Intro to Neuro Lecture 8

What is a synapse?

A specialized junction where a neuron passes information to another cell. This communication is called synaptic transmission.

How do electrical and chemical synapses differ?

Electrical synapses pass ionic current directly through gap junctions. Chemical synapses release neurotransmitter across a cleft to receptors, usually transmitting in one direction.

How do gap junctions electrically couple cells?

Two connexons, one in each cell's membrane, align to form a channel that lets ions flow between the cells. Gap junctions occur in neurons and glia.

What are the main properties of electrical synapses emphasized in the lecture?

Very fast transmission, usually bidirectional current flow, and synchronization of activity between connected cells.

What response does an action potential produce in an electrically coupled neighboring cell?

Current passing through the gap junction produces a small postsynaptic potential. This may remain below threshold, so the neighboring cell does not necessarily fire.

What is an axodendritic synapse?

A synapse where a presynaptic axon contacts a postsynaptic dendrite.

What is an axospinous synapse?

A synapse where a presynaptic axon contacts a dendritic spine, a small projection from a dendrite.

What is an axosomatic synapse?

A synapse where a presynaptic axon contacts the postsynaptic cell body, or soma.

What is an axoaxonic synapse?

A synapse where a presynaptic axon contacts another axon.

What is the synaptic cleft?

The extracellular gap between the two cells at a chemical synapse. The lecture gives a width of approximately 20-50 nm.

What is a neurotransmitter?

A chemical messenger released by a neuron that binds receptors and changes a target cell's activity.

What are synaptic vesicles?

Small membrane-bound containers in the presynaptic terminal that store neurotransmitter. Transmitter is synthesized and packaged before release.

What is an active zone?

A specialized region of the presynaptic membrane where vesicles release neurotransmitter. Release-ready vesicles and voltage-gated Ca2+ channels are located there.

What is the postsynaptic density?

A receptor-rich protein specialization on the receiving side, directly opposite the presynaptic active zone.

What is the sequence of chemical synaptic transmission?

Presynaptic action potential -> terminal depolarization -> Ca2+ channels open -> Ca2+ enters -> vesicles release transmitter -> transmitter diffuses across the cleft -> receptors activate -> postsynaptic response.

What opens voltage-gated Ca2+ channels in the presynaptic terminal?

Depolarization caused by the arriving action potential opens these channels at active zones.

How does Ca2+ cause neurotransmitter release?

Ca2+ enters the terminal down its electrochemical gradient and activates proteins that trigger vesicle fusion and opening of a release pore.

What is exocytosis?

Fusion of a synaptic vesicle with the presynaptic membrane, releasing its neurotransmitter into the synaptic cleft.

Why can exocytosis begin so quickly after an action potential?

Some vesicles are already docked and primed at active zones. The lecture describes release beginning in less than 0.2 ms.

What is the role of endocytosis in synaptic transmission?

It retrieves vesicle membrane from the presynaptic cell surface so vesicles can be recycled.

What are the two main classes of neurotransmitter receptors?

Ionotropic receptors, also called transmitter-gated ion channels; and metabotropic receptors, also called G-protein-coupled receptors.

How do ionotropic receptors work?

Neurotransmitter binding changes the receptor's shape and opens its ion-channel pore. This differs from voltage-gated channels, which respond to changes in membrane voltage.

How do ionotropic and metabotropic responses differ in timing and effects?

Ionotropic responses are generally fast and brief. Metabotropic responses are usually slower, longer-lasting, and can alter channels, enzymes, or cellular metabolism.

What are the steps of metabotropic receptor signaling?

Neurotransmitter binds the receptor -> the receptor activates a G protein -> the G protein regulates an effector, either an ion channel or an enzyme.

What is a second messenger?

An intracellular signaling molecule that carries a receptor's signal inside the cell. For example, the effector enzyme adenylyl cyclase produces the second messenger cAMP.

How does a postsynaptic potential differ from an action potential?

A PSP is a graded voltage change that can vary in size, sum with other PSPs, and decay with distance. An action potential is an all-or-none, regenerated signal.

What is an EPSP, and how does Na+ entry produce one?

An excitatory postsynaptic potential depolarizes the cell toward firing threshold. Na+ entry brings positive charge inside, making the membrane potential less negative.

Which neurotransmitters provide the lecture's examples of fast excitatory signaling?

Glutamate, an amino-acid neurotransmitter, and acetylcholine (ACh), acting through excitatory ionotropic receptors.

Which neurotransmitter is released at human skeletal neuromuscular junctions?

Acetylcholine. It activates nicotinic ACh receptor channels on the muscle cell, causing depolarization.

What is an IPSP?

An inhibitory postsynaptic potential reduces the likelihood of firing. In the lecture's hyperpolarizing examples, it moves membrane voltage farther from threshold.

Which neurotransmitters produce the lecture's fast inhibitory responses?

GABA (gamma-aminobutyric acid) and glycine. Both are amino-acid neurotransmitters; their fast inhibitory receptors allow Cl- to cross the membrane.

