BIO 170

Lecture 2: Neurons and Glia

1. The Neuron Doctrine

• Coined by Wilhelm Waldeyer, but heavily supported by Ramón y Cajal.

• Core Tenets:

  • Neurons are the fundamental structural and functional units of the nervous system.

  • Neurons are discrete cells that communicate by contact, not continuity.

  • Composed of three parts: dendrites, axon, and cell body.

  • Information flows in one direction along the neuron (exceptions possible).

• Key Contributions:

  • Cajal's drawings and Golgi staining techniques clarified neuron structures and connections.

  • Electron micrographs confirmed the discrete nature of neurons over the reticular theory.

2. Neuronal Morphologies

• Unipolar Neurons: Single process from the soma (e.g., sensory neurons).

• Bipolar Neurons: Two processes leave the soma (e.g., retina bipolar cells).

• Multipolar Neurons: Multiple processes leave the soma (e.g., pyramidal cells in the cortex).

• Examples:

  • Vagal motor neuron

  • Pyramidal neuron

  • Cerebellar Purkinje cell

3. Synaptic Structures and Types

• Synapse:

  • Axon terminals specialized for neurotransmission.

  • Contains neurotransmitter vesicles and mitochondria.

  • May exhibit divergence (e.g., at neuromuscular junctions).

• Dendritic Spines:

  • Found in cerebral neurons.

  • Involved in synaptic plasticity and localized protein synthesis.

  • Their number increases during childhood and changes with environmental stimuli.

4. Cytoskeletal Elements in Neurons

• Three types of filaments:

  • Microtubules: Responsible for axoplasmic transport.

  • Neurofilaments: Provide structural support.

  • Microfilaments: Involved in growth and movement.

• Axoplasmic Transport:

  • Kinesins (anterograde) and dyneins (retrograde) transport materials along microtubules.

  • Abnormalities in transport (e.g., interaction of tau with Aβ in Alzheimer’s disease) impair neuronal function.

5. Differences Between Axons and Dendrites

6. Glial Cells

• Central Nervous System (CNS):

  • Astrocytes:

    • Support neuronal function and maintain blood-brain barrier.

    • Involved in synaptic signaling (tripartite synapse).

  • Oligodendrocytes:

    • Myelinate multiple axons.

    • Increase conduction speed and efficiency.

  • Microglia:

    • Immune function; phagocytose debris and pathogens.

  • Ependymal Cells:

    • Line ventricles and produce cerebrospinal fluid.

• Peripheral Nervous System (PNS):

  • Schwann Cells:

    • Myelinate a single section of an axon.

  • Satellite Cells:

    • Provide support to neurons in ganglia.

7. Functional Neuron Types

• Mirror Neurons:

  • Fire during both action and observation of actions.

  • Associated with empathy, self-awareness, and possibly linked to autism.

• Neurotransmitter-based Types:

  • Inhibitory (e.g., GABAergic neurons).

  • Excitatory (e.g., glutamatergic neurons).

8. Neuronal Mapping Techniques

• Retrograde Transport:

  • Tracks connections from target back to the neuron.

• "Brainbow" Technique:

  • Uses genetic cassettes to produce unique fluorescent colors in neurons.

• Array Tomography:

  • High-resolution imaging of neuron networks.

Practice Questions

• True/False: Neurons communicate with each other via direct continuity.

• What are the three parts of a neuron according to the neuron doctrine?

• Compare and contrast the morphology of unipolar, bipolar, and multipolar neurons.

• Describe the role of dendritic spines in neurons.

• Which cytoskeletal filament is primarily involved in axoplasmic transport, and what are the directions of transport?

• Explain the main differences between axons and dendrites.

• Short Answer: What are the primary roles of astrocytes in the CNS?

• Identify two key differences between oligodendrocytes and Schwann cells.

• What is the hypothesized role of mirror neurons in human behavior?

• Describe the significance of the "Brainbow" technique in neuroscience research.

Lecture 3: Membrane and Action Potential

1. Neuronal Membrane and Resting Potential

• Key Characteristics:

  • Maintains an electrical gradient across the membrane in the resting state, called the resting membrane potential.

