Impulse Conduction and Synapses — Comprehensive Study Notes

Impulse Conduction and Synapses

  • Impulse conduction involves excitable membranes generating action potentials that propagate along axons to the axon terminal via depolarizing currents. The lecture covers excitable cells, cable properties, myelination, conduction velocity, axon terminals, neurotransmitter release, and synapses.

  • Resting and peak voltages during an action potential:

    • Resting membrane potential around Vrest ≈ −70 mVV_{rest} \,\approx\, -70\ \text{mV}.
    • Influx of Na⁺ during an action potential depolarizes the patch, driving the potential to approximately VAP≈+30 mVV_{AP} \approx +30\ \text{mV} (briefly).
    • Threshold for triggering a new patch: Vth≈−55 mVV_{th} \approx -55\ \text{mV}.
    • The depolarization is temporary, and the patch returns toward resting as channels reset.

  • Local depolarization and propagation:

    • The reversal at the origin serves as the source of depolarizing current for the adjacent patch.
    • If the adjacent patch depolarizes from V=−70 mVV=-70\ \text{mV} to V≈−55 mVV\approx -55\ \text{mV} (threshold), an action potential is generated there as well.
    • The process continues along the membrane until the axon terminal or it may die out prematurely.
    • This propagation relies on pure electromagnetism: depolarizing current can spread along any conductor, including a saline-soaked string, before the action potential is generated in the next patch.

  • Passive spread vs active propagation:

    • Passive current spread occurs after the initial AP generation and can depolarize neighboring patches; however, only patches with voltage-gated Na⁺ channels (excitable membranes) can generate new action potentials.
    • Most cells in the body are not excitable and do not sustain propagating action potentials, though they can conduct passive currents.
    • Propagation to a distant site (e.g., axon terminal) requires axons and muscle cells that express many voltage-gated Na⁺ channels.

  • Analogy: axon as a conductor vs. copper wire vs resistor/capacitor network:

    • Membrane is modeled as a circuit with resistors and capacitors; voltage across a membrane in one location can be measured at a distance, showing amplitude loss due to leakage.
    • Biological tissue is a poor conductor; the membrane’s capacitive properties damp high-frequency components, leading to a softer, more gradual rise and fall compared with copper wires.
    • Leakage and resistance in the membrane and cytoplasm reduce signal propagation along the membrane.

  • Length constant (lambda) and its significance:

    • Lambda measures how far a potential difference can travel before it decays significantly with distance.
    • Higher lambda means a signal travels farther without decaying to baseline.
    • The equation governing lambda (ignoring Ro for practical purposes) is:
      λ=R<em>mR</em>i\lambda = \sqrt{\dfrac{R<em>m}{R</em>i}}
      where R<em>iR<em>i is the internal (cytoplasmic) resistance and R</em>mR</em>m is the membrane resistance.
    • Definition: lambda is the distance over which the voltage decays to about 1e\dfrac{1}{e} of its original value (approximately 0.37 of the original).
    • In a comparison: axon A (thin) loses voltage rapidly (steep drop), axon B (thicker) retains voltage longer (flatter drop).
    • Internal resistance (Ri) is due to cytoplasmic contents and organelles; membrane leakage is due to Ro and especially membrane leakiness.

  • How to increase lambda (physiological strategies):

    • Increase axon diameter reduces interior resistance (Ri) by increasing cross-sectional area; this is analogous to using a wider straw for less resistance.
    • Increase membrane resistance (Rm) to reduce leak; this is achieved by myelination (wrapping the axon with a myelin sheath) which increases lambda significantly by reducing current leakage.
    • Practical note: increasing diameter physiologically is limited; myelination is the primary practical method to boost lambda in most neurons.

  • Myelination and glial cells:

    • Myelin sheets wrap around axon segments, increasing membrane resistance and reducing leakage.
    • Glial cell types:
    • Schwann cells in the peripheral nervous system (PNS) wrap myelin around single axons.
    • Oligodendrocytes in the central nervous system (CNS) wrap myelin around multiple axons (extensions resemble octopus tentacles).
    • Myelination increases lambda by roughly 25-fold but adds bulk to the axon, so only a subset of axons are myelinated (about 20%).
    • Analogy: coaxial cable – a copper core with plastic insulation; myelin acts like insulation to confine current to the axon.
    • Myelinated segments have gaps called nodes of Ranvier, where the membrane is exposed.

  • Nodes of Ranvier and saltatory conduction:

    • Node of Ranvier is a gap between myelinated segments rich in voltage-gated Na⁺ channels.
    • Action potentials are generated at nodes due to the high density of Na⁺ channels; between nodes, current travels passively through the myelinated segments.
    • Saltatory conduction: the AP appears to jump from node to node, greatly increasing conduction speed.
    • The myelinated internodes are not sites of AP generation; instead, they're efficient conduits for depolarizing current to reach the next node.

  • Consequences of demyelination (Multiple Sclerosis):

    • MS damages myelin sheets in brain and spinal cord, slowing or blocking signal transmission.
    • Symptoms include visual disturbance, muscle weakness, coordination/balance problems, numbness or pins-and-needles sensations, and memory problems, due to impaired myelination.

  • Safety factor and robustness of saltatory conduction:

    • The conduction mechanism has a safety factor: if some nodes become unexcitable, the depolarizing current can skip to the next healthy patch, continuing conduction.
    • This makes transmission resilient to some local failures but requires a fair-length membrane to be damaged before transmission is blocked.
    • The REMak (Remak) bundle concept refers to groups of unmyelinated fibers ensheathed by a single Schwann cell, illustrating bundled protection and redundancy in signal transmission.