What determines whether a neurotransmitter's effect is excitatory or inhibitory?

The receptor it activates, the channels or signaling pathways controlled by that receptor, and the relevant ion gradients.

What are autoreceptors, and what is their main role in this lecture?

Receptors commonly on presynaptic terminals that detect the same neuron's released transmitter. They often provide negative feedback that reduces further release.

Why is neurotransmitter clearance necessary, and what are its three main mechanisms?

Clearance limits continued receptor activation and allows distinct later signals. The mechanisms are diffusion, reuptake, and enzymatic breakdown.

How does diffusion clear neurotransmitter?

Transmitter moves away from the synaptic cleft into surrounding extracellular fluid, lowering its concentration near receptors.

How does reuptake clear neurotransmitter?

Transporter proteins move transmitter into the presynaptic neuron or nearby glia. This is an important clearance mechanism for many amino-acid and amine transmitters.

What happens to neurotransmitter after presynaptic reuptake?

It may be repackaged into vesicles for reuse or broken down inside the neuron.

How does enzymatic breakdown clear neurotransmitter, and what is the ACh example?

Enzymes convert transmitter into inactive products. Acetylcholinesterase breaks down ACh in the synaptic cleft at skeletal neuromuscular junctions.

What is synaptic integration?

The combining of many excitatory and inhibitory inputs within a postsynaptic neuron to influence whether it fires an action potential.

What determines the amplitude of an EPSP?

The amount of transmitter released, including the contents and number of released vesicles, and the number of available postsynaptic receptors.

What is spatial summation?

Postsynaptic potentials from different synapses overlap in time and combine. Multiple EPSPs can produce enough depolarization to reach threshold.

What is temporal summation?

Repeated inputs at the same synapse arrive before earlier PSPs decay, allowing their effects to add. The lecture gives an example interval of about 15 ms.

Where must depolarization reach threshold for a neuron to fire?

At the spike-initiation zone, usually the axon initial segment near the axon hillock. An individual EPSP does not necessarily reach this threshold.

What three factors does the lecture emphasize in determining an EPSP's contribution to firing?

The number and strength of coactive excitatory inputs, the distance from the synapse to the spike-initiation zone, and how far depolarization can spread.

Why do EPSPs weaken as they spread along a dendrite?

Current leaks across the membrane, so less continues along the dendrite and the voltage change becomes smaller with distance.

What is the dendritic length constant, lambda?

The distance over which a passive voltage change falls to about 37% of its starting amplitude. A larger length constant means depolarization spreads farther.

How do internal resistance and membrane resistance differ?

Internal resistance opposes current traveling along the cell's interior. Membrane resistance opposes current crossing the membrane.

How do membrane resistance and internal resistance affect the length constant?

Higher membrane resistance reduces leakage and increases the length constant. Higher internal resistance makes current travel harder and decreases the length constant.

How does opening Cl- channels affect membrane voltage?

It drives voltage toward the Cl- equilibrium potential, approximately -65 mV in the lecture's example. From a less negative voltage, this produces hyperpolarization.

Why may opening Cl- channels cause no visible IPSP at the Cl- equilibrium potential?

There is initially no net Cl- current because the membrane is already at that ion's equilibrium potential. The increased conductance can still inhibit through shunting.

What is shunting inhibition?

Opening inhibitory channels lowers membrane resistance and weakens the voltage change produced by excitatory input. It can inhibit without a visible initial hyperpolarization.

How does a proximal inhibitory synapse shunt a distal excitatory input?

The inhibitory synapse is closer to the soma and provides a current pathway that reduces how much depolarization from the more distant excitatory synapse reaches the axon region.

What is synaptic modulation?

A change in the effectiveness of other synaptic inputs, often through metabotropic signaling. The modulatory input need not directly produce a clear EPSP or IPSP.

What is NE, and what receptor is shown in the lecture's modulation pathway?

NE is norepinephrine, also called noradrenaline. The example uses a beta-adrenergic G-protein-coupled receptor.

What happens immediately after NE binds its receptor in the lecture's example?

The receptor activates a G protein, which then activates the enzyme adenylyl cyclase.

What does adenylyl cyclase do in the NE pathway?

It converts ATP into cAMP, the second messenger.

What does cAMP activate in the NE pathway?

A protein kinase.

What does the protein kinase do to the K+ channel in the NE example?

It phosphorylates the channel, meaning it adds a phosphate group, which causes the channel to close in this example.

How does closing K+ channels increase neuronal excitability in the NE example?

K+ permeability falls, membrane resistance rises, and the length constant increases. EPSPs lose less current through leakage and have a stronger effect near the axon.

What is the complete NE modulation pathway shown in the lecture?

NE -> beta receptor -> G protein -> adenylyl cyclase -> ATP converted to cAMP -> protein kinase -> K+ channel phosphorylation and closure -> increased membrane resistance and length constant -> increased excitability.