Neurons

Neurons

• basic signaling units

• 3 main classes: sensory, motor, interneurons

• human brain: 86 billion interneurons, averaging 1000 synapses on each

• cells in the nervous system that carry information from one place to another by means of a combination of electrical and chemical signals

Glial cells

• give structure and support

• provide electrical insulation to neurons

• modulate neural activity

• outnumber neurons by at least 10 to 1

• critical to the functioning of the nervous system and maintaining the blood-brain barrier

• (glial = glue)

  • Glial cells DO NOT carry nerve impulses (action potentials)

Structure of the Neuron

• cell body (like other cells)

  • also called the Soma

• Dendrites (dendritic tree)

• Axon

• Cytoplasm

  • Ions: e.g., NA+, K+, CA2+, CL- and

  • Molecules such as protein

Resting Potential: electrochemical gradient

Electrical Gradient:

• Inside of the neuron is negative relative to the outside (-70mV)

Concentration Gradient

• more NA+ outside

• more K+ inside

Ion channels and Ion pumps

• The NA+ and K+ gradients are maintained by the sodium-potassium pump

• the ions diffuse back across the plasma membrane through ion channels

• since there are more K+ channels than Na+ channels, there is a net outflow of positive ions

• The net electrical gradient yields a resting potential of -70mV

Sodium-Potassium Pump

Ion channels pump ions across the membrane

The resting potential of a neuron is

-70mV

There are two opposing forces acting upon potassium ions. Select the correct answer:

A. The electrical force keeps potassium inside the cell, the chemical force drives potassium out of the cell

B. The chemical force keeps potassium inside the cell, the electrical force drives potassium out of the cell

A. The electrical force keeps potassium inside the cell, the chemical force drives potassium out of the cell

True or False: The sodium potassium exchange pump moves 3 potassium ions out of the cell and 2 sodium ions into the cell with each cycle.

False

What does the potassium sodium pump accomplish? Select all that apply:

A. It moves ions from areas of low to areas of high concentration

B. It re-establishes and maintains the resting potential

C. It moves sodium into the cell and potassium out of the cell

D. It lets ions passively flow through the plasma membrane

A. It moves ions from areas of low to areas of high concentration

B. It re-establishes and maintains the resting potential

Action Potential (Nerve Impulse)

if threshold of -55mV is reached, action potential is triggered (all-or-none) — voltage-gated sodium channels open

Absolute vs relative refractory periods

absolute refractory period, Na+ channels temporarily inactive

relative refractory period due to continued outflow of K+ ions

Consequences of Refractory Period

• Neuron can only generate ~200 action potentials per second (upper limit on firing rate)

• passive current that flows from action potential cannot re-open the voltage-gated channels that generated it

• propagation of action potential in one direction

Action Potential Phases

The action potential starts at

the axon hillock

The absolute refractory period is caused by

the temporary inactivation of voltage-gated sodium channels

The voltage across the membrane has to reach a threshold of ___ to initiate an action potential

-55mV

During the course of an action potential, voltage-gated potassium channels start to close …

some time after the membrane potential goes back to its resting state of -70mV

Chemical Synapses

Neurotransmitter release at the synapse, into synaptic cleft

1. Action potential depolarizes the terminal membrane, which causes Ca2+ to flow into the cell

2. Ca2+ causes vesicles to bind with cell membrane

3. Release of neurotransmitter by exocytosis into the synaptic cleft

4. Transmitter binds with receptor

Ionotropic Receptors

undergo a change in shape when neurotransmitter binds, causing the channel to open. This may have either an excitatory or an inhibitory effect, depending on the ions that can pass through the channel and their concentrations inside and outside the cell.

Metabotropic Receptors

Signaling through these metabotropic receptors depends on the activation of several molecules inside the cell and often involves a second messenger pathway. Because it involves more steps, signaling through metabotropic receptors is much slower than signaling through ligand-activated ion channels

Neurotransmitters

• the chemicals that neurons release that allow them to communicate with one another

• neurotransmitters have excitatory or inhibitory effects

  • agonists and antagonists

adrenaline

fight or flight neurotransmitter

• Produced in stressful or exciting situations. Increases heart rate & blood flow, leading to a physical boost & heightened awareness.

noradrenaline

concentration neurotransmitter

• Affects attention & responding actions in the brain, & involved in fight or flight response. Contracts blood vessels, increasing blood flow.

