2 primary cell types in nervous system neurons – 10 to 100 billion neurons Role: 2. glial cells – provide support, nutrients, myelin, cleanup, etc. for neurons

2 primary cell types in nervous system neurons – 10 to 100 billion neurons can vary tremendously in size and shape but all have 3 components cell body or soma contains genetic material, provides nutrients,

2 primary cell types in nervous system 1. neurons – 10 to 100 billion neurons Role: can vary tremendously in size and shape but all have 3 components cell body or soma contains genetic material, provides nutrients, dendrites axon

How do neurons communicate? within neurons – electrically between neurons - chemically

Neuron receiving info Information traveling down neuron

Ramon Y Cajal developed Golgi Stain first determined space between neurons “synapse”

A brief discussion about communication within a neuron changes in electrical potential

Neurons can exist in one of 3 states the “resting” state the “active” state or action potential neuron is firing conveying info to other neurons or organs the recovery or “refractory” state

How do we know about what is happening in the neuron? giant squid axon why was work done with the giant squid axon?

At rest: inside of the axon has a slightly negative charge relative to outside the axon called the membrane or resting potential (~ -60 mV) why?

Neuron stimulated see depolarization (change from negative inside neuron to more positive) “threshold” – if a great enough depolarization occurs, an action potential will occur action potential – very quick - milliseconds

When the action potential occurs….. see depolarization (change from negative (~ -60mV) inside neuron to more positive (~ +30 mV))

threshold resting potential

hyperpolarization after action potential – return to negative (actually a more negative state than to begin with)

What causes these changes in electrical potential? All axons and cells have a membrane thin bilayer that surrounds cell allowing some chemicals and ions in but keeping others out axons also have a large number of protein channels that when open allow ions (charged molecules) to flow in or out

What causes these changes in electrical potential? Ions flowing across the membrane causes the changes in the potential Ions are molecules that contain a positive or negative charge anion – negative charge cation – positive charge

Some important ions for neuronal communication Na+ sodium HIGHER CONCENTRATION OUTSIDE THE AXON Cl- chloride HIGHER CONCENTRATION OUTSIDE AXON K+ potassium higher concentration inside the axon A- anions -large (-) molecules with a negative charge (stuck inside the axon)

Neuron at Rest Na+ and Cl- are in higher concentration OUTSIDE AXON (EXTRACELLULAR FLUID) INSIDE AXON (intracellular) Na+ Cl- Na+ A- Cl- Cl- A- Cl- Cl- Na+ Na+ Cl- Cl- A- Na+ Na+ A- Na+ Na+ Cl- A- Na+ Na+ Cl- Na+ Cl- Cl- Na+ A- Na+ Cl- Cl- Cl- Cl- Na+ and Cl- are in higher concentration in the extracellular fluid Neuron at Rest

Neuron at Rest K+ and negative anions are in higher concentration INSIDE AXON OUTSIDE AXON (EXTRACELLULAR FLUID) Cl- K+ K+ K+ Cl- A- Na+ Cl- A- Na+ K+ Na+ A- Cl- Na+ K+ A- Na+ Cl- Na+ K+ K+ K+ and negative anions are in higher concentration in the intracellular or inside the axon Neuron at Rest

Some forces that play a role in maintaining membrane potential concentration gradient – ions diffuse from higher concentration to lower concentration

What would each ion do if the ion channel opened based on the concentration gradient? Na+ K+ Cl-

Some forces that play a role in maintaining membrane potential concentration gradient – ions diffuse from higher concentration to lower concentration electrical gradient - opposite charges attract so ions are attracted to an environment that has a charge that is opposite of the charge they carry!

example of electrostatic forces

What would each ion do if the ion channel opened based on electrostatic forces ? Na+ K+ Cl-

What drives the action potential? opening of Na+ channels and influx of Na+ ions

What happens if sodium channels are blocked? lidocaine, novocaine, cocaine TTX – tetrototoxin Sagitoxin- red tides

http://faculty.washington.edu/chudler/ap.html

What about communication between neurons?

