Zool314 Neurobiology

What is the pathway for an action potential?

Propagate from sensory neurons

Travel through interneurons to motor neurons in muscles

What is the function of these three steps?

Sensory neuron transmits information about external stimuli

Interneuron integrates the information

Motor neurons transmit signals to muscle cells, causing contraction

What is the membrane potential used for in a cell?

Energy source for substance transport across the membrane, to transmit signals from different parts of neuron / muscle cells

How is membrane potential measured?

Intracellular electrode measuring voltage across a membrane relative to outside the cell

What does a resting membrane potential look like?

Normal rate of action potentials, with K+ in high concentration inside the cell, and Na+ and Cl- high concentration extracellularly

What is the passive behaviour of K+ in the cell?

Net outward movement from random, non directional movement - higher concentration in the cell.

Negative intracellular charge caused by low concentration of Cl- channels

What is the function of the Na K pumps?

Ensure there is a concentration gradient by pumping K+ inside and Na+ outside

Why does the membrane potential 'stop' at a certain point?

Positively charged K+ ions are attracted by negatively charged membrane, so they are less likely to actually cross - the positively charged outside repels the K+, causing an electrochemical equilibrium.

What is the resting potential calculated by?

Electrical and chemical free energy

What are the benefits / negatives to extracellular recording of action potentials?

High resolution

Can't single out one neuron

Cannot stain / identify neurons

Easier and cheaper

Needs filtering to see APs

What are the benefits / negatives of intracellular recording of action potentials?

High resolution

Can look at a single neuron or even a neuron compartment

Can be stained to identify neurons

High cost and difficult

Able to record resting membrane potential

How is intracellular able to record resting potential when extracellular cannot?

Extracellular records voltage on the outside, but the potential is across the membrane

Intracellular records across membrane, so sees the change in potential

What occurs during the depolarisation of an action potential?

Voltage gated Na+ channels open, Na+ flows into cell. Membrane more positive = more Na+ open (positive feedback loop) = rising action potential

What happens during the falling phase of an action potential?

Na+ channels inactive, K+ channels open and K+ leaves cell. Undershoot / hyperpolarisation can occur with the permanent K+ and voltage gated K+ channels

What causes the absolute refractory period?

Voltage gated Na+ channels are inactivated, K+ channels opened

Why does an extracellular recording look the way it does?

At the start of the AP, Na+ ions are flowing towards electrode to open Na+ channels (positive reading)

Na+ flow away from electrode into axon (very negative)

Refractory phase, K+ ions flow towards electrode out of the axon (back to positive)

How can the amplitude of the extracellular recording differ?

Size of neuron and distance from electrode influence the amplitude of the AP measured

Recordings may also overlap

What is the difference between a neuron with a long time constant and a short time constant?

Long time constant has a longer refractory period, more likely to cause summation (synaptic output that doesn't cause an AP is higher for longer)

Short time constant drops to resting faster, less likely for summation

What is the time constant (τ, tau)?

Time needed to reach 63% of maximum membrane potential (determines window for temporal summation)

What is a capacitor?

A mechanism that stores and releases electric charge, smoothing out current changes, allowing for less energy released over a longer period of time.

Higher capacitance = more charges stored.

Membranes act as capacitors - what factors influence capacitance and why?

Thicker membrane reduces capacitance by weakening charge attraction

More channels reduce capacitance by loss of insulation

-> basically, the stronger the charge between inner and outer, the higher the capacitance

Why does current flow into the capacitor?

Follow the path of least resistance - low resistance capacitor is filled up without charging the membrane potential, but resistance increases as the capacitor charges, more current is diverted through channels

How does increasing synaptic input shorten the membrane time constant?

Resistance is lower, so τ is lower

Ion channels open, decreasing resistance and capacitance

What is an example of activity dependent changes in input integration?

In the dark, T is higher so sensitivity is higher but vision is slower

In the light, T is low so quick but less sensitive vision

What is the neuron length constant?

