MP7: How do neurons convey information? Flashcards
What 2 important concepts were discovered by Edgar Adrian with regards to how neurons use electrical signals to communicate?
- Individual nerve impulses are of a consistent size (now known as action potentials)
- Neurons use the frequency of action potentials to convey the intensity of the signal
Why are aplysia good model organisms for studying neurons?
They don’t have as many neurons as other model organisms so they’re easier to study.
Where would you find the following neurons:
- pyramidal neuron
- motor neuron
- basket cell
- sensory neuron
- Brain (cerebral cortex, hippocampus…)
- CNS (CNS –> muscles)
- Brain (cortex and cerebellum)
- PNS (form clusters of ganglia)
In which direction does information generally flow in vertebrate neurons?
Dendrites to cell bodies to axons.
What are the functions of glia?
- Forming myelin sheaths in the CNS axons
- Maintain homeostasis
- Support and protection for neurons
How is the nervous system linked to the vascular system?
- The blood-brain barrier (vascular system protects nervous system)
- Autonomic nervous system regulates the functions of the cardiovascular system (sympathetic and parasympathetic)
- Neurovascular coupling - changes in neuronal activity are coupled with changes in blood flow to the brain to ensure active neurons receive adequate oxygen and nutrients.
What are the fundamental steps of neural communication?
- Dendrites receive signals from other neurons/sensory receptors via their dendritic spines
- Integration of signals in the cell body
- If the integrated signals are strong enough, the signal is transmitted down the axon (action potential).
- Release of neurotransmitters at the synapse.
- Reception at the postsynaptic side, resulting in depolarization or hyperpolarization, depending on the type of neurotransmitter and receptor.
- Integration of postsynaptic potentials.
- Termination by removing neurotransmitters from the synaptic cleft.
Describe the process of the knee-jerk reflex.
- A tap is delivered to the knee cap
- The tap causes stretching of the quadricep muscles.
- A signal travels back to the spinal cord without interneurons, completely independent of higher centres.
- A motor neuron conducts an outwards impulse back the the femur muscle, triggering contraction.
- This contraction, coordinated with the relaxation of the antagonist hamstring muscles, causes the leg to kick.
Give an experiment that highlights the speed at which neurons can convey information. Why is this speed important?
Zebrafish larva were exposed to water pulses and resulted in the fish changing its direction of travel within a few milliseconds of the water pulse.
This speed must have been selected for extensively over evolution, allowing for escape from predators.
Many neurons have long extensions, so how are proteins synthesized locally or transported from the soma?
What experiments have shown this?
While some dendritic and axonal proteins are synthesized from mRNAs locally, most proteins are actively transported from the soma. There are lots of ribosomes in the dendrites and axon, meaning there can be local translation and hence quick changes in the proteome.
Injection of radioactively labeled amino acids into a dendrite allowed for observations of protein/mRNA transport. The proteins were then isolated for gel electrophoresis autoradiography, where it was shown that proteins using fast axonal transport are often membrane proteins and secreted proteins, whereas slow transport is used by cytosolic proteins and cytoskeleton proteins.
What is the soma?
The cell body
What is the membrane-associated periodic skeleton (MPS)? What is it composed of? How has it been studied?
A cytoskeletal structures that plays a critical role in maintaining the structural integrity and stability of the cell membrane, as well as in regulating the movement and distribution of membrane-associated proteins and lipids.
Cytoskeletal proteins actin, spectrin, and adducin form periodic structures in the axon to form the MPS.
It’s been studied using super-resolution microscopy to see how these are arranged.
How is cargo moved along microtubules/actin filaments?
Cargo is moved along microtubules and actin filaments in neurons by specialized motor proteins called kinesins and dyneins for microtubules, and myosins for actin filaments.
- Kinesins = plus end
- Dynein = minus end
Kinesins and dyneins are members of the ATPase family of motor proteins, which use energy from ATP hydrolysis to move along microtubules.
How is the cytoskeleton of neurons specialized for transport?
Microtubules in the axon have a very particular direction: plus ends are at the synapse and minus ends are at the soma. In the dendrites, this can be mixed.
Actin forms various structures e.g., rings, although it’s not clear what these are for.
What causes neurons to be electrically polarized at rest? Name the pumps responsible for maintaining this, and give the inside and outside concentrations of relevant ions.
Ion gradients across the plasma membrane and differential ion permeability.
N+-K+ ATPase and K+-Cl- cotransporter
Inside:
- [K+] 120mM
- [Na+] 15mM
- [Cl-] 5mM
Outside:
- [K+] 4mM
- [Na+] 150mM
- [Cl-] 120mM
What equation describes the equilibrium potential of the thought experiment when a membrane is fully permeable to only K+ ions?
Nernst equation –> -85mV
[intracellular]/[extracellular]
What equation describes the membrane potential of the thought experiment when a membrane is permeable to more than one ion?
The Goldman-Hodgkin-Katz equation
What is the membrane potential of an inactive neuron called? Give its exact value.
The resting potential.
-75mV
State Ohm’s law equation.
Current = Voltage / Resistance
How can a neuronal plasma membrane be described in terms of an electrical circuit?
When an ion channel is opened in the plasma membrane, ions can flow across the membrane, creating a transient change in the electrical potential of the neuron. This change in potential can be described as a voltage, and it can be measured using an electrode.
The lipid bilayer of the plasma membrane acts as a capacitor, which can store electrical charge.