  • Resting potential of most neurons: 65 mV.

  • The neuronal membrane is described as "excitable" because it can propagate electrical signals.

2. Key Concepts in Ion Movement

• Cytosol and Extracellular Fluid:

  • Main ions: Na⁺, K⁺, Ca²⁺, Cl⁻.

  • Proteins contribute to negative charge in the cytosol.

• Mechanisms of Ion Movement:

  • Diffusion: Ions move down their concentration gradient.

  • Electrical Current: Ions move due to electrical forces (opposite charges attract, like charges repel).

3. Types of Ion Channels

• Non-Gated Channels:

  • Also called leak channels; always open.

  • Example: K⁺ leak channels are more numerous than Na⁺ leak channels.

  • Role: Maintain baseline potential after signaling events.

• Gated Channels:

  • Open in response to stimuli (e.g., voltage, ligands, mechanical force).

4. Ion Pumps and Gradients

• Na⁺/K⁺ Pump:

  • Actively exchanges 3 Na⁺ out of the cell for 2 K⁺ into the cell.

  • Electrogenic: Creates a net positive charge outside the cell.

• Other Pumps:

  • Calcium pump, chloride pump in some neurons.

5. Membrane Potential Calculations

• Nernst Equation:

  • Calculates equilibrium potential for a specific ion: Eion=zF2.303RTlog[ion]i[ion]o Where:

    Eion=2.303RTzFlog⁡[ion]o[ion]iE_{ion} = \frac{2.303RT}{zF} \log \frac{[ion]{o}}{[ion]{i}}

    • RRR: Gas constant

    • TTT: Absolute temperature

    • zzz: Charge of ion

    • FFF: Faraday's constant

    • [ion]o[ion]_o[ion]o: Extracellular concentration

    • [ion]i[ion]_i[ion]i: Intracellular concentration

• Goldman Equation:

  • Determines membrane potential considering all ions: Vm=FRTlogPK[K]i+PNa[Na]iPK[K]o+PNa[Na]o

    Vm=RTFlog⁡PK[K]o+PNa[Na]oPK[K]i+PNa[Na]iV_m = \frac{RT}{F} \log \frac{P_{K}[K]{o} + P{Na}[Na]{o}}{P{K}[K]{i} + P{Na}[Na]_{i}}

  • Neuronal membranes are 40–50x more permeable to K⁺ than Na⁺, so K⁺ has the greatest influence.

6. Potassium and Membrane Potential

• Extracellular K⁺ Sensitivity:

  • High [K⁺]o leads to depolarization of the membrane.

    o_o

  • Regulation by:

    • Blood-Brain Barrier.

    • Astrocytes through potassium spatial buffering.

7. Historical Context and Experiments

• Julius Bernstein (1902): Proposed unequal K⁺ distribution causes membrane potential.

• Hodgkin & Huxley:

  • Conducted experiments with squid axons.

  • Demonstrated ionic contributions to action potentials.

  • Won Nobel Prize in 1963.

8. Summary

• Establishing Membrane Potential:

  • Requires an ionic concentration gradient and selective ionic permeability.

  • Relies on contributions of individual ions (e.g., Na⁺, K⁺) to Vm.

    VmV_m

Practice Questions

• What is the typical resting membrane potential of a neuron?

• Explain how the Na⁺/K⁺ pump contributes to the resting membrane potential.

• Describe the difference between leak channels and gated ion channels.

• Calculate the equilibrium potential for Na⁺ at 37°C using the Nernst equation ([Na]i=10 mM, [Na]o=150 mM).

  [Na]i=10[Na]_i = 10

  [Na]o=150[Na]_o = 150

• Compare and contrast the Nernst and Goldman equations.

• What happens to the resting membrane potential if extracellular [K⁺] increases?

• True/False: Neuronal membranes are equally permeable to Na⁺ and K⁺.

• What role do astrocytes play in regulating extracellular potassium?

• Explain the term "electrogenic" as it applies to the Na⁺/K⁺ pump.

