Lecture 3: Nerve cells Flashcards
What types of cells comprise nervous system?
neurons and glia
What kind of synapses is in majority in the brain?
chemical synapses
Camillo Golgi
invented silver-based stain -> stained nerve cells with silver salts
Santiago Ramon y Cajal
used staining technique to study tissues
Golgi stain
stains random tissue slice -> allow a view of only occasional cells, selection process unknownn; ORANGE
nissl stain
stains DNA in cell body = so you can only see cell bodies; PURPLE
HRP stain
injection enables retrograde transportation through brain tissue to see neuronal projections
soma
cell body of neuron (nucleus, ribosomes, mitochondria); genetic + metabolic processes
dendrite
neuron entrence
afferent
carry information to soma
axon
neuron exit
efferent
carry information from soma
What are dendritic spines? What is their main function?
lined with specidic synaptic receptors at which dendrite receives information from other neurons => increase dendritic surface area enabling receiving more information
cell membrane
skin of cell, most chemicals cannot cross membrane, but protein channels in membrane permit controlled flow of water, oxygen, sodium, potassium, calcium, chloride and other imporant chemicals
nucleus
with DNA - contains chromosomes, codes for proteins
mitochondria
power plants; help with construction of high energy molecules - metabolic activities
ribosomes
translate genetic material into proteins; synthesis of new protein molecules
endoplasmic reticulum
rNA goes there to be transalted into proteins in ribosomes
Golgi complex
post office
length constant
index of how far depolarization can spread down dendrite or axon
the longer -> the more likely it is that EPSP generated at distant synapses will depolarize membrane at axon hillock
on what depends length constant?
- internal resistance: resistance to current flowing longitudinally down the dendrite
-membrane resistance: resistance to current flowing across membrane
passive dendrites
similar to cable, passive and inexcitable membranes = in spinal motor neurons
excitable dendrites
majority! with voltage-gated sodium, calcium and potassium channels; add current to boost synaptic signal towards the soma
How are proteins released?
1) they must be packed -> translation, transcription, Golgi system
2) they must be shipped -> transported along axons using specialized transport system - packed into vesicle
3) then they are uptaken into membrane
4) enzyme
5) exocytosis -> as neurotransmitters, they are released - by fusion of vesicle with the membrane - into synaptic cleft
cell membrane
forms double-layer of phospholipids
heads - hydrophilic = like water
tails - hydrophobic = dislike water
protection, fatty substances can wiggle through membrane, but mostly forms impermeable layer
there are proteins embedded into the membrane
what are membrane proteins involved in neurotransmission?
1) channels
2) gated channels
3) pumps
channels in membrane
work through diffusion down concentration gradient
permeability depends on number of channels -> usually, permeable to one or two types of ions
gated channels in membrane
can open or close
conformation -> change shape
depend on voltage or chemical stimulus
permeable to selective number of ions
pumps in membrane
active transport
require energy (ATP)
neurons can be classified by structure into…
1) multipolar - multiple dendrites and axons
2) bipolar - with 2 poles
3) pseudounipolar
neurons can be classfied by location/connectivity into…
1) projection neurons - typically myelinated
2) interneurons - typically smaller, shorter dendrites and axons, within local network, often not myelinated
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3) motor neurons -> extending outside nervous system to non-nervous targets
4) sensory neurons -> extending into nervous system from skin
What is main fuel in the system?
glucose! can pass through blood-brain barier; brain consumes a lot of oxygen due to glucose consumptin
can be synthesized in the liver from starch/amylum (primarily)
What are types of glia cells?
astrocytes, oligodendrocytes, Schwann cells, microglia, radial glia
In the cerebral cortex, there is more neurons or glia cells?
glia cells!
astrocytes
star-shaped; wrap around synapses, functions: give brain structure, help synchronize closely related neurons enabling their axons to send messages in waves; maintain tight junctions in blood-brain barrier
oligodendrocytes
in the brain and spinal cord = make myelin sheeth; can wrap around many cells
Schwann cells
make myelin sheeth in periphery; you need multiple cells to cover one projection neuron
microglia
smallest, inflammation causes them to grow and eat inflammation, part of immune system
radial glia
guide migration of neurons during embryonic development, when embryo grows up, they differentiate into neurons, astrocytes and oligodendrocytes
nodes of Ranvier
gaps along myelin sheeth
Is new cell formation possible?
yes - but only in hippocampus and olfactory bulb
Is it possible to regenerate axon?
Yes! If only axon gets damaged, regeneration is possible. However, death of soma has major consequences
What does neuron eat? (nourishment)
almost fullly dependent on glucose! why? because it can cross blood-brain barrier in large quantities
to use glucose, body requires vitamin B1
what substances can passively cross blood-brain barrier?
lipophilic, hydrophobic substances, small molecules (CO2, O2), vitamines A and D
how does water crosss blood-brain barrier?
through special protein channels
what substances need active transport to cross blood-brain barrier?
glucose and amino acids; larger molecules; nutrients
membrane potential
when at rest, membrane maintains electrical potential which is slightly negative inside in respect to outside = resting potential = -70mV
how to record membrane potential?
with the use of oscillioscope
one electrode should be put into bath, the other one in the axon
why resting potential (-70mv) is needed?
to enable neuron to respond rapidly
sodium potassium pump
pumps 3 sodium atoms outside
pumps 2 potassium atoms inside
net exchange results in more negative inside than outside
what forces ions encounter?
