BIO Lecture 3 - The Synapse

Electrical Activity of Cells

• Electrical activity relies on how well ions move across the cell membrane and gradients
• The membrane is very permeable to Potassium (K+) but not Sodium (Na+)
• Ions move across due to concentration and electrical gradients
• High to low concentration gradients and positive to negative/negative to positive electrical gradients are key

Impact of Ion Movement

• Potassium (K+) moves into the cell to neutralize big A-
• K+ also moves out of the cell down the concentration gradient
• K+ concentration is lower outside the cell
• Equilibrium is reached, when the electrical attraction of K+ into the cell equals the concentration attraction of K+ out of the cell
• Even at equilibrium, the inside of the cell remains at -65mV relative to the outside

Ion Channels and Depolarization

• Voltage-gated Sodium (Na+) channels open when cells are depolarized (less negative, more positive)
• Na+ rushes in to neutralize big A- and down its concentration gradient since Na+ is more concentrated outside
• This influx makes the cell interior more positive
• At +40mV, Na+ channels close and voltage-gated Potassium (K+) channels open
• K+ rushes out down the concentration gradient, as it is more concentrated inside
• The cell interior becomes more negative again as positive ions leave

Action Potential

• At rest a neuron has a negative charge of -65 mV due to more negative ions inside
• This is the resting membrane potential
• An action potential occurs if the neuron is stimulated and the equilibrium is upset
• The resting potential becomes an action potential if the excitatory stimulation is large enough
• If the net change at the axon hillock goes above threshold (-50mV), an action potential is generated
• The action potential then propagates down the axon

The Synapse

• When the action potential gets to the presynaptic terminal, neurotransmitter is released
• The junction (synapse) between neurons receives this chemical
• The neurotransmitter released can have an excitatory or inhibitory effect

Seeing the Synapse

• Before electron microscopes, neuron junctions weren't visible, with some doubting their existence
• The first electron microscope images made of well-defined junctions between neurons were available
• These junctions are known as synapses
• A synapse is formed by an axon's termination from one neuron onto another neuron's dendrite

Synapses and Movement

• Most synapses occur between neurons and cause excitation or inhibition
• Specialized synapses between neurons and muscles exist
• Neuromuscular junctions cause muscle contraction and movement
• Spinal cord contains axons from neurons which activate muscles
• Amyotrophic Lateral Sclerosis (ALS) affects these neurons
• The disease restricts movement and eventually leads to death

Neurotransmitter Synthesis and Storage

• Neurotransmitters are packaged into vesicles in the cell body
• Packaged vesicles get transported to the presynaptic terminal along the axon
• Vesicles remain dormant until an action potential arrives
• Calcium (Ca++) ion channels open when an action potential arrives at a synapse
• The synaptic vesicles release neurotransmitters into the synapse when the incoming Ca++ binds to them

Sea Slugs and Calcium

• Sea snails withdraw their gills when confronted with water jets as a defense
• With repeated stimulation by water jets, snails learns that the water jet isn't harmful and shows response weakening (habituation/adaptation)
• Studies suggest that this reduction is caused by reduced calcium influx at the pre-synaptic terminal of the axon
• Less neurotransmitter is released by the reduction of calcium

Ionotropic Neurotransmitter Receptors

• Proteins on dendrites are neurotransmitter receptors
• Two parts: neurotransmitter binding and an ion channel
• The ion channel opens when a neurotransmitter binds to a receptor, allowing ions into the cell

Metabotropic Neurotransmitter Receptors

• Influence ion channels indirectly
• When neurotransmitter binds, the a subunit detaches and causes ion channel to open, allowing ions to pass through
• Influence function more slowly compared to ionotropic receptors

Excitatory and Inhibitory Postsynaptic Potentials

• Neurotransmitters can be excitatory or inhibitory
• Excitatory neurotransmitters are released at Type I synapses
• They bind to receptors that cause an influx of positive ions (Na+)
• Inhibitory neurotransmitters are released at Type II synapses
• They cause an influx of negative ions (Cl-)

Neurotransmitter Removal and Inactivation

• Neurotransmitters must be removed or inactivated following their release
• Prolonged activation can occur if neurotransmitters aren't removed or inactivated quickly
• When blood flow to the brain is reduced, glutamate isn't removed from synapse causing excitotoxicity, resulting in stroke
• Mustard gas prevents acetylcholine deactivation

Synaptic Integration

• Spatial integration of EPSPs occurs
• Temporal integration of EPSPs occurs

Different Neurons Use Different Neurotransmitters

• Glutamate is the brain's major excitatory neurotransmitter and is vital in forming links between neurons for learning and memory
• GABA is the brain’s main inhibitory neurotransmitter
• Dopamine is involved in movement and reward circuits
• Serotonin has a profound effect on mood and anxiety
• Acetylcholine is the neurotransmitter used at the neuro-muscular junction.

Parkinson's Disease, L-dopa, and the Frozen Addict

• Rigidity and trembling caused by the loss of dopaminergic neurons in the brain stem (Substantia Nigra) is known as Parkinson’s
• Symptoms are relieved by the drug levo-dopa, which mimics dopamine’s action (an agonist), though only temporarily
• The neurotoxin MPTP was discovered in heroin taken by addicts who suddenly developed Parkinson's
• L-Dopa includes a side effect of schizophrenic symptoms, suggesting that schizophrenia is caused in part by overactivity of the dopaminergic pathways

Toxins that Poison Ion Channels

• Venoms can deactivate specific ion channels
• Tetrodotoxin from puffer fish inactivates Na+ channels, paralyzing animals
• Scorpion toxins activate Na+ channels by lowering the threshold, scrambling information flow
• Toxins from wasps and bees inactivate K+ channels

Toxins That Affect Transmitter Release

• Alpha-latrotoxin (black widow spider) causes massive neurotransmitter release at the nerve-muscular junction, resulting in paralysis
• Botulism stops the release of excitatory neurotransmitters at the neuro-muscular junction; this stops muscle contraction
• Tetanus toxin prevents inhibitory neurotransmitters from getting released in the spinal cord, causing muscles to become overactive

Toxins That Block Neurotransmitter Receptors

• Many toxins bind to neurotransmitter receptors causing dangerous effects
• Alpha-Bungarotoxin (branded krait venom) blocks neurotransmitter receptors on the nerve-muscle junction leading to prevention from escaping!

Psychoactive Drugs

• Effects of neurotransmitters are mimicked by direct binding of psychoactive drugs to neurotransmitter receptors
• LSD and psilocybe (mushrooms) mimic the effect of serotonin
• These drugs are known as agonists
• Alcohol, acting as an agonist, stimulates GABA receptors (increasing its effect), leading to a sedative effect
• Alcohol blocks glutamate receptors, acting as an antagonist

Drugs That Affect Uptake

• Different drugs affect the uptake of neurotransmitters
• Cocaine stops dopamine reuptake
• It prolongs dopamine's effect, increasing arousal
• Prozac blocks serotonin reuptake
• It enhances the effect of serotonin and gives rise to a feeling of well-being

Addiction

• Association between drug taking and reward is suggested by addiction studies
• The reward system provides pleasure for doing important living tasks (for example: eating)
• Dopamine, a neurotransmitter, is released for reward circuits
• Highly addictive drugs (cocaine, heroin, nicotine) activate this system in the brain