lecture 9 video notes

1. Overview of Neurons

• Neurons are the fundamental units of the nervous system.

• They transmit electrical and chemical signals.

• Three main types:

  • Sensory neurons: Detect stimuli and send signals to the brain/spinal cord.

  • Motor neurons: Send signals from the brain/spinal cord to muscles and glands.

  • Interneurons: Connect neurons within the central nervous system (CNS).

2. Structure of a Neuron

• Dendrites: Receive signals from other neurons.

• Cell body (Soma): Contains the nucleus and essential organelles.

• Axon: Transmits signals to other neurons, muscles, or glands.

• Myelin Sheath: Fatty layer that insulates the axon, increasing signal speed.

• Axon Terminals: End of the neuron where signals are sent to the next cell.

3. Action Potential

• Electrical impulses travel along the neuron to transmit signals.

• Resting potential: Neuron is at -70mV due to ion distribution.

• Depolarization: Sodium (Na+) enters, making the inside positive.

• Repolarization: Potassium (K+) exits, restoring negative charge.

• Refractory period: Time before the neuron can fire again.

4. Synapses and Signal Transmission

• Synapse: Junction between two neurons or a neuron and a target cell.

• Two types:

  • Electrical synapse: Direct flow of ions via gap junctions.

  • Chemical synapse: Neurotransmitters carry the signal across the synaptic cleft.

• Neurotransmitter release:

  • Action potential reaches axon terminal.

  • Vesicles release neurotransmitters into the synaptic cleft.

  • Neurotransmitters bind to receptors on the postsynaptic neuron.

  • Signal is either excitatory or inhibitory.

5. Major Neurotransmitters and Functions

• Acetylcholine (ACh): Muscle contraction, learning, memory.

• Dopamine: Reward, pleasure, movement regulation.

• Serotonin: Mood, sleep, appetite.

• GABA (Gamma-aminobutyric acid): Inhibitory neurotransmitter, reduces neural activity.

• Glutamate: Main excitatory neurotransmitter, involved in learning and memory.

6. Disorders Related to Neuronal Function

• Alzheimer’s disease: Linked to low acetylcholine levels.

• Parkinson’s disease: Caused by dopamine deficiency.

• Depression: Often associated with low serotonin levels.

• Epilepsy: Overactivity of neurons leading to seizures.

7. Neuroplasticity and Learning

• The brain can reorganize and adapt by forming new neural connections.

• Hebbian learning: "Neurons that fire together, wire together."

• Long-term potentiation (LTP): Strengthening of synaptic connections with repeated use.

1. Basics of Electrical Signaling

• Neurons communicate using electrical signals.

• Signals are generated by ion movement across the neuronal membrane.

• Key ions involved: Sodium (Na+), Potassium (K+), Calcium (Ca2+), and Chloride (Cl-).

2. Resting Membrane Potential (RMP)

• Neurons have a resting potential of around -70mV.

• Created by ion concentration gradients and selective permeability.

• Na+/K+ ATPase pump maintains the resting potential:

  • Pumps 3 Na+ out and 2 K+ in.

  • Helps establish negative charge inside the neuron.

3. Graded Potentials

• Small, localized changes in membrane potential.

• Can be depolarizing (excitatory) or hyperpolarizing (inhibitory).

• Occur in dendrites and soma.

• Decay over time and distance.

4. Action Potential (AP)

• Rapid, large change in membrane potential.

• Triggered when threshold (~-55mV) is reached.

Phases of Action Potential:

1. Depolarization:

   • Voltage-gated Na+ channels open → Na+ enters cell.

   • Membrane potential becomes more positive.

2. Repolarization:

   • Voltage-gated K+ channels open → K+ exits cell.

   • Na+ channels inactivate.

   • Membrane potential returns to negative.

3. Hyperpolarization:

   • K+ channels remain open longer than necessary.

   • Membrane potential becomes more negative than RMP.

   • Restored to RMP by Na+/K+ pump.

5. Refractory Periods

• Absolute refractory period: No new AP can be initiated (Na+ channels inactivated).

• Relative refractory period: Stronger stimulus required to initiate AP (due to hyperpolarization).

6. Propagation of Action Potentials

• APs travel along the axon without losing strength.

• Myelination (by Schwann cells or oligodendrocytes) speeds up conduction.

• Saltatory conduction: AP jumps between Nodes of Ranvier in myelinated axons.

• Continuous conduction: Occurs in unmyelinated axons, slower than saltatory conduction.

7. Synaptic Transmission

• AP reaches axon terminal → triggers Ca2+ influx.

• Neurotransmitters released into synaptic cleft.

• Neurotransmitters bind to receptors on postsynaptic neuron → generates graded potentials.

• Types of synapses:

  • Excitatory (EPSP): Depolarizes membrane, increasing likelihood of AP.

  • Inhibitory (IPSP): Hyperpolarizes membrane, decreasing likelihood of AP.

8. Key Neurotransmitters

• Excitatory: Glutamate, Acetylcholine.

• Inhibitory: GABA, Glycine.

• Modulatory: Dopamine, Serotonin, Norepinephrine.

