neurons of the brain. Hydrocephalus is an excessive accumulation of cerebrospinal fluid in the ventricles and, in some cases, the subarachnoid space of the brain. It is usually cause by a congenital (at birth) defect, infection, or tumor that obstructs the flow of cerebrospinal fluid out of the brain. The condition is treated by the surgical implantation of a shunt (tube) between the ventricles and the veins, heart, or abdominal peritoneal cavity to provide for drainage of the excess fluid. Meningitis is an inflammation of the meninges of the brain and/or spinal cord and is caused by a bacterium, virus, fungus, or toxins such as lead and arsenic. Multiple Sclerosis (MS) is a chronic, progressive, disabling condition resulting from a degeneration of the myelin sheath in the central nervous system. Neuralgia is nerve pain. Inflammation, pressure, toxins, and other disease cause it. Paralysis usually results from a brain or spinal cord injury that destroys neurons and results in a loss of function and sensation below the level of injury. Hemiplegia is paralysis on side of the body and is caused by a tumor, injury, or CVA. Paraplegia is paralysis in the lower extremities or lower part of the body and is caused by a spinal cord injury. Quadriplegia is paralysis of t harems, legs, and body below the spinal cord injury. Parkinson’s disease is a chronic, progressive condition involving degeneration of brain cells, usually in persons over 50 years of age
Updated 38d ago
flashcards Flashcards (23)
Axons
Updated 65d ago
flashcards Flashcards (26)
0.00
studied byStudied by 0 people