Neurophysiology

• Neurons are specialized cells transmitting electrical and chemical signals throughout the nervous system.
• Their structure facilitates rapid communication with other neurons, muscles, and glands.

Key Components of a Neuron:

• Cell Body (Soma):
  • Contains the nucleus and organelles.
  • Processes incoming signals and maintains cell function.
  • Acts as the control center of the neuron, integrating information from dendrites.
  • Ensures neuron functions properly and decides whether to send an electrical impulse down the axon.
  • This links to action potential generation, which happens if the signals received are strong enough.
• Dendrites:
  • Branch-like extensions from the cell body.
  • Collect information from synapses with other neurons.
  • Carry signals towards the cell body.
  • Receive chemical signals from other neurons at synapses.
  • These signals can be excitatory or inhibitory, affecting whether the neuron will fire an action potential.
• Axon:
  • A long fiber that transmits electrical signals away from the cell body.
  • Can be very long, for example, the sciatic nerve extends from the spinal cord to the foot.
  • Essential for carrying signals over long distances in the body.
  • The electrical impulse (action potential) moves down the axon toward the synaptic terminals.
• Axon Hillock:
  • The junction between the cell body and the axon.
  • The site where action potentials are initiated.
  • Crucial because it determines whether the neuron reaches the "threshold" required to generate an action potential.
  • If enough positive charge builds up, an action potential is triggered.
• Synaptic Endings (Terminals):
  • Small structures at the end of the axon.
  • Release neurotransmitters to communicate with other neurons or muscles.
  • Electrical signals get converted into chemical signals (neurotransmitters).
  • This process allows neurons to pass messages to other cells, which links to synapse function.
• Myelin Sheath (Produced by Schwann Cells in the PNS, Oligodendrocytes in the CNS):
  • A fatty insulating layer around the axon.
  • Increases signal transmission speed through saltatory conduction (signal jumps between gaps in myelin).
  • Dramatically increases the speed of nerve impulses.
  • Diseases like multiple sclerosis degrade myelin, causing slower nerve transmission and movement issues.
• Nodes of Ranvier:
  • Gaps between myelin where action potentials "jump" from node to node.
  • Speeds up signal transmission.
  • These nodes allow saltatory conduction, making impulses travel much faster compared to unmyelinated neurons.
  • This links to the factors that affect conduction speed, such as myelination and axon diameter.

How Ions Move Across Membranes & Membrane Potentials

• Neurons function using electrical signals, which depend on ion movement across membranes.
• The plasma membrane is made of lipids, therefore charged ions cannot pass through directly.
• Instead, they move through ion transporters and channels.

Types of Ion Transporters & Channels:

• Active Transporters (e.g., Na+/K+ Pump):
  • Move ions against their concentration gradient using ATP.
  • Pumps 3 Na+ out and 2 K+ in, creating a charge difference.
  • Critical for maintaining the resting potential (-70 mV).
  • Keeps sodium outside and potassium inside, creating an electrochemical gradient.
  • Links to how resting potentials are generated.
• Ion Channels (Passive Transport):
  • Allow ions to move down their concentration gradient.
  • Can be leak channels (always open, e.g., K+ leak channels) or voltage-gated channels (open/close based on membrane voltage).
  • Allow the neuron to respond to changes in charge, leading to action potentials.
  • Voltage-gated sodium and potassium channels play a key role in action potential generation and propagation.

Membrane Potential & How It Arises

• Membrane Potential:
  • The difference in electrical charge between the inside and outside of the neuron
  • Measured in millivolts (mV).
  • Resting membrane potential: ~-70 mV (inside is more negative than outside).
  • Exists because of ion gradients (mainly Na+ and K+), maintained by the Na+/K+ pump and ion leak channels.

How is the Resting Potential Generated?

• Na+/K+ ATPase (10%):
  • Pumps 3 Na+ out and 2 K+ in, creating a charge imbalance.
• K+ Leak Channels (70%):
  • Potassium leaks out, making the inside more negative.
• Negatively Charged Proteins Inside the Cell (20%):
  • Large anions (proteins) remain inside, contributing to negativity.
  • Resting potential allows neurons to respond quickly to stimuli by generating action potentials.

Action Potentials: A Step-by-Step Deep Dive

• Action potential: Neurons send electrical signals along their axons to communicate with other neurons, muscles, or glands.
• It happens due to rapid changes in the membrane potential caused by the movement of ions (Na⁺ and K⁺) through voltage-gated ion channels.

