ALL THE CARDS BABY

Neuroscience Today

Scientific Process

1. Explain why progress in science is often slow

   1. Have to follow process and review findings

2. Explain the reductionist approach

   1. Breaking down the brain into different levels of analysis

3. Compare different levels of analysis in neuroscience research (molecular, cellular, systems, behavioral, and cognitive neuroscience)

   1. Molecular is chemistry in the brain

   2. Cellular is studying the nerves in the brain

   3. Systems is studying how groups of nerves serve a function

   4. Behavioral is how systems work together to produce behavior

   5. Cognitive is how brain activity creates the mind

4. List and Describe the four essential steps in the scientific process with examples

   1. Observation: Hypothesize a potential finding

   2. Replication: repeating the experiment on different subjects/trials

   3. Interpretation: Explain the data

   4. Verification: Repeat the experiment to check for similar results

Animal Research

5. Discuss the importance of animal research in the field of neuroscience

   1. Animal brains needed to model the human brain most accurately

6. Explain when animal research is needed

   1. Animal research needed to naturally observe phenomena

7. Describe the three Rs of ethical animal research

   1. Reduction: Keep number of animals used to a minimum

   2. Refinement: Make better living conditions for animals

   3. Replacement: Replace animals with alternative techniques if possible

8. Differentiate animal rights and animal welfare views

   1. Animal welfare is being ethical toward animals in research. Animal rights is being against animals in research completely at detriment to human welfare.

9. Develop a rationale to support your opinion of animal research and enable discussion with other scientists and the general public

   1. Some animals must be sacrificed for the good of the public

Neurons and Methods

1. Identify how many neurons and glia are in the human brain

   1. 85 billion of each

2. Discuss important histological procedures and how they contributed to the advancement of neuroscience (i.e. Golgi method, immunohistochemistry, in situ hybridization)

   1. Golgi method used silver chromate to stain neurons entirely

   2. Compare and contrast IHC and ISH

      1. IHC shows proteins. ISH shows mRNA.

3. Explain what Camillo Golgi and Santiago Ramón y Cajal disagreed about

   1. Golgi believed all neurons fused together. Cajal believed neurons communicated through contact.

4. Compare the the Neuron Doctrine and Reticular Theory

   1. Neuron Doctrine: Neurons are the same as cells, so each one is a unit (right)

   2. Reticular Theory: Neurons are not like cells; one continuous system (wrong)

5. Diagram a neuron and label its components

   1. Soma

   2. Axon

   3. Axon terminals

   4. Dendrites

6. Describe the function of each component of the neuron

   1. Soma: Cell sustaining functions

   2. Axon: propagate action potential

   3. Axon hillock: Initiates action motential

   4. Axon terminals: communicate with postsynaptic targets via neurotransmitters

   5. Dendrites: Receive inputs from other presynaptic neurons

7. Detail the ways in which neurons are specialized for communication

   1. Synapses between neurons

8. Describe the methods used to classify neurons

   1. Number of neurites (axons/dendrites from soma)

      1. Unipolar, bipolar, multipolar

   2. Dendrites

      1. Stellate (star shape)

      2. Pyramidal (pyramid shape)

      3. Spiny

      4. Aspinous

   3. Axon length

      1. Primary sensory

      2. Motor

      3. Interneurons

   4. Connections

      1. Golgi type I: long

      2. Golgi typ2: 2 short

   5. Gene expression

      1. Acetylcholine expression means cholinergic

9. Compare primary sensory neurons, motor neurons, and interneurons

   1. Primary sensory bring in information from receptors

   2. Motor neurons innervate muscles

   3. Interneurons connect other neurons (majority)

Glia and Methods  

1. Describe the methods used to classify neurons and glia

   1. In-Situ Hybridization for mRNA tagging. Immunohistochemisty for protein identification.

2. Describe the main types of glial cells, including the main function of each

   1. Astrocytes: Clean the brain of leftover neurotransmitters. Can also release transmitters. Regulate the extracellular concentrations. Maintain blood brain barrier. Initiate inflammatory response

   2. Oligodendrocytes: Myelinate multiple CNS nerves

   3. Schwann cells: Myelinate single PNS nerve

   4. Ependymal cells: Direct cell migration during brain development

   5. Microglia: Function as phagocytes to remove debris and dead neurons/glia

3. Glia outnumber neurons in the brain, yet neurons are the predominant focus of neuroscience textbooks. Explain why that might be the case.

