Synapses and Neuronal Membrane Properties

Introduction to Neuroscience (PSYCH 254) - Week 4 (Lectures 6 & 7)

Synapses and Neuronal Membrane Properties

How Do Neurons Communicate?

Neurons communicate through two primary mechanisms:

• Chemical Transmission: Involves the release of chemical messengers (neurotransmitters) from one neuron onto another.

• Electrical Transmission: Involves direct electrical coupling between cells via gap junctions and the propagation of electrical signals within a neuron, such as changes in neuronal resting membrane potential (depolarization or hyperpolarization) and action potential propagation.

Chemical Synapse

• Definition: A synapse is the specialized junction between two connected neurons, a term coined by Sherrington in 1906.

• Components of a Synapse:

  • Presynaptic membrane: The membrane of the neuron sending the signal.

  • Synaptic cleft: A narrow gap of approximately $<300 \text{ Å}$ (or $30 \text{ nm}$) between the presynaptic and postsynaptic membranes.

  • Postsynaptic membrane: The membrane of the neuron receiving the signal.

• Neurotransmitter Release:

  • During an electrical impulse (action potential), neurotransmitter-filled vesicles within the presynaptic terminal fuse with the presynaptic membrane.

  • This fusion releases neurotransmitters into the synaptic cleft.

  • These neurotransmitters then diffuse across the synaptic space and bind to specific receptors located on the postsynaptic neuronal membrane, leading to a response in the postsynaptic neuron.

• Types of Synapses in the Nervous System:

  • Axodendritic: Synapses formed by axons onto dendrites. This can include synapses onto the main dendritic shaft or onto dendritic spines (small protrusions on dendrites).

  • Axosomatic: Synapses formed by axons onto the cell body (soma) of another neuron.

  • Axoaxonic: Synapses formed by axons onto other axons, often modulating the release of neurotransmitters from the presynaptic terminal.

  • Dendrodendritic: Synapses between dendrites (not a primary focus in this lecture, but they do exist).

  • Neuromuscular junction: A specialized synapse where an axon terminal synapses onto a muscle cell, mediating muscle contraction.

Neuronal Membrane Properties

Resting Membrane Potential (RMP)

• Environment: Neurons are bathed in a salt solution where salts dissociate into ions (e.g., $NaCl$ dissociates into $Na^+$ and $Cl^-$).

• Ionic Charge Distribution:

  • Inside the neuron, the cytoplasm is typically more negative.

  • Outside the neuron, the extracellular fluid is typically more positive.

• Cell Membrane Role: The cell membrane, a phospholipid bilayer, restricts the movement of ions, preventing them from simply diffusing across. Ions must pass through specific ion channels.

• RMP Value: The RMP is usually approximately $-70 \text{ mV}$ (millivolts).

• Significance: The RMP allows neurons to be electrically excitable, meaning they can rapidly change their electrical state in response to stimuli.

• Historical Context: Hodgkin & Huxley and their colleagues extensively studied ionic movements contributing to neuronal membrane properties using the squid giant axon (specifically, the giant axon of Loligo).

Distribution of Ions & Ion Channels at Rest

• Key Ion Concentrations:

  • High concentrations of $Na^+$ and $Cl^-$ are found outside the cell (low inside).

  • High concentrations of $K^+$ are found inside the cell (low outside).

• Forces Governing Ion Movement: Two main forces influence ion movement across the membrane:

  • Chemical Gradient (Concentration Gradient): Ions tend to move from an area of high concentration to an area of low concentration. For example, $K^+$ tends to leave the cell down its concentration gradient.

  • Electrical Gradient: Ions are attracted to areas of opposite charge and repelled by areas of like charge. For example, $K^+$ tends to enter the cell down its electrical gradient, as the inside is negative.

  • The Sodium-Potassium Pump (Na-K ATPase) actively maintains these gradients by pumping $3 \text{ Na}^+$ ions out of the cell and $2 \text{ K}^+$ ions into the cell, consuming energy in the process, crucial for restoring ion balance after an action potential.

Equilibrium (Reversal) Potential of an Ion

• Definition: The reversal potential (or equilibrium potential) for a specific ion is the membrane potential at which there is no net flow of that particular ion across the membrane, even if there are open channels for that ion. At this potential, the electrical and chemical gradients for that ion are perfectly balanced.

• Variability: The reversal potential is not the same for each ion because each ion has a unique concentration gradient across the membrane and carries a different charge.

• Significance: Understanding reversal potentials helps predict the direction of ion flow and the resulting change in membrane potential when specific ion channels open.

Depolarization & Hyperpolarization

When a neuron is "at rest" (not receiving chemical or electrical inputs and recovered from previous stimuli), its RMP is negative.

• Depolarization:

  • Definition: A change in the RMP that makes it more positive (less negative).

  • Mechanism: Typically caused by an influx of positive ions, such as $Na^+$ or $Ca^{2+}$, into the cell.

  • Example: RMP changes from $-70 \text{ mV}$ to $-65 \text{ mV}$ (a $5 \text{ mV}$ depolarization).

  • Effect: If depolarization is strong enough, it can reach the threshold of excitation and trigger an action potential.

• Hyperpolarization:

  • Definition: A change in the RMP that makes it more negative.

  • Mechanism: Typically caused by an efflux of positive ions out of the cell (e.g., $K^+$) or an influx of negative ions into the cell (e.g., $Cl^-$).

  • Example: RMP changes from $-70 \text{ mV}$ to $-75 \text{ mV}$ (a $5 \text{ mV}$ hyperpolarization).

The Action Potential

• Initiation:

  • Subthreshold Inputs: Small electrical inputs are "subthreshold" (e.g., a small depolarization not strong enough to trigger an AP).

