week 7- lecture 1 into to pharmacology Flashcards
Structure from brain to synapse
100 billion neurons in the brain
~ 0.15 quadrillion synapses in
the cortex
Receptors
- Neurons have a cell “membrane” that acts like a wall preventing things from entering or leaving the neuron.
- The cell wall as two layers with the fatty inside of each layer sticking together like a sandwich.
- Because of the fatty inside layer, fluids and other chemicals like neurotransmitters are not able to pass through.
types of receptors
Receptors located on the outside of the cell membrane allow the released neurotransmitters to influence the post-synaptic neuron.
Two types of receptors:
- Ion Channels
- G-Protein coupled
ION channels
Ion channels act like a gate.
- When a neurotransmitter binds to the receptor outside the neuron, this causes the gate to open and ions (positively and negatively charged molecules), can flow through.
- Channels are normally “selective” and only allow one or a few types of ions to pass through when they are open (e.g. a calcium ion channel).
G protein-coupled receptor
- G-Protein receptors have 7 Transmembrane units that cross through the cell membrane.
- When the neurotransmitter binds to the receptor it activates a “second messenger system” that can either open a channel or cause other things to change within the cell (e.g. DNA being transcribed and new proteins being made).
Receptor specificity
- Receptors are very selective (lock and key).
- Each receptor can generally only be activated by one neurotransmitter (or a drug that is designed to mimic that neurotransmitter).
- They also have a very specific function/action. When a neurotransmitter binds to the receptor this will trigger the same event every time (either opening a channel or triggering a second messenger event).
Receptor specificity
continued
In reality receptors are not simple “open-shut” gates… They have complex structures and it is often a small change in their shape that will “open” a channel, or cause it to “do its thing”.
Criteria for Defining Neurotransmitters
- Present in presynaptic terminals
- Released from presynaptic terminals after the neuron fires.
- Existence of receptors on postsynaptic neurons
Chemical cocktail in the brain
Multiple Neurotransmitters:
Dopamine, Serotonin, Noradrenaline, Glutamate, GABA, Acetylcholine…. and many more…including gasses & peptides
They can activate, inhibit or modulate neuronal activity
excitatory - Glutamate
inhibitory - GABA
modulatory - ie Serotonin, Dopamine & Noradrenaline
Neurotransmission:
Either EXCITATORY or INHIBITORY and serves rapid (millisecond), precise, point to point communication.
Neuromodulation:
Describes slower (milliseconds to seconds) processes that alter the subsequent responsiveness of neurons.
Neurotransmitters: Excitatory
- Glutamate is the neurotransmitter released by ALL excitatory neurons.
- Found in most of the long projection neurons throughout the cortex.
- Acts on both ion channel and G Protein-Coupled receptors
Neurotransmitters: Excitatory
continued
Excitatory connections are “point-to-point”.
Many region-specific functions (e.g. connections along the visual pathways)
Neurotransmitters: Inhibitory
GABA (gamma-amino butyric-acid) is released by inhibitory neurons.
Most short local neurons are inhibitory, so they form a dense web around and between the excitatory neurons
Neuromodulation
- Presynaptic: Alters neurotransmitter release
- Postsynaptic: Alters neurotransmitter action (e.g., alters excitability/ firing pattern)
- Neuromodulation may produce both neurophysiological and biochemical effects.
Psychopharmacology
The study of drug induced changes in mood sensation, thinking & behavior.
Cycle of Neurotransmitters
1 Synthesis
2 Release from synaptic vesicles
3 Binds to receptors
4 +/- influence on post synaptic neuron
5 Broken down by enzymes
6 reuptake of transmitter
7 formation & storage in
synaptic vesicles
Drug Action
can effect all stages of the cycle
Action at the receptor
- Drugs act by “mimicking” natural neurotransmitters or neuromodulators.
- Can act as AGONISTS activating the receptor like the natural compound.
- Or can act as an ANTAGONIST blocking the receptor and preventing the natural compound from activating it.
Synthesis interruption
Neurotransmitter function can be altered by increasing or decreasing synthesis of the neurotransmitter
Neurotransmitters: Slow & Fast
Synthesis and transport to the synapse is relatively slow. BUT
The neurotransmitter action is extremely fast because it sits ready for release
Psychology vs Pharmacology
-Pharmacology can effect psychology
Natural neurotransmitters and artificial drugs can clearly effect mood, cognition & behaviour
-Psychology can also effect pharmacology
Emotional or stressful events, thoughts and behaviour effect us BECAUSE they influence our neurotransmitters.
Cognitive therapy and pharmacology acts on the same brain!!
summary
- Neurons communicate through neurotransmitter release at synapses
- Receptors either act as ion channels (gates) or they cause down stream effects within the neuron through a “second messenger”
- Chemical signals act as “neurotransmitters” in fast/local signals or “neuromodulators” in slower more global signals (still fast, just more sustained) .
- The action of neurotransmitters can be altered by drugs at many stages in many different ways.