• plays a role in sleep - the only difference between waking and dreaming is noradrenaline

• memory processing —> especially memory that has an emotional component, potentially by helping to increase the salience and hence the memorability of such information

dopamine

pleasure neurotransmitter

• Feelings of pleasure, and also addiction, movement, and motivation. People repeat behaviors that lead to dopamine release.

serotonin

mood neurotransmitter

• Contributes to well-being & happiness; helps sleep cycle & digestive system regulation. Affected by exercise & light exposure.

• memory - the function of creating new memories for long-term memory

GABA

calming neurotransmitter

• Calms firing nerves in CNS. High levels improve focus; low levels cause anxiety. Also contributes to motor control & vision.

• inhibitory

• many substances that reduce the activity of the CNS bind to GABA receptors (ex. barbiturates and alcohol)

acetylcholine

learning neurotransmitter

• Involved in thought, learning, & memory. Activates muscle action in the body. Also associated with attention and awakening.

• depletion associated with Alzheimer’s disease

• linked to selective attention (the ability to attend to certain information while tuning out other information) —> acetylcholine sharpens responses of cells to the features of stimuli that are most likely to make them fire, while suppressing responses to less prominent features of a stimulus

glutamate

memory neurotransmitter

• Most common brain neurotransmitter. Involved in learning & memory, regulates development & creation of nerve contacts.

• excitatory

• overactivity —> development of epilepsy (a disease in which an abnormal lowering of a cell’s firing threshold causes it to misfire)

• too much produces excitotoxicity

endorphins

euphoria neurotransmitter

• Released during exercise, excitement, & sex, producing well-being & euphoria, reducing pain. Biologically active section shown.

Postsynaptic Potentials

• IPSP (inhibitory postsynaptic potential)

• EPSP (excitatory postsynaptic potential)

Postsynaptic potentials vs. Action potentials

Action Potentials

• all or nothing

• higher in magnitude

• excitatory

Postsynaptic Potentials

• graded

• smaller in magnitude (0.5 - 5 mV)

• excitatory and inhibitory

Information transmission

• Within a neuron, the transmission of information usually electrical (action potentials, voltage-gated ion channels).

• Between neurons, chemical (neurotransmitters, ligand-gated ion channels).

• Exception: electrical synapses

Electrical Synapse

How do Neurons Code Information?

• Action Potentials = All-or-none

• Firing strength does not change

  • The amplitude of an action potential does not vary

• Firing rate can change

Types of Glial Cells in the CNS

• Astrocytes

• Microglia

• Oligodendrocytes

• Radial

Astrocyte (Astroglia)

1. Skeleton of the brain

2. Homeostasis

3. Blood-brain barrier (BBB)

4. Synapse cleanup

influence the communication between neurons by modifying the chemical milieu between them, as well as refining and sculpting the physical connections between neighboring neurons

Microglia

• immune defense

• recognize foreign substances, engulf and try to destroy them

  • protects against infection

aid with reorganization after brain damage by removing dead neurons and they serve some of the nutritive needs of neurons and provide structural support

Oligodendrocytes

• provide the insulation (myelin) to neurons in the central nervous system

• multiple sclerosis: abnormal immune response that causes destruction of myelin

What are the two main classes of cells the human nervous system is composed of?

neurons and glia

Dendritic Tree

the part of the neuron that receives input from other cells

Cell body

the part of the cell containing the nucleus and other cellular apparatus responsible for manufacturing the proteins and enzymes that sustain cell functioning

Axon

the appendage of the cell along which information is carried

• varies in length

Sensory Neurons

bring information to the CNS

Interneurons

associate information within the CNS

Motor Neurons

send information from the brain and spinal cord to the muscles

Radial Glia

Guide neurons as they migrate from the site of creation to their final position within the brain

Blood-Brain Barrier

the mechanism by which many harmful substances, such as toxins, are prevented from reaching the brain

