Neuronale en hormonale informatie
Lecture 1: Neuronal communication
Neuronal communication
- Neurons
o Ingericht om met elkaar te communiceren
o Dendrieten ontvangers
o Axonen doorgevers
o Contact plaatsen= synapsen neurotransmitters
o Dendritic spines (transmitter detection)
Neuron diversiteit:
Neuron groeperingen
- Number of neurites
o (pseudo)unipolar, bipolar, multipolar
- Shape of dentrites/ dentritic trees
o Pyramidal cells, stellate cells, purinkje cells
- Length of axon
o Projection neurons (lange axonen), interneurons (schakels om info door teg
even)
- Function
o Afferent neurons (eg sensory neurons) efferent neurons (eg motor neurons)
- Transmitter secretion
o Glutamatergic, dopaminergic, cholinergic etc.
Neuron diversity SLIDE
- Anaxonic
- Bipolar
o In retina that connect photoreceptors to ganglion cells
- Unipolar
o Sensory neurons in retina that connect photoreceptors to ganglion cells
- Multiplorar
o Most neurons
Langste axon in het menselijke lichaam
Neuron numbers
- The human brain contains 3-5 x 10^11 neurons (300-500 miljard)
o 1.6 x10^11 in the cerebral cortex
o 10^11 small granule cells in the cerebellum
Purinkje cells
- There are 10 times more non-neuronal cells in the brain
o Glia cells important for information communication
Oligodentrocytes: myelination in the CNS
1
,Astrocyten: 1. bloedvat barriere blood brain barriere
2. zenuwcellen contact maken
Microglia= immuuncel van het brein (hier in het brein gemaakt, maar in lymphocytes)
Myelination:
- Schwann cells: peripheral ns (meerdere schwann cellen nodig om een axon te
myeliniceren)
- Oligodendrocytes: CNS (1 oligodendrocyte kan meerdere axonen myelinseren)
Multiple sclerisis (MS): impaired nerve signal conduction due to inflammation of the myelin
sheath
- Visual disturbances
- Loss of sensation
- Difficulties with walking
- Fatigue
Neurons are ecitable cells
- Excitable cells can generate action potentials
- Action potentials are rapid and brief reversals in membrane potential that actively
propagate along the cell surface
- Geladen ionen naar binnen en buiten wisselingen
Intrecellular recordings
Electical activities in neurons
- Rust membraan potentiaal
- Gragded potential
- Action potential (active neuron)
- Synaptic activity
Resting membrane potentials
- The resting membrane potential (Vm) is the membrane potential of a cell in an
unstimulated state
- In cell= K+
- Out cell= Na+ and Cl-
- Rest: -70 mV
o Equilibrium potential for kalium (Ek) = -90 mV
o Electrostatic forces are both positive later 0mV
o active pump (ATP), sodium, potassium pump! Na/K-ATPase
Neuronal stimulation SLIDE 15
- Depolarization(inward)= richting positief
- Hyperpolarization (outward)= more negative
Ligand-gated ion channels (LGICs) open in response to the binding of a chemical substance
(a ligand; often a neurotransmitter), resulting in the influx of a spe
cific ion type (ion-specificity) and a small change in membrane potential
2
,LGIC play an important role in the induction of neuronal depolarization or hyperpolarization
Neurotransmitter= acetylcholine Ach Na goes inward depolarization stimulus action
potential
Gabba LGIC Cl goes inward hyperpolarization
Suprathreshold depolarization of a neuron results in the generation of an action potential
- Threshold depolarization repolarization hyperpolarization relative
refractory period
Voltage-gates ion channels (VGICs) open in response to small changes in membrane
potential, resulting in the massive influx or efflux of a specific ion type (ion-specificity),
causing a rapid and robust peak in the membrane potential change.
VGICs play an important role in the onset and termination of action potentials.
SLIDE 20!!
