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Date Created: 09/09/14
Chapter 1 The Stuff of the Mind Psyche Greek for soul which referred to the mental and emotional aspect of a person o Greek for Psychedelics mind opening drugs their word for soul or spirit psychology is study of the soul o Soul has different connotations o Google search human soul and human mind and soul you get ghosts and mind you get the brain 0 PSI abbreviated for psychology Psyche Now soul usually means a person39s incorporeal identity a nonphysical but essential part of her or him Psychology is the study of the mind Mind in this sense includes mental phenomenon like o Emotions Feelings what we feel o Voluntary non re exive Behaviors what we do o Thoughts what we think no such thing as purely emotional or rational experience LOVE the iceberg picture Freud o Most of our mind and what drives our emotions is not something we have awareness of o Most of what goes on in our mind is unconscious not aware of ID o Conscious is the tip of the iceberg what you are aware of and thinking is right at the surface and tiny fracture of your psyche But of what is the stuf of the mind Made of matter neutrons protons That is of what are our minds made o Two basic options o The mind human psyche is made of I 1 One kind of stuff I 2 More than one kind of stuff relationship between physical body and the mind if believe made of one top of stuff you fall until monistic or other option believe dualistic system Mind Body Dualism Mind and body are not completely identical They are made of different stuff the person39s being is not just their brain there is some other thing like their soul that makes them them how does nonphysical world affect the physical world mind and body are distinct You have a physical aspect and a nonphysical aspect Mind Body Monism Mind and body are made of the same stuff made of only one thing completely nonphysical complete mind proposed by George Burkley he advocates idealism which is mentalistic monism Mentalistic Monism The body is a product of the mind everything in the universe is just a projection of the universe everything is made by the mind the mind is the essence of everything problem for science because how would you disapprove Berkely you can39t the brain and vat you are a brain that exists in the cosmos and you don39t have a body just a brain that is oating and aliens are beaming lights into your brain which makes you believe you are in a classroom and isn39t really real if that39s true how would you prove that nonfalsifiable don39t like this type of monism Materialistic Monism Beliefs The mind is a product of the body foundation for neuroscience abbr MM only one substance to the brain and psyche and the basis for that is physical and based upon neurons and ions and this gives rise to consciousness everything that goes into mental world is constructed by matter alone is this true We don39t know the only sound philosophy suggests only one type of essence to you which is physical body The mind is what the brain does the brain does nonmental stuff like re exes but also does mental stuff too like regulate breathing but mainly it produces the psyche MM is the philosophical basis of neuroscience the scientific study of the brain and behavior all of our evidence points towards this Mental events are brain events plus nothing according to MM Science has verified that the following mental events can occur independent of brain activity o 1 Nothing scientifically we have not been able to verify about brain events and conscious experiments that can occur independent of the physical workings of the brain Note that I have just made a truth claim I have made a claim about something I believe to be true But quotI have my beliefs and you have yours right Your beliefs are what you assert to be true on what basis do you claim to know something Truth is that which corresponds to reality Picture of chimps closest evolutionary animals 95 of our history was spent as hunter gatherers and we lived in little communities that were nomadic and there were predators and prey to catch most of these people were related bans would come across other people to share or go to war a lot of uncertainty and this is context that our species lived in for thousands of years brain is social and works together with groups of people and people don39t like to be alienated what type of mental processes about belief systems one that is under pressure to conform and adopt other people39s belief systems But science is all about what is demonstrably true every person has some false and some true beliefs the scientific method was developed for this reason to give us knowledge about what is true and can be demonstrated what is demonstrable true 0 The Dragon in my Garage Veridical What does this word mean A true claim The Dragon in my Garage exercise there is a dragon in the class that is invisible and people feel