Comprehensive Notes on How Neurons Work

How Neurons Work

• Some neurons excite others, while some inhibit.

Overview of Neurotransmission

• Example: Dropping a hot cup involves a neural signal from hand to spinal cord and back to hand muscles.

Excitation Example

• Sensory neuron responds to heat.
• Sends signal to spinal cord neuron.
• Motor neuron activated, causing muscles to drop the cup.

Inhibition Example

• Sensory neuron responds to heat.
• Sends signal to spinal cord neuron.
• Brain recognizes the cup is expensive and sends an inhibitory signal.
• Inhibitory signal cancels out the heat signal.

Ion Channels

• Sodium (Na+) must pass into the neuron for activation through ion channels.
• Sufficient Na+ entry leads to neuron depolarization.
• Signal reaches axon terminals, releasing neurotransmitters that excite receiving neuron.

Membrane Potential

• Definition: Charge inside compared to outside the neuron.
• Measured using electrodes and a voltmeter.
• Resting potential: ~ -70 mV (more negative inside).
• Neurons are activated by Na+ entry, causing depolarization.
• Polarized neuron: when inside and outside of a neuron are very different in charge.
• If a small amount of $Na+$ enters the neuron, the membrane potential changes from $-70$ to $-68 mV$. Therefore, the neuron has become slightly depolarized.
• If a lot of $Na+$ enters the neuron, the membrane potential changes from $-70$ to $-66 mV$. The neuron has become more strongly depolarized.

Firing Threshold and Action Potential

• Membrane potential must reach firing threshold for neuron to fire.
• Firing threshold reached at axon hillock triggers action potential.
• Action potential sweeps along the axon to the terminal.
• The opening of voltage-gated ion channels at the axon hillock allows an 'explosion' of sodium ($NA+$) to enter neuron, which causes the membrane potential to briefly become more positive.
• When we say that a neuron has fired, we mean that the action potential has swept along the axon (like dominoes), from the axon hillock to the terminal.
• Rapid firing neurons can fire up to 1,000 per second in humans.

Action Potential Propagation

• Na+ channels open sequentially along the axon.
• Na+ entry causes depolarization to open the next Na+ channel.

Depolarization and Repolarization

• Rising phase (depolarization): $NA+$ gates open, $Na+$ brings positive charge inside the cell.
• Falling phase (repolarization): $K+$ gates open, $K+$ carries positive charge outside the cell.
• $\frac{Na+}{K+}$ pump exports 3 sodium ($Na+$) ions for every 2 potassium ($K+$) ions that are imported, so there is a net export of a single positive charge per pump cycle, so negative charge inside.

Sodium-Potassium Pump

• Maintains high $Na+$ concentration outside and high $K+$ concentration inside.
• Protein pump pushes $Na+$ out and pulls $K+$ in.
• Continually active.
• For every two $K+$ ions pulled back inside, three $Na+$ ions are pumped out contributing to negative charge inside.

Detailed Mechanism of Sodium-Potassium Pump

• Three $Na+$ ions bind to transport protein.
• ATP transfers a phosphate group, changing protein shape.
• $Na+$ ions are released outside.
• Two $K+$ ions bind to the protein.
• Phosphate is removed, restoring original shape and releasing $K+$ inside.

Myelinated Axons and Saltatory Conduction

• Myelin surrounds the axon with Nodes of Ranvier between.
• Action potential “jumps” from node to node (saltatory conduction).
• Increases speed of action potential.
• Express trains are faster because they skip stops, just like myelinated axons.

Neuron Diversity

• Worms and snails have unmyelinated neurons, resulting in slower information travel.
• Humans have ~86 billion neurons with ~100 trillion connections.

Neurotransmission

• Neurotransmitters are released into the synapse and bind to receptors.

Neurotransmitter Release

• Action potential arrives at axon terminal.
• Calcium ($Ca++$) channels open, and $Ca++$ rushes in.
• $Ca++$ inflow causes neurotransmitter-filled vesicles to fuse with the membrane.
• Exocytosis: Vesicle merges with membrane and releases contents into the synaptic cleft.

Neurotransmitter Binding

• Neurotransmitter released from presynaptic neuron.
• Crosses synaptic cleft and binds to receptor on postsynaptic neuron.

Neurotransmitter Clearance

• Cleared from synapse via:
  • Reuptake into presynaptic neuron.
  • Degradation by enzymes into inactive components.

Neurotransmitter Effects

• Excite, inhibit, or modulate neuron activity.
• Two most abundant neurotransmitters in the brain:
  • Glutamate: Almost always excitatory.
  • GABA (Gamma-Aminobutyric Acid): Almost always inhibitory.
• Other transmitters (dopamine, serotonin, norepinephrine) have more complex, modulatory effects.

Receptors and Ion Channels

• Some receptors contain ion channels.
• Neurotransmitter binding opens the ion channel.

