Neurobiology (20-25) Flashcards
What does the nervous system do?
Sensory → receive and interpret information about external and internal environments (hunger/thirst, visual/audio)
Integrating → makes decisions about this information
Motor → organise and carry out action
What is the unit of the nervous system?
Neurons → structural and functional unit of the nervous system
→ individual cells, not continuous with other neurons
→ 3 parts: dendrites, soma (cell body) and axon
→ conduction takes place dendrites → soma → axon
What are dendrites?
Where a neuron receives input from other cells
→ increase surface area for receiving inputs
What is the axon?
A thin fibre that extends from a neuron
→ carries electrical signals long distances
What is myelin?
The myelin sheet coats the axon (adaptation)
→ improves conduction - increases velocity and fidelity
→ node of ranvier: break in myelin sheath
oligodendrocytes can myelinated multiple axons
What happens at the terminals of neurones?
Release of chemical transmitters
→ synapse with other neurones
→ excites/inhibits next cell in the chain
What are the two types of transport that occur in neurones?
Anterograde transport (forward)
soma → axon → terminals
→ rapid/slow
Retrograde transport (backward)
terminals → soma (towards cell body)
→ remove worn out mitochondria, SER for degradation
→ rapid
What is the mechanism of axonal transport?
Protein shuttles that move along microtubules (have polarity)
→ catalysed by ATP so energy intensive
What is the function of astrocytes?
Specialed glial cells that wrap around blood vessels, extract glucose from blood
Supporting role
→ mop up transmitters
→ correct ionic environment
→ release gliotransmitters (ATP, glutamate, D-serine) to provide metabolic fuel for neurones
Glial cells don’t produce electrical signals
What is the function of microglial cells?
‘The brain’s macrophages’
→ act as scavengers - clean up debris, like dying neurones
→ launch immune response
What makes up the central nervous system?
Brain and spinal cord
What makes up the peripheral nervous system?
Autonomic (involuntary) nervous system → heart rate, breathing, vasodilation, secretion of digestive enzymes
Somatic (voluntary) nervous system → skeletal muscles
How is the spinal cord arranged?
Dermatomes - the different regions of the spinal cord
→ segmented into cervical, thoracic, lumbar, sacral
Cross section → inner part cell bodies (grey matter), outer part axons (white matter)
What are the meninges?
3 layers of membrane that protect the CNS
→ allows the brain to be suspended in spinal fluid
- tough outer layer: dura mater
- arachnoid mater
- pia mater
What is the ventricular system?
Cavities filled with cerebrospinal fluid
→ principal source of CSF
→ allows waste products to be drained
→ supplies brain and sp cord with nutrients
→ buffers changes in blood pressure and protects brain
→ supplies brain with fluid during dehydration
→ allows the brain to remain buoyant
→ under normal circumstances equilibrium between production and drainage
What are the major regions of the brain?
Frontal lobe
Cerebral cortex
Parietal lobe
Occipital lobe
Temporal lobe
Cerebellum
Pituitary gland
Brain stem
What is the corpus callosum?
White matter that connects the left and right hemispheres of the brain
→ need to communicate
What is hyper polarising?
Making the membrane potential more negative
→ become more negative than -70
What is depolarising?
Making the membrane potential more positive
→ becomes less negative
→ positive ions moving in
What does the resting membrane potential require?
- Intact cell membrane → only allows certain ions through
- Ionic concentration gradients and ionic permeabilities (particularly K+) → energy dependant pumps create conc grad
- Over the long term: metabolic processes
What are intracellular ionic concentrations like?
low [Na+]
high [K+]
low [Cl-]
proteins, phosphates groups contribute to the -ve potential inside cells
At resting membrane potential are membranes permeable to Na+?
No
→ changing [Na+] doesn’t effect membrane potential
What maintains the balance of [K+] in cells?
At resting potential there is a balance between K+ ion movement
→ concentration gradient drives efflux and electrical gradient drives influx
Why is membrane potential usually less negative than the ideal membrane potential (Ek)?
