Nervous System

• Brain, spinal cord, efferent and afferent neurons

• Pattern of information flow:

Receptor Afferent path Integration Efferent Path Effect

Central Nervous System (CNS)

• Main cell types are neurons and glial cells

Typical Arrangement of Neural Connections

• Neurons communicate via electrical signaling

• They are excitable

• Structurally the soma (cell body) has an extensive ER and prominent nucleoli

• Long appendages or processes:

• Dendrites (receive info)

• Axons (deliver info); some are covered by myelin

A collection of axons is called a NERVE

Types of glial cells:

CNS = oligodendrocytes, astrocytes, microglia, ependymal cells

PNS = Schwann cells, satellite cells

Myelin acts as an insulator and inhibits ion movement in the axonal membrane that it surrounds.

Neurons as Excitable Tissue

• Excited by altering the resting membrane potential (-90 mV)

• Depolarize

• Hyperpolarize

• Most changes in membrane potential occur through the opening or closing of certain ion channels (they are voltage-gated or gated via second messenger system activation).

Ion Intracellular (mM)

Extracellular

(mM)

Na+ 2 140

Cl- 10 105

Ca2+ 10-8 2.5

K+ 150 5

Proteins (-) 65 2

• Gates can be chemically opened by neurotransmitters

• Gates can be opened via signal transduction mechanisms linked to neurotransmitter binding to receptor

• Gates can be opened by stretch, pressure, etc.

Stimulus = anything that can cause the opening or closing of gated channels in a neuronal membrane

What happens to the resting membrane potential of the membrane adjacent to the site of Na+ entry?

How about here?

What determines whether an action potential will occur or not?

The axon hillock (trigger zone) is sensitive to changes in ion concentration and is the site at which an action potential is initiated.

An action potential is a self-propagating depolarization of the axonal membrane that initiates at the hillock and runs to the axon terminus without diminishing in strength.

All action potentials are the same “size”.

If the graded potential doesn’t change the resting membrane potential enough, the signal from the stimulus will die out and the neuron will not respond with an action potential.

The amount of change in membrane potential necessary to generate an action potential is called a threshold stimulus.

Action Potential = depolarization along the axon

1

2

3

If the trigger area of the axon reaches threshold, the influx of Na+ and the generation of the action potential will be repeated over and over again in one direction, at each segment of membrane, down the axon.

What will happen at this area of membrane?

What will happen at this area of membrane?

One portion of the membrane has just been depolarized and is relatively insensitive to changes in cation concentration. It is said to be refractory to stimulus. Downstream membrane is at resting potential, and can be influenced by cation influx.

Saltatory conduction in myelinated neurons

Action potentials cause the release of neurotransmitter from the presynaptic axon terminus

What will happen to the resting membrane potential if the activation gate is opened?

How could a cell open this activation gate?

Strength of stimulus determines neuronal response

mV

mV

time

time

time

EPSP

IPSP

Neurotransmitter activity is stopped by: diffusion away from the synapse, transport into cells (glial or back into presynaptic neuron), or degradation by specific enzymes.

What is the response in the post-synaptic neuron?

What will determine whether this postsynaptic neuron will respond?

Red neuron is releasing serotonin which causes an IPSP. The neuron is firing at 70 APs/sec

Neuron A is releasing dopamine, causing and EPSP. The neuron is firing at 40 APs/sec

Neuron B is releasing acetylcholine to create an EPSP. It is firing at 20 APs/sec.

What will the outcome be in the postsynaptic cell?

A B

Transmitter Molecule Derived From Site of Synthesis

Acetylcholine Choline CNS, parasympathetic nerves

Serotonin 5-Hydroxytryptamine (5-HT)

Tryptophan CNS, chromaffin cells of the gut, enteric cells

GABA Glutamate CNS

Glutamate CNS

Aspartate CNS

Glycine spinal cord

Histamine Histidine hypothalamus

Epinephrine Tyrosine adrenal medulla, some CNS cells

Norpinephrine Tyrosine CNS, sympathetic nerves

Dopamine Tyrosine CNS

Adenosine ATP CNS, periperal nerves

Neurotrans. Types of receptors

Mode of action Result in postsynaptic cell

Target

Acetylcholine Nicotinic

Muscarinic

Opens ion channels EPSP CNS neurons; skeletal muscle

Serotonin Two main classes; multiple subclasses

G-protein coupled receptors; both AC and IP3/DAG

Depends on receptor type

Platelet aggregation, smooth muscle contraction, satiety, vomiting

GABA GABA-A

GABA-B

Receptor Cl- channel

G-linked K+ channel IPSP in all cases

Throughout CNS and in retina

Norepinephrine Receptor

receptor

G-protein linked to cAMP

G-protein linked to cAMP

IPSP

EPSP

Relaxes smooth muscles of gut, bronchial tree, and vessels to skel. muscle

Increases rate and strength of cardiac contraction; excites smooth muscle in vessels

Dopamine D1, D2, D3, D4, and D5

G-protein linked to cAMP, direct channel opening, cAMP to K+ channel opening

EPSP and IPSP D1-3 are located in the striatum of the CNS, and the basal ganglia

D3-5 play a role in mood, psychosis and neuroprotection