around but can39t feel because she doesn39t have a body nonphysical fire breathing dragon we keep proposing tests and evidence points that there is no dragon Now what39s the difference between an invisible incorporeal oating dragon who spits heatless fire and no dragon at all If there39s no way to disprove my contention no conceivable experiment that would count against it what does it mean to say that my dragon exists Your inability to invalidate my hypothesis is not at all the same thing as proving it true Claims that cannot be tested assertions immune to disproof are veridically worthless whatever value they may have in inspiring us or in exciting our sense of wonder What I39m asking you to do comes down to believing in the absence of evidence on my say soWhy scientific method matters people have a lot of biases but method was developed to minimize beliefs based on bias things like authority Epistemology Epistemology is about knowledge Knowledge is justified true belief have to be true and justified Have truth and belief and the intersection of the two is knowledge can have beliefs about true and false things can39t have knowledge about something that is untrue Is materialistic monism knowledge That is is MM justified true belief Empirical justification of MM Mental states can be altered by physical manipulations alter brain get corresponding experiences of how they perceive reality and the brain 0 Examples I 1 Brain Damage Blindsight guy had damage to his brain and had life threatening injury when he was kid his optic nerves are there but neurons that make up primary visual cortex were obliterated Unilateral Neglect happens in stroke patients elderly patients will shave left side of face only or eat all food on the left image of half of their reality I 2 Psychotropic Drug Effects take chemical substance and put it in the brain LSD most potent causes hallucinations I 3 Transcranial Magnetic Stimulation TMS Empirical Justification of MM Mental states can be altered by physical manipulations o 1 Brain Damage I Blindsight I Split Brain Communication between cerebral hemispheres Corpus colosum Severed so left and right brains can39t communicate I Split Brain 2 I Unilateral Neglect I The Capgras Delusion Amygdala not being stimulated like it should I Temporal Lobe Epilepsy Excess of emotion neurons fire at random in temporal lobes thinks he is God everything has significant meaning Is Materialistic Monism true After all who39s to say there isn39t something else going on in addition to and in parallel with the physical events of the brain in each of the scenarios depicted earlier types of dualism God arranged things in perfect harmony presupposes something science can39t prove Occam s Razor No more things should be presumed to exist that are absolutely necessary ie the fewer assumptions an explanation of a phenomenon depends on the better the explanation William of Occam if have two different theories that are equal go with the theory that makes fewer assumptions Example Tolomy s universe put Earth as the center of the universe and the sun revolves around the earth Copernicus and Galileo demonstrate through science that it is not the case Tolomy had a model and with mad demonstrated that this model was true you just have to make more assumptions than with Copernicus theory If the entire gamut of human experience can be explained by appealing only to the workings of the physical brain then why posit that there is an additional unnecessary component to us that makes us us why should we suppose anything other than physical brain for psychology Why we assume other propositions that are not justifiable Species Narcissism what is narcissism it39s all about you narcissistic episode in US and people becoming self centered sense of being special o Da Vinci s creation of man it39s all about us and we are the earth and everything revolving around us endemic in our brains ust as MM is a necessary presupposition to scientific inquiry in general Darwinian evolution is at the heart of an internally consistent understanding of modern biology Darwin anticipated the people would be upset with what he was saying he changed his views upon data that he gathered people opposed because of narcissism and makes people feel less special o According to Darwinism you are a primate o Started out with the Origin of Species and he left out man because he knew it would upset people so then he wrote The Descent of Man The tragedy of young earth creationism is that it takes a relatively recent and extreme view of Genesis applies to it an unjustified scientific gloss and then asks sincere and well meaning seekers to swallow this whole despite the massive discordance with decades of scientific evidence from multiple disciplines Is it any wonder that many sadly turn away from faith concluding that they cannot believe in a God who asks for an abandonment of logic and reason o Dr Francis S Collins