Resting State (-70 mV)

• At rest, the inside of the neuron is more negative compared to the outside
• Na⁺/K⁺ pump (Sodium-Potassium ATPase):
  • Pumps 3 Na⁺ out and 2 K⁺ in, using ATP.
  • This creates a concentration gradient where:
    • More Na⁺ is outside the cell.
    • More K⁺ is inside the cell.
  • Voltage-gated Na⁺ and K⁺ channels are closed.
  • The membrane potential is at -70 mV, meaning the inside is 70 mV more negative than the outside.
  • The neuron is polarized, meaning there is a difference in charge across the membrane.

Depolarization (Rising Phase)

• A stimulus (such as a neurotransmitter) binds to receptors on the neuron, causing some Na⁺ channels to open.
• If the stimulus is strong enough to bring the membrane to threshold (-55 mV):
  • Voltage-gated Na⁺ channels fully open.
  • Na⁺ rushes into the cell, following:
    • Its concentration gradient (high outside → low inside).
    • Its electrical gradient (inside is negative, attracting positive Na⁺).
  • As Na⁺ enters, the inside of the neuron becomes less negative, and the membrane potential rapidly increases to +30 mV.
  • If the stimulus does not reach -55 mV, nothing happens (no action potential).
  • If it does, an action potential always occurs (all-or-nothing principle).

Repolarization (Falling Phase)

• At +30 mV, the neuron must return to its resting state.
• Voltage-gated Na⁺ channels inactivate (they close temporarily and cannot reopen immediately).
• Voltage-gated K⁺ channels open, allowing K⁺ to leave the cell.
• Since K⁺ is positively charged, its exit makes the inside of the cell more negative again.
• The membrane potential drops back towards -70 mV.
• The closing of Na⁺ channels prevents the action potential from moving backward.

Hyperpolarization

• K⁺ channels stay open too long, allowing too much K⁺ to leave.
• This overcorrects the membrane potential, making it more negative than the resting state (about -80 mV instead of -70 mV).
• This is why a neuron cannot fire again immediately—it’s harder to reach threshold when it’s extra negative.

Restoring the Resting Potential (-70 mV)

• Voltage-gated K⁺ channels close.
• The Na⁺/K⁺ pump starts working again, pumping Na⁺ out and K⁺ in, restoring the original ion distribution.
• The neuron is now ready for another action potential.

Refractory Periods: Preventing Overlapping Signals

• Refractory period prevents the neuron from firing again immediately after an action potential
• Absolute Refractory Period:
  • The neuron cannot fire another action potential because Na⁺ channels are inactivated.
  • Lasts until repolarization is complete.
• Relative Refractory Period:
  • The neuron can fire another action potential, but it requires a stronger stimulus.
  • Occurs during hyperpolarization (-80 mV), when the membrane potential is extra negative.
  • Ensures action potentials travel in one direction and do not overlap.

Ion Movements in Each Phase

• Resting State:
  • Na+ Channels:Closed
  • K+ Channels:Closed
  • Main Ion Movement: None (Na+/K+ pump active)
  • Membrane Potential:-70 mV
• Depolarization:
  • Na+ Channels: Open (Na+ enters)
  • K+ Channels: Closed
  • Main Ion Movement:Na⁺ enters cell
  • Membrane Potential: -55 mV → +30 mV
• Repolarization:
  • Na+ Channels: Inactivated (Closed)
  • K+ Channels: Open (K+ exits)
  • Main Ion Movement: K⁺ leaves cell
  • Membrane Potential:+30 mV → -70 mV
• Hyperpolarization:
  • Na+ Channels: Closed
  • K+ Channels: Open (K+ still exits)
  • Main Ion Movement:K⁺ continues to leave
  • Membrane Potential:-80 mV
• Return to Resting:
  • Na+ Channels: Closed
  • K+ Channels: Closed
  • Main Ion Movement:Na+/K+ pump restores balance
  • Membrane Potential: -70 mV

Key Takeaways

• Action potentials allow neurons to communicate via electrical impulses.
• Na⁺ influx causes depolarization (+30 mV), K⁺ efflux causes repolarization (-70 mV).
• Refractory periods prevent backwards signals and ensure one-way travel.
• The Na⁺/K⁺ pump restores ion balance after hyperpolarization.
• More Sodium (Na⁺) is Outside than Potassium (K⁺) is Inside:
  • The Na⁺/K⁺ pump pumps out 3 Na⁺ ions for every 2 K⁺ ions it brings in.
  • This means the outside of the cell has more positive charges than the inside.
  • Since more positive charge is leaving than entering, the inside of the cell remains negative compared to the outside.
• Large Negative Proteins Inside the Cell:
  • Inside the neuron, there are large negatively charged molecules (proteins, DNA, phosphates) that cannot leave the cell.
  • These contribute to the inside being negative even though K⁺ is there.

