NEUR200 9/25 Neurotransmission Pirnciples

Where are neurotransmitters released?

into the synapse

Neurotransmitters actions are limnited to ____

the neurons that have synapses with the releasing cell

Neurtransmitters actions are relatively ____

short due to rapid uptake/breakdown

Where are hormones released?

Released into the blood

Hormones can affect ____

an enormous number of cells

Hormone ex;

Epinephrine is released into the circulatory system —> Actions typically linger

The same molecule (chemical) can act as

BOTH a neurotransmitter and hormone

Transmitters have different effects on their targets because

they bind to different receptors

The same transmitter can have different effects depending on

the type of receptor it binds to

Transmitter release

When spike reaches the terminal, voltage gated Ca2+ channels open and Ca2+ ions enter, triggering the proteins (SNAREs) that cause exocytosis.

Exoctytosis

Presynaptic axon terminals contain vesicles (small, spherical membranes) that

contain neurotransmitters, the vesicles fuse with the membrane and

neurotransmitters are released in the synaptic cleft.

Dale’s Law

a given neuron will consistently release the same neurotransmitter/s at all ofc its synapses;

Although ONCE BELIEVED to release only one neurotransmitter, it is known that a single

neuron can release more than one transmitter

Neural Nomenclature

Because neurons release typically release (mostly) one transmitter, sometimes two, they are often referred to by the neurotransmitter that they release

Cells that release glutamate =

glutamatergic neurons

Cells that release GABA =

GABAergic neurons

Receptor Signaling Mechanisms

Two types of receptors; Ionotropic and Metabotropic

Ionotropic:

Neurotransmitter binds to an ionotropic receptor and opens its channels (ion channels for sodium, potassium, calcium and chloride).

Effects are fast (less than a millisecond)

Metabotropic:

When metabotropic receptors are activated, they activate intracellular signaling cascades that, ultimately, change how excitable the neuron is. And lots of other things.

Effects are slower (on the order of tens to hundreds of milliseconds or longer), but longer lasting (few seconds) than ionotropic.

Ionotropic Receptors

Membrane-bound receptors;

Membrane-bound receptors

The receptor is embedded in the cell membrane

Membrane-bound receptors are coupled in which ion channels?

Na+, Cl-, K+, Ca2+

Transmitter binding in membrane-bound receptors

opens the ion channel; produces rapid excitation/inhibition

Receptor Signaling Mechanisms

The major excitatory neurotransmitter within the brain

Glutamatergic neurons are found ____ of the brain

Throughout much

Receptor signaling mechanisms act on ___ receptors

two types of ionotropic

AMPA receptor are

Ligand-gated

NMDA receptors are

Ligand-gated and voltage-gated;

There are also metabotropic glutamate receptors

AMPA Receptors

When glutamate binds to AMPA receptors, their conformation changes, allowing sodium to rush in (through sodium channels) and cause an EPSP

NMDA Receptors

NMDA receptors have channels that are permeable to sodium and calcium NMDA receptors have two requirements:

• Glutamate must bind to them (ligand-gated)

• The cell must be depolarized (voltage-gated)

As we will discuss later, NMDA receptors play an important role in learning and memory. It is

because of these properties.

GABA is a major ____ neurotransmitter

inhibitory

GABAergic neurons are found ___

throughout the brain

GABA acts on ____

GABA-A ionotropic receptors

There are also ____

metabotropic GABA-B receptors. They are also inhibitory

Metabotropic SIgnaling

Metabotropic receptors are coupled to an intracellular g-protein that becomes activated upon neurotransmitter binding to them

• Can trigger an array of intracellular changes

• Can alter activity of cellular proteins, including ion channels

• Can increase/decrease gene transcription

These changes are generally on a slower timescale than those of ionotropic receptors

• Can affect the activity and responsiveness of a cell for long periods of time

The net effect of metabotropic receptor activation is often increased or decreased excitability of the cell by ionotropic receptor activation.

In other words, if X level of glutamate input depolarizes the neuron 5mV, X level of glutamate + concurrent metabotropic signaling might depolarize the neuron 7mV

Can be thought of as “gain control”

Synthesis

Transmitter is synthesized from a precursor molecule by enzymes in the presynaptic cell

Storage

transmitter stored in presynaptic vesicles —> Electrical impulse action potential

1.Release

Action Potential opens voltage-

Gated Ca++ channels

2.Release

here is an influx of Ca++ into the terminal

3.Release

Ca++ influx promotes several processes that lead the vesicles to go from a pre-release state into a fusion with release sites on the membrane.

Transmitter is released —> Transmitter diffuses across synaptic cleft

1.Postsynaptic Action

a) Transmitter binds to postsynaptic receptors (receptor proteins

2.Postsynaptic Action

b) Transmitter binding induces intrinsic biological activity (i.e. signal transduction effects) in postsynaptic cell.

Inactivation

Transmission can be ended by:

a. Uptake

b. Metabolism by enzymes