Chapter 39: Neurons

Organism's survival and homeostasis depends on ability to respond to internal & external signals

• Stimulus = change within body or in outside environment that can be detected by an organism
• Nervous system responds to stimuli

Neuron = nerve cell, specialized to transmit electrical and chemical signals, receive and send info

Nervous system = neuron and supporting cells (glial cells tht support and protect neurons)

• Takes in info
• Integrates info
• Responds to info

Neurotransmitters = chemical messengers used by neurons to signal other neurons

• Bind to receptors on cell membrane
• Mood, disorders linked to NT's and receptors.

Endocrine system works with nervous system to regulate behaviors, physiology

• Endocrine = slow, long-lasting response
• Nervous system = rapid, brief response.

Reception = process of detecting stimulus (neurons and sense organs)

Transmission = process of sending messages along neuron (to neuron or muscle or gland)

• Sensory neurons aka afferent neurons transmit info to central nervous system
• CNS = brain and spinal cord
• Interneurons aka association neurons receive info from afferent neurons .
• integrate input and output
• integration = sorting / interpretting incoming sensory info and determining response
• Efferent neurons aka motor neurons take info to effectors
• Effector = muscle or gland
• Peripheral nervous system (PNS) = sensory receptors, afferent and efferent neurons

Neuroglia = all glial cells

• Microglia near blood vessels, migrate into CNS if injury or infection, remove debris. Prion disease
• Astrocytes = star-shaped cells in CNS
• Phagocytic, remove microorgansism and debris
• Regulate concentration of K+ ions in extracell fluid
• Regulate concentration of neurotransmitters
• Oligodendrocytes = cells that envelop neurons, make insulating sheaths in CNS
• Myelin = white, fatty substance in plasma membrane of glial cell, forms sheath
• Speeds transmission of neural impulses
• Multiple sclerosis: myelin deteriorates along axon, replaced by scar tissue
• Bad impulse conduction
• Lose coordination, tremors, paralysis
• May be autoimmune disease
• Schwann cells in PNS can form sheath around some neurons

Neuron produces, transmits nerve impulse aka action potential aka electrical impulse

• Cell body = nucleus, most cytoplasm, most organelles
• Long cytoplasmic extenions or processes from cell body
• Dendrites = short, highly branched processes
• Numerous
• Receive stimuli, send signals TO cell body
• Cell body integrates incoming signals
• Axon = very long processs
• May divide into branches called axon collaterals
• Takes nerve impulse AWAY from cell body
• At end, axon divides into terminal branches with synaptic terminals
• Synaptic terminals release neurotransmitters
• Synapse = junction between synaptic terminal and another neuron or effector (small space)

Myelin sheath around neurons outside CNS

• Series of Schwann cells give insulating covering
• Nodes of Ranvier = gaps between myelin sheath of successive Schwann cells
• Axons less than 2um unmyelinated, no sheath

Nerve = 100's or 1000's of axons wrapped together in connective tissue

• Telephone cable
• Tract aka pathway = bundles of axons within CNS (brain and spinal cord)
• Ganglia = cell bodies of neurons grouped together outside CNS
• Nuclei = collections of cell bodies within CNS

Most animal cells polarized: one side of plasma membrane has different charge than other side

• More NEGATIVE INSIDE animal cell, more positive outside in interstitial fluid
• Because charges are separated, have potential energy
• Membrane potential aka resting potential = difference in electrical charge across plasma membrane
• Bring charges together and they can do work (battery)

Resting potential

• Measured in millivolts (mV)
• Voltage = force that causes charged particles to flow between 2 points
• Neuron -70mV
• Electrode inside cell, voltmeter or oscilliscope, electrode outside cell
• WHY? More positive ions outside plasma membrane, slight excess of negative ions inside cell
• K+ concentrated INSIDE cell
• Na+ concentrated outside cell
• Ions diffuse down electrochemical gradients. K+ wants to move outside cell, Na+ wants inside.
• Sodium/potassium pumps are proteins in cell membrane that actively transport 3 Na+ outside cell and 2 K+ inside cell. Need ATP, moving against concentration gradient
• Ion channels = membrane proteins that allow specific ions to diffuse across membrane. Charged regions = gates. When gate open, ion moves thru.
• Passive ion channels open, move specific ion: Na+. K+, Cl-, Ca2+
• Voltage activated channel aka voltage gated channel closed until change in voltage opens gate
• Chemically activated ion channels in dendrites, cell body.
• All together
• Na/K pump moves Na out of cell, K into cell
• K ions leak back out of cell by passive channels along concentration gradient
• Equilibrium potential has K+ outflow = K+ inflow. -70mV
• Cl- ions flow into cell, accumulate along plasma membrane, adding to negative potential