The cell membrane is not completely impermeable to Na+ (so Na+ moves in) and there is K+ leakage
→ depolarises: makes membrane potential less negative
What maintains ionic gradients across membranes in the long term?
ATP-dependant ion pumps
→ pushes ions against conc grad
→ energy expensive
What is an action potential?
Major mechanisms of neuronal communication
→ travels down axon to terminals
→ triggers transmitter release
→ occurs when threshold potential crossed
→ triggered by depolarisation
Why do action potentials depend on Na+?
Influx of Na+ through voltage-gated channels creates depolarisation
→ resting ~ 70mV, channels: closed
→ depolarised ~ 30mV, channels: open
Why does Na+ move into cells when channels are open?
Huge chemical concentration gradient and electrical gradients
→ drives movement into cells
What initially depolarises neurones to open the voltage-gates Na+ channels?
- Synaptic transmission → excitatory postsynaptic potentials
- Generator (receptor) potentials (sensory neurones)
- Intrinsic properties (like heart pacemaker activity)
- Experimental (electrical stimulation)
Why do action potentials have a threshold?
So not all depolarisation gives rise to action potential
→ if the threshold is met all AP are the same size ‘all or nothing’
What happens during repolarisation of the action potential?
Na+ channels close
K+ voltage-gated channels open: K+ moves out of neurone
→ becomes more negative
What is the absolute refractory period?
Starts when voltage-gates Na+ channels open continues for ~1ms
→ during this time it is not possible to elicit another action potential
→ due to channel inactivation - ball and chain model
What is the relative refractory period?
Continues 2-3 ms after the absolute RF
→ action potential can be elicited but require stronger/longer stimulation
→ increased K+ permeability during RFP makes it harder to depolarise the membrane
What do refractory periods ensure?
That the action potential travels in one direction
Where are action potentials initiated?
Axon hillock
→ depends on size of depolarisation
→ speed of action potential depends on axon diameter: bigger = faster
How does myelination affect action potentials?
Myelination preserves fidelity of the action potential and accelerated action potential conduction
What is a synapse?
A junction where information is passed from one neurone to another (or to e.g. muscle)
→ point of communication
What is the difference between electrical and chemical synapses?
Electrical → no delay, can be bidirectional, little plasticity
Chemical → delay (at least 0.5ms, one way, plastic - change behaviour in response to long-term activity)
What is the structure of a chemical synapse?
Presynaptic terminal → end of axon, where electric signal (action potential) turned into chemical signal (neurotransmitter release)
→ has mitochondria
→ vesicles - with small volume, high conc. neurotransmitter
→ wide synaptic cleft
What are some neurotransmitters?
Amino acids → GABA, glutamate
Amines → noradrenaline, dopamine, 5 hydroxytryptamine (serotonin)
Neuroactive peptides (slow) → orexin, neurotensin, enkephalins…
Others → acetylcholine, nitric oxide, ATP
Where do chemical synapses occur?
Everywhere…
Axodentritic → synapses made onto the dendrite
Axosomatic → synapses made onto the soma
Axoaxonic → synapses made onto the axon
Why are neurotransmitters packaged into vesicles?
Want to release a lot of neurotransmitter and prevent from breakdown
→ to concentrate and protect neurotransmitters
How are neurotransmitters packaged into vesicles?
- Vesicle and peptide neurotransmitter precursors are synthesised in the cell body and are released from golgi
- Vesicles travel through the axon on microtubule tracks, peptide neurotransmitters are already in some vesicles
- Nonpeptide neurotransmitters are synthesised and transported into vesicles in the nerve terminal
→ pump uses ATP to pump H+ into vesicle: proton gradient drives vesicle filling
Where are non peptide neurotransmitters synthesised?
In the nerve terminal
→ where they are also transported into vesicles
How are neurotransmitters released?
- vesicles dock to presynaptic membrane
- Ca+ entry - catalyses fusion
- vesicle fusion (exocytosis)
- recycling of vesicles (endocytosis)
How to vesicles dock to the presynaptic membrane?
