 This chapter is about introducing the function of neurons ◦ How they conduct & transmit electrochemical signals through the nervous system

 Function of neurons centers around the membrane potential ◦ The difference in electrical charge between the inside & outside of the cell  Can measure membrane potential using a microelectrode ◦ Measure the charge inside the cell & the charge outside.

 A neuron’s resting potential is -70mV ◦ Meaning, the charge inside the cell is 70mV less than the charge outside ◦ Inside < Outside  Because this value is beyond 0, it is said to be polarized  So at rest, neurons are polarized.

 It is polarized due to the arrangement of ions ◦ The salts in neural tissues separate into + and – charged particles called ions  4 main ions are responsible: 1. K + (potassium) 2. Na + (sodium) 3. Cl - (chloride) 4. - charged proteins

 The ratio of – to + ions is greater inside a neuron than out, so you have a more – charge inside ◦ Again, why the neuron’s resting potential is polarized  2 things cause this imbalance & 2 things try to equalize (homogenize)

 Equalizers (homogenizers) 1. Random motion 2. Electrostatic pressure  Cause imbalance 1. Passive flow 2. Active transport

1. Random Motion  Ions are in constant random motion  Tend to be evenly distributed because they move down their concentration gradient ◦ Move from areas of higher concentration to lower concentration 2. Electrostatic Pressure  Ions with the same charge will repel each other  Opposite charges attract

 Concentrations of Na + and Cl - are greater outside the neuron (extracellularly)  K + concentration is greater inside the cell (intracellularly)  Negatively charged proteins generally stay inside the neuron

1. Passive Flow ◦ Does not require energy ◦ The membrane is selectively permeable to the different ions  K + and Cl - ions easily pass through the membrane  Na + ions have difficulty passing through ◦ Ions passively flow across the membrane via ion channels  Special pores in the membrane 2. Active transport ◦ Needs energy to power the pumps

2. Active transport ◦ Requires energy to power the pumps that transport the ions ◦ Discovered by Hodgkin & Huxley  Nobel prize winning research  Why is there high Na+ and Cl- outside and high K+ inside? Why are they not passively flowing down their concentration gradients & reaching equilibrium?  Calculated the electrostatic pressure (mV) that would be necessary to counteract the passive flow down the concentration gradient (aka keep the concentrations uneven across the membrane) & how this differed from the actual resting potential

 Discovered that there are active pumps that counteract the passive flow of ions in & out of the cell (specifically for Na+ and K+)  Sodium-potassium pumps ◦ Actively (using energy) pumps Na+ out & K+ in ◦ 3 Na+ ions out for every 2 K+ ions pumped in  Other types of active transporters also exist *Summary Table 4.1 (pg. 79)*

 Remember: At a synapse, the presynaptic neuron releases NT that bind with receptors on the postsynaptic neuron, to transmit the signal from one neuron to the next  When the NT bind with the postsynaptic neuron, they have either of 2 effects 1. Depolarize the membrane ◦ Decrease the resting potential ◦ **this means become less negative, aka approach zero** 2. Hyperpolarize the membrane ◦ Increase the resting potential ◦ ** make it more negative; further from zero**

hyperpolarize depolarize

 Postsynaptic depolarizations: ◦ Excitatory postsynaptic potentials ◦ EPSPs ◦ Increase the likelihood that the neuron will fire  Postsynaptic hyperpolarizations: ◦ Inhibitory postsynaptic potentials ◦ IPSPs ◦ Decrease the likelihood that the neuron will fire  Graded responses ◦ Weak signals cause small PSPs; strong signals cause large PSPs

 Travel passively ◦ Very rapid (practically instantaneous)  Like a cable ◦ Deteriorate over distance  Lose amplitude as they go along  Fade out  Like sound

 Individual PSPs have almost no effect on getting a neuron to fire  However, neurons can have thousands of synapses on them & combining the PSPs from all of those can initiate firing ◦ Called integration ◦ Add all the EPSPs + IPSPs ◦ Remember:  PSPs are graded & have different strengths  ExcitatoryPSPs increase the likelihood of firing & InhibitoryPSPs decrease the likelihood

 Neurons integrates PSPs in 2 ways 1. Over space: spatial summation ◦ EPSP + EPSP = big EPSP ◦ EPSP + IPSP = 0 (cancel each other out; assuming of equal strength) ◦ IPSP + IPSP = big IPSP 2. Over time: temporal summation ◦ 2 PSPs in rapid succession coming from the same synapse can produce a larger PSP

 If the sum of the PSPs reaching the axon hillock area at any one time is enough to reach the threshold of excitation, an action potential is generated ◦ The threshold is -65mV  So the resting membrane potential must be depolarized 5mV for the neuron to fire  Action potential ◦ Massive, 1ms reversal of the membrane potential  -70 to +50mV ◦ Not graded; they are all-or-nothing responses  Either fire at full force or don’t fire at all

 APs are generated & conducted via voltage- activated ion channels  When the threshold of excitation is hit, the voltage-activated Na+ channels open & Na+ rushes in  The Na+ influx causes the membrane potential to spike to +50mV  This triggers the voltage-gated K+ channels to open & K+ flows out  After 1ms, Na+ channels close  End of rising phase

