How Neurons Work

1. How Neurons Work Nancy Alvarado, Ph.D. Dr. Goldman’s PSY 210 Class April 16, 2003

2. Two Kinds of Cells • Neurons (nerve cells) – signaling units • Glia (glial cells) – supporting elements: • Separate and insulate groups of neurons • Produce myelin for the axons of neurons • Scavengers, removing debris after injury • Buffer and maintain potassium ion concentrations • Guide migration of neurons during development • Create blood-brain barrier, nourish neurons

3. Neuronal Circuits • Neurons send and receive messages. • Neurons are linked in pathways called “circuits” • The brain consists of a few patterns of circuits with many minor variations. • Circuits can connect a few to 10,000+ neurons.

4. Parts of the Neuron • Soma – the cell body • Neurites – two kinds of extensions (processes) from the cell: • Axon • Dendrites • All parts of the cell are made up of protein molecules of different kinds.

5. How Neurons Communicate • An electrical signal, called an action potential, is propagated down the axon. • An action potential is an all-or-nothing signal. • The amplitude (size) of the action potential stays constant because the signal is regenerated. • The speed of the action potential is determined by the size of the axon. • Action potentials are highly stereotyped (very similar) throughout the brain.

6. How to Tell Axons from Dendrites • Dendrites receive signals – axons send them. • There are hundreds of dendrites but usually just one axon. • Axons can be very long (> 1 m) while dendrites are < 2 mm. • Axons have the same diameter the entire length – dendrites taper. • Axons have terminals (synapses) and no ribosomes. Dendrites have spines (punching bags). • Don’t be fooled by the branches – both have them.

7. Ramon y Cajal’s Principles • Principle of dynamic polarization – electrical signals flow in only one, predictable direction within the neuron. • Principle of connectional specificity: • Neurons are not connected to each other, but are separated by a small gap (synaptic cleft). • Neurons communicate with specific other neurons in organized networks – not randomly.

8. Ways of Classifying Neurons • By the number of neurites (processes): • Unipolar, bipolar, multipolar • By the type of dendrites: • Pyramidal & stellate (star-shaped) • By their connections (function) • Sensory, motor, relay interneurons, local interneurons • By neurotransmitter – by their chemistry

9. Parts of the Soma (Cell Body) • Nucleus – stores genes of the cell (DNA) • Organelles – synthesize the proteins of the cell • Cytosol – fluid inside cell • Plasmic membrane – wall of the cell separating it from the fluid outside the cell.

10. Organelles • Mitochondria – provide energy • Microtubules – give the cell structure • Rough endoplasmic reticulum – produces proteins needed to carry out cell functioning • Ribosomes – produce neurotransmitter proteins • Smooth endoplasmic reticulum – packages neurotransmitter in synaptic vesicles • Golgi apparatus – Part of the smooth endoplasmic reticulum that sorts proteins for delivery to the axon and dendrites

11. Kinds of Glia • Oligodendrocytes – surround neurons and give them support. • In white matter, provides myelination • In gray matter, surround cell bodies • Schwann cells – provide the myelin sheath for peripheral neurons (1 mm long). • Astrocytes – absorb potassium, perhaps nutritive because endfeet contact capillaries (blood vessels), form blood-brain barrier.

12. Four Signals Within the Neuron • Input signal – occurs at sensor or at points where dendrites are touched by other neurons. • Integration (trigger) signal – occurs at first node (in sensory neuron) or at axon hillock. • Conducting signal – travels down axon. • Output signal – releases neurotransmitter at axon terminal.

13. The Neuron at Rest • Neurons have potassium (K+) inside and sodium (Na+) outside in the extracellular fluid. • Ion channels in the cell wall (membrane) are selectively permeable to potassium, sodium or calcium. • Ion pumps maintain the cell’s inner environment.