• Discuss the significance of Hodgkin and Huxley’s research on squid axons.

Lecture 4: Action Potential

1. Overview of Action Potential

• Definition:

  • Rapid, temporary reversal of the resting membrane potential.

  • Initiated at the axon hillock, propagates to axon terminals.

• Four Phases:

  • Rising Phase: Depolarization as Na+ channels open; Vm reaches ~+40 mV.

    Na+\text{Na}^+

    VmV_m

  • Overshoot: Membrane potential becomes positive.

  • Falling Phase: K+ efflux repolarizes the membrane.

    K+\text{K}^+

  • Undershoot: Membrane potential becomes more negative than resting state.

2. Ionic Basis of the Action Potential

3. Gated Ion Channels

• Voltage-Gated Sodium Channels:

  • Single polypeptide with four domains.

  • Features:

    • Voltage sensors (S4 segments).

    • Ion selectivity filter.

  • Sensitive to local anesthetics (e.g., Lidocaine).

  • Mutations can lead to conditions like epilepsy with febrile seizures.

• Voltage-Gated Potassium Channels:

  • Composed of four polypeptide subunits.

  • Delayed rectification: Contributes to repolarization.

4. Measuring Action Potentials

• Voltage Clamp Technique:

  • Measures ionic currents while holding membrane voltage constant.

  • Key blockers:

    • Tetrodotoxin (TTX): Blocks Na+ channels.

      Na+\text{Na}^+

    • Tetraethylammonium (TEA): Blocks K+ channels.

      K+\text{K}^+

• Patch Clamp Technique:

  • Measures single or multiple channel activity.

  • Reveals the "ball and chain" inactivation mechanism.

5. Refractory Periods

6. Optogenetics

• Channelrhodopsins:

  • Light-activated ion channels induce action potentials.

  • Applications in modern neuroscience for precise neuronal activation.

Practice Questions

• Multiple Choice: What ion is responsible for the rising phase of the action potential?

  • a. Na+

  • b. K+

  • c. Cl−

  • d. Ca2+

• Describe the phases of an action potential and their ionic basis.

• What role does the refractory period play in unidirectional propagation of action potentials?

• Explain the mechanism of channel inactivation using the "ball and chain" model.

• How does the voltage clamp technique differentiate Na+ and K+ currents?

  Na+:

  K+:

Lecture 5: Action Potential Wrap-Up & Synaptic Transmission

Lecture 5: Action Potential Wrap-Up & Synaptic Transmission

1. Synaptic Transmission Overview

• Excitatory Post-Synaptic Potentials (EPSPs):

  • Depolarizing events (e.g., Na+ or Ca2+ influx).

    Na+

    Ca2+

  • Generated by excitatory ligand-gated ion channels (e.g., NMDA, kainate receptors).

• Inhibitory Post-Synaptic Potentials (IPSPs):

  • Hyperpolarizing events (e.g., Cl− influx or K+ efflux).

    Cl−

    K+

  • Generated by inhibitory channels (e.g., GABA, glycine receptors).

2. Synaptic Integration

• Threshold for Action Potential:

  • Low at axon hillock (many voltage-gated sodium channels).

  • High in dendrites (few voltage-gated sodium channels).

3. Backpropagating Action Potentials

• Definition:

  • Action potentials travel from axon hillock back to dendrites.

  • Facilitates gene transcription and synaptic plasticity.

• Mechanism:

  • Voltage-gated calcium channels supplement sodium and potassium channels.

  • Neurons with high dendritic Na+/K+ ratios have regenerative back propagation.

    Na+/K+

Practice Questions

• Compare and contrast EPSPs and IPSPs.

• What is the significance of back propagating action potentials in neuronal plasticity?

• How does temporal summation differ from spatial summation?

• True/False: The axon hillock has a lower threshold for action potential generation than dendrites.

• Explain the role of voltage-gated calcium channels in back propagating action potentials.

Lecture 6: Synaptic Transmission

1. Synapse Types

• Electrical Synapses:

  • Direct current flow between cells via gap junctions.

  • Key Features:

    • Bidirectional transmission.