Excitability = neuron can respond to stimuli and convert stimulus into nerve impulse by increasing membrane permeability to sodium

• Slightly excited = local disturbance
• Strong enough stimulus causes action potential or nerve impulse.
• Electrical change along axon to terminal
• Action potential = electrical current strong enough to induce change in resting potential in adjacent area of membrane
• Action potential causes voltage-gated ion channels to open. Voltage at/above threshold changes protein shape.
• If depolarization greater than -55mV, opens gated channels
• Na+ moves into cell
• After certain time, gates close again
• Voltage gated K+ channels open, stay open til resting potential restored
• Positive feedback: when some channels open, more depolarization, leading more channels to open
• Membrane potential from -70mV to +35mV or more.
• Spike = sharp rise and gall of action potential
• Wave of depolarization = action potential spikes moving from one area of membrane to next area. Chain reaction.
• Repolarization = restoring resting potential
• Na+ gates close at certain time
• K+ gates open, so K+ moves out of cell, cell becomes negative
• Na/K pump moves Na+ out of cell and K+ into cell, normal resting concentrations.
• Absolute refractory period = nerve cannot transmit another action potential no matter how high stimulus
• Membrane is depolarized
• Voltage activated Na+ chanels are inactive, need to be reset
• Relative refractory period = axon can transmit impulses with higher threshold

Conduction

• Continuous conduction = smooth, progressive impulse transmission in unmyelinated neurons.
• 1-10m.sec
• speed proportional to diameter of neuron.
• Larger diameter quicker. Less resistant to ion flow along length.
• Squid giant axons used in research
• Saltatory conduction = action potenital jumps from one node of Ranvier to next in myelinated neuron
• Voltage gated Na/K ion channels at node
• Node is only contact with interstitial fluid.
• Farther apart the nodes, faster transmission
• 50x's faster than unmyelinated. Fewer ions displaced.
• Don't need as much ATP to put Na+ and K+ ions back in place to restore resting potential

All or none law: either transmits impulse or doesn't

• Weak stimulus below threshold gives local response, but no action potential along cell
• Stimulus above threshold gives transmission
• Doesn't matter how high above threshold stimulus is, depolarization is the same
• Intensity of sensations depends on number of neurons stimulated and on frequency of discharge.
• Stronger stimulus = greater number of action potentials each neuron transmits per unit time.

Any substance that increases neuron membrane permeability to sodium makes neuron more excitable than normal. Substance that decreases sodium permeability makes neuron less excitable.

• Too much Ca2+, neuron less permeable to Na+.
• Ca2+ binds to proteins of sodium ion channel
• Not enough Ca2+, neuron fires easily, maybe spontaneously
• Na gates don't close completely without some Ca2+
• Na+ leaks into cell, less negative resting potential
• Tetany or spasm in muscle innervated by motor neuron that fires spontaneously
• Narcotics and anesthetics block nerve impulse conduction.
• Cocaine, lidocaine, procaine affect voltage gated Na channels, decrease Na permeability
• DDT cholorinated hydrocarbon pesticide affects Na/K pumps, can't transmit impulse esp bugs
• TTX tetrodotoxin from pufferfish blocks Na movement thru gated channels. Stop breathing.

Neuromuscular junction or motor end plate = junction between nerve and muscle. Nerves also join other nerves

• Presynaptic neuron ends at synapse

• Postsynaptic neuron starts at synapse.

