Nervous System - Neurons and Communication

What are the cellular and network properties of neurons?

• Organization of the nervous system

• Cells of the nervous system

• Electrical signals in neurons → lead to action potentials

• Cell-to-cell communication in the nervous system

• Integration of neural info transfer

What are the components of the nervous system?

• Central nervous system (CNS)

  • Brain

  • Spinal cord:

    • Transmits signals between brain and body

    • Controls reflexes

📌 Think: CNS = decision-making HQ

• Peripheral Nervous System (PNS)

  • Sensory (afferent neurons)

    • Carry information FROM the body TO the CNS

    • Detect: Touch, pain, temp, pressure, body position (proprioception)

    📌 Mnemonic: Afferent = Arriving at the CNS

  • Efferent neurons

    • Carry commands FROM the CNS TO the body

    • Control muscles and glands

      • Somatic motor neurons: Voluntary, controls skeletal muscles

      • Autonomic nervous systems

        • Involuntary

        • Controls smooth muscle, cardiac muscle, and glands

        • Maintains homeostasis

      • Sympathetic:

        • “Fight or Flight”

        • Activated during stress or emergencies

      • Parasympathetic

        • “Rest and Digest”

        • Active during relaxation

  • 📌 Mnemonic: Efferent = Exiting the CNS

• Enteric Nervous System

  • Controls the gastrointestinal (GI) tract

  • Can function independently of the CNS

What are the components of a neuron?

• Cell body: Contains nucleus and most of the cellular machinery

• Dendrites: Receive information

  • Short, branched extensions

  • Carry signals toward the cell body

• Axon: Sends information

  • Nerves: PNS

  • Tracts: CNS

  • Axon Hillock:

    • Junction between cell body and axon

    • Trigger zone for action potentials

    • If summed input reaches threshold → neuron fires

  • Axon Terminal:

    • End of axon

    • Releases neurotransmitters

    • Converts electrical signal → chemical signal

• Myelin sheath: Insulator (makes signal go faster)

  • Allows saltatory conduction (jumping between nodes → signaling faster)

• Synapse: Site of communication between neurons (or where an axon terminal communicates with its postsynaptic target cells)

  • Synaptic cleft: Small gap between neurons. Neurotransmitters diffuse across this space

  • Postsynaptic Dendrite: Receives neurotransmitters

Input signal: Dendrites → Cell body (integration) → Axon hillock (decision point - whether action potential should be released) → Axon → Axon terminals → Postsynaptic dendrite → Output signal

1) What are sensory neurons?

2) How are sensory neurons classified structurally?

1) Carry information from receptors → CNS

2) Pseudopolar: Single process (axon). During development, the dendrite fused with the axon

Bipolar: Two relatively equal fibers extending off the central cell body

1) What are interneurons neurons?

2) How are interneurons neurons classified structurally?

1) Located entirely within the CNS. Integrate and process information. Connect sensory → motor pathways

2) Anaxonic: Have no apparent axon

Multipolar: Highly branched but lacks long extensions

1) What are efferent neurons?

2) How are efferent neurons classified structurally?

1) Carry commands from CNS → muscles or glands. Control responses

2) Multipolar: 5-7 dendrites, each branching 4-6 times. A single long axon may branch several times and end at enlarged axon terminals

What is the function of the synapse?

• Presynaptic: The sending cell

  • Contains the axon terminal

  • Releases neurotransmitter (chemical synapse)
    or passes current directly (electrical synapse)

• Postsynaptic: The receiving celll; contains receptors (chemical synapse)

  • Electric synapses:

    • Cells are connected by gap junctions

    • Ions flow directly from cell to cell

    • Very fast

    • Bidirectional

    • Chemical synapse:

      • Most common type in the nervous system

      • Cells separated by a synaptic cleft → communication via neurotransmitters

      • Unidirectional

What’s the difference between slow and fast axonal transport?

• Slow axonal transport: Moves soluble material by axoplasmic (cytoplasmic) flow at 0.2-2.5 mm/day

• Fast axonal transport:

  • Moves organelles at rates up to 400 mm/day

  • Forward (or anterograde) transport: From cell body → axon terminal

  • Backward (retrograde) transport: From axon terminal → cell body

• Local protein synthesis → helps with fast transport

How does fast axonal transport work?