    • No synaptic delay.

  • Example: Synchronization in goldfish Mauthner cells.

• Chemical Synapses:

  • Use neurotransmitters to transmit signals.

  • Key Mechanism: Calcium (Ca2+)-triggered vesicle fusion and neurotransmitter release.

2. Excitatory and Inhibitory Synapses

3. Synaptic Plasticity

• Long-Term Potentiation (LTP):

  • Strengthening of synapses due to repeated stimulation.

  • Example: Hippocampus.

• Long-Term Depression (LTD):

  • Weakening of synapses due to reduced stimulation.

Lecture 6 Practice Questions

1. Compare the key features of electrical and chemical synapses.

2. What triggers neurotransmitter release in chemical synapses?

3. Define EPSP and IPSP. How do they differ in terms of ion movement?

4. Explain the significance of synaptic plasticity (LTP and LTD) in learning and memory.

Lecture 7: Synaptic Transmission II and Passive Conductance

1. Glutamate Receptors

• Types:

  • AMPA: Fast EPSPs.

  • NMDA: Slower, long-lasting EPSPs; requires depolarization and glutamate binding.

2. Synapse at Neuromuscular Junction

• Neurotransmitter: Acetylcholine (ACh).

• Receptor: Nicotinic AChR (ligand-gated ion channels).

3. Cable Properties of Dendrites

• Key Parameters:

  • Membrane resistance (rm), axial resistance (ra), and capacitance (cm).

    rmr_m

    rar_a

    cmc_m

• Length Constant (λ\lambdaλ):

  • Determines how far voltage changes travel.

  • λ=rmra\lambda = \sqrt{\frac{r_m}{r_a}}λ=rarm.

• Time Constant (τ\tauτ):

  • Determines how fast voltage changes occur.

  • τ=rmcm\tau = r_m c_mτ=rmcm.

Lecture 7 Practice Questions

1. Explain the functional difference between AMPA and NMDA receptors.

2. How does myelination affect conduction velocity?

3. Define the length and time constants. How do they influence signal propagation?

Lecture 8: Neurotransmitters

1. Neurotransmitter Types

2. Depression Hypotheses

• Monoamine Hypothesis:

  • Depression linked to low serotonin, norepinephrine, or dopamine.

• Glutamate Hypothesis:

  • Dysregulated glutamate activity may underlie depression.

Lecture 8 Practice Questions

1. Compare the monoamine and glutamate hypotheses of depression.

2. What is the role of endocannabinoids in neuronal signaling?

3. Why are most neurons specific to one neurotransmitter?

Lecture 9: Sensation & Perception

1. Color Perception

• Trichromatic Theory:

  • Three cone types: Blue, Green, Red.

• Opponent-Process Theory:

  • Opponent pairs: Red-Green, Blue-Yellow, Black-White.

2. Color Deficiencies

Lecture 9 Practice Questions

1. Differentiate between the trichromatic and opponent-process theories of color perception.

2. What brain regions are implicated in cerebral achromatopsia?

Lecture 10: Vision I

1. Retinal Organization

• Photoreceptors:

  • Rods: Sensitive to low light.

  • Cones: Color vision.

• Retinal Processing:

  • Involves ganglion, bipolar, horizontal, and amacrine cells.

2. Phototransduction

• Light triggers rhodopsin activation, leading to:

  • cGMP breakdown.

  • Closure of Na+ channels.

  • Hyperpolarization of photoreceptors.

Lecture 10 Practice Questions

1. Compare rods and cones in terms of function and distribution.

2. Explain the process of phototransduction in rods.

3. What are the roles of horizontal and amacrine cells in retinal processing?

Lecture 11 & 12: Vision III

1. Retinal Processing

• Receptive Fields:

  • ON-center cells: Depolarize in light.

  • OFF-center cells: Hyperpolarize in light.

• Types of Ganglion Cells:

  • M-type: Larger, sensitive to low contrast, transient response.

  • P-type: Smaller, sustained response, involved in color processing.

  • NonM-NonP: Yellow-blue color opponency.