SNAP & SNARE proteins anchor vesicles to the presynaptic vesicles
→ proteins twist to bring vesicle close proximity with membrane
→ docked vesicles are ready to release their contents
How does Ca2+ enter nerve terminals?
The action potential:
1. depolarises nerve terminal via voltage-gated Na+ channels
2. opens voltage-gated Ca+ channels
3. Ca+ moves into the nerve terminal down its electrochemical gradient into the neurone
What does Ca2+ entry into neurones lead to?
Fusion of docked vesicles and release of neurotransmitter (exocytosis)
→ Ca2+ binds to one of the SNARE proteins
→ after fusion pore opens - rapid release of neurotransmitter due to high conc inside vesicle
What does neurotransmitter release require?
Binding of multiple Ca+ ions
→ neurotransmitter release occurs very quickly after Ca2+ entry
→ blocking Ca2+ entry blocks synaptic transmission
What happens when synaptotagmins are knocked out?
(synaptotagmins: facilitates synaptic vesicle membrane fusion with the presynaptic membrane)
facilitates synaptic vesicle membrane fusion with the presynaptic membrane
→ knockout loses fast synchronous neurotransmitter release
What happens to neurotransmitter when its released?
Released neurotransmitter binds to postsynaptic receptors and produces cellular effects
→ different receptors produce different speeds of signalling
Why is removal of transmitter required?
Lots of neurotransmitter roaming about can desensitise receptors and slow transmission
Neurotransmitter removed by:
→ reuptake into neurones
→ extracellular metabolism
→ diffusion
→ uptake into glia cells
What are the two types of receptor that acetylcholine acts at?
- nicotinic → inotropic (modifies the force or speed of contraction of muscles), permeable to Na+/K+, fast signalling
- muscarinic → metabotropic (requires activation of secondary messenger cascade), slower signalling
Why is synaptic transmission carefully regulated?
Careful regulation of synaptic transmission ensures that synapses operate efficient and within physiological limits
How many pairs of spinal nerves are there in humans?
31 pairs of spinal nerves
→ grouped regionally by spinal region
What is the structure of peripheral nerves?
Multiple layers of connective tissue surrounding axons (unmyelinated and myelinated)
→ endometrium surrounds axons, then perineurium and epineurium
→ blood vessels to carry nutrients and oxygen to neurone cells
What is a motor unit?
1 axon synapsed to multiple muscles fibres
→ when the motor unit activated fires action potential and all synapsed muscle fibres contract
→ intermingles throughout muscles
fine control = small motor units (eye muscles)
coarse control = large motor units (calf muscles - movement not complex)
What is a neuromuscular junction?
Synapse between nerve and muscle
→ neurotransmitter at the NMJ is acetylcholine - activates nicotinic receptors
→ ionic channel → allows cation depolarise muscle cells → causes contraction
How can you change the fore of contraction?
- Recruit more motor units
→ recuits more muscles fibres
→ more fore of contraction - Termporal summation
→ high frequency of of action potentials in presynaptic neurones - twitches don’t have time to decay (tetany)
How does a fused tetanus occur?
Rapid action potentials in motor neurone
→ no time for relaxation
→ sustained contractions all sum up
→ doesn’t occur in heart as action potential and muscle contraction occur together
Why do muscles show fatigue?
Protective/defence mechanism - so don’t damage muscle
→ causes: depletion of glycogen, accumulation of extracellular K+ (can’t reploarise correctly), lactate, ADP and Pi, central fatigue in the brain
What is the function of golgi tendon organs and muscle spindles?
Regulation of muscle tone, damage and movement
Golgi tendon organs → detect muscle tension
Muscle spindles → detect muscle stretch, found in middle of muscles
What is the order of sensory transduction?
Stimulus (touch, pressure, hot)
→ receptor
→ change in permeability of nerve ending (increased to Na)
→ change in membrane potential of nerve ending (generator potential)
→ generation of action potentials in nerve ending
→ propagation of action potentials to the CNS
→ integration of information by the CNS
What are tonic receptors?