1. Peptides are synthesized on rough ER and packaged by the Golgi apparatus

2. Fast axonal transport walks vesicles and mitochondria along microtubule network

3. Vesicle contents are released by exocytosis

4. Synaptic vesicles recycling

5. Retrograde fast axonal transport

6. Old membrane components digested in lysosomes (which is in the cell body)

What are the function of glial cells?

• Glial cells ≠ neurons

• Support, protect, insulate, and nourish neurons

• Are essential for normal neural function

• Organize glial cells by location: CNS and PNS

What are the glial cells of the CNS?

• Ependymal cells:

  • Create barriers between compartments

  • Form the lining of the ventricles

  • Source of neural stem cells

• Astrocytes:

  • Take up K+, water, neurotransmitters

  • Source of neural stem cells

  • Secrete neurotrophic factors

  • Helps form a blood-brain barrier

  • Provide substrates for ATP production

• Oligodendrocytes:

  • Form myelin sheaths

What are the glial cells of the PNS?

• Schwann cells:

  • Form myelin sheaths

  • Secrete neurotrophic factors

• Satellite cells:

  • Support cell bodies by forming supportive capsules around a ganglion (plural ganglia)

    • Ganglia: Collections of neuronal cell bodies in the PNS

    • Nuclei: Collections of neuronal cell bodies in CNS

What is an action potential?

• Conduction is the high-speed movement of an action potential along an axon

• AP: Wave of electrical signal at constant amplitude

• Action potentials are all-or-none

• AP’s Go in one direction

• AP’s Do not change ion concentration gradients

1) Explain how the signal travels and induces action potential.

2) Explain the steps of action potential.

1)

• The action potential travels in one direction down the axon

• Pos charges (Na+ influx) move forward

• The region behind is refractory, preventing backward movement (explain why signals don’t go backward - like the seps

2)

1. Resting Membrane Potential (~ -70 mV)

• Neuron is at rest

• Maintained by: Na+/K+ pump, leak channels

2. Stimulus:

• Causes local depolarization

• If small → failed initiation

• If strong enough → reaches threshold

3. Threshold (~ - 55 mV)

• Point of no return

• Voltage-gated Na+ channels open

4. Depolarization

• Rapid Na+ influx

• Membrane potential rises to ~ + 40 mV

5. Repolarization

• Na+ channels inactivate

• Voltage-gated K+ channels open

• K+ exits the cell

6. Hyperpolarization

• Membrane becomes more negative than rest

• K+ channels close slowly

• Refractory period:

  • Absolute: Can’t fire another AP

  • Relative: Stronger stimulus needed

7. Return to Resting State:

• Na+/K+ restores ion gradients

• Neuron ready to fire again

Why can’t an action potential go backward?

Domino analogy: A domino that already fell can’t fall again immediately. Only the next upright domino can fall

1. Action potential moves forward

2. The region behind is refractory b/c during depolarization occurs, the Na+ channel becomes inactivated, and it can’t reopen regardless of how strong the stimulus is (basically the steps can’t work backwards - what’s done is done)
   

What happens when the membrane is at rest?

• The membrane potential is influenced by:

  • Concentration gradient of ions

  • Membrane permeability to those ions

• ECF contains a lot of Na+, Cl-, Ca2+

• ICF contains a lot of K+

How are electric signals created?

• Through ion movement!

• Resting membrane potential determined primarily by:

  • K⁺ concentration gradient

  • Resting permeability to K⁺, Na⁺, and Cl^-

• Voltage-gated channels control ion permeability

• Different channels open at different threshold voltages

• Kinetics of channel opening and closing varies from one channel type to another

Explain how ions move across the membrane during action potentials.

1. The neuron is at its resting membrane potential of -70 mV

2. Depolarization stimulus enters the trigger zone

3. Membrane depolarizes to threshold and voltage-gated Na⁺ and K⁺ channels open

4. Na⁺ channels open first leading to rapid Na⁺ influx that depolarizes the cell (becomes more +)

5. At peak, Na+ channels close and slow K+ channels open

6. K⁺ moves out of the cell

7. K⁺ channels stay open and more K⁺ leaves the cell, hyperpolarizing it

8. Voltage-gated K⁺ channels close, less K⁺ leaks out of the cell

9. Cell returns to resting ion permeability and resting membrane potential

Why is action potential propagation a “one-way street”?