Geneticist and Director of The Human Genome Project Faith and the Human Genome Specialized characteristics are acquired by species across generations by selection pressures Cosmos A Spacetime Odyssey 0 Darwin thinking 0 Wild wolves evolve into dogs 0 Artificial selection or breeding is where we took evolution into our own hands to shape dogs the way we want to 0 Darwin credited with the act of evolution what drives it 0 He is credited with main driving force of evolution systematic changes and species changing over time o Theory doesn39t mean an idea a theory is something that has been researched and there is evidence and way of making sense o Evolution is both scientific theory and also a scientific fact o Says natural selection is driving force between common ancestory he gives idea that existing species can be traced back to common branch on tree So humans and dog choice can exert selection pressures In just a few thousand years these selection pressures can radically alter dogs bodies and temperaments Darwin39s brilliant idea was that the environment itself can act as a systematic selector calls this process natural selection o He begins origin of species and left out mention of humans due to anticipated backlash and 12 years later published the descent of man which looks at human ancestory with primates o The environment itself can act as systematic selector random part is genetic changes like mutations but natural selection is what caused the evolution it39s not a random process Natural Selection Animals over reproduce and resources are too limited to support the survival and reproduction of all of their offspring All species produce more young than resources can sustain and so competition for survival and mates all offspring can39t make it into next generation not all of genes that represent each organism will make it into next generation o For Survival Food Safe Shelter Water et cetera o For Reproduction Mates Due to heritable individual differences in physical and mental characteristics some offspring end up out reproducing others Darwin articulated theory before modern genetics selection can be for size or strength or color of coat some offspring are better at surviving and reproducing the others The inherited differences that led to their success will necessarily be more common in the winners quot own offspring Biological Evolution Systematic Genetic change in a population across generations biological def of evolution Evolution is a fact Evolution is also a scientific theory you can39t understand biology without Scientific theories are built from facts and used to explain how and why things happen as they do They are also used to generate new testable hypotheses they work as theoretical scaffolds they generate research predictions have to be testable and falsifiable theories can be modified over time What39s all of this have to do with the scientific study of the brain and behavior Functional hierarchy deep within core of brain we have reptilian core we share things in common with animal brain we have reptilian core and then move up to rat and then the higher functions are monkey and we have front part of the brain only seen in dolphins higher mammalian ideas and concepts when we realize other brains exist core reptilian brain and around that is limbic system and more cortex around that is neocortex and has higher functions 0 Everything Nothing in biology makes sense except for in the light of evolution I H90 create or se the theory modify The to make 0 theory reduction Observation Pred ction design an perform the experiment experiment to test me prediction Unit Two Basics of Neurophysiology Unit Overview Main cells of nervous system esp CNS brain and spinal cord Electrochemical Events give rise to different potentials Membrane Potential Action Potential Exocytosis release of products of cell outside of cell release of neurotransmitter molecules in axon terminals Pt 1 Background Review Info Important Terms Concepts CNS PNS GreyWhite Matter Glial Cell Types and Functions Myelin MS Neuron Diagram Neuron Morphology Structure Suggests Function DRGS and Dermatomes Re ex Arcs Basic Parts of Eukaryotic Cell Other General Physio Neuron Terms Blood Brain Barrier Nervous System Central Nervous System CNS 0 Everything encased in bone brain in cranium spinal cord in vertical column a continuous network Peripheral Nervous System PNS 0 Neurons send signals to body and cause muscles to contract 0 Activity of glands everything outside of CNS CNS Matter Grey Matter 0 Dendrites axon terminals the outer cortex different nuclei White Matter o Primarily connectivity myelin and produce fatty white insulation for axon of neurons areas of connection or one brain area sending connections to another brain area 5050 by Mass 0 50 grey matter and 50 white matter Neuroglia Glial cells or simply glia Non neuronal do play a role in communication but not primary communication