What Happens During Repolarization?

• At +30 mV, the neuron needs to return to resting (-70 mV)
• Na⁺ Channels Inactivate (Close):
  • No more Na⁺ can enter the cell.
• K⁺ Channels Open:
  • Voltage-gated K⁺ channels open, and K⁺ exits the cell.
  • K⁺ is moving down its concentration gradient (high inside → low outside).
  • K⁺ is positively charged, so as it leaves, the inside of the cell becomes more negative again.

Why Does the Closing of Na⁺ Channels Prevent Backward Movement?

• When an action potential moves along the axon, it only moves forward because:
  • The Na⁺ channels that just opened will now inactivate and cannot reopen right away.
  • This prevents the action potential from going backward and ensures that it moves in one direction along the neuron.

Key Takeaways

• The inside of the neuron is negative at rest because of the Na⁺/K⁺ pump and large negative molecules.
• During repolarization, K⁺ exits the cell, making the inside more negative again.
• Na⁺ channels inactivate after they open, preventing the signal from going backward.

Propagation of Action Potential

• Once an action potential starts at the axon hillock, it travels along the axon.
• In unmyelinated axons, the impulse moves continuously.
• In myelinated axons, the impulse "jumps" between Nodes of Ranvier (saltatory conduction), making it faster.
• Factors like myelination and axon diameter affect conduction speed.
• Myelinated neurons conduct impulses much faster than unmyelinated ones.

Synapses & Neurotransmitter Release

• At the synapse, electrical signals are converted into chemical signals. Neurotransmitters (NTs) are released from synaptic vesicles.
• NTs bind to receptors on the postsynaptic neuron, causing either:
  • Excitatory Postsynaptic Potential (EPSP) → depolarization.
  • Inhibitory Postsynaptic Potential (IPSP) → hyperpolarization.
• The balance of EPSPs and IPSPs determines whether the neuron fires an action potential.
• This process underlies learning, memory, and many brain functions

How All Parts Work Together

• Neurons are specialized cells designed to transmit information rapidly throughout the nervous system.
• The structure of the neuron enables these functions, with each part playing a distinct role in processing and transmitting electrical and chemical signals
• The cell body is located centrally, and it acts as the control center of the neuron.
• It's where the nucleus and most of the organelles are found.
• The soma integrates all the incoming signals from the dendrites and determines whether the neuron should generate an action potential.
• The soma processes these signals and maintains cell function (like energy production and protein synthesis).
• The action potential only happens if the signal is strong enough to reach a specific threshold.
• Once the soma receives signals from the dendrites, it decides whether these signals are enough to cause an action potential at the axon hillock.
• The soma contains ion channels and pumps to maintain the resting potential, ensuring the neuron is ready for action when needed.
• Dendrites are tree-like extensions that protrude from the soma.
• They are the "input" regions of the neuron
• Dendrites receive incoming chemical signals from other neurons.
• These signals are either excitatory (encouraging the neuron to fire) or inhibitory (discouraging the neuron from firing).
• The sum of these signals determines whether an action potential is triggered
• Signals from other neurons arrive at the dendrites, and if enough excitatory signals come through, the neuron becomes depolarize.
• This leads to the generation of an action potential that will travel down the axon.
• If inhibitory signals predominate, the neuron will not fire an action potential.
• The combination of excitatory and inhibitory input from various neurons is crucial for processing complex information, such as learning or decision-making.
• The axon is a long, thin extension of the neuron that can extend from the soma all the way to distant target cells (other neurons, muscles, or glands).
• Axons can be very long
• The axon transmits electrical signals (action potentials) away from the soma toward the synaptic endings.
• It's responsible for long-distance communication within the nervous system.
• Once the soma decides an action potential is needed, the signal travels down the axon.
• The axon hillock is the key junction where this decision is made, determining whether the neuron will fire or remain inactive.
• The myelin sheath, which surrounds the axon, dramatically speeds up this signal transmission
• The Axon Hillock is located at the junction where the axon meets the soma.:
• The axon hillock is the decision point where the neuron "decides" whether to fire an action potential
• The electrical signal from the soma accumulates at the axon hillock, and if it is strong enough (reaching a certain threshold), an action potential is initiated.
• It acts as a gatekeeper that determines whether or not the signal is strong enough to send an impulse down the axon.
• It’s crucial for the all-or-nothing principle of action potentials
• The Synaptic Endings (Terminals) are small structures at the end of the axon, where the axon branches into multiple smaller branches.
• They come into close contact with other neurons or muscle cells.
• the electrical signal (action potential) is converted into a chemical signal in the form of neurotransmitters
• These neurotransmitters cross the synapse (the gap between two neurons) and bind to receptors on the next cell, passing on the signal.
• Once the action potential travels down the axon, it reaches the synaptic endings, where the signal is transferred to the next neuron or muscle via neurotransmitter release.
• This is where the electrical signal becomes a chemical one, allowing communication across synapses.
• This is the key step in neurotransmission, where the neuron communicates with another neuron or a muscle, initiating processes like muscle contraction or the firing of another neuron
• The Myelin Sheath surrounds the axon in segments
• In the Peripheral Nervous System (PNS), it's produced by Schwann cells, and in the Central Nervous System (CNS), it's produced by oligodendrocyte
• The myelin sheath acts as an insulator, speeding up the transmission of electrical signals by preventing the ions from leaking out as they travel down the axon
• This makes the electrical signal travel faster via saltatory conduction, where the action potential jumps between gaps in the myelin called Nodes of Ranvier.
• By allowing saltatory conduction, the myelin sheath speeds up signal transmission, making the neuron much more efficient.
• Without myelin, neurons would transmit signals much slower, which could affect functions like movement and coordination.
• Diseases like multiple sclerosis degrade the myelin sheath, slowing down or blocking action potentials, which is why motor skills and sensation are impaired in such conditions.
• Nodes of Ranvier are small gaps in the myelin sheath along the axon
• The nodes allow for saltatory conduction, where the action potential jumps from one node to the next, speeding up the signal transmission
• These nodes are essential for speeding up the action potential.
• The voltage-gated sodium channels located at the nodes enable the action potential to jump, drastically increasing conduction speed.
• This is why myelinated axons transmit signals faster than unmyelinated axons.