- +30 mV kalium kanalen gaan open
- Absolute refractory period
- Relative refractory period moeilijker om nieuwe treshold the bereiken
- Action potentials are all-or-non phenomena
Remmende neurostranmitter kan activerende neurotransmitter compenseren om geen
nieuwe AP the laten ontstaan
VGICs and toxins
• - and -conotoxins (CTX)
– Fish-hunting cone snails (e.g., Conus purpurascens)
– Sodium channel blockers
• Saxitoxin (STX)
– Gonyaulax polyedra
– Sodium channel blockers
• Tetrodotoxin (TTX)
– Puffer fish (Fugu rubripes)
– Sodium channel blockers
• Palytoxin (PTX)
– Coral (e.g., Palythoa toxica)
– Turns Na/K pump into a channel
Pharmacology of VGIC
• Sodium channel blockers:
– Anticonvulsants (carbamazepine; valproate)
– Diuretics (amiloride)
– Local anaesthetics (lidocaine; bupivacaine)
• Potassium channels activators:
– Antihypertensives (diazoxide)
• Potassium channel blockers:
– Antiarrhythmics (amiodarone)
– Hypoglycaemics (sulphonylureas)
3
, Action potential propagation
- Continuous conduction is unmyelinated axons is carried by lcal currents and is
directional due to the refractory period
Action potential propagation in myelinated axons
- Saltatory conduction: Nodes of Ranvier have high concentrations of sodium
channels and the action potential seems to jump form node to node. Internodal
segments are well insulted by myelin, so local currents can travel fast. Saltatory
conduction is up to 100 times faster than conduction in unmyelinated neurons.
Neuronal integration
- Spatial summation
- Temporal summation
Summation is extremely important:
- Individual synaptic inputs are too small to trigger action potentials
- On average, each neuron in the brain receives 100-1,000 synaptic inputs
- Pyramidal cells require 100 excitatory synaptic inputs at the same time to generate
an action potential
- Summation allows integration of excitatory and inhibitory inputs
- Neurons are decision-making devices; the decision to fire an action potential is made
at the axon hillock when the sum of all excitatory and inhibitory inputs exceeds the
firing threshold potential
Take home massages
ü Neurons are polarized cells
ü Dendrites receive signals, axons transmit signals
ü Non-neuronal cells are 10 times more abundant than neurons
ü Glial cells are involved in myelination, regulation of neurotransmission, and
immune responses
ü Neurons are excitable cells
ü Neurons can produce action potentials
ü Neurons have a resting membrane potential of -70 mV
ü The neuronal resting membrane potential is actively maintained
ü Ligand-gated ion channels cause graded potentials in neurons
ü Graded potentials are small changes in a neurons membrane potential
ü Voltage-gated ion channels regulate initiation and propagation of action potentials
ü Action potential are rapid and brief changes in a neurons membrane
potential
ü Myelination increases the speed at which action potential are propagated
ü Myelinated axons propagate action potentials 100 times faster than
unmyelinated axons
ü Summation of signals allows neurons to integrate diverse inputs
ü Summation can be spatial or temporal in nature
4
Lecture 1: Neuronal communication
Neuronal communication
- Neurons
o Ingericht om met elkaar te communiceren
o Dendrieten ontvangers
o Axonen doorgevers
o Contact plaatsen= synapsen neurotransmitters
o Dendritic spines (transmitter detection)
Neuron diversiteit:
Neuron groeperingen
- Number of neurites
o (pseudo)unipolar, bipolar, multipolar
- Shape of dentrites/ dentritic trees
o Pyramidal cells, stellate cells, purinkje cells
- Length of axon
o Projection neurons (lange axonen), interneurons (schakels om info door teg
even)
- Function
o Afferent neurons (eg sensory neurons) efferent neurons (eg motor neurons)
- Transmitter secretion
o Glutamatergic, dopaminergic, cholinergic etc.
Neuron diversity SLIDE
- Anaxonic
- Bipolar
o In retina that connect photoreceptors to ganglion cells
- Unipolar
o Sensory neurons in retina that connect photoreceptors to ganglion cells
- Multiplorar
o Most neurons
Langste axon in het menselijke lichaam
Neuron numbers
- The human brain contains 3-5 x 10^11 neurons (300-500 miljard)
o 1.6 x10^11 in the cerebral cortex
o 10^11 small granule cells in the cerebellum
Purinkje cells
- There are 10 times more non-neuronal cells in the brain
o Glia cells important for information communication
Oligodentrocytes: myelination in the CNS
1
,Astrocyten: 1. bloedvat barriere blood brain barriere
2. zenuwcellen contact maken
Microglia= immuuncel van het brein (hier in het brein gemaakt, maar in lymphocytes)
Myelination:
- Schwann cells: peripheral ns (meerdere schwann cellen nodig om een axon te
myeliniceren)
- Oligodendrocytes: CNS (1 oligodendrocyte kan meerdere axonen myelinseren)
Multiple sclerisis (MS): impaired nerve signal conduction due to inflammation of the myelin
sheath
- Visual disturbances
- Loss of sensation
- Difficulties with walking
- Fatigue
Neurons are ecitable cells