cells which are neurons 101 they are support cells term derived from glue and partial understanding of what glial do makes everything stick together have important roles outnumber neurons by factor of 101 they are one tenth the size so 50 50 mass Four primary types oligodendrocyte is single most important Four Types of Glial Cells Star shaped cell oligodendrocyte each branch with find axon of neuron and wrap around it and provide insulation for neurons myelination Piaget as children are developing cognitively they are not just acquiring factual information but how you explain certain phenomenon process is contingent on myelination brain finally done myelinating 25 years when done maturing orbital frontal cortex areas of brain that have highest in executive chain areas of brain that can override temptation to do something impulsive if have full maturation Glia Different Types of Glial Cells Astrocytes blood brain barrier protective against diseases help remove excess glutamate provide buffers Microglia are the main immune cells of the brain immune system is different in brain if pathogen gets into brain or spinal cord you don39t have strong immune response that acts against it if have splinter your immune system kills own skin cells to get rid of bad cells but also healthy cells it doesn39t happen in brain because can39t regenerate cells in your brain in event of pathogen is microglia is activated and surround and digest the pathogen phagocytosis Oligodendrocytes Schwann Cells myelinating cells of peripheral system Astrocytes aka Astroglia Star Cell Provide structural support ie scaffolding and metabolic support eg nutrients and other necessary chemicals to neurons Take up think vacuum substances whose concentrations mustn39t exceed certain critical toxic levels Help coordinate the firing of groups of neurons Astrocytes synchronize firing in groups of functionally related neurons Microglia The primary immune cell representative in the CNS Act as phagocytes engulfing and ingesting potential pathogens and mediating the in ammatory reactions that follow brain damage Myelinating Glial Cells Myelin is an 80 lipid fat substance that surrounds and insulates most axons in the body and brain Oligodendrocytes CNS Schwann Cells PNS MS A De Myelinating Autoimmune Disease It is specifically an autoimmune disease that attacks myelin sheathing body39s immune system recognizes myelin and attacks it Tends to leave characteristics in the brain like hypodensities in connective tissue Neurons By the Numbers 10000 100000000000 1000000000000000 1000000000000000000000000000000000000000000000000000 000000000000000000000000000000 Talking about neurons have about 100 billion of them they sample from different areas throughout brain and get estimate interesting similarity 100 billion neurons the astronomers says 100 billion galaxies which have 100 billion stars average neuron makes 10000 connections sending signals to other cells neuron is communicating with thousand times a day 10 quintillion synapses in the brain spots where one neuron can say something to another neuron number of unique signals generated by human brain exceeds number of protons neutrons electrons ect in the universe neuroscience is in it39s infancy Sketch a Neuron Terms Dendrite maximize surface area because they get signals from the terminal buttons of other neurons Dendritic Spines in dendritic spine is cell membrane little receptors the neurotransmitter receptors fuzzy things on the ends the spines can be changed want to learn to play guitar have modifications to neurons expression of dendritic spines allow neurons to work in new ways Soma Cell Body take signal to ribosomes transcription of new proteins and send to brain happen in the nucleus Axon Hillock bottleneck each neuron only has one of these where axon potential is created excitatory input is being weighed out for final verdict which is binary decision that we fire a potential or do not action potential is a big event massive release of electrical energy and travels quickly down axon and travel down collaterals and reach axon terminal what39s the point Occurs to serve as queue for exocytosis stuff being released from cell which are neurotransmitter molecules from axon terminals enables chemical communication between cells Axon extends away from cell body highway that carries signal towards axon terminals starts at region called hillock Terminal Buttons Axon Terminals at ends of collaterals buds that occur at the very end right before synapse Synapse not part of the neuron gap between axon terminal of one cell and the dendrites of the next cell Nodes of Ranvier gaps between myelin unmyelinated Myelin sheathing Axon Collaterals axon is single unit but then it branches off which allow there to be multiple targets for neurotransmission Individual neurons chemical basis for neural communication between cells we rely on neurotransmitters neurons use