  • Conduction velocity and species differences:

    • Fastest axons conduct at about vmax≈80 m/sv_{max} \approx 80\ \text{m/s}.
    • Unmyelinated axons conduct about v≈2 m/sv \approx 2\ \text{m/s} (roughly 40-fold slower).
    • Cats can reach speeds up to around 120 m/s120\ \text{m/s} in some axons; humans compensate by having more axons rather than the absolute fastest axons.

  • Propagation direction and refractory period:

    • An action potential propagates along the axon; the direction is inherently forward toward the axon terminal.
    • The region just behind a propagated spike is in absolute refractory period, where voltage-gated Na⁺ channels are inactivated and cannot fire again.
    • This prevents the impulse from turning around and propagating backward, ensuring unidirectional transmission.
    • At the axon terminal, the depolarizing current ends, and the AP dies out unless a fresh trigger zone initiates another AP downstream.

  • Synapses: electrical vs chemical

    • Electrical (electrotonic) synapses:
    • Cells are connected by gap junctions, enabling direct depolarization transfer.
    • Mechanism is bidirectional and does not involve neurotransmitter release; used for rapid signaling.
    • Chemical synapses:
    • Involve a presynaptic neuron and a postsynaptic membrane with receptor proteins.
    • The presynaptic terminal houses vesicles filled with neurotransmitters.
    • An arriving action potential at the axon terminal triggers neurotransmitter release via exocytosis.
    • Exocytosis is triggered by calcium ions (Ca²⁺) entering through voltage-gated Ca²⁺ channels.
    • Neurotransmitters bind to receptors on the postsynaptic membrane, producing postsynaptic responses.

  • Mechanism of neurotransmitter release at chemical synapses:

    • Action potential arrives at the axon terminal, depolarizing the presynaptic membrane.
    • Voltage-gated calcium channels open, allowing Ca²⁺ to enter the terminal.
    • Ca²⁺ triggers docking and fusion of vesicles with the presynaptic membrane (exocytosis).
    • Neurotransmitters are released into the synaptic cleft and bind to postsynaptic receptors, generating a response.

  • Why chemical synapses instead of purely electrical transfer:

    • Even with an electrical AP reaching the terminal, neurotransmitter release is probabilistic rather than guaranteed.
    • The probability of release per AP ranges roughly from 10% to 90%, and sometimes results in no release or full release.
    • This probabilistic nature allows synapses to act as processing stations, enabling modulation, plasticity, and complex neural computation.
    • Purely electrical synapses, while robust, do not provide the same level of flexibility and computational capability of chemical synapses.

  • Final reflections and implications:

    • The combination of electrical signaling, myelination, and chemical synapses enables rapid, efficient, and flexible neural communication.
    • The probabilistic nature of chemical transmission adds a level of stochasticity that may be essential for learning and neural computation.
    • Understanding these elements provides insight into neurological diseases (e.g., MS) and the design principles behind neural networks in biology.

  • Illustrative metaphors and distinctions:

    • Passive transmission is like a chain of whisper-down-the-line where the message attenuates with distance unless a robust node restarts it.
    • Saltatory conduction is like a relay race where the baton (AP) is handed from node to node, skipping leaky stretches due to insulation (myelin).
    • A REMak bundle analogy emphasizes redundancy and resilience in cable-like nerve fibers.

  • Notable equations and numerical references:

    • Resting and peak potentials:
    • V<em>rest≈−70 mV,V</em>AP≈+30 mVV<em>{rest} \approx -70\ \text{mV},\quad V</em>{AP} \approx +30\ \text{mV}
    • Threshold: Vth≈−55 mVV_{th} \approx -55\ \text{mV}
    • Length constant:
    • λ=R<em>mR</em>i\lambda = \sqrt{\dfrac{R<em>m}{R</em>i}}
    • Definition: distance where the voltage decays to 1e≈0.37\dfrac{1}{e} \approx 0.37 of its original value.
    • Conduction velocities (typical values):
    • Myelinated axons: up to about 80 m/s80\ \text{m/s} (fastest in humans ~80 m/s; cats up to 120 m/s120\ \text{m/s} in some cases).
    • Unmyelinated axons: about 2 m/s2\ \text{m/s}.
    • Myelin increases lambda by approximately a factor of ≈25\approx 25 (the exact factor varies with geometry and membrane properties).

  • Key terms to remember:

    • Trigger zone (initial segment) – where the first AP is generated.
    • Node of Ranvier – gap in myelin with high density of voltage-gated Na⁺ channels, site of AP regeneration.
    • Saltatory conduction – AP propagation through myelinated axons by jumping between nodes.
    • Remak bundle – a Schwann cell ensheathing multiple unmyelinated axons.
    • Absolute refractory period – period after an AP during which no new AP can be initiated.
    • Electrical synapse – gap junction-mediated, bidirectional, no neurotransmitter release.
    • Chemical synapse – neurotransmitter release via Ca²⁺-triggered vesicle fusion; probabilistic transmission.

  • Real-world relevance and connections:

    • Myelination and nodes of Ranvier are critical for rapid nerve signaling in motor and sensory pathways.
    • Demyelinating diseases such as multiple sclerosis illustrate the importance of membrane resistance and intact myelin for proper neural communication.
    • Synaptic probabilistic transmission underpins learning, memory, and neural plasticity.

  • Practical takeaways for exams:

    • Be able to explain the difference between passive current spread and active action potential propagation.
    • Know the lambda equation and how diameter and membrane resistance influence lambda.
    • Describe the role of myelin and nodes of Ranvier in saltatory conduction and give typical velocity ranges.
    • Distinguish electrical vs chemical synapses and outline the sequence of events leading to neurotransmitter release.
    • Understand the significance of the refractory period in preventing backward propagation.
    • Recall MS symptoms and their relation to loss of myelin.