Communication between neurons most psychoactive drugs work via this mechanism chemical transmission via the synapse neurotransmitters

label some things presynaptic ending – axon – releases chemical if the neuron generated an action potential

presynaptic ending (axon)

label some things presynaptic ending – axon – releases chemical if the neuron generated an acton potential postsynaptic ending – can be dendrite, cell body, or axon receives chemical signal from neuron – synapse – tiny gap between neurons

Other things to notice in presynaptic ending Ca+ channels - synaptic vesicles contain neurotransmitter

What happens at level of synapse when an action potential occurs? Ca+2 enters presynaptic ending via Ca+ channels synaptic vesicles bind to presynaptic ending and release their neurotransmitter Neurotransmitter crosses synapse and binds to receptor on postsynaptic side

http://www.williams.edu/imput/synapse/pages/II.html

postsynaptic receptors protein embedded in membrane mechanism for neurotransmitter to influence postsynaptic activity by binding to receptor

What happens when neurotransmitter binds to the postsynaptic receptor? can cause the opening of localized ion channels in the postsynaptic ending Na+ or K+ or Cl-

What happens when neurotransmitter binds to the postsynaptic receptor? can cause the opening of localized ion channels in the postsynaptic ending IF: Na+ channels open - Na+ enters local excitation (or depolarization) K+ or Cl-

What happens when neurotransmitter binds to the postsynaptic receptor? can cause the opening of localized ion channels in the postsynaptic ending IF: Na+ K+ channels open – K+ leaves the cell causes local inhibition or hyperpolarization Cl-

What happens when neurotransmitter binds to the postsynaptic receptor? can cause the opening of localized ion channels in the postsynaptic ending IF: Na+ K+ or Cl- channels open – influx of Cl- causes local inhibition or hyperpolarization

Graded Potentials- these local changes in ion flow are called graded potentials has impact in limited region increases or decreases the likelihood of the neuron receiving info to generate an action potential.

How do graded potentials contribute to the likelihood of an action potential? graded potentials are summed at axon hillock – if great enough depolarization to reach “threshold” – axon generates an action potential

What happens when neurotransmitter binds to the postsynaptic receptor? if Na+ channels open - increases likelihood of generating an action potential if K+ channels open - - decreases the likelihood of an action potential if Cl- channels open - decreases the likelihood of an action potential

Ways that graded potentials differ from action potentials action potentials are “all or none” while graded potentials decrease over space and time localized – has impact in limited region action potentials always excitatory while graded potentials can be excitatory or inhibitory

Two types of graded potentials excitatory - EPSPs – excitatory postsynaptic potentials Na+ ion channels IPSPs inhibitory postsynaptic potentials K+ or Cl- ion channels

2 ways that neurotransmitter exert these effects ionotrophic - directly opening the ion channel occurs and terminates very quickly

2 ways that neurotransmitter exert these effects ionotrophic - directly opening the ion channel occurs and terminates very quickly metabotropic - more indirect ultimately opens ion channel via stimulating a chemical reaction through a "second messenger system" takes longer but lasts longer

How do we get rid of the transmitter from the synapse? 2 main ways 1. reuptake - most common transporter on presynaptic ending a means of recycling a common way for drugs to alter normal communication

transporter

enzyme degradation enzyme - speeds up a reaction ex. acetylcholine (ACh) is broken down by acetylcholinesterase (AChE)

http://et.middlebury.edu/scivizlab/animations/neurotransmission/lowres/normal.mov

NT binding to postsynaptic receptor “lock and key analogy”

Neurotransmitter represents a key Receptor represents the lock Other keys can represent drugs

What are possibilities? agonist – mimics the neurotransmitter antagonist – blocks the neurotransmitter partial agonists/ partial antagonists –