  • Threshold of Excitation: If the input (depolarization) is large enough, the membrane potential reaches a critical level called the threshold of excitation (typically around $-55 \text{ mV}$).

  • All-or-None Law: Once the threshold is reached, an action potential is initiated and propagates down the axon completely, without decrement. It either fires at its full amplitude or not at all.

• Summary of Ion Channel Activity During an Action Potential:

  1. Resting State: Voltage-gated $Na^+$ and $K^+$ channels are closed. RMP is $-70 \text{ mV}$.

  2. Depolarization to Threshold: A stimulus causes the membrane potential to depolarize to threshold.

  3. Rising Phase (Depolarization): Voltage-gated $Na^+$ channels open rapidly, leading to a massive influx of $Na^+$ ions into the cell. This makes the inside of the cell significantly more positive, peaking around $+40 \text{ mV}$.

  4. Peak and Repolarization Phase:

     • $Na^+$ channels become inactivated (refractory), preventing further $Na^+$ entry.

     • Voltage-gated $K^+$ channels open slowly, leading to an efflux of $K^+$ ions out of the cell. This makes the inside of the cell more negative again, returning towards the resting potential.

  5. Hyperpolarization (Undershoot): $K^+$ channels remain open for a short period after the membrane potential reaches RMP, causing an excess efflux of $K^+$ and making the membrane potential even more negative than the RMP (e.g., $-75 \text{ mV}$). This is known as the undershoot or after-hyperpolarization.

  6. Return to Resting Potential: $K^+$ channels close, and the $Na^+$ channels reset from their inactivated state to a closed but ready state. The $Na^+$/$K^+$ pump and passive leak channels restore the RMP.

• Refractory Periods:

  • Absolute Refractory Period: During the rising phase and early repolarization, the $Na^+$ channels are either open or inactivated, making it impossible to generate another action potential, regardless of stimulus strength. This ensures unidirectional propagation.

  • Relative Refractory Period: During the later repolarization and hyperpolarization (undershoot), the $Na^+$ channels are largely reset, but $K^+$ channels are still open, and the membrane is hyperpolarized. A stronger-than-normal stimulus is required to elicit another action potential during this period.

Action Potential Propagation

• Mechanism in Unmyelinated Axons:

  1. $Na^+$ influx at one point depolarizes the adjacent segment of the membrane to threshold.

  2. This triggers the opening of voltage-gated $Na^+$ channels in the new segment, causing further $Na^+$ influx.

  3. Simultaneously, $K^+$ efflux occurs in the previously depolarized segment, restoring the resting potential.

  4. This sequential depolarization and repolarization propagates the action potential unidirectionally down the axon.

Saltatory Conduction (in Myelinated Axons)

• Myelin Sheath: A fatty insulating layer (formed by Schwann cells in the PNS and oligodendrocytes in the CNS) that wraps around the axon.

• Nodes of Ranvier: Gaps in the myelin sheath that expose the axon membrane at regular intervals.

• Mechanism:

  • Myelin electrically insulates the axon, preventing ion flow across the membrane.

  • Voltage-gated $Na^+$ and $K^+$ channels are highly concentrated at the Nodes of Ranvier.

  • When an action potential occurs at one node, the depolarization spreads rapidly and decrementally (without regenerating an AP) under the myelin sheath to the next node.

  • At the next Node of Ranvier, the depolarization is strong enough to trigger a new action potential, which then "jumps" to the subsequent node.

• Benefits:

  • Increased Conduction Speed: Action potentials effectively jump from node to node, significantly speeding up propagation (up to $120 \text{ m/s}$ or $432 \text{ km/hr}$).

  • Energy Conservation: Less energy is expended by the $Na^+$/$K^+$ pump because ion exchange only occurs at the nodes, reducing the area that needs to be repolarized.

• Demyelination: A demyelinated axon is not the same as an unmyelinated axon. In an unmyelinated axon, voltage-gated channels are distributed evenly. In a demyelinated axon, the channels were originally clustered at the nodes. If myelin is lost, the exposed internodal regions lack sufficient ion channels to regenerate the action potential, leading to conduction failure or significantly impaired propagation, unlike naturally unmyelinated axons which still conduct, albeit slowly.

Decremental Propagation of an Electrical Impulse (e.g., EPSP)

• Subthreshold depolarizations, like Excitatory Postsynaptic Potentials (EPSPs), spread passively along the membrane. They decrease in amplitude over distance and time. This is called decremental conduction.

Signal Integration

Neurons integrate multiple inputs to determine whether to fire an action potential.

• Summation Criteria:

  • Temporal Summation: Occurs when multiple presynaptic impulses from a single neuron arrive at the postsynaptic neuron in rapid succession over time. The effects of these impulses add up, potentially reaching threshold.

  • Spatial Summation: Occurs when impulses from several different neurons arrive at different synaptic locations on the postsynaptic neuron at the same time. Their combined effects add up.

• Excitation and Inhibition:

  • Excitatory Postsynaptic Potentials (EPSPs): Depolarizations that bring the membrane potential closer to threshold.

  • Inhibitory Postsynaptic Potentials (IPSPs): Hyperpolarizations (or stabilize the membrane potential further from threshold) that make it harder to reach threshold.

  • Neurons summate both EPSPs and IPSPs. If the cumulative effect of all inputs depolarizes the membrane to threshold, an action potential is fired.

Stimulus Intensity Encoding and Adaptation

• Stimulus Intensity Encoding: The intensity of a stimulus is typically encoded by the frequency (or rate) of action potentials generated by a neuron. A stronger stimulus leads to a higher firing rate.

• Adaptation: A decrease in the firing rate of a neuron despite continuous presentation of a stimulus. This mechanism allows the nervous system to filter out constant, non-critical stimuli and respond more to changes (e.g., getting used to an odor).