to communicate between synapses serotonin binds to receptors dopamine is excitatory and inhibitory must be able to sketch out main parts of neuron Dendrites Terminal buttons R Soma quotI e x Myelin sheath 3 cell body a O 3 Axon inside gt myelm sheath quot Direction of messages FIGURE 21 The Principal Parts of a Multipolar Neuron Neuron Morphology has to do with shape of neurons tells us about function role of neuron Structure suggests function 0 Unipolar o Pseudo unipolar o Bipolar cell that rods and cones are sending signals to bipolar cells and these cells are collecting info from rods and cones and relaying signals to ganglion cells carry visual signals to the rest of the brain are shaped unusually the dendritic field is restrictive with only a few dendrites especially ones in middle of vision receiving signals from 2 or 3 cones in eyes and on other end doesn39t do collateral stuff bipolar cell is concerned with sending specific signal wants to break down visual input into tiny pieces so that vision can see very small stuff central vision wants to pick up on detail and have high quity sends precise neural signals back to brain 0 Multipolar I Purkinje cell of cerebellum dendritic field is extremely elaborate they are concerned with getting info from thousands of other neurons about sensation and movement and inputs are converging in cerebellum and it is trying to sort through that deals with integration DRGs house pseudo unipolar neurons Dorsal Root Ganglion is example of pseudo unipolar cell have branch that goes in periperhi and central nervous system and important for spinal cord find DRG in swelling outside back of spinal cord and that is where all of cell bodies that represent dermatone cell body right outside and has one branch to body branch of one neuron whose cell body is right out of spinal cord and branches go all the way down to foot receiving sensory signals same cell will send its other branch into the central nervous system sensory inputs come in through dorsal root and carry touch and pain info into CNS Bipolar Neurons Dendrites of bipolar neurons do not branch out much except from a single process Dendritic field is very limited sparse One type is prevalent in the retina Retinal bipolar neurons connect photoreceptors rods and cones with ganglion cell neurons the neurons that send visual signals back to the rest of the brain Go between cells for signals produced by the cones and rods and sent to the brain via the optic nerve Cones Bipolars B Y ganglion Multipolar Neurons Most common morphological type Thick multifaceted elaborate dendritic arbors Ex Purkinje cells of cerebellum Shape suggests function A Purkinj e Cell of the Cerebellum fuzzy appendages at end are dendritic spines About Cells You are made of about 100 trillion cells 1014 Cells are the structural and functional units of all living organisms In other words cells are the building blocks of life o Largely self contained o Largely self maintaining 0 Think of a well designed industrialized metropolis YouYou Eukaryote you Eukaryotic cells make up multicellular organisms like ourselves Membrane bound compartments for specific metabolic functions Most significantly a nucleus containing DNA Basic Components of Eukaryotic Cells Nucleus 2 Blueprints for entire organism Ribosome 3 Builds new proteins Endoplasmic Reticulum ER 5 8 Transport newly formed proteins Golgi Apparatus 6 Package store cell s products mediate exocytosis Mitochondria 9 Generate ATP cellular currency wards off ENTROPY Cytoplasm 11 ello like filling inside cell Lysosome 12 Break down food worn out organelles Some More General Physiology Terms Chromosome One of 46 in humans 23 pairs tightly coiled strands of DNA and other proteins found in the nucleus to store the blueprints for building and maintaining the organism Gene A functional unit of a chromosome that traditionally directs the production of a particular protein how many genes do humans have Look at fruit ies and we have almost the exact same number grapes have more genes than humans noncoding genes used to be called junk DNA giving percent of DNA not coding for gene classic role of a gene one gene codes for specific protein majority of genetic code doesn t code humans over 90 of DNA doesn t code for proteins like a pseudo gene take Vitamin C and have dog they don t have to take in this vitamin why not They can make their own all mammals have enzyme that allows them to make Vitamin C one of the ancestors of primates coding error that environment it rose in didn t matter because ancestor was eating lots of fruit and got plenty of vitamin C benign mutation led to all primates lacking ability to biosynthesize vitamin C have to get through diets mRNA Carries the instructions for the synthesis of a particular protein from the chromosome to the ribosome assembly factory Enzyme One of a vast number of biological proteins that controls chemical reactions in the body