14. How Ions Cross the Membrane • Diffusion – an ionic concentration gradient exists • Differences in electrical membrane potential and equilibrium potential • Ionic driving force • Ion pumps • Sodium/potassium, calcium

15. The Action Potential • Depolarization – influx of sodium (Na+) or another positive ion makes the membrane potential more positive. • When the membrane potential reaches threshold, voltage-gated Na+ ion channels open. • After 1 msec, voltage-gated K+ channels open, polarizing the neuron again. • Sodium-potassium pump helps restore neuron to its resting potential. • Resting potential is polarized, typically -65 mV

16. Conduction Down the Axon • Rapid depolarization in one spot causes membrane just ahead to depolarize too. • Speed of conduction depends on the size of the axon and the number of ion channels. • Myelin permits the action potential to travel rapidly from node to node by blocking the membrane between nodes. • Ion channels occur at the nodes, permitting an influx of Sodium to regenerate the action potential.

17. Graded Response • If action potentials are all-or-nothing and always have the same amplitude (size), how is a graded response produced? • More intense and longer duration stimuli produce more frequent action potentials. • More frequent action potentials release more neurotransmitter. • More neurotransmitter increases the likelihood the next neuron will have an action potential.

18. Two Kinds of Neural Activity • Excitatory – causes another neuron to be more likely to fire (have an action potential). • Inhibitory – causes another neuron to become hyperpolarized (more negatively charged), making it less likely to fire.

19. Interpretation of the Signals • Action potentials are the same in neurons all over the brain. • The meaning of an action potential comes from the interconnections among the neurons, not from the action potential itself. • It is the flow of information through a network that is important -- what is connected to what. • Connectionist models try to simulate this approach using computer software.

20. Differences Among Neurons • Some local interneurons do not generate action potentials because their axons are short. • Some neurons do not have a steady resting potential and are spontaneously active. • Neurons differ in the types and combinations of ion channels in their cell membranes. • Neurons differ in their neurotransmitters released and their receptors for transmitters.

21. Consequences for Disease • The nervous system has more diseases than any other organ of the body. • Some diseases attack a particular kind of neuron (e.g., motor neurons in ALS & polio). • Parkinson’s attacks certain interneurons using a particular neurotransmitter (dopamine). • Some diseases affect only parts of the neuron (e.g., cell body, axon).

22. Ion Channels

23. Ion Channels • Found in all cells throughout the body. • Open and close in response to signals. • Selectively permeable to specific ions • High rate of flow (conductance) • Resting channels – usually open • Gated channels – open and close • Refractory period – temporarily cannot be opened

24. Control of Gating • Binding of neurotransmitters, hormones, or second messengers from within the cell. • Phosphorylation – energy comes from a phosphate that binds with the channel. • Dephosphorylation – removal of the phosphate. • Voltage-gated – responds to a change in the membrane potential. • Stretch or pressure gated – mechanical forces.

25. Kinds of Receptors • All neurotransmitters bind and act at more than one kind of receptor. • Two main kinds of receptors: • Ion channel receptors • G-protein-coupled receptors

26. G-Protein-Coupled Receptors • Change the excitability of the neuron in two ways: • Change calcium ion levels (releasing neurotransmitter). • Activate intra-cellular second messengers: • Signal amplification • Signaling at a distance • Cascades of activation • Long-lasting chemical changes in neuron

27. Importance of Calcium • Voltage-gated calcium (CA2) channels permit CA to enter the cell. • As CA2 rises, it binds with the neuron, preventing additional calcium from entering. • Increased calcium concentrations can cause dephosphorylation or permanent inactivation of a channel. • Calcium signals neurotransmitter release.

28. Effects of Drugs • Exogenous ligands – drugs that come from outside the body. • Endogenous ligands – naturally occurring • Agonist – binds with and opens a channel. • Endogenous or exogenous (e.g., drug) • Antagonist – binds with and closes a channel. • Reversible (curare) or irreversible (snake venom)

29. Kinds of Neurotransmitters • Amino acids & amines • GABA, Glycine (Gly), Glutamate (Glu) • GABA is inhibitory, Glu is excitatory • Strychnine blocks GABA receptors interfering with inhibition so excitations overwhelm the brain. • Monoamines • Cholinergic – Acetylcholine (ACh), used by muscles • Catecholaminergic – regulate thinking, mood

30. Kinds of Neurotransmitters (Cont.) • Catecholamines synethesized from tyrosine: • Dopamine • Norepinephrine (Noradrenaline) • Epinephrine (Adrenaline) -- widespread • Serotonin (5-HT) – broken down by MAO, LSD binds at receptors. • Peptides • Oxytocin & vasopressin • Opioids (endorphins)