A1. The Nervous System and Signal Transmission

The Nervous System

• The nervous system is crucial for maintaining homeostasis and controlling body functions, including breathing, fine motor coordination, learning, and thought.

Components of the Nervous System

• Brain

• Spinal cord

• Nerves

• Neurons

Functions

• Control: Works alongside the endocrine system to control bodily functions.

• Maintenance: Involved in the maintenance of the body, including:

  • Circulatory system

  • Lymphatic and immune systems

  • Integumentary system

  • Muscular system

  • Skeletal system

  • Reproduction

  • Digestive system

  • Respiratory system

  • Excretory system

  • Reproductive system

Divisions of the Nervous System

• Central Nervous System (CNS):

  • Brain

  • Spinal cord

• Peripheral Nervous System (PNS):

  • Somatic nervous system (voluntary):

    • Motor neurons

    • Sensory neurons

  • Autonomic nervous system (involuntary):

    • Sympathetic nervous system

    • Parasympathetic nervous system

Neurons, Synapses, and Signaling

Information Processing in the Nervous System

1. Sensory Input:

   • Stimulus

   • Receptor

   • Sensory Neuron carries information to the CNS

2. Integration:

   • Interneurons make connections in the CNS

   • Spinal Reflex Arc (rapid, involuntary)

   • Decision making (conscious thought)

3. Motor output

   • Effector

   • Motor Neuron carries information to effectors (muscles, glands, other organs)

Types of Neurons

1. Sensory Neurons: Carry information to the CNS.

2. Interneurons: Make connections within the CNS; found only in the CNS; create links between sensory and motor neurons.

3. Motor Neurons: Carry information to effectors (muscles, glands, other organs).

Neuron Structure

• Dendrites: Short, branching terminals that receive nerve impulses from other neurons or sensory receptors and send information to the cell body.

• Cell Body (soma): Contains the nucleus and is the site of metabolic reactions; processes information from dendrites.

• Axon: An extension of the cytoplasm from the cell body that conducts nerve impulses away from the cell body; some can extend up to 1 meter.

• Axon Terminals: The branched end of the axon that transmits information to another cell or neuron.

• Axon Hillock

• Myelin Sheath: A glistening white coat of fatty protein that acts as insulation for the neurons, speeding up nerve transmission by preventing loss of ions; created by glial cells (Schwann cells in PNS and oligodendrocytes in CNS).

• Nodes of Ranvier: Gaps between adjacent myelin sheaths.

Glial Cells

• Supporting cells in the nervous system.

• Functions:

  • Nourish neurons, remove wastes, and defend against infection.

  • Provide a supporting framework for nervous system tissue.

  • Outnumber neurons by about 10:1.

• Examples:

  • Schwann Cells (PNS)

  • Oligodendrocytes (CNS)

Neurilemma

• A thin outer membrane found within the PNS formed by Schwann cells.

• Promotes the regeneration of damaged axons.

• CNS lacks neurilemmas; therefore, damage to axons is usually permanent, leading to paralysis.

Adrenoleukodystrophy (ALD)

• A genetic condition that damages the myelin sheath in the brain and spinal cord.

• Forms:

  • CALD (Childhood Cerebral ALD):

    • Onset between ages 4 and 10.

    • Symptoms: hyperactivity, learning difficulties, behavioral changes (e.g., increased aggression).

    • Rapid breakdown of the myelin sheath.

    • Early diagnosis is vital; can be fatal within 5-10 years if untreated.

    • Treatments are effective before symptoms fully develop due to the irreversible loss of myelin sheath.

  • AMN (Adrenomyeloneuropathy):

    • Also called adult-onset ALD; symptoms develop in early to mid-adulthood (20s or 30s).

    • Symptoms: Neurological issues, progressive lower limb weakness and stiffness, bowel and bladder dysfunction.

    • Progression is slower compared to CALD but leads to a decline in physical and mental abilities.

    • Severe cases involve brain and spinal cord impact, affecting life expectancy.

  • Addison’s Disease:

    • In about 10% of ALD patients, the only symptom is adrenocortical insufficiency.

    • Adrenal hormones regulate metabolism and help respond to stress; abnormal levels can be life-threatening.

    • Managed with hormone supplements.

Signal Transmission

Membrane Transport

• Passive Transport: Does not require energy; solute moves along its concentration or electrochemical gradient.