The ion channels act as resistors, which can control the flow of ions across the membrane. The movement of ions across the membrane can create an electrical current, which can be described using Ohm’s law.
The battery is the equilibrium potential of an ion.
Give the equation that relates resistance to conductance.
Conductance = 1/Resistance
Describe the voltage clamp method.
The voltage clamp method is a technique used in electrophysiology to measure the flow of ions across the neuronal membrane in response to changes in membrane potential.
The voltage clamp method involves placing a patch pipette, which is a small glass electrode, onto the neuronal membrane and applying a controlled voltage across the membrane using an amplifier. This voltage is controlled by a feedback mechanism that measures the voltage across the membrane and adjusts the voltage being applied to maintain a constant membrane potential.
By holding the membrane potential at a specific level and recording the current flowing across the membrane, researchers can measure the conductance of ion channels and study their properties. The voltage clamp method can also be used to generate artificial action potentials, which can be used to study the mechanisms of action potential generation and propagation in neurons.
What key discoveries were made through the voltage clamp method.
- The rising phase of the action potential resulted from an influx of Na+
- Na+ influx was caused by a rapid increase in Na+ conductance as a consequence of membrane depolarization
- Na+ conductance decreases despite continued depolarization, accounting for the falling phase (inactivation)
- Depolarization also caused increase in K+ conductance and this lagged behind Na+ conductance.
- The conductances are independent of each other, but both depend on the membrane potential
What are the key three properties of an action potential?
- All or nothing
- Regenerative
- Unidirectional
How do action potentials propagate in a single direction?
Action potentials propagate in a single direction along the axon of a neuron due to the refractory period of the voltage-gated ion channels involved in generating the action potential.
What is saltatory conduction and why is it important for action potentials?
Saltatory conduction is the process by which action potentials propagate rapidly along the axon of a myelinated neuron by “jumping” from one node of Ranvier to the next, rather than propagating continuously along the entire length of the axon.
Saltatory conduction is important for action potentials because it allows for faster and more efficient propagation of electrical signals along the axon, which is essential for proper functioning of the nervous system.
What is the patch clamp technique and what does it enable the study of?
Enables the study of current flow through individual ion channels.
The patch clamp technique involves placing a small glass pipette, called a patch pipette, onto the surface of a cell membrane. The pipette is filled with an electrolyte solution that contains ions, and a small electrical current is passed through the pipette to create a seal with the membrane. Once a seal is formed, the electrical activity of the cell can be measured by recording the movement of ions across the membrane.
State the equation that describes the current carried by a particular ion species.
I = NPoɣ(Vm-E)
N= number of relevant channel proteins
Po = probability of being open
E = equilibrium potential of ion
How were potassium channel genes discovered?
Analyzing Shaker fly mutants which have mutations in potassium channels, making their legs shake where anesthetized.
Describe the structure-driven kinetic cycle for KcsA gating.
- Closed state - ion conduction pathway is blocked by a gate of valine and leucine.
- Open state - opened by the movement of the inner helix in response to changes in the electrostatic environment of the channel.
- Inactivated state - conformational changes results in the collapse of the ion conduction pathway, thought to protect against excessive ion flow.
- Recovery state - channel returns to its closed state.
What is an EPSP?
Excitatory postsynaptic potential
A transient depolarization of the membrane potential of a post-synaptic neuron that makes the neuron more likely to fire an action potential.
List 3 excitatory and 3 inhibitory neurotransmitters, and the receptors they bind to.
Excitatory:
- Glutamate (ionotropic receptors e.g., AMPA)
- ACh (nicotinic and muscarinic receptors)
- Histamine (H1 receptors)
Inhibitory:
- GABA (ionotropic e.g., GABA-A)
- Glycine (ionotropic receptors)
- Serotonin/5-HT (5-HT3)
What is the neuromuscular junction and how was it discovered?
The neuromuscular junction (NMJ) is a specialized synapse between a motor neuron and a muscle fiber that allows for the transmission of nerve impulses from the motor neuron to the muscle fiber, leading to muscle contraction.
It was shown that applying liquid from heart 1 with a slow heart rate will also reduce the heart rate of heart rate 2. This was because it contained ACh. Later on, the synapses were identified via microscopy.
What is end-plate potential? How was this discovered experimentally?
End-plate potential (EPP) is a depolarization of the postsynaptic membrane at the neuromuscular junction (NMJ) that occurs in response to the release of acetylcholine (ACh) from the presynaptic motor neuron.
A motor axon had an intracellular electrode placed in it to trigger an action potential that was then measured by an intracellular microelectrode located in muscle fibre, near the NMJ.
This was repeated, but instead of the electrode triggering an action potential, Ach was injected and triggered an EPP directly.
How did Bernard Katz show that neurotransmitters are released in discrete packets?
In the 1950s, Katz used a technique called “noise analysis” to show that neurotransmitters are released from presynaptic terminals in discrete packets or “quanta.”
Katz recorded the electrical activity of muscle fibers in response to the release of neurotransmitters from presynaptic motor neurons at the neuromuscular junction. He found that the electrical signals recorded from the muscle fibers were not continuous, but rather consisted of discrete “bursts” or “quanta” of activity. These bursts corresponded to the release of individual packets of neurotransmitter molecules from the presynaptic terminal and the subsequent opening of postsynaptic ion channels.
Katz’s discovery of quanta provided strong evidence for the idea that synaptic transmission occurs through the release of discrete packets of neurotransmitter, rather than a continuous stream.