Ion Movement & Membrane Potentials: The Driving Forces Behind Electrical Signals

• Neurons rely on the movement of ions across the membrane to create electrical signals, and this process is crucial for both resting potentials and action potentials
• Ion Transporters (Active Transport):
  • Found in the neuron’s membrane, including the Na+/K+ pump.
  • These pumps move ions against their concentration gradients using ATP (energy), a process called active transport.
  • the Na+/K+ pump moves three sodium ions (Na+) out of the neuron and two potassium ions (K+) in
  • This process maintains the resting membrane potential by creating a concentration gradient of Na+ and K+ ions, with Na+ being high outside the neuron and K+ being high inside.
  • This electrochemical gradient is essential for the rapid changes in voltage that occur during action potentials
• Ion Channels (Passive Transport):
  • Embedded in the neuron's membrane and crucial for controlling ion movement during action potentials
  • Ion channels allow ions to pass through the membrane by passive transport, following their concentration gradients
  • Some are leak channels (always open), while others are voltage-gated channels (open and close based on the membrane’s voltage).
  • Voltage-gated sodium channels open during depolarization, allowing Na+ to rush into the neuron, making the inside of the cell more positive.
  • Voltage-gated potassium channels open during repolarization, allowing K+ to leave the neuron, restoring the negative charge inside.
  • This is what creates the rapid rise and fall of membrane potential that constitutes the action potential.

How Membrane Potentials Arise: The Resting Potential and Action Potentials

• The resting membrane potential (approximately -70mV) and the action potential are the foundation of neuronal communication
• Resting Membrane Potential:
  • The resting potential exists across the entire membrane of the neuron when it's not transmitting a signal.
  • The resting potential is maintained by the action of the Na+/K+ pump, the potassium leak channels, and the negatively charged proteins inside the neuron
  • This keeps the neuron ready to fire when a signal arrives.
  • Without this negative charge, the neuron wouldn't be able to respond to stimuli.
  • The resting membrane potential acts like the "ready-to-go" state for the neuron, enabling the rapid changes in voltage necessary for action potentials
• Action Potential:
  • The action potential is the process by which neurons send signals over long distances = The action potential occurs along the axon, starting at the axon hillock and propagating to the synaptic endings.
  • An action potential involves the rapid depolarization (inside becomes positive) followed by repolarization (inside becomes negative again), with hyperpolarization briefly occurring as the neuron resets

How Everything Links Together

• Neurophysiology is like a complex relay race: each part of the neuron plays a key role in passing signals along
• From the dendrites receiving input to the axon transmitting the signal, everything works in harmony
• Ions move across the membrane, creating electrical signals that form the foundation for communication.
• These signals travel down the axon, and when they reach the synaptic endings, they are passed to the next neuron via neurotransmitter release.
• Each part of the neuron—soma, dendrites, axon, synaptic endings, myelin, and nodes of Ranvier—interact in an incredibly coordinated way to ensure signals are processed and transmitted effectively.
• Without one part working properly, the whole process would fail