2. Retinofugal Pathway

• Sequence: Retina → Optic Nerve → Optic Chiasm → LGN → Visual Cortex.

• LGN Segregation:

  • Inputs from nasal retina cross; temporal inputs stay ipsilateral.

3. Cortical Processing

• Primary Visual Cortex (V1):

  • Orientation-selective neurons respond to specific angles of light.

  • Parallel visual pathways:

    • Motion detection (dorsal stream).

    • Object recognition (ventral stream).

Lecture 11 & 12 Practice Questions

1. What is the difference between ON-center and OFF-center ganglion cells?

2. Describe the retinofugal pathway and LGN segregation.

3. How do dorsal and ventral visual streams differ functionally?

Lecture 13: Auditory System

1. Anatomy of the Cochlea

• Basilar Membrane:

  • High frequencies vibrate the base; low frequencies vibrate the apex.

• Organ of Corti:

  • Inner hair cells transduce sound; outer hair cells amplify it.

2. Auditory Pathway

• Sequence: Cochlea → Cochlear Nucleus → Superior Olive → Inferior Colliculus → MGN → Auditory Cortex.

• Sound Localization:

  • Low frequencies: Interaural time delay.

  • High frequencies: Interaural intensity difference.

Lecture 13 Practice Questions

1. Explain how the basilar membrane encodes sound frequency.

2. Compare the roles of inner and outer hair cells in auditory transduction.

3. What mechanisms does the auditory system use for sound localization?

Lecture 14 & 15: Somatosensation

1. Mechanoreceptors

• Pacinian Corpuscles: High-frequency vibrations.

• Meissner's Corpuscles: Low-frequency vibrations.

• Merkel Disks: Spatial detail.

• Ruffini Endings: Skin stretch.

2. Pain Pathways

• Spinothalamic Tract: Transmits pain and temperature.

• Gate Control Theory:

  • Spinal cord gates modulate pain signals based on sensory input.

Lecture 14 & 15 Practice Questions

1. Describe the functional differences between Pacinian and Merkel receptors.

2. Explain the gate control theory of pain modulation.

3. How does the spinothalamic tract differ from the dorsal column-medial lemniscal pathway?

Lecture 16: Taste & Olfaction

1. Taste Mechanisms

• Taste Modalities:

  • Sweet: T1R2 + T1R3 receptors.

  • Bitter: T2R family.

  • Umami: T1R1 + T1R3.

  • Salty: Amiloride-sensitive sodium channels.

2. Olfaction

• Olfactory Bulb Processing:

  • Axons project ipsilaterally to the brain.

  • Representations in the olfactory cortex encode odor identity.

Lecture 16 Practice Questions

1. Describe the molecular mechanisms underlying salt and bitter taste perception.

2. What role does the olfactory bulb play in odor processing?

3. How does olfaction integrate with memory and emotion?

Lecture 17 & 18: Motor System I & II

1. Motor Neurons

• Alpha Motor Neurons:

  • Control extrafusal fibers for contraction.

• Gamma Motor Neurons:

  • Maintain muscle spindle sensitivity.

2. Descending Pathways

• Corticospinal Tract: Controls fine motor movements.

• Vestibulospinal Tract: Maintains posture and balance.

Lecture 17 & 18 Practice Questions

1. Compare alpha and gamma motor neurons in function.

2. What are the primary roles of the corticospinal and vestibulospinal tracts?

3. Explain the role of the basal ganglia in movement initiation.

Lecture 19 & 20: Brain Development I & II

1. Neurogenesis

• Radial glial cells generate neurons.

• Migration and differentiation establish cortical layers.

2. Synaptic Plasticity

• Hebbian Learning:

  • "Neurons that fire together wire together."

• Critical Periods:

  • Developmental windows for synaptic pruning and rearrangement.

Lecture 19 & 20 Practice Questions

1. Describe the process of radial migration in cortical development.

2. What is the role of Hebbian plasticity in synapse development?

3. How does the critical period influence neural circuit refinement?

Lecture 21: Memory I

1. Types of Memory

• Declarative Memory (explicit):

  • Episodic (events) and Semantic (facts).