Slow adapting mechanoreceptors
→ respond to stimulus as long as to exists, continuous action potentials generated
→ continually feel sensation
→ information about duration of stimulus
What are phasic receptors?
Rapidly adapting mechanoreceptors
→ response to stimulus diminishes quickly then stops
→ only feel sensation at the beginning, no info about duration of stimulus
→ e.g. clothes
What are receptive fields?
An area where a sensory neurone can pick up stimulus
→ multiple nerve endings
→ touching skin surface far away two signals to the brain, 2 points close together one signal to the brain
What is the flexion reflex?
Produces a withdrawal of the stimulated limb in order to protect against tissue damage
→ e.g. standing on a pin → activates sensory neurone → muscle contracts → occurs without sensory control
What are the functions of autonomic nervous system?
Functions are not under conscious control
→ contraction/relaxation of smooth muscle
→ exocrine and endocrine secretion
→ control of the heartbeat
→ steps in intermediary metabolism
What is the pathway of the somatic nervous system?
Motorneurons
→ cell body in spinal cord or brain stem → axon → neuromuscular junction → skeletal muscle
What is the pathway of the autonomic nervous system?
Cell body in spinal cord or brainstem → preganglionic neurone → autonomic ganglion (synaptic transmission) → postganglionic neurone → target organ/tissue
Whats the difference between pre and post ganglionic fibres?
Preganglionic fibres → thin myelinated axons from the brain or spinal cord
Postganglionic fibres → more numerous, an example of divergence
What are the two branches of the autonomic nervous system?
Sympathetic → controls ‘fight or flight’ response
→ acetylcholine then noradrenaline transmitters
Parasympathetic → controls body’s response during rest
→ acetylcholine then acetylcholine transmitters
Does the sympathetic nervous system stimulate adrenal glands?
Yes
→ sympathetic preganglion neurone from spinal cord synapses to autonomic ganglion, post ganglion neurone releases epinephrine and norepinephrine (to circulation)
Do both sympathetic and parasympathetic receptors release acetylcholine?
Yes
→ via preganglion neurone to nicotinic Ach receptors
Do both sympathetic and parasympathetic Ach receptors release noradrenaline?
No
→ sympathetic: noradrenaline (to alpha and beta adrenoceptors)
→ parasympathetic: acetylcholine (to muscarinic Ach receptors)
What tissues does the sympathetic nervous system involve?
Eye, lacrimal glands, salivary glands
Heart
Larynx, trachea, bronchi lung
Oesophagus, stomach, small intestine
Liver, binary system
Large intestine
Adrenal gland
Kidney, bladder
Reproductive organs
What is the paravertebral chain (sympathetic chain)?
A series of ganglia that lie lateral and vertical to to the vertebral bodies of the spinal column
What are some sympathetic actions?
Eye → dilate pupil
Salivary glands → secretion
Heart → increase rate and force
Liver → increase glycogenolysis
Blood vessels → constrict
Kidneys → renin secretion
Reproductive organs → ejaculation
What are some parasympathetic actions?
Eye → constrict pupil
Salivary glands → secretion
Heart → decrease rate
Liver → no effect
Blood vessels → no effect
Kidneys → no effect
Reproductive organs → erection
What is autonomic tone?
Most muscles receive a basal level of autonomic activity
→ blood vessels - sympathetic tone, particle constriction
→ heart - vagal tone, decrease during exercise
How are autonomic reflexes controlled?
Sensory fibres
→ interneurones (in neural circuits in hypothalamus/spinal cord)
→ sympathetic and parasympathetic pre/postganglionic neurones
→ effector organs (e.g. heart, eye)
e.g. increase heart rate - increased blood flow to muscles
What does the hypothalamus control?
Regulation of homeostasis
Motivation emotional behaviour
Damage hypothalamus → failure of homeostatic mechanisms
What is the micturition reflex?
Bladder-to-bladder contraction reflex
What is Horner’s syndrome?
Neurodegenerative disease
→ autonomic failure
→ dizziness, fatigue, blackouts, postural hypertension
What are the two types of muscular contraction?