9. Clinical Relevance

• Multiple Sclerosis (MS): Damage to myelin slows down AP conduction.

• Epilepsy: Uncontrolled neuronal firing due to disrupted AP regulation.

• Local Anesthetics (e.g., Lidocaine): Block Na+ channels, preventing AP generation.

• Introduction to Neurons and Synapses:

  • The Central Nervous System (CNS) contains about 100 billion neurons.

  • A single neuron can have hundreds to 200,000 synapses connecting it to other neurons.

  • Communication between neurons occurs at the synapse.

• Types of Synapses:

  • Electrical Synapses:

    • Fast transmission of signals.

    • Electrical currents (ions) pass through gap junctions connecting neurons.

    • Quick responses are needed in areas like the heart.

    • Example: Sodium ions move from the presynaptic neuron to the postsynaptic neuron through gap junctions.

  • Chemical Synapses:

    • Slower than electrical synapses.

    • Involve neurotransmitters as middlemen.

    • The presynaptic neuron releases neurotransmitters via exocytosis, which bind to ligand-gated channels on the postsynaptic neuron, allowing ions to enter the second neuron.

    • Slower due to the involvement of neurotransmitter release and binding.

    • Enable plasticity, allowing for more flexible and varied communication between neurons.

• Plasticity:

  • Chemical synapses enable plasticity, meaning they can allow for different types of functions and more adaptable communication between neurons.

1. Neurotransmitter Release:

   • Stimulus triggers neurotransmitter release.

   • A weak stimulus results in a small release of neurotransmitters and less frequent action potentials.

   • A strong stimulus leads to more neurotransmitter release and frequent action potentials.

2. Mechanism of Neurotransmitter Release:

   • Action potential travels down the axon to the axon terminal, causing depolarization.

   • Voltage-gated calcium channels open when depolarization occurs, allowing calcium ions to flow in.

   • Calcium triggers exocytosis of neurotransmitters from vesicles into the synaptic cleft.

   • Neurotransmitters bind to ligand-gated channels on the postsynaptic neuron.

   • The binding of neurotransmitters opens channels, allowing positive ions to flow into the postsynaptic neuron, depolarizing it and transmitting the signal.

3. Neurotransmitter Termination:

   • To turn off the signal, neurotransmitters must be removed from the synapse.

   • Methods of termination:

     1. Reuptake channels: Transport neurotransmitters back into the presynaptic neuron for reuse.

     2. Enzyme degradation: Enzymes break down neurotransmitters, preventing them from binding to receptors.

     3. Diffusion: Neurotransmitters diffuse out of the synaptic cleft, reducing concentration.

4. Importance of Termination Mechanisms:

   • Without proper termination, neurotransmitters may remain in the synapse and continuously bind to receptors, prolonging the signal.

   • Scenario comparison:

     • Scenario 1: More neurotransmitters in the synapse prevent binding from being terminated.

     • Scenario 2: Less neurotransmitter presence allows for easier unbinding of neurotransmitters from receptors.

   • Neurotransmitter removal is essential to allow bound neurotransmitters to detach.

1. Introduction to Neurotransmitter Signaling

• Neurotransmitter release and termination are key for communication between neurons.

• Focus on neurotransmitter acetylcholine (ACh) and its role in the body.

2. Acetylcholine Overview

• Importance: ACh is crucial for movement (muscle contraction) and memory.

• ACh works by binding to specific receptors on cells.

3. ACh Receptor Subtypes

• ACh has two main receptor types: Nicotinic and Muscarinic.

  • Nicotinic Receptors (nAChR): Ligand-gated channels, lead to depolarization (e.g., muscle contraction).

  • Muscarinic Receptors (mAChR): G-protein-coupled receptors, which can lead to either depolarization or hyperpolarization, depending on the subtype.

4. Neurotransmitter Release and Termination

• Release: ACh is released into the synaptic cleft, binds to its receptor, causing a cellular response.

• Termination: ACh is broken down by acetylcholinesterase into acetate and choline. Choline is then reabsorbed into the presynaptic neuron for recycling.

5. ACh Receptor Types and Functions

• Nicotinic Receptors:

  • Found in muscles, ligands like nicotine activate these receptors, leading to muscle contraction.

  • Sodium enters the cell, causing depolarization.

• Muscarinic Receptors:

  • Two main subtypes:

    • M1/M3 (depolarizing): Lead to cellular excitation.

    • M2/M4 (hyperpolarizing): Cause inhibition of cellular activity.

  • Subtypes determine whether ACh causes depolarization or hyperpolarization in target cells.

6. Acetylcholine and its Role

• ACh is involved in skeletal muscle contraction and autonomic nervous system regulation.

• Receptors found on muscles (nicotinic) and organs (muscarinic).

7. Neurotoxin Examples That Block Synaptic Transmission

• Tetrodotoxin (from pufferfish): Blocks sodium channels, preventing sodium influx required for action potentials.

  • Symptoms: Paralysis, loss of sensation, inability to breathe, can lead to death.

• Botulinum toxin (Botox): Blocks ACh release, preventing muscle contraction.

