Fundamental Types of Neurons Sensory (afferent) neurons receptors detect changes in body and external environment this information is transmitted into brain or spinal cord Interneurons (association neurons) lie between sensory & motor pathways in CNS 90% of our neurons are interneurons process, store & retrieve information Motor (efferent) neuron send signals out to muscles & gland cells organs that carry out responses called effectors What do you need to percieve? We’ll talk about that in more detail later, but pressure, light, vibrations, chemical flavors, you need docking bays to receive these and change transduce those types of energy into chemical energy.

Fundamental Types of Neurons The trick that interneurons pull off is taking the information from thousands of inputs and being able to focus on a few of them, coordinate the important ones. Realize if you had to consciously think about walking; long ago you taught your brain the walking program and it will carry out the thousands of muscle, and joint movements smoothly non linearly, all at once so you can strut strut your stuff on the cat walk. If you had to think about it one move at a time; okay pull up right thigh, pull forward right calf, extend left calf, plant right heel, plant right toe, reverse. And while focusing on that what aren’t you thinking of? Diaphragm up, Diaphragm down, Heart pump blood in, Heart Pump blood out. How many times have I pumped my heart this minute? Digest Digest Digest. Focus Eyes. Girl! Girl! Control the nether regions Control the nether regions. System failure. Brain overload. Dump stomach contents. Which of course brings me to the properties of neurons

Fundamental Properties of Neurons Excitability (irritability) ability to respond to changes in the body and external environment called stimuli Conductivity produce traveling electrical signals Secretion when electrical signal reaches end of nerve fiber, a chemical neurotransmitter is secreted They can be triggered, set off, activated, booted up. Electricity of course coming from the greek elektra which was the greek word for Amber which caused static electricity. Then in the 1700’s Ben Franklin figured out the flow of + and – particles which your cells do with ions Do these so they can communicate which electricity and chemicals in an aqueous environment.

Structure of a Neuron Cell body = soma Vast number of short dendrites single, central nucleus with large nucleolus cytoskeleton of microtubules & neurofibrils (bundles of actin filaments) compartmentalizes RER into Nissl bodies lipofuscin product of breakdown of worn-out organelles -- more with age Vast number of short dendrites for receiving signals Singe axon (nerve fiber) arising from axon hillock for rapid conduction axoplasm & axolemma & synaptic vesicles Dendr = Tree Nissl bodies are unique to neurons and offer a useful way to identify them under the microscope Lipofuscin are alos called wear and tear molecules, they are apparently harmless, the left overs of metabolism Where would a neuron be receiving signals from? What will it have to do if its receiving multiple and varied signals? You go home, Mom: Clean room, Dad Do as Mother says, Friend: Big Party Ex Girlfriend who just dumped you: I’m going to party don’t come. What do you do hot shot what do you do? “ Dennis Hopper as Howard Payne in Speed 1994 rated R for violence and language Also note the Schwann cells insulating the neuron, wrapping them in myelin sheaths, and the Nodes of Ranvier between the cells

Axonal Transport Many proteins made in soma must be transported to axon & axon terminal repair axolemma, for gated ion channel proteins, as enzymes or neurotransmitters Fast anterograde axonal transport either direction up to 400 mm/day for organelles, enzymes, vesicles & small molecules Fast retrograde for recycled materials & pathogens Slow axonal transport or axoplasmic flow moves cytoskeletal & new axoplasm at 10 mm/day during repair & regeneration in damaged axons Axolemma: membrane Pictured is Schwann the german for whom schwann cells are named, also one of the cofounders of the cell theory, figured out what pepsin was doing in your stomach. the man knew his cells

Electrical Potentials & Currents Neuron doctrine -- nerve pathway is not a continuous “wire” but a series of separate cells Neuronal communication is based on mechanisms for producing electrical potentials & currents electrical potential - difference in concentration of charged particles between different parts of the cell electrical current - flow of charged particles from one point to another within the cell Living cells are polarized resting membrane potential is -70 mV with a relatively negative charge on the inside of nerve cell membranes Picture of Samuel Morse, Electrical potential its like Girls walk by outside, there’s a difference in concentration. There is some tension and it leads to things. In this case electricity. Resting potential: So a cell has more negative ionis than positive ions inside

Resting Membrane Potential Unequal electrolytes distribution diffusion of ions down their concentration gradients selective permeability of plasma membrane electrical attraction of cations and anions Explanation for -70 mV resting potential membrane very permeable to K+ leaks out until electrical gradient created attracts it back in membrane much less permeable to Na+ Na+/K+ pumps out 3 Na+ for every 2 K+ it brings in works continuously & requires great deal of ATP necessitates glucose & oxygen be supplied to nerve tissue If potassium wants out why not just let it out? Why can’t I just let the ions go where they want? If there’s no gradient, there’s no change, there’s no signal.

Be clear on vocabulary Polarize = to increase the difference in ion concentration. To move away from 0mV. Resting potential is polarized (-70mV). There’s a difference in Na+/K+ conc. Depolarize = To move toward no electrical potential. Allowing Na+/K+ to go where they want. “Opening flood gates” Repolarize = To go back to original potential

Ionic Basis of Resting Membrane Potential Does sodium want out? No. Does Potassium want in? No its your body fighting physics. Every time I try to get they keep pulling me back in. It takes ATP. Na+ more concentrated outside of cell (ECF) K+ more concentrated inside cell (ICF)

Local Potentials Local disturbances in membrane potential occur when neuron is stimulated by chemicals, light, heat or mechanical disturbance depolarization decreases potential across cell membrane due to opening of gated Na+ channels Na+ rushes in down concentration and electrical gradients Na+ diffuses for short distance inside membrane producing a change in voltage called a local potential Differences from action potential are graded (vary in magnitude with stimulus strength) are decremental (get weaker the farther they spread) are reversible as K+ diffuses out, pumps restore balance can be either excitatory or inhibitory (hyperpolarize) So you mess with resting potential. Something happens. You’re asleep you wake up you feel something, whats that on your leg? Why is it wet, slippery, Dare you look under your expensive silk sheets? What’s that lump? Oh my gosh they cut off the head of your prize race horse! NOOOO. See that first little stimulus leads to all kinds of crazyness. Now the Sodium Channels we’re talking about here are different from the Sodium Potassium Pumps, This is that pumps neighbor and its not a nice neighbor, The Na/K pump is keeping out the Na, and this is letting them in.

