Synaptic Action, Neuropharmacology and Neurochemistry

PSY/BIO250

Dale Meets Loewi 1936 Nobel Prize winners

Sir Henry Dale

Otto Loewi

Loewis experiment

Vagustoff (Acetylcholine) reduces heart rate of the frog

Synapse

Synaptic terminals

Some Neurotransmitters
Acetylcholine Glutamate Serotonin Dopamine Norepinephrine Epinephrine GABA Nitric Oxide (Gas)

Synaptic events

Dopamine Synthesis

Synaptic Events
Axoplasmic transport* Transmitter/precursor arrives* Action potential* Release of neurotransmitter Dales law*
Reuptake: Enzymatic breakdown

Post synaptic receptor Response to transmitter: Receptor activation

Ionotropic Metabotropic

Integration of temporal/spatial summation Plastic steps Other types of synapses

Synaptic Transmission
Neurotransmitter release Calcium ion channels open when action potential reaches pre-synaptic terminal Ca++ ions cause vesicles to move to release sites Number of vesicles released vary Transmitter substance diffuses across synaptic cleft Attach to receptor sites on post-synaptic membrane

Cessation of Neurotransmitter Effects

Enzymatic degradation enzymes break down at receptor site Neurotransmitter reuptake - returned to presynaptic membrane Allows for transmission of many messages

Cessation of Neurotransmitter Effects: Acetylcholine

Acetylcholinesterase - enzyme that deactivates Broken down into acetate & choline Then reuptake to presynaptic membrane Alzheimer's disease - death of ACh receptors

Synaptic Events
Axoplasmic transport* Transmitter/precursor arrives* Action potential* Release of neurotransmitter*
Reuptake: Cocaine and amphetamine block* Enzymatic breakdown: acetlycholinesterase*

Post synaptic receptor* Response to transmitter: Receptor activation*

Ionotropic Metabotropic

Integration of temporal/spatial summation Plastic steps Other types of synapses

Receptors
Key in lock model Ion-channels on postsynaptic membrane are chemically gated Not all or none Ionotropic: Direct actions on ion channels Metabotropic: Indirect action on ion channels

Agents of Synaptic Transmission

Acetylcholine (ACh)transmitter substance Two types of cholinergic receptors Nicotinic receptors with 4 subtypes Muscarinic receptors with 5 subtypes

Mechanisms of Metabotropic Receptors

Figure 3.13 Sequence of events at a metabolic synapse, using a second messenger within the postsynaptic neuron

Second Messengers
Neurotransmitter can produce chemical changes within the cell These second messengers produce ion channel changes
Acting on ionotrophic receptor - direct effects Acting on metabotrophic receptor - indirect effects

Neurotransmitters can act in both ways

Second Messenger Cascade

Second Messenger System

Synaptic Events
Axoplasmic transport* Transmitter/precursor arrives* Action potential* Release of neurotransmitter*
Reuptake: Cocaine and amphetamine block* Enzymatic breakdown: acetlycholinesterase*

Post synaptic receptor* Response to transmitter: Receptor activation*

Ionotropic* Metabotropic*

Integration of temporal/spatial summation Plastic steps Other types of synapses

Post-Synaptic Membrane Effects

Transmitter-gated ion channels Channels on post synaptic membrane Sensitive to specific neurotransmitter substances Results in depolarization or hyperpolarization depending on channel type Depolarization - excitatory EPSP (excitatory post-synaptic potential) Sodium influx

...Post-Synaptic Membrane Effects

Hyperpolarization inhibitory - IPSP (inhibitory postsynaptic potential) Example: Chloride influx

Spatial and Temporal Summation

Temporal Summation: Electrophysiology

Summation Effects
EPSP & IPSP's are graded not all-or-none Only if combined effects reach threshold at axon hillock will action potential occur

Examples of Neural Codes

Population codes (involving groups of neurons).
Interactions among neurons are interpreted at the synapse
Blue Green Yellow

