Neurons, Synapses, and Signaling

Sensory input Sensor Integration

Motor output

Effector

Peripheral nervous system (PNS)

Central nervous system (CNS)

Overview: Lines of Communication

Neurons are nerve cells that transfer information within the body
Neurons use two types of signals to communicate: electrical signals (long-distance) and chemical signals (short-distance)

Processing of information takes place in simple clusters of neurons called ganglia or a more complex organization of neurons called a brain

Ganglia

Nerves with giant axons

Brain Arm

Eye

Mantle

Nerve

Neuron organization

 The synaptic terminal of one axon passes information across the synapse by release of neurotransmitters

Information is transmitted from a presynaptic cell (a neuron) to a postsynaptic cell (a neuron, muscle, or gland cell)

Neuron Shape and Size

Pyramidal cells

Glial cells

Ion pumps and ion channels establish the resting potential of a neuron
Membrane Potential: voltage (difference in electrical charge) across the cells plasma membrane Resting Potential: membrane potential of a neuron not sending signals

Key

Na K Sodiumpotassium pump

Potassium channel
Sodium channel

OUTSIDE OF CELL

INSIDE OF CELL

Tetrodotoxin: a sodium channel blocker

Key

Na+ K+

Sodiumpotassium pump

Potassium channel

Sodium channel

OUTSIDE CELL

INSIDE CELL
(b)

OUTSIDE [K+] CELL 5 mM

[Na+] [Cl] 150 mM 120 mM [A] 100 mM

INSIDE [K+] CELL 140 mM

[Na+] 15 mM

[Cl] 10 mM

(a)

Depolarization in an action potential

Adding a poison that specifically disables the Na+/K+ pumps to a culture of neurons will cause
A. the resting membrane potential to drop to 0 mV. B. the inside of the neuron to become more negative relative to the outside. C. the inside of the neuron to become positively charged relative to the outside. D. sodium to diffuse out of the cell and potassium to diffuse into the cell.

For a nerve cell at its resting potential, the forces acting on potassium ions (K+) are
A. none: K+ ions do not move at the resting potential.

B. an electrical gradient, pulling K+ inward, and a chemical gradient, pushing K+ inward.

C. an electrical gradient, pushing K+ outward, and a chemical gradient, pulling K+ inward. D. an electrical gradient, pulling K+ inward, and a chemical gradient, pushing K+ outward. E. an electrical gradient, pushing K+ outward, and a chemical gradient, pushing K+ outward.

Nernst Equation

R (universal gas constant) = 8.314 J . K-1 . mol-1 (Joules per Kelvin per mole). T = temperature in Kelvin (K = C + 273.15). z = valence of the ionic species e.g z is +1 for Na+, +1 for K+, -1 for Cl-, etc. F (Faraday's constant) = 96485 C . mol-1 (Coulombs per mole).

Inner chamber 140 mM KCl

90 mV

Outer chamber

Inner chamber 15 mM NaCl Cl

62 mV

Outer chamber 150 mM NaCl

5 mM KCl

K
Potassium channel

Cl

Na
Sodium channel

Artificial membrane

(a) Membrane selectively permeable to K

(b) Membrane selectively permeable to Na ENa 62 mV 62 mV

EK 62 mV

90 mV

A(n) ___ in Na+ permeability and/or a(n) ___ in K+ permeability across a neurons plasma membrane could shift membrane potential from 70 mV to 80 mV. A. increase; increase
B. increase; decrease C. decrease; increase D. decrease; decrease

Determining resting potential and the changes during anaction potential

Action potentials - signals conducted by axons

gated ion channels: open/close by stimuli
Stimuli +50 +50 Stimuli +50 Action potential Membrane potential (mV) Membrane potential (mV) Membrane potential (mV) Strong depolarizing stimulus

50

Threshold

50

Threshold

50

Threshold

Resting potential Hyperpolarizations 100 0 1 2 3 4 5 Time (msec) 100

Resting potential Depolarizations 100 0 1 2 3 4 Time (msec) 5

Resting potential

2 3 4 5 Time (msec)

(a) Graded hyperpolarizations

(b) Graded depolarizations

(c) Action potential

gated K+ channels: K+ diffuses outinside more negative gated Na+ channels: Na+ diffuses ininside less negative

At time ZERO msec on the graph, it is likely that there was

A. a localized opening of K+ channels. B. a localized opening of some Na+ channels. C. a rapid opening of most K+ channels. D. a rapid opening of most Na+ channels.