1) electrical gradient
2) chemical gradient
-> sum of the two determines whether specific ions will diffuse in or out (net diffusion)
what happens when neuron is stimulated?
that depends whether stimulation is negative (hyperpolarization) or positive (depolarization)
in case of hyperpolarization, inside gets even more negative
in case of depolarization, inside gets more positive -> if threshold is reached, action potential can be obtained and neuron can fire
EPSP -> excitatory post-synaptic potentials
Na channels in membrane open
positive charge flows inside the cell
depolarization
IPSP -> inhibitory post-synaptic potentials
Cl channels in membrane open
negative charge flows inside the cell
hyperpolarization
what is shunting inhibition?
inward movement of negatively charged chlorine ions, preventing the current flowing through soma to axon hillock
What happens with action potentials at axon hillock?
voltage-dependent Na channels in axon hillock undergo a change - open when certain level of voltage passes through them -> massive influx of Na enables action potential (when threshold is reached)
How action potential is terminated?
K channels open -> there is K efflux causing hyperpolarization
moreover, Na channels get deactivatied
refractory period
occurs right after action potential
absolute: neuron cannot fire, +/- 1 ms
relative: larger than usual stimulation can cause firing, +/- 2-4 ms
what does all-or-none law mean?
all action potentials are the same = have equal amplitude, shape, duration, propagation speed etc.
however, larger stimulation leads to more action potentials
what is main difference between graded potentials vs action potentials?
graded potentials get smaller and smaller over the distance
action potentials are always the same across distance
why action potentials are always the same across distance?
due to meylin sheeth -> at each node of Ranvier, action potentials get renewed
ACTION POTENTIALS SUMMARY
1) voltage dependent Na and K channels in axon
2) cause initiation/termination action potential
3) when crossing treshold = all or none principle
4) amplitude and speed independent of stimulus strength
5) refractory period
electrical synapses
allow direct transfer of ioninc current from one cell to the next
seperated by gap junctions
very fast transmission
common in mammalian CNS = useful in situations requiring synchronization of neurons
chemical synapses
more common type
seperated by synaptic cleft
neurotransmitters are released from presynaptic side to bind to postsynaptic receptors in the membrane
what happens at electrochemical synapses?
1) transmitter is synthesized and stored in vesicle
2) action potential invades presynaptic terminal
3) depolarization causes opening of voltage-gated Ca channels
4) influx of Ca through channels
5) Ca causes vesicles to fuse with presynaptic membrane
6) transmitter is released into synaptic cleft (exocytosis)
7) transmitter binds to receptor molecules
8) opening/closing of postsynaptic channels
9) postsynaptic current causes excitatory/inhibitory postsynaptic potential which travels further down postsynaptic cell
10) removal of neurotransmitter by glial uptake or enzymatic degradation
11) retrieval of vesicular membrane from plasma membrane
neuromuscular junction (motor nerves x muscles)
synaptic junction outside CNS
single action potential causes exocytosis of 200 synaptic vesicles -> evolved to be fail-safe: needs to work every time due to huge size of EPSP
CNS synapses
low EPSP -> single vesicle is released in response to action potential -> more neurons perform sophisticated computations and require many EPSP produced together to produce significant depolarization
spatial summation in CNS
adding together EPSP generated simultaneously at many different synapses of dendrite
temporal summation in CNS
adding together EPSP generated at the same synapse as they occur in rapid succession
what types of synapses can be found in CNS?
1) assymetrical = pre and post synaptic membranes are not equally thickened, depolarization! excitatory
2) symmetrical thickening of two membranes, hyperpolarization! inhibitory
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-> axodendritic = axon x dendrite
-> axosomatic = axon x soma
-> axoaxonic = axon x axon
-> dendodenritic = dendrite x dendrite
What are types of neurotransmitters?
amino acids, amines, peptides
amino acids
examples: GABA, glutamate, glycine
amines
examples: acetylcholine, dopamine, epinephrine, histamine, norepinephrine, serotonin
How are amino acids and amines synthesized?
both types of neurotransmitters are transported to axon terminal where they locally direct transmitter synthesis
their transporters are special proteins embedded in vesicle membrane
peptides
large molecules
chains of amino acids
stored and released from secretory granules
How are peptides synthesized?
they are formed via connecting amino acids by ribosomes of cell body
long peptides are then split in Golgi apparatus
secretory granules bud off from Golgi apparatus and carry them to axon terminals
what types of neurotransmitter receptors are present in postsynaptic membranes?
transmitter gated ion channels
g-protein-coupled receptors
transmitter gated ion channels
membrane-spanning proteins forming pore (closed when neurotransmitter is absent) -> when neurotransmitter binds, they undergo conformational change
may be permeable to Na (depolarization) or Cl (hyperpolarization)
g-protein-coupled receptors
slower, long lasting postsynaptic action
upon binding of neurotransmitter, tehy activate small proteins
(g proteins) which are free to move along intracellular face of postsynaptic membrane -> activated g proteins activate effector proteins
metabotropic messengers
g proteins can trigger widespread metabolic effects
How neurotransmitters are cleared from synaptic cleft?
1) simple diffusion = through extracellular fluid, away from synapse
2) amino acids + amines => diffusion is aided by reuptake into postsynaptic axon terminal -> then neurotransmitters are reloaded into synaptic vesicles or degraded
3) neurotransmitters may be destroyed in the synaptic cleft itself
Why is it important to remove neurotransmitter from the cleft?
example: acetylcholine
high concentrations of acetylchline lead to desensitization (transmitter-gated channels close) - failure of neuronal transmission
What are effects of drugs on nervous system?
That depends whether drugs are antagonists or agonists.
Antagonists are called inhbitors because they inhibit normal function of specific proteins involved in synaptic transmission/
Agonists are mimicking actions of neurotransmitters
What are modulators?
synapses with g-protein coupled neurotransmitter receptors that are NOT directly associated with ion channels
synaptic activation does not evoke EPSP or IPSP but instead modifies their effectiveness!