Synaptic Events
Axoplasmic transport* Transmitter/precursor arrives* Action potential* Release of neurotransmitter*
Reuptake: Cocaine and amphetamine block* Enzymatic breakdown: acetlycholinesterase*

Post synaptic receptor* Response to transmitter: Receptor activation*

Ionotropic* Metabotropic*

Integration of temporal/spatial summation* Plastic steps Other types of synapses

Plastic Steps
Neural interconnections are use-dependent
Synaptic connections become stronger with use Synaptic connections become weaker with disuse

Learning Brain development

Synaptic Events
Axoplasmic transport* Transmitter/precursor arrives* Action potential* Release of neurotransmitter*
Reuptake: Cocaine and amphetamine block* Enzymatic breakdown: acetlycholinesterase*

Post synaptic receptor* Response to transmitter: Receptor activation*

Ionotropic* Metabotropic*

Integration of temporal/spatial summation* Plastic steps* Other types of synapses

...Neuromodulators
Endorphins belong to a class called neuromodulators Work to affect amount of neurotransmitter release Unlike transmitters have general effect in brain

Neuromodulators
Endorphin - term for peptides with opiate-like effects Both endorphins and opiates inhibit substance P release Substance P - released by pain receptors Runners high - pain causes release of endorphins

Neural Pathways Associated with Dopamine

Agonists
A drug which stimulates the effects of a particular neurotransmitter or acts to enhance the transmitters effect.

Antagonists
A drug which inhibits or counteracts the effects of a particular neurotransmitter

Drugs working at Dopamine Synapse

Drug Actions at the Synapse

Synaptic Action, Neuropharmacology and Neurochemistry

PSY/BIO250

Norepinephrine (NE)
Produced from tyrosine Monoamine class of compounds Four types of noradrenergic receptors Reuptake or monoamine oxidase deactivates Depression associated with norepinephrine depletion

Dopamine (DA)
Also produced from tyrosine Five types of dopaminergic receptors Reuptake or monoamine oxidase deactivates Parkinson's disease associated with dopamine depletion Also associated with schizophrenia

Serotonin (5-HT)
Synthesized from tryptophan Ten types of serotonergic receptors Reuptake or monoamine oxidase deactivates Important in sleep regulation, depression, & mood disorders

Gamma-aminobutyric Acid (GABA)

Main effect is to inhibit action of other neurons Reuptake or GABA transaminase deactivates GABAa receptors control CL- ion movement GABAb receptors control K+ ion movement Lower levels associated with anxiety or panic attacks; decreased levels in Huntington's disease

Neural Codes: methods of communicating information

Code Morse code: --- Digital computer: 011001 Action potential Message SOS; trouble, fear, anxiety, panic Turn pixel number 1263 blue Moonlight sonata

Tapping Code used by POWs

Primitive Phones
Analogue signals only OK for short distances What are the problems with using analogue technology over long distances?

Neural Codes
Analogue: Using continuously varying physical quantities (e.g., electric currents or voltages) to represent data Digital: Data represented by a series of discrete digits (usually 1s or Os)

Neural Codes
Nervous system uses analogue codes for short distances around receptors
Graded potentials: Neuron hyperpolarizes or depolarizes in proportion to the intensity of the stimulation (and amount of transmitter released).

Nervous system uses digital codes for long distances

Signal is action potential (all or none) Signal is still understandable with noise superimposed

Examples of Neural Codes

Labelled lines (Mullers Doctrine of specific nerve energies)
Seeing stars Sensory homunculus

The Intensity of a Stimulus

Amplitude of action potential is independent of stimulus intensity Neurons fire more rapidly with more intense stimuli Rate Law - greater the stimulus intensity the faster the rate of firing Faster rate occurs by stronger stimulus causing firing during relative refractory period

Coding of Acceleration

Arenz et al., 2008, Science, 321, 977-980.

Examples of Neural Codes

Population codes (involving groups of neurons).
Interactions among neurons are interpreted at the synapse
Blue Green Yellow

...Summation Effects
Temporal Summation - Rapid events at the same location