Enzymes are typically used for either synthetic reactions or for breaking complex substances down Microtubules Stranded protein filaments that form the sturdiest portion of a neuron s cytoskelton Used to transport cellular products from place to place inside the cell ie for axoplasmic transport o Anterograde Transport From soma toward axon terminal Up to about 18 inches per day 0 Retrograde Transport From terminal region back toward soma Up to about 9 inches day The Blood Brain Barrier Buffers Brain eg electrolyte concentrations Keeps bit polar molecules out eg toxins Keeps most bad stuff out capillaries in body are leaky will be a mechanism function is to protect the brain one of ways is to help maintain relative constant electrolyte environments when eat sodium or potassium rich food what happens in capillaries you get major uctuations in levels if allow wild swings of levels we would have seizures so this barrier will help maintain static environment for the brain will keep a lot of bad stuff out like toxins if toxin gets in body large proteins have electrical charge and the barrier is going to keep these large toxin molecules from passing through brain capillaries into brain tissue formed by fact that capillaries that feed brain have tight junctions two ways out of blood stream and into tissue if molecules are highly lipid soluble and dissolves in lipids and substance can pass easily out of capillaries into brain tissue and specific transport like amino acids out of blood stream and deposit in uid of the brain 0 Plant toxins and bacteria for example Formed by tight junctions of the capillaries feeding CNS 0 Less leaky The BBB Is Not Impregnable o Herpes viruses West Nile Virus Viral Meningitis pychoactive drugs eg cocaine THC opium CNS has been breached a la drugs THC extremely soluble glucose transported across amino acids will be basis for neurotransmitters large charged molecules like ionized molecules get trapped and no gaps big enough for them to leak out Neural Communication is Electrochemical Pt 2 Communication within the Neuron Terms Concepts Ions Cations and Anions Extracellular uid Cytosol intracellular uid Selective permeability Resting potential Graded potentials Threshold of excitation Action potential NaK Transporter Ion Channels 0 Voltage dependent o Ligand gated All or none law Salutatory conduction Pt 2 Central Principles Virtually all neural communication occurs via action potentials eg cells firing Action potentials are electrochemical events The relative balances of positively and negatively charged ions inside and outside of the neuron provide the stored energy that is released during the action potential 0 Think Battery Water Water Everywhere Water is the best universal solvent you are water and solution of sodium chloride water is essential to life and universally water is the overall solvent stuff dissolves in water better than anything else when mix lipids with water get blobs on the inside of blobs there is water so it goes water layer of fat and water on outside this is setup of cells Phospholipids When phospholipids contact water the hydrophobic fatty acid tails automatically align away from water molecules forming a double layer barrier with water inside and outside they will form main part of cell membrane the heads of phospholipids are hydrophilic meaning they are water loving or seeking and the tails are hydrophobic meaning they avoiding with cell membrane have a lot of phospholipids coming together get spontaneous arrangement of heads on the outside towards the water and the tails will arrange themselves inwards forming trans membrane area Fluid Mosaic everything jammed together The Plasma Membrane Packed tighter than the UGA Orbit bus have cell membrane and a bunch of stuff plugged into it not just phospholipid bilayer but also have proteins embedded in it the bilayer is semipermeable stuff can cross through it but only under certain conditions substances that are highly lipophilic will pass right through will enable basis for creating a battery The Membrane Potential Storing the Energy to be Released during Action Potential o Have membranes and unequal distributions and charge electrical current and allow ions to ow o When distribute ions unequally across a cell membrane and have higher sodium levels outside of cell and negative charges inside you have electrical charge across membrane 0 3 types of membrane potentials the electrical difference between inside and outside of cell electrical differences between semi permeable cell member Resting Potential Flow Action Potential SPSP I Birds sitting on high voltage lines and these lines are not insulted and feet are connecting to electrical current the birds aren39t dying because cycle isn39t complete unless there is connection between one of these wires and the ground the birds are fine electricity needs cycle to be complete before it can ow 0 Sodium chloride Sodium is