Presentation Slides 9

Synapses and Neurotransmitters

Ligand-gated ion channel

(= Ionotropic receptor)

Depolarize or hyperpolarize the postsynaptic membrane

G-protein coupled channel

(= Metabotropic recpetor)

• Initiate another chemical reaction

• Create a new synapse

• Bring about changes in another cell

Dendrodentric synapse

dendrites send messages to other dendrites

Axodendritic synapse

Axon terminal of neuron synapses on dendritic spine of another

Axonextracellular synapse

Terminal with no specific target. Secrets transmitter into extracellular fluid

Axosomatic synapse

Axon terminal ends on cell body

Axosynaptic synapse

Axon terminal ends on another axon terminal

Axoaxonic synapse

Axon terminal ends on another axon

Axosecretory synapse

Axon terminal ends on a tiny blood vessel and secretes transmitter directly into the blood

Type 1 synapse

excitatory synapses

excitatory synapses

• typically occupy spines and dendritic shafts on neuron

• round synaptic vesicles

• denser pre-and postsynaptic membranes

• synaptic cleft is wider

• larger active zone

Type 2 synapses

inhibitory synapses

inhibitory synapses

• typically found on the cell body

• flattened synaptic vesicles

Resting potential at neuronal cell membranes

Equilibrium maintained through diffusion and electrical push/pull actions of ions

Hyper- and depolarization of cell membranes

Leak and voltage-dependent membrane channels open or close

Spatial and temporal summation of EPSPs and IPSPs

May lead to AP when over threshold; propagating along the axons

Depolarization of presynaptic terminals cause Ca2+ channels to open

Neurotransmitters released into synaptic cleft, bind to receptors at postsynaptic membrane; may lead to closing or opening of ion channels

Autoreceptors

Receptors on the presynaptic membrane that the neurotransmitter can interact with

Deactivation

1. Diffusion

2. Degradation

3. Reuptake

4. Glial cells

Difussion

diffuses away from synaptic cleft

Degradation

enzymes in cleft break down neurotransmitter

Reuptake

transmitter taken back into presynaptic axon terminal for reuse

Glial cells

take up some neurotransmitters

classes of neurotransmitters

• Small-molecules

• Peptides

• Lipids

• Gases

Small Molecule Transmitters

• Small organic molecules

• Quick-acting

• Synthesized and packaged in axon terminals

• Derived from the food we eat

Rate-limiting factor

Any enzyme that is in limited supply, so that the pace

at which a chemical can be synthesized is restricted

Acetylcholine

• Normal waking behavior and memory

• Loss of cholinergic neurons is associated with Alzheimer’s disease

• Thought to function in attention and memory

Nigrostriatial Pathway

Movement

• Maintaining normal motor behavior

• Degenerates during Parkinson’s disease

Mesolimbic Pathway

Affected by Addictive Drugs

• DA release causes feelings of reward and pleasure

• Excessive dopamine may lead to schizophrenia

• Decreased DA may be related to attention deficits

Noradrenaline

• Plays a role in learning by stimulating neurons to change structure

• Also active in maintaining emotional tone

• May also facilitate normal development of the brain and organize movements

• Decreased NE activity may lead to Major Depression, ADD, ADHD

• Increased NE activity may lead to Mania

Serotonine

• Active in maintaining waking EEG pattern, learning, emotion

• Decreased 5-HT activity related to Depression

• Increased 5-HT activity related to schizophrenia or OCD

• Abnormalities in brainstem 5-HT linked to sudden infant death syndrome (SIDS) or Sleep Apnea (=syndrome in which the brain fails to tell the muscles to breathe)

Amino Acids

• Glutamate

• GABA

• Glycine

• Histamine

Glutamate

Excitatory Neurotransmitter (amino acid)

GABA, Glycine

Inhibitory Neurotransmitters (amino acid)

Histamine

Causes constriction of smooth muscles

Peptide Transmitters

• Have no direct effects on postsynaptic

  membrane voltage

• Cannot be taken orally as drugs, as small-molecule

  transmitters can be

Functions of Peptide Transmitters

• Serve as hormones

• Activate in response to stress

• Encourage mother-child bonding

• Facilitate learning

• Regulate eating and drinking

• Respond to pleasure and pain

endocannabinoids

a class of lipid neurotransmitters synthesized at the postsynaptic membrane to act on receptors at the presynaptic membrane

Cannabinoids

act as neuromodulators to inhibit release of glutamate and GABA

Transmitter Gases

• Synthesized as needed by the cell

• Can be produced in many regions of the cell

• Diffuse away from the cell after production

Nitric Oxide (NO)

• Controls muscles in intestinal walls

• Dilates blood vessels in the brain and in the genital organs

• Viagra acts by enhancing action of NO

When activated by a neurotransmitter, the ionotropic receptors

change shape

receptors

protein molecules in the postsynaptic membrane on neurons

When activated by a neurotransmitter, the metabotrobic receptors

Alter chemical reactions in the target cell

Ionotropic Receptors (direct effects)

• Binding sites for neurotransmitter

• Allow the movement of ions across the membrane

• Rapid changes in voltage

• Do not last long

• excitatory effect on the target cell

Metabotropic Receptors (Indirect Effects)

inhibitory effect

• Amplification cascade

• Second messenger

Amplification cascade

• Cascade effect is that many downstream proteins (second messengers or channels or both) are activated or deactivated

• Allows that a single neurotransmitter’s binding to a receptor can activate an escalating sequence of events.

Second messenger

• Binds to a membrane-bound channel, causing the channel to change its structure and thus alter ion flow through the membrane.

• Initiates a reaction incorporating intracellular (within the cell) protein molecules into the cell membrane, leading to formation of new ion channels.

• Binds to sites on the cell’s DNA to initiate or cease the production of specific proteins

Dale’s Principle

Same neurotransmitter is released from all axonal terminals of a neuron

Neurotransmitter criteria

• Synthesized in a neuron

• Release → Response

• Chemical specific

• Removal mechanism