  • Medical use: Treats conditions like migraine headaches by reducing muscle contraction.

8. Botox Mechanism of Action

• Exocytosis: Process of neurotransmitter release.

  • Vesicles containing ACh bind with the plasma membrane, releasing contents.

  • SNARE proteins: Facilitate vesicle fusion with the membrane for exocytosis.

  • Calcium: Required for SNARE proteins to function, initiating vesicle fusion.

9. Reuptake and Recycling of ACh

• After ACh breakdown, choline is transported back into the neuron for recycling and synthesis of new ACh.

1. Neurotransmitter Types:

• Excitatory Neurotransmitters:

  • When released and bind to receptors, they cause depolarization of the postsynaptic neuron (cell becomes more positive).

  • EPSP (Excitatory Postsynaptic Potential): Graded depolarization that moves the membrane potential closer to the threshold for firing an action potential.

• Inhibitory Neurotransmitters:

  • These inhibit or stop a signal from propagating by hyperpolarizing the postsynaptic neuron (cell becomes more negative).

  • IPSP (Inhibitory Postsynaptic Potential): Graded hyperpolarization that prevents the neuron from reaching the threshold.

2. Depolarization vs Hyperpolarization:

• Depolarization (Excitatory):

  • Positive charge enters the neuron (e.g., sodium or calcium), making the membrane potential more positive.

  • Results in EPSP.

• Hyperpolarization (Inhibitory):

  • Negative ions (e.g., chloride) enter or positive ions (e.g., potassium) exit, making the membrane potential more negative.

  • Results in IPSP.

3. Neurons in Communication:

• Neurons receive signals from multiple other neurons.

• The axon hillock of a neuron sums these incoming signals (positive and negative).

• Summation: The total of all charges arriving at the axon hillock.

  • If the threshold is reached, an action potential is triggered.

4. Neurotransmitter Effects and Ions:

• Excitatory Neurotransmitters:

  • Often cause the opening of sodium channels, allowing sodium ions to flow in, leading to depolarization.

• Inhibitory Neurotransmitters:

  • Chloride (Cl-) flowing into the cell causes a negative charge (hyperpolarization).

  • Potassium (K+) leaving the cell also causes hyperpolarization.

5. Threshold and Action Potential:

• A neuron must reach the threshold at the axon hillock for an action potential to occur.

• Threshold: The point where the depolarization is strong enough to trigger an action potential.

Long-Term Potentiation (LTP) and Depression (LTD)

Overview:

• Short-term signaling: EPSP (Excitatory Postsynaptic Potential) and IPSP (Inhibitory Postsynaptic Potential) last for milliseconds and are short-lived, primarily due to ion movement and ATP pumps maintaining the resting potential.

• Long-term signaling: LTP and LTD are long-lasting changes, involving the strengthening or weakening of synapses.

Key Concepts:

• LTP (Long-Term Potentiation):

  • Long-lasting, strong signaling lasting from weeks to a lifetime.

  • LTP involves changes in the brain’s structure, including more tracks (neural connections) between neurons.

  • Similar to muscle growth: regular "exercise" (neural activity) leads to morphological changes in the brain.

  • Involves neuroplasticity: the brain's ability to change structurally (dendrites and axons growing).

  • Requires protein synthesis to maintain and strengthen synapses.

• LTD (Long-Term Depression):

  • Opposite of LTP, it involves the weakening of neural connections, undoing the gains made through LTP.

  • "Use it or lose it" principle: If you stop practicing or training, neural tracks weaken.

Neuroplasticity:

• The brain's ability to change and adapt over time.

• Neurons are limited in their ability to regenerate but can form new connections through dendrites and axons.

• Training the brain: Like physical muscles, the brain can change its morphology with sustained effort.

Importance of Persistent Effort:

• Consistency is key: Just like muscles require regular exercise, the brain requires consistent effort for lasting change.

• Glutamate: The key neurotransmitter for learning and memory.

  • Initiates signaling that strengthens synapses and supports long-term changes.

  • Essential for creating long-term memory and facilitating strong recall.

Glutamate’s Role:

• Excitatory neurotransmitter: Needed for forming memories and learning.

• Drug addiction: Can hijack glutamate signaling, strengthening the connection between drug use and reward, making it hard to break the cycle.

Mechanism of LTP:

• Glutamate Binds to Two Receptors:

  1. AMPA: When glutamate binds to the AMPA receptor, sodium enters the cell, leading to depolarization.

  2. NMDA: Requires both glutamate binding and sufficient depolarization to activate calcium channels.

• Calcium's Role:

  • Once calcium enters through NMDA receptors, it activates second messengers.

  • Calcium helps to phosphorylate (add a phosphate group to) the AMPA receptor.

  • Phosphorylation keeps AMPA receptors open even when glutamate is no longer present, allowing continued sodium influx.

Strengthening Synapses:

• More Sodium Influx: More sodium coming in means greater depolarization and stronger signaling between neurons.

• Long-Term Changes: Repeated signaling strengthens synapses, leading to lasting memory and deeper learning.