Lecture 14

Synapse

point where an axon terminal meets the next cell (another neuron, gland cell, muscle cell)

What triggers a neuron-to-neuron synapse?

an action potential arrives at the end of the axon of the presynaptic neuron

What happens after the action potential arrives at the axon terminal?

1. The presynaptic neuron releases a neurotransmitter

2. The postsynaptic neuron responds to it

What are the two types of synapses?

Electrical and chemical synapses

Electrical synapses

direct physical contact between cells - links the cytoplasm of adjacent cells

Characteristics of electrical synapses

• are locked together at gap junctions (connexons)

• allow ions to pass between cells

• produce continuous local current and action potential propagation

• are found in areas of brain, eye, ciliary ganglia (PNS), cardiac muscle cells

Chemical synapses

signal transmitted across a gap by chemical neurotransmitters. In a chemical synapse, the two cells do not touch

Synaptic Cleft

gap between presynaptic neuron and postsynaptic neuron

• discovered by Ramon y Cajal

Otto Loewi

demonstrated that neurons can communicate by releasing chemicals

• flooded exposed hearts of two frogs with saline

• stimulated vagus nerve of first frog and its heart slowed

• removed saline from first frog and found it slowed heart of second frog

• Named Vagusstoff

Vagusstoff

a neurotransmitter released by the nerve stimulation that inhibits heart rate.

• vagus substance

• later renamed acetylcholine, the first known neurotransmitter

What is the advantage and disadvantage of gap junctions joining adjacent cells

Gap junctions allow for direct cell-to-cell communication, facilitating quicker, no delay release, diffusion, and bonding. However, they can not integrate information

Where does the action potential arrive to initiate a neuron-to-neuron synapse?

At the end of the axon of the presynaptic neuron.

What is the direct result of an action potential reaching the end of the presynaptic axon?

The presynaptic neuron releases a neurotransmitter.

What chemical messenger bridges the gap between the presynaptic and postsynaptic neurons?

Neurotransmitter.

How does the postsynaptic neuron react to the released neurotransmitter?

The postsynaptic neuron responds to it (receiving the chemical signal).

What causes synaptic delay

since chemical synapses are not directly in contact with the postsynaptic cell and require the release of a near transmitter to stimulate/inhibit the target cell, there is a delay

Synaptic delay

• delay of a few seconds

• arrival of the action potential at the synaptic terminal

• and effect on postsynaptic membrane

• neurotransmitter has to be released from axon terminal, then diffuse across synaptic cleft, bind onto postsynaptic receptor, and cause the receptor to open an ionchannel

What leads to less of a synaptic delay?

fewer synapses found between the transmission of the information means the faster the response

How do synapses affect reflexes

reflexes may involve only one synapse (monosynaptic reflexes) or multiple synapses (polysynaptic reflexes). Monosynaptic reflexes are faster than polysynaptic reflexes

synaptic fatigue

occurs when neurotransmitter cannot recycle fast enough to meet demands of intense stimuli

Example of synaptic fatigue

if we look at a cholinergic synapse, formation of new ACh from recycled choline is not fast enough to meet demand

• If too many action potentials are reaching the axon terminal, there will not be enough neurotransmitters produced for exocytosis and release into the synaptic cleft

• The synapse becomes inactive until ACh is replenished so it can be released later on when there is an action potential that reaches the axon termina

Excitatory vs Inhibitory

refers to the two main types of neurotransmitter effects on postsynaptic neurons. Excitatory(depolarizing) neurotransmitters increase the likelihood of an action potential, while inhibitory(hyperpolarizing) neurotransmitters decrease that likelihood.

Major chemical categories of neurotransmitters

1. Acetylcholine

2. Amino acids

3. monoamines (biogenic amines)

4. Gases

5. Neuropeptides

Acetylcholine

formed from acetic acid and choline

Amino Acids

include glycine, glutamate, aspartate, and γ-aminobutyric acid (GABA)

• γ-aminobutyric acid (GABA) affect the cell directly by binding onto a plasma membrane receptor

  
  

Monoamines

synthesized from amino acids

examples of monoamines

serotonin and the catecholamines epinephrine, norepinephrine, and dopamine

What are serotonin and catecholamine derived from

serotonin is derived from the amino acid tryptophan,

catecholamines are derived from the amino acid tyrosine

serotonin

CNS neurotransmitter that affects attention and emotional states

• decreased serotonin may result in chronic depression

Norepinephrine (NE)

also noradrenaline

• its released at adrenergic synapses

• has excitatory and depolarizing effect and is widely distributed in the brain

Dopamine

CNS neurotransmitter that may be excitatory or inhibitory that is used for movement control. Damage to neurons that produce dopamine involved in Parkinson’s disease and cocaine use.

• cocaine inhibits dopamine removal from synapse

Neurotransmitters: Gases

Nitric oxide(NO) and carbon monoxide (CO); synthesized as needed

• diffuse into cell and affect intracellular enzymes

Neuropeptides

chains of 2-40 amino acids

• indirect effect

• stored in large secretory granules

• function as hormones or neuuromodualtors

Substance P

A neuropeptide involved in pain perception, inflammation, and stress response. It acts as a neurotransmitter and modulates the transmission of pain signals in the nervous system.

3 Kinds of synapses

Excitatory cholinergic synapse (ACh)

Inhibitory GABA-ergic synapse (GABA)

Excitatory adrenergic synapse (NE)

Cholinergic synapse

• acetylcholine is the transmitter

• synapses located at all neuromuscular junctions, many CNS synapses, and all neuron to neuron synapses

What are the steps of acetylcholine synaptic transmission?