• consists of tightly packed glial cells between blood vessels and neurons

• also blocks certain nutrients, drugs, and immune system cells in the bloodstream from reaching the nervous system directly

Nuclei

distinct groups of neurons whose cell bodies are all situated in the same region in a brain structure called the thalamus

Two broad principles to electrochemical signaling of neurons

information is relayed within a neuron by means of an electrical signal, whereas one neuron influences another via a chemical signal

Resting Potential

at rest, there is a difference in the electrical charge between the inside and outside of a neuron (known as neuron’s resting potential)

• typically about -70mV

• occurs because the cell membrane of the neuron acts as a barrier separating ions on the inside from those on the outside

Ions

electrically charged particles

• ions like sodium and potassium can traverse the cell membrane only through special passageways known as ion channels

Ion channels

in some configurations they allow ions to flow in and out of the cell, and in other configurations the passageway is blocked and ions cannot move from one side of the cell membrane to the other

• input from other neurons can affect the opening and closing of ion channels

Action potential

• when ion channels open and allow ions to flow in and out of the cell the resulting change in ion concentration on each side of the membrane drives the neuron’s electrical charge away from its resting potential, making it either more negative or more positive

• if the cell receives enough stimulation to reduce the voltage across the membrane to -55mV, a threshold is passed and the cell “fires” —> electrical charge rapidly goes to a peak of +40 mV

• after reaching the peak (depolarization), the electrical charge then retreats toward the baseline resting potential (repolarization) —> hyperpolarization (voltage briefly becomes more negative than resting potential

• then neuron returns to resting potential

Important Properties of Action Potential

1. self-propagating: once it is set in motion nothing else need be done (like knocking over the first domino)

2. strength does not dissipate with the distance it travels (peak remains +40mV for its entire trip down the axon)

3. all-or-nothing (either the cell fires or it doesn’t)

Axon hillock

a specific part of the neuron near the cell body where the action potential is first produced

How does action potential travel through the neuron

• first produced at axon hillock

• then it is carried along the entire length of the axon to the terminal button

• at the terminal bouton action potential ends and the electrical signal gets transformed into a chemical message

Synaptic Vesicles

little balloons in the terminal bouton which are filled with neurotransmitter

• some reside in the terminal bouton and others are fused to the outside wall of the neuron

• action potential causes synaptic vesicles that are fused to the outside walls of the neuron to burst open, pouring their contents into the area between neurons (synaptic cleft)

Synapse

the region of contact between the neuron

contains the terminal button, the synaptic cleft, and the postsynaptic region

How information is transferred between neurons

• at the synapse, neurotransmitter molecules are released from the presynaptic neuron and received by the postsynaptic neuron

• when a neurotransmitter reaches the postsynaptic membrane, it fits into a specific region of the receptor (called the binding site), much the way a key fits into a lock

• the binding of the neurotransmitter changes the configuration of the receptor, which in turn changes the electrical charge of the postsynaptic neuron in a small local area near the receptor site by altering the flow of ions across the membrane

• chemical signal is transformed back into an electrical one

Receptors

the membrane of the dendritic trees of the postsynaptic neuron contains regions known as receptors

• these receptors are specially configured proteins that are embedded within the postsynaptic membrane

Excitatory postsynaptic potentials (EPSPs)

make the cell’s electrical charge a bit more positive, bringing it closer to the threshold value of -55mV at which the cell will fire

Inhibitory Postsynaptic Potentials (IPSPs)

make the inside of the cell a bit more negative than the outside and move the cell further away from the threshold at which it will fire

Postsynaptic Potentials

• the local changes in the electrical potential that occur near the receptor

• either excitatory or inhibitory

  • whether a particular neurotransmitter has an excitatory or inhibitory effect depends on the receptor to which it binds

• combined effect is needed to make neuron fire (two EPSPs/IPSPs have a greater influence if they occur together in time or space)

Postsynaptic Potentials differ from action potentials in three important ways

1. they are graded: the further they travel from their source, the more they dissipate

2. postsynaptic potentials are much smaller in magnitude than an action potential, usually in the range of 0.5-5 mV

3. whereas action potentials are always excitatory, in that they make the cell fire, postsynaptic potentials can be either excitatory or inhibitory