   1. Discovery of glial functions is newer. Neurons do the communication.

4. Find and describe a recent research study regarding the role of glia in the brain.

   1. Astrocytes can convert to neurons to fight Parkinson’s disease

Resting Membrane Potential  I

1. Explain why resting membrane potential is essential to how neurons signal one another

   1. The state of the neuron between signals.

2. Discuss how the resting membrane potential is maintained 

   1. Define the resting membrane potential, how it is measured and its value in a “typical” neuron

      1. The difference in electrical charge across the membrane of a neuron at rest. Measured with one electrode in the neuron and one in the extracellular fluid. Typical is -65mV

   2. Include discussion of the 3 major players: ions, the membrane, membrane proteins

      1. Ions carry the charge. Membrane is generally impermeable to ions. Membrane proteins allow some ions to move across the membrane.

   3. Identify two physical forces that determine a neuron’s resting potential

3. Explain the importance of the sodium-potassium pump

   1. Maintains RMP. Establishes a concentration gradient for Na+ and K+. 3 Na+ out, 2 K+ in.

4. Explain what it means if K+ ions are at equilibrium

   1. Diffusion causing K+ to leave the cell is cancelled out by electric potential causing K+ to enter the cell, leading to unchanging concentration

   2. Discuss why E_K is relevant to the resting membrane potential (RMP)

      1. RMP is closest to equilibrium potential of K+ because K+ channels are open, and K+ is most permeable.

Calculate equilibrium potential for K⁺ using the nernst equation

1. Describe what happens to the membrane potential when the brain is deprived of oxygen

   1. Sodium potassium pump cannot function. RMP goes to 0.

Resting Membrane Potential  II

1. Differentiate when to use the nernst and goldman equations

   1. Nernst is for a specific ion. Goldman is for the membrane that is permeable to different ions.

   2. Discuss why RMP doesn’t match Ek

      1. Membrane is somewhat permeable to Na+ as well.

2. Calculate (a) equilbrium potential for an ion using the nernst equation (b) resting membrane potential using the goldman equation 

   1. Assess how altering the external and internal concentrations of various ions impacts equilibrium potentials and the RMP

Action Potential I  

1. Draw a typical action potential. Label the axes and each phase of the action potential

   

2. Describe the key molecular events that underlie each phase: Threshold; Rising phase; Overshoot phase; Falling phase; Undershoot phase; Refractory period

   1. Threshold: Enough voltage-gated sodium channels open so that relative permeability factors sodium over potassium

   2. Rising phase: Na+ channels open. Na+ floods the cell.

   3. Overshoot: Potential nearly reaches ENa because relative permeability favors sodium.

   4. Falling phase: Na+ channels close. K+ channels open triggered by depolarization. K+ floods out of the cell.

   5. Undershoot: Membrane permeability now favors K+, so it goes toward Ek, which is lower than RMP

   6. Absolute refractory: Na+ channels cannot be reactivated until potential becomes negative enough, so depolarization cannot happen.

   7. Relative refractory: Membrane potential stays hyperpolarized until voltage-gated sodium channels close, meaning more depolarizing current is required to bring membrane potential to threshold. Follows absolute refractory.