Action Potential
Membrane potential (mV)

Strong depolarizing stimulus +50 Action potential

50 Threshold

Resting potential 100 0 1 2 3 4 5 Time (msec) 6

(c) Action potential

Key

Na+ K+

+50 Membrane potential (mV) Action potential 0

2 3

50

Threshold
1 5 1

Resting potential 100 Extracellular fluid Sodium channel Time

Potassium channel

Plasma membrane Cytosol Inactivation loop

1

Resting state

Key

Na+ K+

+50 Membrane potential (mV) Action potential 0

2 3

50

Threshold
1 5 1

Depolarization Extracellular fluid Sodium channel

Resting potential 100 Time

Potassium channel

Plasma membrane Cytosol Inactivation loop

1

Resting state

Key

Na+ K+

Rising phase of the action potential +50 Membrane potential (mV) Action potential 0
2 3

50

Threshold
1 5 1

Depolarization Extracellular fluid Sodium channel

Resting potential 100 Time

Potassium channel

Plasma membrane Cytosol Inactivation loop

1

Resting state

Key

Na+ K+

Rising phase of the action potential +50 Membrane potential (mV) Action potential 0
2 3

Falling phase of the action potential

50

Threshold
1 5 1

Depolarization Extracellular fluid Sodium channel

Resting potential 100 Time

Potassium channel

Plasma membrane Cytosol Inactivation loop

1

Resting state

Key

Na+ K+

Rising phase of the action potential +50 Membrane potential (mV) Action potential 0
2 3

Falling phase of the action potential

50

Threshold
1 5 1

Depolarization Extracellular fluid Sodium channel

Resting potential 100 Time

Potassium channel

Plasma membrane Cytosol Inactivation loop

5 1

Undershoot

Resting state

Axon

Action potential

Plasma membrane

Na+

Cytosol

K+

Action potential

Na+

K+

K+

Action potential

Na+

K+

Action potentials are normally carried in one direction from the axon hillock to the axon terminals. By using an electronic probe, you experimentally depolarize the middle of the axon to threshold. What do you expect?
A. B. No action potential will be initiated. An action potential will be initiated & proceed in the normal direction toward the axon terminal. An action potential will be initiated & proceed back toward the axon hillock. Two action potentials will be initiated, one going toward the axon terminal & one going back toward the hillock. An action potential will be initiated, but it will die out before it reaches the axon terminal.

C. D.

E.

Conduction of Action Potentials

action potentials travel long distances by regenerating themselves along axon
Dendrites Stimulus Nucleus Cell body Axon hillock

Axon

Synaptic terminals

Node of Ranvier
Layers of myelin Axon Schwann cell Nodes of Ranvier

Axon

Myelin sheath

Schwann cell Nucleus of Schwann cell

Action potentials are formed only at nodes of Ranvier, gaps in the myelin sheath where voltage-gated Na+ channels are found Action potentials in myelinated axons jump between the nodes of Ranvier in a process called saltatory conduction
0.1 m

Saltatory action potential conduction along a myelinated axon. (A) Diagram of a myelinated axon. (B) Local current in response to action potential initiation at a particular site flows locally. However, the presence of myelin prevents the local current from leaking across the internodal membrane; it therefore flows farther along the axon than it would in the absence of myelin. Moreover, voltage-gated Na+ channels are present only at the nodes of Ranvier. This arrangement means that the generation of active, voltage-gated currents need only occur at these unmyelinated regions. The result is a greatly enhanced velocity of action potential conduction.

Comparison of speed of action potential conduction in unmyelinated (upper) and myelinated (lower) axons.

Length of axon where polarization occurs in unmyelinated and myelinated axons.

Giuliodori M J , DiCarlo S E Advan in Physiol Edu 2004;28:80-81

2004 by American Physiological Society

Miami Project Doctors Perform First-Ever Schwann Cell Transplant

January 24, 2013 @ 4:50 pm In News

Doctors at The Miami Project to Cure Paralysis, a Center of Excellence at the University of Miami Miller School of Medicine, performed the first-ever Food and Drug Administration-approved Schwann cell transplantation in a patient with a new spinal cord injury. The procedure, performed at the University of Miami/Jackson Memorial Medical Center, is a Phase 1 clinical trial designed to evaluate the safety and feasibility of transplanting the patients own Schwann cells.