How far a membrane potential change can spread (how strong the threshold is in terms of reach and summation)

What is electrotonic spread?

Passive conduction of depolarised electrons, which causes an electrical current when shit goes down

What are the characteristics of electrotonic spread?

Fast (faster than APs)

Decrease exponentially with distance from a triggering AP (high depolarisation close to the current but low further from current)

What is the length constant of a neuron?

How far along an axon an electrical impulse can propagate, determined by inner resistance (Ri) and membrane resistance (Rm)

What is inner and membrane resistance?

Inner is resistance for ion to flow down axon

Membrane is resistance of ion to flow across membrane

How does resistance influence length constant (λ)?

Lower inner resistance = more current flow = larger λ

Higher membrane resistance = less leakage = larger λ

What is the length constant (λ) actually defining?

Exponential decay of a membrane potential change (ΔVm) with distance -> λ=distance at which ΔVm=37% of original ΔVm

= to sqrt (Rm/Ri)

How does axon diametre influence length constant?

Same ion channel density, but surface area rules dictate that inner resistance decreases at a faster rate than membrane resistance (large diametre = reduced membrane resistance, larger diametre = reduced inner resistance. πr² decreases at a faster rate tha 2πr)

How does myelin increase conduction velocity of APs?

Increases length constant (further spread)

Decreases time constant (capacitance decreased more than resistance increased)

How does myelin allow for faster electrotonic spread?

Myelin sheaths are in sausage-like Schwann cells, which allow for nodes of Ranvier which electrotonic spread can jump between

How does myelin change the time constant τ?

Decreases capacitance more than increases resistance, and τ=Rm×Cm.

Capacitator is far away, low attraction = low capacitance

How do the nodes of Ranvier allow for faster electrotonic spread?

Voltage gated sodium channels are concentrated in nodes

APs jump between nodes via saltatory conduction

What is the path of a signal in a neuron?

Dendrite -> soma -> hillcock -> axon -> axon terminals

What are three names of synapses?

Axodendritic (to a dendrite)

Axosomatic (to a cell body)

Axoaxonic (to an axon terminal)

What is the name for the space between sender / receiver neuron cells?

Synaptic cleft (between the presynapse and the post synapse)

How are membranes connected?

100-1000 channels, that connect cyclostome between synapse cells (connexon bridges made of 6 connexins)

Transmembrane helixes are hydrophilic/phobic opposite to the membrane to anchor it in place

What are the pros and cons of electrical synapses?

Low energy cost, low maintenance, fast transmission signals

Cannot change or amplify signal, lower computational power

How do connected cells respond to apoptosis?

Channels close - increased H⁺ or Ca²⁺ rise = leaky mitochondria = close channels

What does a standard chemical synapse look like?

Neurotransmitters stored in presynapse vesicles

Voltage change causes Ca²⁺ channels to open

Ca²⁺ in presynaptic cleft, causing postsynaptic Na⁺ channels to open, allowing for neurotransmitters ot bind to postsynapse cell

How is an electrical signal used in the chemical synapse?

Electrical signals trigger the chemical synapse across the membrane, which is converted back into an electrical signal on the other side

What is the Tyranny of Receptors?

Receiver shapes response of a neurotransmitter, not the sender

What is direct gating?

Receptor opens ion channels and is a part of the macromolecule forming channel. Fast and precise

What is indirect gating?

Allows for signal amplification and modulation by indirectly opening ion channels separate from modulating channel.

What is shunting inhibition?

Negative postsynapse binds to a positive, and is able to select inputs for the post synaptic cell, preventing specific inputs without limiting others

How do drugs influence the dopaminergic system?

Reward system uses dopaminergic neurotransmitters, usually regulated by reuptake carrier

Drugs (coke) block the reuptake carrier for longer rewards, but damages recycling of dopamine

What is the simplest cell, and what makes modern cells more complex?

Phospholipid bilayer with pores

Modern ion channels need to selectively transport ions and respond to biological signals

How did Na⁺ channels evolve?