- Excitable cells can generate action potentials
- Action potentials are rapid and brief reversals in membrane potential that actively
propagate along the cell surface
- Geladen ionen naar binnen en buiten wisselingen
Intrecellular recordings
Electical activities in neurons
- Rust membraan potentiaal
- Gragded potential
- Action potential (active neuron)
- Synaptic activity
Resting membrane potentials
- The resting membrane potential (Vm) is the membrane potential of a cell in an
unstimulated state
- In cell= K+
- Out cell= Na+ and Cl-
- Rest: -70 mV
o Equilibrium potential for kalium (Ek) = -90 mV
o Electrostatic forces are both positive later 0mV
o active pump (ATP), sodium, potassium pump! Na/K-ATPase
Neuronal stimulation SLIDE 15
- Depolarization(inward)= richting positief
- Hyperpolarization (outward)= more negative
Ligand-gated ion channels (LGICs) open in response to the binding of a chemical substance
(a ligand; often a neurotransmitter), resulting in the influx of a spe
cific ion type (ion-specificity) and a small change in membrane potential
2
,LGIC play an important role in the induction of neuronal depolarization or hyperpolarization
Neurotransmitter= acetylcholine Ach Na goes inward depolarization stimulus action
potential
Gabba LGIC Cl goes inward hyperpolarization
Suprathreshold depolarization of a neuron results in the generation of an action potential
- Threshold depolarization repolarization hyperpolarization relative
refractory period
Voltage-gates ion channels (VGICs) open in response to small changes in membrane
potential, resulting in the massive influx or efflux of a specific ion type (ion-specificity),
causing a rapid and robust peak in the membrane potential change.
VGICs play an important role in the onset and termination of action potentials.
SLIDE 20!!
- +30 mV kalium kanalen gaan open
- Absolute refractory period
- Relative refractory period moeilijker om nieuwe treshold the bereiken
- Action potentials are all-or-non phenomena
Remmende neurostranmitter kan activerende neurotransmitter compenseren om geen
nieuwe AP the laten ontstaan
VGICs and toxins
• - and -conotoxins (CTX)
– Fish-hunting cone snails (e.g., Conus purpurascens)
– Sodium channel blockers
• Saxitoxin (STX)
– Gonyaulax polyedra
– Sodium channel blockers
• Tetrodotoxin (TTX)
– Puffer fish (Fugu rubripes)
– Sodium channel blockers
• Palytoxin (PTX)
– Coral (e.g., Palythoa toxica)
– Turns Na/K pump into a channel
Pharmacology of VGIC
• Sodium channel blockers:
– Anticonvulsants (carbamazepine; valproate)
– Diuretics (amiloride)
– Local anaesthetics (lidocaine; bupivacaine)
• Potassium channels activators:
– Antihypertensives (diazoxide)
• Potassium channel blockers:
– Antiarrhythmics (amiodarone)
– Hypoglycaemics (sulphonylureas)
3
, Action potential propagation
- Continuous conduction is unmyelinated axons is carried by lcal currents and is
directional due to the refractory period
Action potential propagation in myelinated axons
- Saltatory conduction: Nodes of Ranvier have high concentrations of sodium
channels and the action potential seems to jump form node to node. Internodal
segments are well insulted by myelin, so local currents can travel fast. Saltatory
conduction is up to 100 times faster than conduction in unmyelinated neurons.
Neuronal integration
- Spatial summation
- Temporal summation
Summation is extremely important:
- Individual synaptic inputs are too small to trigger action potentials
- On average, each neuron in the brain receives 100-1,000 synaptic inputs
- Pyramidal cells require 100 excitatory synaptic inputs at the same time to generate
an action potential
- Summation allows integration of excitatory and inhibitory inputs
- Neurons are decision-making devices; the decision to fire an action potential is made
at the axon hillock when the sum of all excitatory and inhibitory inputs exceeds the
firing threshold potential
Take home massages
ü Neurons are polarized cells
ü Dendrites receive signals, axons transmit signals
ü Non-neuronal cells are 10 times more abundant than neurons
ü Glial cells are involved in myelination, regulation of neurotransmission, and
immune responses
ü Neurons are excitable cells
ü Neurons can produce action potentials
ü Neurons have a resting membrane potential of -70 mV
ü The neuronal resting membrane potential is actively maintained
ü Ligand-gated ion channels cause graded potentials in neurons
ü Graded potentials are small changes in a neurons membrane potential
ü Voltage-gated ion channels regulate initiation and propagation of action potentials
ü Action potential are rapid and brief changes in a neurons membrane
potential
ü Myelination increases the speed at which action potential are propagated
ü Myelinated axons propagate action potentials 100 times faster than
unmyelinated axons
ü Summation of signals allows neurons to integrate diverse inputs
ü Summation can be spatial or temporal in nature
4