An up-close look at human Schwann cells

Of the following choices, the slowest conduction velocity for moving action potentials is likely seen in
A. a large-diameter, nonmyelinated axon.
B. a small-diameter, nonmyelinated axon. C. A myelinated axon. D. any of the above, as all neurons conduct action potentials at the same speed.

Postsynaptic neuron

Synaptic terminals of presynaptic neurons

5 m

Synaptic vesicles containing neurotransmitter

K+

Na+

Presynaptic membrane

Voltage-gated Ca2+ channel

1 Ca2+ 2 4 3

Postsynaptic membrane
6

Synaptic cleft

Ligand-gated ion channels

After release, the neurotransmitter May diffuse out of the synaptic cleft May be taken up by surrounding cells May be degraded by enzymes

Injecting ethylene glycol tetraacetic acid (EGTA), a chelating agent that prevents calcium ions from moving across membranes, to a synaptic region would likely
A. increase the release of neurotransmitters by the presynaptic neuron. B. decrease the release of neurotransmitters by the presynaptic neuron. C. result in neurotransmitters being released, but could not bind to its receptors on the post synaptic neuron.

D. result in the lack of calcium ions keeping the ligand-gated ion channels open on the post synaptic neurons.

Generation of Postsynaptic Potentials

Direct synaptic transmission involves binding of neurotransmitters to ligand-gated ion channels in the postsynaptic cell Neurotransmitter binding causes ion channels to open, generating a postsynaptic potential
Excitatory postsynaptic potentials (EPSPs) are depolarizations that bring the membrane potential toward threshold Inhibitory postsynaptic potentials (IPSPs) are hyperpolarizations that move the membrane potential farther from threshold

Postsynaptic Potentials
Unlike action potentials, postsynaptic potentials are graded & do not regenerate
single EPSP is usually too small to trigger an action potential in a postsynaptic neuron if two EPSPs are produced in rapid succession: temporal summation

E1 E2
Postsynaptic neuron Membrane potential (mV)

Terminal branch of presynaptic neuron

E1

E2
Axon hillock

0 Threshold of axon of postsynaptic neuron Resting potential 70 Action potential

E1

E1

E1

E1

(a) Subthreshold, no summation

(b) Temporal summation

E1 E2 E2

E1

I
Membrane potential (mV)

0
Action potential

70

E1 + E2
(c) Spatial summation

E1

E1 + I

(d) Spatial summation of EPSP & IPSP

Integrating information

Neurotransmitters
There are more than 100 neurotransmitters, belonging to five groups: acetylcholine, biogenic amines, amino acids, neuropeptides, and gases A single neurotransmitter may have more than a dozen different receptors

Adderall (Dextroamphetamine)
D-amphetamine acts primarily on the dopaminergic (DA) systems. The primary reinforcing and behavioral-stimulant effects of amphetamine,are linked to enhanced dopaminergic activity, primarily in the mesolimbic dopaminergic pathway (reward pathway). Amphetamine binds to the dopamine transporter (DAT) and blocks the transporter's ability to clear DA from the synaptic space. In addition, amphetamine is transported into the cell, which leads to dopamine efflux (DA is transported out of the cell and into the synaptic space via reverse transport of the DAT).

The use of organophosphate pesticides that inhibit acetylcholinesterase, an enzyme that breaks down acetylcholine, could cause skeletal muscle cells to
A. undergo more graded depolarizations, because acetylcholine would remain in the synaptic cleft longer. B. undergo more graded hyperpolarizations, because acetylcholine would remain in the synaptic cleft longer. C. undergo more graded depolarizations, because acetylcholine would prevent ligand-gated ion channels from opening. D. undergo more graded hyperpolarizations, because excess acetylcholine opens Cl channels.

Adderall, an amphetamine stimulant, works on the CNS by

A. increasing the release of GABA and decreasing its catabolism/reuptake. B. increasing the release of serotonin and decreasing its catabolism/reuptake. C. increasing the release of endorphins and decreasing their catabolism/reuptake. D. increasing the release of dopamine and norepinephrine and decreasing their catabolism/reuptake.

Questions
What two functions do proteins in the neural membrane perform to establish and maintain the resting membrane potential? On which side of the membrane are sodium ions more abundant? When the membrane is at the potassium equilibrium potential, in which direction (in or out) is there a net movement of potassium ions? There is much greater concentration of potassium ions inside than outside the membrane. Why, then is the resting potential negative? When the brain is deprived of oxygen, the mitochondria within neurons cease producing ATP. What effect would this have on the membrane potential? Why?