• Active Transport: Requires energy; moves a solute against its concentration gradient.

Cell Membrane Permeability

• Selectively permeable – allows only certain molecules to pass.

• Large and/or charged molecules cannot pass through.

• Channel proteins: Provide a channel for large molecules and charged ions to pass; many are gated channels that only allow passage when there is a stimulus.

Sodium-Potassium Pump

• Animal cells regulate relative concentrations of $Na^+$ and $K^+$.

• 3 $Na^+$ are pumped out of the cell.

• 2 $K^+$ are pumped into the cell.

• Results in a +1 net charge to the extracellular fluid.

• Electrogenic pumps: Proteins that generate voltage across membranes, which can be used later as an energy source for cellular processes.

• The sodium-potassium pump binds three sodium ions and a molecule of ATP.

• The splitting of ATP provides energy to change the shape of the channel. The sodium ions are driven through the channel.

• The sodium ions are released to the outside of the membrane, and the new shape of the channel allows two potassium ions to bind.

• Release of the phosphate allows the channel to revert to its original form, releasing the potassium ions on the inside of the membrane.

Resting Potential of a Neuron

• Ions are unequally distributed between the intracellular fluid (ICF) and the extracellular fluid (ECF).

• The inside of the neuron or cell is negatively charged relative to the outside.

• The difference in charge or voltage across the cell membrane is called the resting membrane potential; there is a difference of -70 mV.

• Cause of Unequal Balance:

  • Outside: High concentration of $Na^+$ ions.

  • Inside: High concentration of $K^+$ ions.

• The $Na^+$ and $K^+$ concentration gradient is maintained by the sodium-potassium pump.

• The process of generating a resting potential (-70mV) is called polarization.

• Changes in the concentration of ions lead to an electrochemical gradient inside and outside the cell.

Action Potential of a Neuron

• Generates a nerve impulse, which is an action potential.

• Ion Channels: Ion membrane proteins that open and close in response to stimuli

  • $Na^+$ channel

  • $K^+$ channel

• Steps:

  1. Resting State:

     • Gated $Na^+$ and $K^+$ channels are closed.

     • The sodium-potassium pump maintains the membrane potential.

  2. Depolarization:

     • A stimulus from the dendrites opens some sodium channels.

     • $Na^+$ ions rush into the neuron (axon) due to the concentration gradient (high to low) and attraction to the negative side of the membrane.

     • More positive ions inside change the charge.

     • ICF becomes more positive.

  3. Action Potential:

     • If depolarization reaches the threshold of -55mV, it triggers an action potential (ALL or NOTHING event).

     • More sodium channels open, while potassium channels remain closed.

     • Influx of more $Na^+$ ions into the neuron, making it even more positive until it reaches a charge of +40 mV.

  4. Repolarization:

     • As soon as the ICF of the neuron reaches +40 mV, the sodium channels close, stopping the flow of $Na^+$ ions into the cell.

     • Potassium channels open, permitting $K^+$ ions outflow (out of the cell).

     • The neuron loses positive ions, which leads to the ICF of the neuron becoming negative again, restoring the original membrane polarization.

  5. Undershoot (Refractory Period):

     • As the $K^+$ ions flow out of the neuron, it makes the ICF negative again.

     • Potassium channels close slowly, leading to more $K^+$ ions out of the cell than necessary to establish the original polarized potential.

     • The membrane becomes hyperpolarized (undershoot = too negative).

     • The membrane is polarized, BUT the $Na^+$ and $K^+$ are on the wrong sides.

     • The axon WILL NOT respond to a new stimulus (refractory period).

     • The $Na^+$ and $K^+$ are returned to their original resting potential location by the sodium-potassium pump and puts the charge back to -70 mV.

Movement of Action Potential

• The conduction of action potential is not the same as an electric wire.

• An action potential does not move, they are generated one after another along the cell membrane causing a wave of depolarization.

  • Action potential only moves in one direction, from the axon hillock to the axon terminals.

• After depolarization, the sodium channels remained inactivated making the membrane temporarily refractory (not responsive) to another action potential.

• Refractory period ensures that action potentials do not overlap and that action potentials are unidirectional.

• Vertebrate axons has an adaptation that enables fast conduction – myelin sheath, because insulation allows depolarizing current with action potential to travel farther along the axon interior.