and chloride is o In cytosol you have stuff dissolved in aqueous environment higher concentration of enzymes and proteins A higher concentration inside cell and will help get polarization of the axon o More sodium outside of cell and inside is relatively low 0 Organic anions are both inside and outside but mostly inside 0 Starting out at rest with charge inside and positive charge outside 70 says defining events as happen inside of cell o Other half of salt is chloride and is charged more concentrated outside of cell 0 K is potassium and is more concentrated inside of cell o If plug all things into Nert s equation at rest the average neuron is polarized 70mV outside and inside o High concentration of sodium chloride know relative distributions of these 0 Concentration gradient force o Electrostatic pressure 0 How those two forces act upon sodium in terms of generating action potential 0 If at complete rest all areas in cell will be at 70 o Generate graded potentials EPSP will move us in direction of firing action potential and action potential itself time scale is millisecond action potential lasts about that long polarity on y axis reference point 0 will not be at origin we put it half way on the y axis because we start at 70 o 0 no electrical difference across membrane 70 resting membrane potential 0 High concentration of sodium out and high concentration of Potassium in 0 Sodium potassium pump uses ATP each time these thing turns is going to spend metabolic energy in order to take 3 sodium ions inside to outside and take 2 potassium and bring them inside o Purpose for doing this It creates and maintains an electrostatic gradient across the cell membrane allow for repeated firing of action potentials brain uses 10 times metabolic energy 0 Sodium Potassium Pump Helps maintain proper ion concentrations The neuron pays a fortune to say nothing Now we are thinking of what happens in the dendrites If take a cylinder and stick it in there so sodium could cross what would it do Sodium molecules would come in because the concentration gradient force will seek to equilibrize across cell membrane and wants to push sodium in electrostatic force wants to push it in so if there was cylinder sodium will ood into dendritic region Much force wants to push Na into the neuron at resting potential EPSP starting point for getting this pushing sodium into dendritic region is way to get EPSP Concentration Gradient Electrostatic The key in this case is a neurotransmitter that released in synapse as a ligand molecules that bind to receptors and main type of ligand is our neurotransmitter molecules chemical produced by cells released in synapse and bind to receptors one way neurotransmitters work and will be one of way drugs work Dendrites express membrane bound proteins called receptors serotonin or dopamine receptors Once released from the presynaptic neuron a neurotransmitter molecule may bind a receptor causing it to twist open goes into synapse which is extracellular space causes receptor to twist open like an empty toilet paper roll and want to drop marbles through it and twisted tube so none of the marbles can pass through but if twist it back the marbles will pass through neurotransmitter binding will cause the same thing and opportunity sodium has been waiting for to rush into the dendritic region Membrane Potentials Resting is going to be in uenced by four primary factors fully charged battery that is kept to release current ions ow across membrane during action potential Graded this leads to one of two types of graded potentials can take on any value between resting potential and the threshold of excitation or can be in opposite direction Action Graded Potentials Exciting or Inhibiting either propels it towards action potential or inhibits it Excitatory Postsynaptic Potentials EPSPs moving the neuron toward action potential generation involve depolarizing currents one branch of the dendrites 0 Start at 70 and measure 0 Operating like a weak battery 0 Graphs that show the spikes should be able to understand put one of oscilloscope questions on there and ask questions about it 0 At 70 and need to get to threshold of excitation which is about at 55 have to get to 70 to the threshold and get there through accumulating EPSPs and add them up through neural integration the events that one dendrite isn39t enough to get you through threshold so summing up EPSPs across big areas and points in the dendritic field at one point in time is net excitation in moment of time is enough to get you to threshold if it is you get action potential the little blips are currents from EPSPs and don39t make it but when get 4th attempt get sufficient current and reach it 0 We are at dendrite neurotransmitter comes in and binds Ach is common in brain and binds to receptor opens up receptor on dendrite sodium rushes in and what will happen to 70 Will get upswing will move towards zero fact that