3. Explain why the action potential is referred to as all-or-none

   1. Either threshold is reached and an action potential is fired, or threshold is not reached and nothing happens.

4. Describe the structure and functional properties of the sodium channel

   1. Four domains each with 6 alpha helices. Twists to let Na+ in once threshold reached. Voltage sensor in S4.

   2. Consider how sodium channel mutations can impact function & neuron excitability

      1. Overreactive sodium channel makes neuron too excitable (epilepsy). Underreactive

5. Summarize how the grasshopper mouse is resistant to scorpion venom

   1. Mutation makes the sodium channel inactivate in presence of scorpion venom

6. Imagine experimental ways to reduce how many action potentials a given neuron can fire – propose a way to do this

   1. Inhibit sodium channels

Action Potential II

1. Describe how an action potential is propagated along an axon

   1. Opening of sodium channels depolarizes a patch of axon that triggers sodium channels down the axon to open.

2. Explain why action potentials move away from the cell body

   1. Sodium channels close behind the action potential

3. Identify factors that influence conduction velocity

   1. Axon structure, path of positive charge, axonal diameter, number of voltage gated channels, myelin, saltatory conduction

   2. Explain how the conduction velocity of a neuron varies with axonal diameter (draw a diagram to illustrate this)

      1. Wider is faster.

4. Describe the factors that enable salutatory conduction to occur

   1. Nodes of ranvier have high concentration of Na+ channels, so they regenerate the action potential and send it to the next node. Myelin between the nodes prevents loss of current.

5. Describe what factors determine each neuron’s unique physiology

   1. Genetics, function

6. Describe adaptation

   1. Slowing of action potential firing over time.

7. Explain how local anesthetics work

   

   1. Diagram the structure of a voltage gated sodium channel

   2. Identify where lidocaine interacts with VG sodium channels and how this impacts their function

      1. Binds to S6 while it is open. Interferes with the flow of Na+

8. Discuss the demyelinating disease multiple sclerosis and ways to alleviate failed action potential propagation in the disease

   1. MS attacks myelin sheath in the brain, spine, and optic nerves. 

   2. Describe the term remyelination

      1. Using glia to rebuild myelin sheath

Synaptic Transmission I

1. Compare the similarities and differences between electrical and chemical synapses

   1. Electrical: 6 connexins make connexon, 2 connexon make 1 gap junction. Ions pass through gap junction from one cell to another bidirectionally

   2. Chemical: Unidirectional. Synaptic cleft (wider than gap junction).

2. Draw a diagram to help you describe each of the steps in synaptic transmission

   1. Summarize in your own words each step in synaptic transmission

      

   2. Discuss three mechanisms for termination of synaptic transmission

      1. Diffusion; Reuptake; Break down

3. Describe how vesicles fuse with the membrane

V Snare binds to vessicle. T Snare binds to membrane. V and T bind to each other.

4. Explain the differences between agonists and antagonists

Agonists mimic the action of transmitter. Antagonists block the receptor.

5. Compare and contrast neurotransmitter-gated ion channels and g-protein-coupled receptors

Synaptic Transmission II

1. Explain the purpose of synaptic integration

Combine multiple synaptic inputs into one neuron to code information

2. Describe how EPSPs and IPSPs contribute to the generation of an action potential in the post-synaptic cell (draw a diagram to illustrate this)

3. Compare and contrast spatial summation and temporal summation

Spatial: combine inputs from different parts of the cell. Temporal: combine potentials that arrive to the axon hillock at different times.

4. Explain the dendritic length constant (draw a diagram to illustrate this)

5. Compare membrane resistance and internal resistance

Membrane resistance: How well the axon resistance current leaking out of the axon

Internal resistance: How well the axons resists current traveling down

6. Describe how a modulator can change length constant

ß NE receptor closes K+ channels. Increase membrane resistance. Increases length constant.

