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

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

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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).

Ion Channels

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

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.

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

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

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.

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)

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

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)