 Beginning of repolarizing phase ◦ K+ continues to flow out until the cell has been repolarized; then the K+ channels close  Cell returns to baseline resting membrane potential

 For about 1-2ms after the AP, it is impossible to fire another one ◦ Absolute refractory period  Followed by a period during which another AP can be fired, but it requires higher than normal levels of stimulation ◦ Relative refractory period  Afterwards, the neuron returns to baseline & another AP can be fired as usual

 Ions can pass through the membrane at the nodes of Ranvier between myelin segments  APs move instantly through myelinated segments to the next node, where concentrated Na+ channels allow the signal to be “recharged” and sent to the next

 Overall, this allows APs to be conducted much faster than in unmyelinated axons, because the AP “jumps” from node to node and effectively “skips” the lengths covered in myelin (saltatory conduction)

 Speed of conduction is faster with myelin  Faster in thicker axons  Ex: mammalian motor neurons are thick & myelinated & can conduct signals at around 224 mph!!

 Different types of synapses based on the location of the connection on each neuron ◦ Axodendritic  “Normal” synapses  Terminal button of axon on Neuron1 to dendritic spine of Neuron2 ◦ Axosomatic  Axon of N1 to soma of N2 ◦ Dendrodendritic ◦ Axoaxonic

 2 categories of NTs ◦ Large:  Neuropeptides ◦ Small:  Made in terminal buttons & stored in vesicles

 NTs are released via exocytosis  At rest, NTs are in vesicles near membrane of presynaptic neurons  When an AP reaches the terminal button, voltage-activated Ca 2+ channels open & Ca2+ rushes in ◦ Ca2+ causes the vesicles to fuse with the membrane & release contents into the synaptic cleft

 NTs released from the presynaptic neuron cross the cleft & bind to receptors on the postsynaptic neuron  Receptors contain binding sites for only certain NTs  Any molecule that binds is a ligand  There are often multiple receptors that allow one kind of NT to bind: receptor subtypes ◦ Different subtypes can cause different reactions

 There are 2 general types of receptors 1. Ionotropic ◦ NT binds & ion channel opens & ions flow through ◦ Immediate reaction 2. Metabotropic ◦ NT binds & initiates a G-protein to trigger a second messenger, which moves within the cell to create a reaction ◦ Slow, longer lasting effects ◦ More abundant

 A special type of metabotropic receptor  Located on the presynaptic neuron & bind with NTs from its own neuron  Function to monitor the # of NTs in the synapse ◦ If too few, signal to release more ◦ Too many, signal to slow/stop release

 In order to allow the synapses to be available to signal again, the extra NT in the synaptic cleft need to be “cleaned up” by:  Reuptake ◦ Most of the extra NT are quickly taken back into the presynaptic neuron by transporters to be repackaged in vesicles for future release  Enzymatic degradation ◦ NTs in the cleft are broken down by enzymes ◦ Ex: acetylcholine broken down by acetylcholinesterase ◦ Even these pieces are taken back into the neuron & recycled

 Unique signal transmission alternative to traditional synapses  Called electrical synapses  Narrow gaps between neurons connected by fine tubes called connexins that let electrical signals pass  Very fast & allow communication in both directions  Not yet fully understood in mammalian systems

 Amino Acid NTs  Monoamine NTs  Acetylecholine  Unconventional/Misc. NTs  Neuropeptides

 AAs are the building blocks of proteins  Glutamate ◦ Most common excitatory NT in the CNS  Aspartate  Glycine  GABA ◦ Most common inhibitory NT

 2 groups with a total of 4 NTs in this class  Catecholamines: 1. Dopamine (DA) ◦ Made from tyrosine/L-Dopa 2. Norepinephrine (NE) ◦ Made from dopamine 3. Epinephrine ◦ Made from NE  Indolamines: 4. Serotonin (5-HT) ◦ Made from tryptophan

 Functions at neuromuscular junctions, in ANS & CNS  Extra is mostly broken down in the synapse; by acetylcholinesterase  Receptors for Ach are said to be cholinergic

 Act differently than traditional NTs  Nitric oxide & carbon monoxide ◦ Gases that diffuse across the membrane, across the extracellular fluid & across the membrane of the next neuron  Endocannabinoids ◦ Essentially, the brain’s natural version of THC (main active chemical in marijuana) ◦ Ex: annandimide

 Don’t worry about the specific types  Just know that they are another type of NT  Generally large NTs

 Pharmaceutical drugs generally affect synaptic in 2 ways ◦ Agonists facilitate the effects of a NT  Can bind to a receptor & activate it like the NT would ◦ Antagonists inhibit  Can bind to a receptor & block it so NTs cannot bind

 Acetylcholine has 2 types of receptors 1. Nicotinic ◦ Many in the PNS between motor neurons & muscle fibers ◦ Ionotropic ◦ Nicotine: agonist ◦ Curare: antagonist (causes paralysis) ◦ Botox: antagonist 2. Muscarinic ◦ Many located in the ANS ◦ Metabotropic ◦ Atropine: antagonist, receptor blocker

 Endogenous ◦ Compounds naturally made within the body ◦ Ex: enkephalins & endorphins  The body’s endogenous opioids  An exogenous opioid is morphine  Opioids are analgesics (pain relievers)