Chemical Excitation Show corresponding on the board: Stimuli that open K+ gates hyperpolarize the neuron, moving it away from A.P. Stimuli that open the Na+ gates depolarize the neuron. A depolarizing influence of sufficient strength depolarizes enough to get to the threshold.

Action Potentials More dramatic change in membrane produced where high density of voltage-gated channels occur trigger zone has 500 channels/m2 (normal is 75) If threshold potential (-55mV) is reached voltage-gated Na+ channels open (Na+ enters causing depolarization) Passes 0 mV & Na+ channels close (peaks at +35) K+ gates fully open, K+ exits no longer opposed by electrical gradient repolarization occurs Negative overshoot produces hyperpolarization

Action Potentials Called a spike Characteristics of AP follows an all-or-none law voltage gates either open or don’t nondecremental (do not get weaker with distance) irreversible (once started goes to completion and can not be stopped)

The Refractory Period Period of resistance to stimulation Absolute refractory period while Na+ gates are open no stimulus will trigger AP Relative refractory period as long as K+ gates are open only especially strong stimulus will trigger new AP Refractory period is occurring only to a small patch of membrane at one time (quickly recovers)

Impulse Conduction in Unmyelinated Fibers Threshold voltage in trigger zone begins impulse Nerve signal (impulse) - a chain reaction of sequential opening of voltage-gated Na+ channels down entire length of axon Nerve signal (nondecremental) travels at 2m/sec

Impulse Conduction in Unmyelinated Fibers

Saltatory Conduction in Myelinated Fibers Voltage-gated channels needed for APs fewer than 25 per m2 in myelin-covered regions up to 12,000 per m2 in nodes of Ranvier Fast Na+ diffusion occurs between nodes

Saltatory Conduction of Myelinated Fiber The Action potential moves in only one direction because of the refractory period Notice how the action potentials jump from node of Ranvier to node of Ranvier.

Synapses Between Two Neurons First neuron in path releases neurotransmitter onto second neuron that responds to it 1st neuron is presynaptic neuron 2nd neuron is postsynaptic neuron Number of synapses on postsynaptic cell variable 8000 on spinal motor neuron 100,000 on neuron in cerebellum Pictured: Otto Loewi (1873-1961) first to demonstrate function of neurotransmitters at chemical synapse

The Discovery of Neurotransmitters Histological observations revealed a 20 to 40 nm gap between neurons (synaptic cleft) Otto Loewi (1873-1961) first to demonstrate function of neurotransmitters at chemical synapse flooded exposed hearts of 2 frogs with saline stimulated vagus nerve of one frog --- heart slows removed saline from that frog & found it would slow heart of 2nd frog --- “vagus substance” later renamed acetylcholine Acetycholine: excitatory to muscles, it depolarizes, opening Na gates letting Na in, In the Heart its inhibitory slowing things, hyperpolarizing cells, opening K gates letting K out.

Chemical Synapse Structure Presynaptic neurons have synaptic vesicles with neurotransmitter and postsynaptic have receptors

Postsynaptic Potentials Excitatory postsynaptic potentials (EPSP) a positive voltage change causing postsynaptic cell to be more likely to fire result from Na+ flowing into the cell glutamate & aspartate are excitatory neurotransmitters Inhibitory postsynaptic potentials (IPSP) a negative voltage change causing postsynaptic cell to be less likely to fire (hyperpolarize) result of Cl- flowing into the cell or K+ leaving the cell glycine & GABA are inhibitory neurotransmitters ACh & norepinephrine vary depending on cell

Types of Neurotransmitters 100 neurotransmitter types in 4 major categories Acetylcholine formed from acetic acid & choline Amino acid neurotransmitters Monoamines synthesized by replacing -COOH in amino acids with another functional group catecholamines (epi, NE & dopamine) indolamines (serotonin & histamine) Neuropeptides (next)

Neuropeptides Chains of 2 to 40 amino acids Stored in axon terminal as larger secretory granules Act at lower concentrations Longer lasting effects Some released from nonneural tissue gut-brain peptides cause food cravings Some function as hormones modify actions of neurotransmitters

Monamines, Catecholines: Come from amino acid tyrosine Made in adrenal medulla Blood soluable Prepare body for activity High levels in stressed people Norepinephrine: raises heart rate, releases E Dopamine: elevates mood Helps with movement, balance Low levels = Parkinson’s disease Pictured: Julius Axlerod 1970 Nobel winner for studies of the release & uptake in the brain Pleasureable things release dopamine. Addictive things mess with dopamine Cocaine acts as a dopamine transporter blocker, competively inhibiting dopamine uptake to increase the lifetime of dopamine. On the other hand, amphetamines act as dopamine transporter substrates to competitively inhibit dopamine uptake and increase the dopamine efflux via a dopamine transporter. Dopamine is linked to psychosis, & many anti-psychotic drugs like throazine plug up the receptor sites for dopamine

Picture some of those blue lines are red and sum are green Picture some of those blue lines are red and sum are green. Some tell it to go and some tell it to not. The summation of all the lines gives the total effect. Sometimes there’s more red or more green.