1. Calcium Trigger: An action potential opens voltage-gated Ca2+ channels, letting Ca2+ enter and release ACh-filled vesicles.

2. Chemical Bridge: ACh crosses the gap and binds to sodium receptors (Na+ channels) on the next cell.

3. Sodium Entry & Depolarization: Na+ rushes in, generating an excitatory postsynaptic potential.

4. New Action Potential: If strong enough, the signal reaches threshold and fires a new action potential in the next cell.

GABA-ergic synapse

γ-aminobutyric acid (GABA) is an amino acid neurotransmitter

What are the steps of inhibitory (GABA) synaptic transmission?

1. GABA Release: An action potential triggers the release of GABA into the synaptic cleft.

2. Receptor Binding: GABA binds to receptors linked to chloride (Cl−) channels.

3. Chloride Influx & Hyperpolarization: Cl− channels open, letting negatively charged Cl− ions rush into the cell (since there's more outside), making the inside more negative (hyperpolarization).

4. Inhibition: The postsynaptic neuron is inhibited and becomes less likely to fire an action potential.

Adrenergic synapse

norepinephrine (NE) is the neurotransmitter

• Monoamines and neuropeptides bind to G-protein coupled receptors

• Activate second-messenger systems such as cyclic AMP(cAMP)

• Has advantage of enzyme amplification

how doe the signal end

• Presynaptic cell stops releasing neurotransmitter

• Neurotransmitter already in synapse is cleared in various ways

Neurotransmitter degradation

enzyme in synaptic cleft breaks down neurotransmitter

• Example: acetylcholinesterase (AChE) breaks ACh down into acetate and choline

Reuptake

neurotransmitter or its breakdown products reabsorbed into axon terminal

• Example: choline from ACh recycled to make new ACh

monoamine oxidase (MAO) vs monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase (MAO) is an enzyme that breaks down monoamines in the brain. Monoamine oxidase inhibitors (MAOIs) are a class of drugs that block this enzyme, increasing the levels of monoamines available in the synaptic cleft, often used to treat depression.

Diffusion

neurotransmitter or its breakdown products simply diffuse away from synapse into the nearby ECF

Neuromodulators

chemicals secreted by neurons that have long term effects on groups of neurons

• May alter the rate of neurotransmitter synthesis

• May adjust sensitivity of postsynaptic membrane

• Nitric oxide (NO) is a simple neuromodulator

Enkephalins and endorphins

neuropeptides that inhibit pain signals in the CNS – these neuropeptides are opioids

Neural integration

the ability to process, store, and recall information and use it to make decisions

Excitatory postsynaptic potential (EPSP)

voltage change from the RMP toward threshold (depolarizing)

• An EPSP usually results from Na+ flowing into the cell

Inhibitory postsynaptic potential (IPSP)

voltage becomes more negative than it is at rest (hyperpolarizing)

• An IPSP can result from Cl- entry or K+ exit from the cell

Different neurotransmitters cause different types of postsynaptic potentials

Examples:

• Glutamate and aspartate produce EPSPs in brain cells

• Glycine and GABA produce IPSPs

A neurotransmitter might excite some cells and inhibit others, depending on the type of receptors in the postsynaptic membrane

Example:

ACh excites skeletal muscle but inhibits cardiac muscle due to the expression of different types of ACh receptors on the different types of muscle cells

Summation

the process of adding up postsynaptic potentials and responding to their net effect

Temporal summation

a single synapse generates EPSPs so quickly that each is generated before the previous one fades

• Allows EPSPs to add up over time to a threshold voltage that

  triggers an action potential

Spatial summation

EPSPs from several different synapses add up to threshold at an axon hillock

• Simultaneous input from multiple presynaptic neurons required for

  the postsynaptic neuron to fire

facilitation

a process in which one neuron enhances the effect of another

Presynaptic facilitation

occurs when one presynaptic neuron enhances another one

• Increases necessary synaptic transmission

Presynaptic inhibition

occurs when one presynaptic neuron suppresses another one

• Reduces or halts unwanted synaptic transmission

Neural coding

converting stimulus information into meaningful pattern of action potentials

Labeled line code

mechanism for transmitting qualitative information (type of stimulus)

How do neurons encode the intensity (strength) of a stimulus?

1. Firing Frequency: Weak stimuli cause a slower firing rate; strong stimuli cause a higher firing frequency.

2. Constant Amplitude: The size/strength of an individual action potential never changes. Only the frequency changes with stronger stimuli.

Heavy metal poisoning

chronic exposure to heavy metals can damage neuroglia and lead to demyelination which causes axons to irreversibly deteriorate

Diphtheria

disease caused by bacterial toxin

• Damages Schwann cells and destroys PNS myelin sheath

• Can lead to fatal paralysis

• Rare occurrence since diphtheria vaccine is available

Multiple sclerosis (MS)

autoimmune disorder caused by inflammation of nerves triggered by immune cells (immune cells probably triggered by virus or defective gene)

• Demyelination disease affecting CNS axons

• Vision, speech, balance, motor coordination affected

• Treated with corticosteroids (anti-inflammatory agents) and interferon to slow disease progression

Guillain-Barre syndrome

autoimmune disorder that is triggered by a virus

• Demyelination disease affecting peripheral nerves

• Sensation of weakness or tingling of legs that spreads to arms

• Progression of disease leads to paralysis (diaphragm also affected)

• Most fully recover, but some continue to have residual weakness