Derived from Ca²⁺ channels, needed for electrical excitability (before neurons)

What do sponges have that are similar to neural communication?

All animals have the proteins / genes for neural activity

Sponges have electrically active cells that have calcium spikes with refractory periods, however, one spike takes ~10 seconds

Where did centran nervous systems evolve?

Sponges and ctenophores (multiple origins)

Human (+tetrapod, arthropod etc) evolved from sponges, but neural nets have evolved twice in comb jellies and sponges

What are specialised nerve nets?

Brain-like structures of 100 to 1000s neurons (seen in hydra)

Sensory and ganglion cells

Simple systems of non overlapping functional networks

No nerve centre - each network is specialised

How did cephalisation evolve?

Increased nerve sensitivity around mouth, with gene duplication causing increased complexity in information computation

What does the CNS look like along the anterior-posterior axis?

Symmetry along midline

Conserved patterning

Evolved from ancestral nerve net

Origin is uncertain

What is the CNS along the doral-ventral axis?

Location is based on BMP2/4, ventral in protostomes and dorsal in deuterostomes

Develops where BMP2/4 is absent

BMP2/4 indicates a common ancestor

What are some conserved mechanisms in CNS development?

Neural tissue patterns similar in insects and vertebrates

Mirror symmetry preceeded by mirror gene expression of transcription factors during development

What two types of brain expressions exist?

Spitting (neurosecretory action)

Twitching (muscle contraction)

What is a muscle?

Tissue of fibres that contract for bodily movement

What is a tendon?

Inelastic cord attaching muscle to bone

What is a fascicle?

Bundle of muscle fibers surrounded by connective tissue (perimysium)

What is a muscle fiber?

Single muscle cell with multiple nucleii

What is a sarcolemma?

Transparent sheath that envelops muscle fibres

What is a myofibril?

Rod-like structures within muscle fibres that cause contraction

What are dark and light bands?

Alternating patterns in myofibrils responsible for striated muscle appearance

What are motorn neurons?

Specialised neurons that form muscle connections

What is the neuromuscular junction?

Output synapse of the motor neuron, functionally similar to the chemical synapse

What are the transverse (t) tubules?

Tunnels formed by sarcolemma that transmit NMJ signals into the fibre

What is the sarcoplasmic reticulum?

Organelle surrounding each myofibril, stores Ca⁺

What is the sarcomere?

Dark-light bands on myofibril, unit of muscle contraction

What is a z-disk?

'Walls' of the sarcomere that move closer together when contracting

What is the thick filament?

Myosin - two entertwined proteins that move during contraction

What is the thin filament?

Actin - static filament attached to z-disk

What other proteins are involved in contraction?

Nebulin and tropomodulin

What are I bands?

Areas with only thin filaments (actin)

What are A bands?

Areas with overlapping thin and thick filaments (actin and myosin)

Describe (in full) the steps of a neuromuscular junction signal process thing

1) Acetylcholine neurotransmitter crosses the synaptic cleft, triggering an action potential in the muscle fibre

2) AP travels along sarcolemma and into the t-tubules (to the sarcoplasmic reticulum)

3) AP in SR opens voltage gated Ca²⁺ channels in SR

4) Ca²⁺ is released into muscle fibre cytosol

5) Calcium binds to troponin in thin filament, opens myosin binding sites, initiating the power stroke

6) Calcium pumps (energy requiring) pump Ca²⁺ back into the SR, terminating power stroke

7) Myosin binding sites blocked, muscle relaxation

What are the 4 steps to the Power Stroke ;)

1) Myosin detaches from actin, ATP binds to myosin neck domain - head region detached from actin

2) Different ATP molecule converted into ADP. Tail of myosin stretches, myosin attaches to new binding site, and actin filament glides along myosin filament

3) ATP attached to the head releases a phosphate (ADP), reverting myosin head to original form

4) ADP released from myosin head - starting position allows for binding of a new ATP

What characteristics does muscle activation in striated vertebrate muscles have?