• Electrical synapse = neurons very close together
• Gap junction with protein channel between cells
• Ions pass from one cell to the other, impulse moves quickly
• Escape tail flick of crayfish, lobster.
• Chemical synapse = space between neurons called synaptic cleft
• Action potential hits end of presynaptic neuron
• Presynaptic neuron releases neurotransmitter chemical
• NT binds to chemically activated ion channels in postsynaptic neuron membrane
• At threshold, action potential generated along postsynaptic neuron cell.
• Delay at each synaptic cleft for NT to release, diffuse and bind

Neurotransmitters

• Acetylcholine released from nerve to muscle, triggers muscle contraction
• Also between some neurons in brain, autonomic nervous system
• Cholinergic neurons
• Norepinephrine from adrenergic neurons
• Biogenic amines aka catecholamines= norepi, serotonin, dopamine
• Affect mood, imbalance in depression schizophrenia, ADD
• Antidepressants like selective serotonin reuptake inhibitors (ProzacTM)
• GABA = gamma-aminobutyric acid
• Inhibits nerves in brain, spinal cord
• Linked to epilepsy
• Benzodiazapines like valium, barbiturates enhance GABA, treat anxiety
• Opiate enkephalin, beta-endorphin block pain, bind to opiate receptors. Modulate other NT
• Synaptic vessicles membrane bound sacs that store NT in synaptic terminal
• Nt made within synaptic terminal
• Mitochondrial ATP for energy.
• Enzymes imported from cell body
• Action potential opens voltage-gated Ca2+ ions in terminal membrane
• Ca2+ moves into synaptic terminal, cause vesicles to fuse with plasma membrane
• NT released into synaptic cleft by exocytosis.

• NT binds with receptors on postsynaptic cell membrane: dendrite/cell body/muscle
• Can open ligand-gated ion channels. Ach opens Na and K channels
• Can work indirectly thru second messenger.
• Binding activates G protein
• G protein activates enzyme, like adenyl cyclase
• Converts ATP to cyclic AMP cAMP, which is second messenger
• CAMP activates protein kinase.
• Proteins get phosphate group added (phosphorylation)
• Excess Nt destroyed by enzymes or reuptake into neuron.

Same neurotransmitter can have different effects depending on postsynaptic neuron

• Ach excites skeletal muscle by opening Na channels, inhibits cardiac muscle drop heartbeat
• Depolarized membrane = less negative. Hyperpolarized membrane = more negative
• Excitatory postsynaptic potential EPSP brings neuron closer to firing
• Open Na channels makes cell less negative
• Weaker stimulus can cause slight change to make neuron fire
• If K+ channels close, K+ inside makes cell less negative.
• Inhibitory postsynaptic potential IPSP makes neuron farther from firing
• Hyperpolarized
• GABA can open K+ channels, K+ leaves cell, cell more negative.
• GABA can open Cl- channels, Cl-into cell, cell more negative.
• Modulator neurotransmitters can have long-term affects on neurons (years). Affect genes or activate enzymes to change receptor number.

Graded potentials vary in magnitude depending on strength of stimulus applied.

• IPSP and EPSP is local response in neuron membrane, fades out over distance
• Summation is adding EPSP together
• One EPSP is below threshold usually, but still affects membrane potential
• Temporal summation: repeated stimuli cause new EPSP before previous EPSP decay. Can fire
• Spatial summation: several synpatic terminals release NT simultaneously, so neuron stimulated in several places at once.

Integration = summing incoming signals

• 1 neuron can synapse with 100's of others
• Dendrites and cell body integrate all these messages
• IPSP and EPSP may cancel each other out. Not all-or-none, but local response.
• Add up positive EPSP and negative IPSP before the neuron is brought to all or none threshold
• Vertebrates 90% neurons in CNS, so integration there

CNS neurons organized nto neural networks

• Within network, neurons arranged in pathways called neural circuits.
• Convergence = single neuron controlled by converging signals from 2+ presynaptic neurons
• Interneuron in spinal cord
• Integrates info before action potential sent to stimulate motor neuron
• Divergence = single presynaptic neuron stimulates many postsynaptic neurons.
• From motor area of brain to hundreds of interneurons in spinal cord, each with hundreds of muscle fibers.

Reverberating circuit = neural pathway arranged so that an axon collateral synapses with an interneuron

• Interneuron synapses with neuron that can send new impulses thru circuit.
• Positive feedback: new impulses generated again and again until fatigue (deplete NT) or til stopped by inhibition.
• Rhythmic breathing, mental alertness, short-term memory.