Neuronal Excitation

• Excitatory neurotransmitter opens channels for positively charged ions (e.g., $Na+$).
• Produces excitatory postsynaptic potential (EPSP), a depolarization.
• Increases likelihood of neuron firing.
• If a neuron has a resting membrane potential of -70 mV and undergoes a depolarization bringing the membrane potential to -68 mV, the size of the excitatory postsynaptic potential (EPSP) is 2 mV.
• If the neuron's firing threshold is -60mV, from -68mV, another 8mV depolarization would be required to fire.

Neuronal Inhibition

• Inhibitory neurotransmitter produces inhibitory postsynaptic potential (IPSP), a hyperpolarization.
• Decreases likelihood of neuron firing.
• GABA binding causes hyperpolarization.
• Membrane potential shifts (e.g., –70 to –72 mV).
• More depolarization is needed to reach the firing threshold.

Hyperpolarization

• Inhibitory neurotransmitters open chloride ($Cl–$) channels, allowing $Cl–$ to enter.
• Or $K+$ channels open, causing $K+$ to flow out.
• Increases polarization; interior becomes more negative.
• If a neurotransmitter causes hyperpolarization of a postsynaptic neuron, from –70 to –72 mV, we say that it has caused an inhibitory postsynaptic potential or IPSP, in this case an IPSP of 2 mV. Just like EPSPs, IPSPs can add together.

Neuronal Excitation and Inhibition Summary

• Excitation: Neurotransmitter produces EPSP (depolarization), increases firing likelihood.
• Inhibition: Neurotransmitter produces IPSP (hyperpolarization), decreases firing likelihood.

EPSP/IPSP Concept Test

• If a neuron has a resting membrane potential of -70 mV and undergoes a hyperpolarization bringing the membrane potential to –73 mV, what is the size of the IPSP?
  • 3 mV
• If a neurotransmitter binds to a receptor, and the neuron’s membrane potential changes from - 70 to -73, does it undergo an EPSP or an IPSP?
  • an IPSP
• If it undergoes a change from -70 to -67, did it undergo an EPSP or IPSP?
  • an EPSP
• If a neuron’s membrane potential is -70mV and its action potential threshold is -60. How much depolarization is required for it to fire?
  • 10 mV
• If a neuron’s membrane potential is -73mV and its action potential threshold is -60. How much depolarization is required for it to fire?
  • 13mV (Notice that a neuron with a more hyperpolarized membrane potential requires more depolarization in order to cross its firing threshold.)

Spatial and Temporal Summation

• Spatial summation: Simultaneous inputs at different locations add together.
• Temporal summation: Inputs arriving quickly in succession at the same location add together.

Graded Potentials

• A neurotransmitter is excitatory at a synapse if interacts with receptor to produce EPSP (depolarization) and increases likelihood of neuron firing.
• A neurotransmitter is inhibitory at a synapse if interacts with receptor to produce IPSP (hyperpolarization) and decreases likelihood of neuron firing.
• EPSPs and IPSPs diminish as they move along the membrane of the dendrites and cell body, called graded potentials.
• At the point of synaptic input, Na+ concentration and depolarization is greatest. As Na+ moves along the inner wall of the membrane, further from this point, its concentration decreases. As a result, EPSP decreases at it spreads along the dendrites and cell body.

Gap Junction

• Neurons communicate through chemical synapses (neurotransmitters) or electrical synapses (gap junctions).
• Gap junctions allow direct ion flow, spreading excitation rapidly (e.g., cardiac muscle).

Connections of Neurons

• Divergent: small number of neurons broadcast to a large # of recipients
• Convergent: many neurons send signals to a few neurons
• Recurrent: loop of signals back and forth

Recurrent, Divergent, and Convergent Connections

• Recurrent: Involve a loop of signals back and forth allowing them to remain active over a period of time (e.g., fear circuitry and PFC).
• Divergent: A small number of neurons broadcast to a large number of recipients (e.g., midbrain dopamine neurons can make contact w/ ~ million postsynaptic neurons).
• Convergent: Many neurons send signals to a few neurons (e.g., convergent signals from the cortex to the striatum).

Psychoactive Drugs and Transmission

• Psychoactive drugs may affect transmission in 4 ways:
  1. Neurotransmitter synthesis
  2. Release of neurotransmitter
  3. Binding to receptors
  4. Blocking Reuptake

Agonists and Antagonists

• Agonist: Mimics or enhances neurotransmitter activity.
  • Examples: L-DOPA, MDMA (“ecstasy”), heroin, SSRIs, Ritalin
• Antagonist: Blocks or reduces neurotransmitter effects.
  • Examples: Haldol, Clozapine
  • Haldol blocks DA receptor

Local Anesthetics

• Example: Lidocaine (used by dentists)
• Blocks sodium channels in peripheral neurons, preventing pain signals from reaching the brain.