Neurotransmitter systems I 

1. Identify the criteria used to determine if a substance in the brain is a neurotransmitter

   1. Synthesized and stored in a presynaptic neuron

   2. Released by axon terminal after stimulation

   3. The molecule when experimentally applied, produces the same response

2. Describe the major neurotransmitters (ACh, glutamate, and GABA) in terms of anatomy, function, receptors and drugs targeting the systems

   

1. Explain how a neurotransmitter transporter works

   1. Build up concentration of transmitter across membranes

2. Describe the difference between a “tract” and a “nucleus”, using examples

   1. Nucleus: origin of release (cell bodies). Tract: where the neurons extend (axons)

3. Discuss methods for studying neurotransmitter systems including immunohistochemistry, in situ hybridization, neuropharmacological analysis (agonists, antagonists, etc) and ligand binding methods

   1. Neuropharmacological: Use agonists and antagonists to see physiological effects of each on each receptor

   2. Ligand binding: Radioactively label a ligand and see where it binds in the brain

4. Describe cre technology and how it can be used to identify the structure and function of neurons

   1. Can identify neurons that express a certain gene by selectively knocking it down or making it glow

Neurotransmitter systems II 

1. Describe the major neurotransmitters (DA, NE, 5-HT) in terms of anatomy, function, receptors and drugs targeting the systems

1. ACh

   1. AChE degradative enzyme

   2. Basal forebrain nucleus of Meynert

   3. Choline transporter rate limiting step for synthesis

   4. Muscarinic receptors

   5. Nerve agents target this system

   6. Nicotinic receptors

   7. NT at the NMJ (neuromuscular junction)

   8. Requires ChAT for synthesis (unique marker of cells)

   9. Synthesized by motor neurons in spinal cord and brain stem 

2. NE

   

   1. Antidepressants

   2. Amino acid tyrosine is a precursor

   3. Contains a catechol

   4. Catecholamine

   5. Degraded by monoamine oxidase (MAO)

   6. Enzyme dopamine-β-hydroxylase is required

   7. Locus Coeruleus and other cell bodies in the brainstem

   8. Made in synaptic vesicles

   9. modulates attention, mood, memory, etc.

   10. Tyrosine hydroxylase is rate limiting

   11. Taken up by NET

   12. Vigilance, Alzheimer’s, Parkinson’s

3. 5-HT

   

   1. 5HT-1A, 5HT-1B, etc

   2. Antidepressants

   3. Anxiolytics (Prozac)

   4. Degraded by monoamine oxidase (MAO)

   5. Derived from tryptophan

   6. Modulates Mood and sleep

   7. Raphe nuclei

   8. SERT

   9. Tryptophan hydroxylase

4. DA

   

   1. Amino acid tyrosine is a precursor

   2. Contains a catechol

   3. Catecholamine

   4. Degraded by monoamine oxidase (MAO)

   5. Substantia Nigra

   6. Tyrosine hydroxylase is rate limiting

2. Describe the unconventional neurotransmitters, endocannabinoids, in terms of anatomy, function, receptors and drugs targeting the systems

   1. Small lipid molecules released from postsynaptic neurons retrograde signaling

   2. Vigorous AP firing in the postsynaptic neurons causes voltage gated calcium channels to open → calcium flows in → elevated calcium then stimulates synthesis of endocannabinoid synthesizing enzymes

   3. Not packaged in vesicles! Manufactured rapidly and on demand

   4. Small membrane permeable

   5. Bind selectively to the CB1 type of cannabinoid receptor (presynaptic recptor mainly)--> reduce calcium channel opening so they inhibit release of NT

   6. Receptors discovered BEFORE the NT  (CB1 receptor mainly in the brain; CB2 immune tissue)  More CB1 receptor than any other GPCR

   7. High doses -hallucinations

   8. Treatment of nausea and vomiting and stimulate appetite in aids patients

3. Compare convergence and divergence of neurotransmitter systems

   1. Convergence: Multiple transmitters/receptors for one response

   2. Divergence: One transmitter for multiple receptors and multiple responses