• Non-declarative Memory (implicit):

  • Procedural memory for skills and habits.

2. Memory Disorders

• Amnesia:

  • Retrograde: Loss of past memories.

  • Anterograde: Inability to form new memories.

• Engram:

  • Physical representation of memory, distributed across the neocortex.

3. Brain Regions in Memory

• Medial Temporal Lobe:

  • Essential for declarative memory.

  • Patient HM: Severe anterograde amnesia post-surgery.

• Prefrontal Cortex:

  • Working memory; distinct neurons for recognition and memory.

4. Synaptic Plasticity

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

  • Key mechanisms for memory formation.

  • Requires synaptic strengthening and new synapse formation.

Lecture 21 Practice Questions

1. Compare episodic and procedural memory.

2. What is the role of the medial temporal lobe in memory formation?

3. How do LTP and LTD contribute to memory?

Lecture 22: Memory II

1. Specialized Memory Cells

• Place Cells (Hippocampus):

  • Encode spatial information.

• Grid Cells (Entorhinal Cortex):

  • Provide spatial frameworks.

• Time Cells (Hippocampus):

  • Encode temporal sequences.

2. Molecular Basis of Memory

• Short-Term Memory:

  • Protein-synthesis independent; relies on CaMKII.

• Long-Term Memory:

  • Requires protein synthesis and gene transcription (CREB activation).

Lecture 22 Practice Questions

1. Differentiate between place, grid, and time cells.

2. What is the molecular basis of long-term memory consolidation?

Lecture 23: Brain Rhythms and Sleep

1. EEG Rhythms

• Categorized by frequency:

  • Gamma (>25 Hz), Beta (14–20 Hz), Alpha (8–13 Hz), Theta (4–7 Hz), Delta (<4 Hz).

2. Sleep Cycles

• NREM Sleep:

  • Slow-wave sleep, reduced responsiveness.

• REM Sleep:

  • Dreaming, brain activity similar to wakefulness.

3. Sleep and Memory

• Essential for memory consolidation.

• Sleep deprivation impairs cognitive and emotional regulation.

Lecture 23 Practice Questions

1. Describe the EEG rhythms associated with wakefulness and sleep.

2. How does REM sleep contribute to memory consolidation?

Lecture 24: Emotion and Attention

1. Theories of Emotion

• James-Lange: Emotions arise from physiological changes.

• Cannon-Bard: Emotions and physiological responses occur simultaneously.

2. Amygdala

• Central to fear and emotional memory.

• Lesions reduce fear and aggression.

3. Attention

• Bottom-Up:

  • Stimulus-driven (e.g., detecting predators).

• Top-Down:

  • Goal-directed focus (e.g., reading).

Lecture 24 Practice Questions

1. Compare the James-Lange and Cannon-Bard theories of emotion.

2. What is the role of the amygdala in emotional processing?

Lecture 25: Language

1. Brain Areas

• Broca’s Area:

  • Speech production; damage causes Broca’s aphasia (non-fluent speech).

• Wernicke’s Area:

  • Language comprehension; damage causes Wernicke’s aphasia (fluent but nonsensical speech).

2. Split-Brain Studies

• Demonstrated hemispheric specialization in language processing.

3. Genetic Basis

• FOXP2 gene: Key for language development and articulation.

Lecture 25 Practice Questions

1. Differentiate between Broca’s and Wernicke’s aphasia.

2. What insights into language processing have been provided by split-brain studies?

Lecture 26: Major Depression and Happiness

1. Biological Basis of Depression

• Monoamine Hypothesis:

  • Suggests serotonin, norepinephrine, and dopamine deficits.

• Brain Regions:

  • Subcallosal cingulate cortex (BA25): Hyperactive in depression.

2. Neurochemistry of Happiness

• Hedonia (Pleasure):

  • Dopamine and opioid-mediated.

• Eudaimonia (Meaningful Life):

  • Involves social connections and personal engagement.

Lecture 26 Practice Questions

1. What is the monoamine hypothesis of depression?

2. Compare hedonia and eudaimonia in terms of neurobiology.