How do neurons code the intensity of a stimulus

via the rate, or pace, of its firing

• (not by the size of of the electrical response - because the value of the action potential is always the same)

• when there is a strong stimulus, the cell fires many times in succession; when there is a weak input, it fires only occasionally

How postsynaptic potentials can cause an action potential

• postsynaptic potentials summate at the axon hillock (where axon meets the body)

• if the differential charge across the membrane at the axon hillock reaches -55mV, the cell will fire (otherwise it won’t)

• postsynaptic potentials generated close to the axon hillock have a larger influence (because they are graded)

Phases of the action potential

1. when the threshold of activation is reached, sodium (NA+) begins to enter the cell

2. Potassium (K+) begins to leave the cell

3. no more sodium enters the cell, and the voltage reaches its peak positive value

4. the leakage of potassium drives the voltage in the negative direction, hyperpolarizing the cell; potassium channels then close and the cell returns to its resting potential, at which point it can fire again

Two major classes of neurotransmitters

1. amino acids

2. the other main class consists of neurotransmitters that are organized into systems; these are produced by specific sets of neurons whose cell bodies are located subcortically and whose axons project diffusely throughout the cortex

Amino Acids

the smallest and most basic building blocks of proteins

• act as the main excitatory and inhibitory neurotransmitters in the brain

two main amino acids

glutamate and gamma-aminobutyric acid (GABA)

excitotoxicity

excessive activity of receptors that can literally excite neurons to death (the neurons get “fried” by too much stimulation)

Barbiturates

reduce seizure activity and induce sedation and sleep

Alcohol and GABA

alcohol produces its anxiolytic (anxiety-reducing) and sedative effects by affecting GABA receptors

Neurotransmitter systems

1. cholinergic - acetylcholine

2. serotonergic - serotonin

3. noradrenergic - noradrenaline

4. dopaminergic - dopamine

Serotonin-Selective Reuptake Inhibitors (SSRIs)

most popular drug to treat depression

• increase the amount of serotonin in the synaptic cleft by inhibiting its presynaptic uptake

• ex. Prozac

• side effects: interfering with sleep, reducing appetite, and impairing sexual performance

Myelin

• the speed at which neurons propagate electrical signals down their axons depends on the degree to which the axon is insulated by a fatty sheath called myelin

  • the longer the myelin sheath is, the greater the speed with which the electrical signal is propagated down the axon

  • some have no myelin sheath —> small and generally synapse on nearby neurons

Oligodendrocytes

produces myelin sheath

• a portion of oligodendrocyte wraps itself around the axon; such wrapping creates a discrete section of myelin

  • the more turns there are around the neuron, the greater the insulation and therefore the greater the conduction speed

Nodes of Ranvier

• gaps between myelinated sections of an axon

• because the electrical signal must jump across these nodes, which have a high concentration of ion channels, they serve to keep the electrical signal constant in size rather than degrading as it travels down the axon

white matter

areas through which myelinated fibers run

• because myelin is fatty, it is white

gray matter

• concentrations of unmyelinated cell bodies

Fiber tract

when a group of cells sends their axons to the same place, the group of axons is known as a fiber tract

• because these axons usually traverse long distances, they tend to be myelinated

• ex. corpus callosum

Corpus callosum

• the main fiber tract connecting the two halves (hemispheres) of the brain

• composed mainly of myelinated fibers

  • allows a speedy transfer of information from a neuron in one hemisphere to a distant neuron in the other hemisphere

Multiple Sclerosis

causes the myelin surrounding a neuron to be thinned in a patchy or haphazard manner with deleterious effects on motor function, cognitive function, and quality of life

Important elements of neural transmission

1. action potential reaches terminal

2. calcium ion channels open, allowing Ca+ ions in

3. Ca2+ causes synaptic vesicles to release from microtubules

4. Synaptic vesicles fuse with axon membrane at release sites

5. vesicles open, releasing neurotransmitters into synaptic cleft

6. neurotransmitter binds with receptor

7. vesicle material is recycled

8. vesicles either return to neuron cell body via retrograde transport or are refilled at axon terminal