Postsynaptic Cell Responses and Synaptic Integration

Ionotropic Receptors: Directly linked to ion channels; neurotransmitter binding causes a rapid opening of the channel, leading to immediate ion flux.
Metabotropic Receptors: Activate a G-protein signaling cascade, which can then indirectly open or close ion channels or trigger other intracellular changes. Their effects are typically slower and longer-lasting.

The membrane potential ( $V_m$ ) of the postsynaptic cell is regulated by postsynaptic potentials (PSPs).
PSPs are graded potentials: This means their amplitude varies depending on the strength of the stimulus (amount of neurotransmitter released and number of receptors activated), and they decrement over distance and time.

Effect: Hyperpolarize the membrane potential ( $V_m$ ), moving it further away from the threshold for an action potential.
Mechanism: Typically involve the opening of chloride ( $Cl^-$ ) or potassium ( $K^+$ ) channels.
- Opening of $Cl^-$ channels allows chloride ions to enter the cell, making the inside more negative.
- Opening of $K^+$ channels allows potassium ions to leave the cell, making the inside more negative.
Most common neurotransmitters (NTs): GABA (gamma-aminobutyric acid) and Glycine.
Characteristics (from slide 4): Hyperpolarize membrane, more negative or less positive; $K^+$ charge leaving cell or $Cl^-$ charge entering cell (most common).

Effect: Depolarize the membrane potential ( $V_m$ ), moving it closer to the threshold for an action potential.
Mechanism: Typically involve the opening of sodium ( $Na^+$ ) channels, allowing $Na^+$ to enter the cell and make the inside more positive. Occasionally, calcium ( $Ca^{2+}$ ) channels may also be opened.
Most common neurotransmitters (NTs): Acetylcholine and Glutamate.
Characteristics (from slide 4): Depolarize cell, less negative, more positive; brings positive charge into the cell (very common);
Note: A single EPSP or IPSP usually has only marginal effects on the membrane potential. Significant changes in $V_m$ require the process of spatial and/or temporal summation.

Since a single EPSP is usually insufficient to bring a membrane to threshold, repeated synaptic transmission results in two types of summation in the postsynaptic neuron:

Definition: Occurs when multiple postsynaptic potentials from different presynaptic neurons (a process known as convergence) occur simultaneously and induce changes in the membrane potential to either depolarize or hyperpolarize the postsynaptic cell.
Example: Several different presynaptic neurons firing at the same moment in time, each releasing neurotransmitters that cause PSPs on the postsynaptic cell. The combined effect of these simultaneous PSPs can reach the threshold.

Definition: Occurs when multiple postsynaptic potentials are generated by the same presynaptic neuron firing multiple times in rapid succession (over a short period). These successive PSPs add up before the previous ones have fully decayed, inducing changes in the membrane potential to either depolarize or hyperpolarize the postsynaptic cell.
Example: One presynaptic neuron firing multiple times rapidly, leading to a buildup of PSPs.

Neurons are remarkable integrators of information.
If the sum of all excitatory (EPSPs) and inhibitory (IPSPs) inputs moves the membrane potential to the threshold (typically around $-55$ mV), an action potential will be generated.
This allows neurons to integrate information from multiple converging neurons, effectively processing complex signals before sending an output via an action potential.

These processes modify the strength of a single EPSP or IPSP by altering the amount of neurotransmitter released from the presynaptic terminal.
This modulation is often mediated by metabotropic receptors located on the presynaptic terminal itself.

Effect: Increases the strength of an EPSP or IPSP by increasing the amount of neurotransmitter released from the presynaptic terminal in response to an action potential.
Mechanism: An input from a modulating neuron activates metabotropic receptors on the terminal end of the presynaptic neuron. This activation, via a G-protein cascade, leads to an increase in neurotransmitter release from the presynaptic neuron into the synapse.
Example (from slide 13): Neuron E activates metabotropic receptors on the terminal of neuron D, leading to an increase in the release of neurotransmitters from neuron D.

Effect: Decreases the strength of an EPSP or IPSP by decreasing the amount of neurotransmitter released from the presynaptic terminal in response to an action potential.
Mechanism: Similar to facilitation, a modulating neuron releases neurotransmitters that activate metabotropic receptors on the terminal end of a presynaptic neuron. This activation, however, leads to a decrease in neurotransmitter release from the presynaptic neuron.
Example (from slide 13): Neuron B activates metabotropic receptors on the terminal of neuron A, which inhibits the release of neurotransmitters from neuron A.

Activation of metabotropic receptors on the terminal end of a presynaptic neuron can either increase or decrease the amount of neurotransmitter released in response to an action potential from that presynaptic neuron. This allows for fine-tuning of synaptic strength by modulating the output of a neuron.