Voluntary, mononeuronal, and multiterminal

What characteristics does muscle activation in vertebrate smooth muscles have?

Involuntary, polyneuronal, monoterminal

No sarcolemma or z-disks, can be stretch activated

Calcium binds to calmodulin, activatin gmyosin light chain kinase (MLCK), which causes muscle contraction

Contraction inhibited by norepinephrine

What characteristics does muscle activation in invertebrate striated muscles have?

Smooth or striated, mono or polyneuronal

Fast and strong motor neurons primarily excited by glutamate

Slow and weak by aspartate

Can be polyterminal - innervates multiple muscle fibres

How does muscle force gradation work in vertebrates?

Made up of motor units (single neuron with its innervated muscle fibres)

Large generate fast, high force and are larger, but fatigue quickly. Recruited as force increases

Small generate slow, low force and are smaller, but are barely fatigued and used more often

How does muscle force gradation work in arthropods?

Limited motor units, typically just a slow, fast, and inhibitory motor neuron

Polyneuronal and can activate multiple fibres with the same neuron

Fibres heterogenious rather than neurons

How else can insects control muscles?

Neurogenic or myogenic

Neurogenic, each contraction elicited by action potential

myogenic, stretching induces next contraction (wings for flight)

How does undulatory swimming use central pattern generators?

Needs contraction of muscles down body line, one side at a time to prevent cramps

Pattern from spinal cord, brain not needed

What is the structure of a central pattern generator?

Mirrored, with motor neuron, exitatory neuron, and contralateral inhibitory neuron.

EN is attached to the CIN and MN, and CIN is attached to the opposite motor neuron, opposite CIN, and opposite EN.

One EN firing allows the motor neuron to activate, and activates the CIN that stops the opposite MN, CIN, and EN from firing

What are afferences?

Sensory pathways thay send information to the brain / spinal cord ('Aha' moment)

What are efferences?

Motor pathways that transmit signals from the brain / spinal cord to muscles / glands

(have an 'effect' on the world)

How is a stimulus transformed into an action potential in a single cell system?

Transduction protein translates simuli into neuronal analogue signals

Generator proteins release exitatory potentials when ion channels are openes

Signal transcoded to action potential in spike generating zone

Travel to brain where perception occurs

How does the two cell system differ?

Also has a sensory epithelial cell, which transduces a physical stimulus into a graded membrane potential

Neurotransmitters are used between the two cells, allowing for amplification. AP is inititated if enough EPSPs are induced

Epithelial cell does transduction, neuron does transcoding

What is a graded potential?

Action potential that is analogue.

Cannot travel long distance, but allows for fine resolution of stimulus intensity

Baseline allows for coding high and low (depolarising vs hyperpolarising)

Response based on mV, not frequency

What is a spiking potential?

Action potential that uses frequency rather than amplitude

May use negative coding space as a baseline to allow increase or decrease in frequency.

Can travel using voltage gated channels (graded cannot)

What is transduction?

Transformation of a physical stimulus into a biological / neuronal signal

What is the difference between early and late pain?

Early is immediate and localised, with signals sent to primary and secondary somatosensory cortex. Aδ myelinated fibres

Late pain is more emotional, sent to thalamus, limbic system, and anterior cinculate cortex. C fibres

What do Aδ and C fibres having free nerve endings mean?

Free endings, that can be activated by thermal, mechanical, and painful stimuli

Simple, unencapsulated structure

Different endings adapt at different rates to different stimuli

What two transient receptor proteins make up group 2?

TRPP and TRPML

Why are group 2 proteins special

Don't contain an N-terminal intracellular repeat sequence or a c-terminal TRP domain sequence

Do have large extracytoplasmic domains between S1 and S2

What is the structure of a TRP?

Four copies of a TRP channel protein

Each has 6 transmembrane domains with a pore loop between 5th and 6th

How do TRP channels regulate flow, probably?

Change tertiary structure, move 4 subunits to open and close gates

Small ions cannot pass because of charge, but can when channel is open