All muscles traduce chemical and electrical commands to produce a mechanical response
→ isometric: muscle length constant, tension increased
→ isotonic: muscle length shortness, tension constant
What are the 3 types of muscle?
Cardiac
Smooth (glands, blood vessels, gut…)
Skeletal (striated)
What is the structure of cardiac muscle?
Myocytes 15um diameter, 100um length
→ linked together via intercalated disks
→ electrically coupled via gap junctions
(all commented, when one cell activated all change in potential)
What are the properties of cardiac muscle?
Striated like skeletal muscle
Shows myogenic activity → spontaneous rhythm generated within the heart
Cells are electrically couples
Controlled by autonomic nervous system and hormones
What are the properties of smooth muscle?
Muscle of internal organs (glands, blood vessels, gut…)
→ heterogeneous - lots of different types
→ produce slow long lasting contractions
→ spindle-shaped cells linked together by mechanical and electrical junctions
→ no cross striations, but does have loose lattice of actin and myosin
→ innervated by the ANS
→ very plastic properties, can adjust over large range
What is the properties of skeletal muscle?
Alignment of sarcomeres gives striated appearance
Bundles of muscle fibres made of myofibrils
Filaments slide over each other
What does the force produced by a muscle depend on?
- number of active muscle fibres (recruitment)
- frequency of stimulation
- rate at which muscle shortens
- cross sectional area of the muscle
- initial resting length of the muscle
What is the T system of sarcoplasmic reticulum?
Transverse tubular system → branched network of tubules along the fibre
→ allows action potential to propagate, excitation-relaxation coupling in muscle cells
What is the cross-bridge cycle?
Method by which all muscle types contract
→ ATP binds, myosin head detaches
→ ATP hydrolysed, myosin resting
→ cross bridge formed, myosin head binds to new position on actin
→ P release, myosin head changes conformation - power stroke filaments slide past each other
→ ADP released
What are the sources of ATP for muscle contraction?
ADP + creatine phosphate
Glycogen (stored in muscle) → broke down into glucose
What are slow-twitch fibres (type 1)?
Used for muscular endurance → resistant to fatigue, can maintain tension for long
metabolism: oxidative phosphorylation
mitochondria: numerous
glycogen storage: high
contraction rate: slow
relaxation rate: slow
e.g. muscles in lower leg that maintain posture
What are fast-twitch fibres (type 2)?
Contraction rate: high → short, powerful bursts of energy
Type 2a (fast oxidative fibres)
metabolism: oxidative phosphorylation
mitochondria: very numerous
glycogen storage: high
fatigue resistant
Type 2b (large diameter, white muscle)
metabolism: glycolytic (aerobic)
mitochondria: less numerous (limited blood supply)
glycogen storage: high
rapid fatigue
required for short periods → sprinting
Why are calcium ions requires for muscle contraction?
Ca2+ reveals the myosin binding site
How does muscle intracellular [Ca2+] increase?
→ opening of voltage gated Ca2+ channels following depolarisation
→ opening of intracellular Ca2+ release channels
→ Ca2+ entry from SR (action of hormones)
How is skeletal muscle depolarised?
Acetylcholine at neuromuscular junctions
→ receptors: nicotinic receptors (inotropic)
Does skeletal or cardiac muscle have longer action potentials?
Cardiac (200msec)
→ skeletal (5msec)
How is contraction terminated?
Calcium removal
→ removal necessary otherwise constant contraction, requires ATP to activate proteins
Small amount of Ca2+ is extruded form cell
→ most taken up into the sarcoplasmic reticulum by SERCA-type pump
How is excitation-contraction coupling different in smooth muscle?
No T-system
→ contraction regulated by myosin
→ contraction slower and longer lasting than skeletal muscle
→ contraction terminated by Ca2+ removal and dephospho rylation
What is sarcoplasmic reticulum?
A specialized form of the endoplasmic reticulum of muscle cells
→ dedicated to calcium ion handling
→ necessary for muscle contraction and relaxation
What is myosin?
A superfamily of motor proteins involved in muscle contraction
hey are ATP-dependent and responsible for actin-based motility