• Potential delay of 1-2 msec between action potentials independent of intensity of trigger

• The refractory period always prevents backward conduction

• Due to Na⁺ gases resetting

• Relative refractory period follows an absolute refractory period

• Positive charge spreads along adjacent sections of axon by local current flow

• Local current flow causes a new section of the membrane to depolarize

How does an action potential move forward along the axon?

• A segment of the axon (yellow) is depolarized → lots of + charge (Na⁺) inside

• That + charge spreads locally to adjacent axon segments

• The forward segment (toward the terminal):

  • Reaches threshold (bc the next segment is still at its resting membrane potential)

  • Triggers a new action potential

• Backward segment (toward soma)

  • Refractory period (the segment behind just fired so it won’t fire anytime soon/again & Na⁺ channels are inactivated)

  • Can’t fire another action potential

1) How do action potentials travel fast in myelinated axons?

2) What happens when myelin is damaged?

1) Saltatory conduction

• The axon is wrapped in myelin (acts as an insulator)

• Voltage-gated Na⁺ channels are only at the Nodes of Ranvier (small gaps in the myelin sheath along a myelinated axon)

• When an action potential occurs at one node:

  • Na⁺ enters

  • + charge spreads rapidly under the myelin

  • The next node reaches the threshold

• The action potential appears to jump from node to node

2) Loss of myelin

• The myelin sheath is damaged

• Current leaks out of the axon between nodes

• Less charge reaches the next node

• This leads to slowed conduction or complete conduction block

1) What is the speed of action potentials influenced by?

2) What diseases are associated with demyelinating disease?

1)

• Diameter of axon: Larger axons are faster

• Resistance of axon membrane to ion leakage out of the cell → myelinated axons are faster

  • Saltatory conduction between nodes of Ranvier

2)

• Multiple sclerosis

• Guillain-Barre syndrome

What is the difference between a graded potential and an action potential?

What are the characteristics of graded potentials?

[INCOMPLETE + insert pic + review]

1) Graded potentials decrease in strength as they spread out from the point of origin

• A stimulus opens ion channels → local depolarization

• The signal spreads out in all directions

• Amplitude decreases as it moves away from the stimuli

Explain the process of action potentials

[INCOMPLETE + insert pic + review']

1. A graded potential above threshold reaches the trigger zone

2. Voltage-gated Na⁺ channels open, and Na⁺ enters the axon

3. Positive charge flows into adjacent sections of the axon by local current flow

4. Low current flow from the active region causes new sections of the membrane to depolarize

5. The refractory period prevents backward conduction. Loss of K⁺ from the cytoplasm repolarizes the membrane

How can sushi be dangerous?

• Tetrodoxin: Blocks voltage-gated Na⁺ channels

• Found in pufferfish, octopuses/octupi/octopodes, some bacteria, some newts

• Paralysis throughout the body

• Death occurs from 20 mins to 8 hrs after digestion

1) How do neurons communicate at synapses?

2) What is the difference between chemical and electrical synapses?

1)

• An AP travels down the axon of the presynaptic (sending) neuron

• It reaches the axon terminals

• The synapse is the area between the presynaptic axon terminal and the postsynaptic dendrite (or soma) → where cell-to-cell communication happens

• The postsynaptic (receiving) neuron gets the signal at its dendrites

2)

• Electrical synapse:

  • Pass electrical signals through gap junctions

  • Ions flow directly between cells

  • Very fast

  • Bidirectional

  • Synchronizes the activity of a network of cells

• Chemical synapse:

  • Neurotransmitters released into the synaptic clef

  • Bind receptors on postsynaptic cell

    • Target cell must have matching receptor

  • Slower

  • Unidirectional

  • Highly modifiable

What are neurotransmitters, neuromodulators, and neurohormones?