Saltatory Conduction in Myelinated Axons

• Action potentials travel faster in myelinated axons because the opening and closing of ions only occurs at the nodes.

• This mechanism is called saltatory conduction (from the Latin saltare, to leap or jump) because the action potential appears to jump from node to node along the axon.

• The myelin sheath is interrupted by bare patches of axons called nodes of Ranvier, where sodium and potassium channels are concentrated.

Signal Transmission: The Synapse

Synaptic Transmission

• Synaptic cleft: The gap that separates the presynaptic neuron from the postsynaptic neuron/cell; less than 50 nm across.

• The connection between two neurons or a neuron and an effector is known as a synapse.

• Neurotransmitters carry the neuron signal from one neuron to the next or to an effector gland (muscle).

• Process of Signal Transmission Across the Synapse:

  1. Action Potential arrives at the end of a presynaptic neuron

  2. The impulse causes the sacs that contain neurotransmitters to fuse with the membrane of the axon “synaptic vesicles”

  3. These vesicles release their contents into the synaptic cleft by Exocytosis

  4. Through Diffusion neurotransmitters reach the dendrites of the postsynaptic neuron or cell membrane of the effector

  5. Once in the postsynaptic membrane, neurotransmitters will bind to specific receptor proteins

  6. When complete the receptor proteins trigger ion specific channels to open which depolarizes the postsynaptic membrane and if the threshold potential is reached it will initiate an action potential

Termination of Neurotransmitter Signaling

• After a response is triggered, the chemical synapse returns to its resting state by removing the neurotransmitter molecules from the synaptic cleft.

• Methods of Neurotransmitter Removal:

  • Inactivation by enzymes: Inactivating enzymes bind to the neurotransmitter and break it apart.

  • Reuptake (recaptured) by the pre-synaptic neurons: Neurotransmitters are reabsorbed (endocytosis), recycled and repackaged in synaptic vesicles in the neurons for another use.

Neurotransmitters

• Chemical signals released into the synaptic cleft that can trigger a response in the post-synaptic cleft.

• Neurotransmitters can either excite or inhibit postsynaptic cells.

• Excitatory Effect:

  • Receptor protein will trigger sodium channels to open, allowing $Na^+$ to flow in.

  • Result: The membrane becomes slightly depolarized, bringing the membrane potential closer to the threshold (-55MV), which can lead to action potential in the post-synaptic cell.

• Inhibitory Effect:

  • Receptor proteins will trigger potassium channels to open, allowing $K^+$ to flow out, also open chlorine channels to open which allows $Cl^-$ ions to flow in.

  • Result: The membrane becomes more negative or hyperpolarizes, bringing the membrane potential farther from the threshold.

Neurotransmitters: Acetylcholine

• An excitatory neurotransmitter.

• Opens sodium channels, causing depolarization on the post-synaptic neuron.

• Excites muscle-fibers in the neuromuscular junction – a synapse between a motor neuron and a muscle cell.

• Problem: As long as acetylcholine is attached to the receptors, the sodium channels are open, and the neurons remain in a constant state of depolarization.

• Solution: The enzyme, cholinesterase, destroys acetylcholine, closing the sodium channels and allowing the neuron to begin its recovery phase.

• Many insecticides block the enzyme cholinesterase.

Neurotransmitters: Other Ones

• Serotonin and dopamine: affect sleep, mood, attention, and learning

  • Serotonin – generally inhibitory

    • Decreased levels associated with depression

    • Medication or ↑ exercise

  • Dopamine – excitatory and inhibitory, depending on sites

    • Released as rewarding of a behavior

• GABA – inhibitory - As a drug, calms the body

• Glutamic acid – excitatory - Memory

• Endorphins – inhibitory (reduce pain perception)

• Norepinephrine (noradrenaline) is found in both CNS and PNS

  • In the PNS - Excitatory

  • In the CNS - Excitatory or inhibitory

Neurotransmitter Functions and Effects of Abnormal Production

Disorders Associated with Transmitter Chemicals

• Parkinson's disease - involuntary muscle contractions and tremors - inadequate production of dopamine

• Schizophrenia – excess dopamine

• Alzheimer's disease - deterioration of memory and mental capacity - related to decreased production of acetylcholine