• Neurotransmitters and neuromodulators: Paracrine signals that act at short distances (neurocrines)

  • Neurotransmitters are fast acting at synpases

  • Neuromodulators are slow acting at synaptic and non-synaptic sites

  • Autocrine signals can act on the neurons that release them

• Neurohormones act over long distances

  • Secreted into the blood and distributed throughout the body

List the different type of neurocrine receptors

All neurotransmitters bind to specific receptors

• Ionotropic receptors: Ligand-gated ion channels

  • Mediate rapid responses

  • Alter ion flow across membranes

• Metabotropic receptors:

  • G protein-coupled receptors (GPCRs)

  • Mediate slower responses

  • Some open or close ion channels

Note:

• Agonist and antagonist molecules either mimic or inhibit activity by binding to receptors

What are the 7 kinds of neurotransmitters/neurocrines?

Acetylcholine, amines, amino acids, peptides, purines, gases, lipids

What is acetylcholine?

• Synthesized from choline and acetyl CoA

• Cholinergic receptors

  • Nicotinic:

    • Skeletal muscle, autonomic division of PNS, and CNS

    • Monovalent cation channels → Na⁺ and K⁺

  • Muscarinic:

    • CNS and autonomic parasympathetic division of PNS

    • G protein-coupled receptors

What are amines?

• Active in the CNS

• Each is derived from single amino acid

  • Tryptophan → Serotonin

  • Histidine → Histamine

  • Tyrosine → Dopamine → Norephinephrine/Noradrenaline → Epinephrine/Adrenaline

What is norepinephrine (amines)?

• Secreted by noradrenergic neurons

  • Major neurotransmitter of the autonomic sympathetic division of the PNS

• Adrenergic receptors

  • Alpha and beta

  • G protein-coupled receptors

What are amino acids?

• Excitatory:

  • Depolarize target cells by opening ion channels to allow the flow of positive ions into the cell

  • Glutamate: Primary excitatory neurotransmitter in the CNS, also acts as a neuromodulator

  • Aspartate: Excitatory neurotransmitter in the brain

• Inhibitory:

  • GABA: Primary inhibitory neurotransmitter in the brain

  • Hyperpolarizes target cells by opening Cl^- channels

What are glutamate receptors?

• Glutamate can act as a neurotransmitter or a neuromodulator

  • AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)

    • Ligand-gated monovalent cation channel (Na⁺)

  • NMDA (N-methyl-D-aspartate)

    • Non-selective cation channels (Na⁺, K⁺, Ca²⁺)

    • Opening of channel requires glutamate binding and a change in membrane potential

What are peptides?

Substance P and opioid peptides

What are purines?

Adenosine, AMP, ATP

What are some gaseous neurotransmitters that diffuse in the cells?

NO, CO, H₂S

What is an example of a lipid?

Eicosanoids: Some are endogenous ligands for cannabinoid receptors

How are neurotransmitters released?

• Classic exocytosis:

  • Vessicles fuse with membrane

  • Neurotransmitters spill into synaptic cleft

  • Vesicle membrane is incorporated into axon terminal membrane

  • Vesicles are recycled by endocytosis and refilled with neurotransmitters

• Kiss-and-run:

  • Vesicles fuse with membrane at the fusion pore

  • Neurotransmitters pass through a channel

  • Vesicles pull back from fusion pore

  • Vesicles are refilled

How does a chemical synapse release neurotransmitters?

1. An AP depolarizes the axon terminal

2. The depolarization opens voltage-gated Ca²⁺ channels and Ca²⁺ enters the cell

3. Calcium entry triggers exocytosis of synaptic vesicle contents

4. Neurotransmitter diffuses across the synpatic cleft and binds with receptors on the postsynaptic cell

5. Neurotransmitter binding initiates a response in the postsynaptic cell

How does neurotransmitter termination occur in a chemical synapse?

1. Neurotransmitters can be returned to axon terminals for reuse or transported into glial cells

2. Enzymes inactivate neurotransmitters

3. Neurotransmitters can diffuse out of the synaptic cleft

How does a stronger stimulus affect the release of neurotransmitters?

• A single action potential releases a set amount of neurotransmitter

• A stronger stimulus produces more frequent action potentials leading to a more neurotransmitter release

• CNS neurons have different patterns of firing, in addition to frequency

  • Bursts

  • Pacemakers

How is neural info integrated?

• Divergent and convergent pathways at synapses

• Postsynaptic responses may be slow or fast

• Synaptic plasticity is a change in activity at the synapses based on past activity