moving toward zero is losing polarity the inside of the cell is being slightly less charged compared to the outside so we call it depoliazation o EPSPs depolarizing currents because moving us towards zero if at 70 and let charges in will bump you in direction of zero 0 55 threshold of excitation EPSP Summation under Neural integration Temporal the instance in which one synapse that is exciting is firing an intense volley of excitatory input into dendritic region hundreds of stimulation per second so really intense input will give you more of a bump time based so temporal keep exciting one dendritic area before have time to fuse away on bottom right quick succession of excitatory stimuli which helps move us along to threshold of excitation Spatial you don39t have extremely intense bombardment at any one dendritic but have a lot of little excitatory at multiple points in dendritic field summation across space 25 have both processes going on at same time in cell Will also have some inhibition allows graded potential to take on any value it wants There is another type of graded potential Yes IPSPs 0 They involve membrane hyperpolarization s and moving away from threshold of excitation more polarizing the membrane drugs shift balance towards hyperpolarization suppress neural o The chloride is more outside then inside working against electrostastic force under certain conditions the GABAa receptor brains main inhibitory neurotransmitter chloride channel which is little cylinder and opens up and allows chloride to come into dendritic region and lead to small hyperpolarizing unit and moving away from threshold and becoming less likely that cell has action potential o Inhibitory Postsynaptic Potentials IPSP I Moving the Neuron Away From Action Potential Generation I At any one moment hundreds or thousands of EPSPs and IPSPs are being sorted out in the soma region in a process called neural integration Be familiar with figures that copy from book and use to explain in class Showing that red stuff is net excitation neural integration of EPSPs signals Blue stuff is integration of IPSPs Show what39s going on at axon hillock because it makes decision if to fire an action potential or not Membrane Potentials Action Action Potential All or None Principle Propagated Voltage Dependent Na Channels Hillock Different category of ion channels Talked about ligand gated ion channels plugged in dendritic regions nicontinic channel is sodium channel and opens up in response to ligand gated These are sodium channels and allow to come in they are voltage gated or dependent they are found in very dense population at axon hillock thousands of these at axon hillock if ligand channels open up to ligand then these open up to certain voltage or threshold of excitation Mechanism built into them where can detect electrical difference inside and outside of cell and remain closed until reach threshold then opens up and sodium can come in High concentration at axon hillock We have now gotten to our threshold axon potential occurs only at one place in axon at a time same cell that has long axon can have 20 action potentials happening at the same time but in different parts of it Axon hillock generates action potential by opening up gates so much sodium rushes in have lots of depolarization depolarization then action potential For one second it is positive inside and not outside Get activation of voltage dependent potassium will leave the cell following concentration gradient then that will make it action potential peak and then head in other direction will rapidly rehyperpolarize cell and return us to resting potential and recharge battery and send another action potential So much potassium rushes out and get a little overshoot and for second hyperpolarized beyond the resting potential and makes it difficult for cell to fire another action potential until get back to baseline refractory period time it takes for something to recharge Will limit maximum frequency of action potentials upper limit is about 500 action potentials per second busy neuron will be around 50 all neurons fire some action potentials everything has to do with rate Certain natural toxins block voltage gated Na channels and inhibit APs Tetrodotoxin Japanese Puffer Fish produce by puffer fish part of delicacy is to cause slight numbing of mouth and happens because of toxin that will kill you if eat too much of it the toxin blocks voltage gated sodium channels and will prevent establishment of action potentials TTX binding site toxin binds to it if take too much of it cause neural signals that allow you to breath and so you suffocate Local anesthetics exert similar action on peripheral noriceptors will numb you first and these are drugs that have activity at voltage gated sodium channels and cant become active and cant send pain signals to brain they are there to tell your brain if you are being exposed to stimulus that cause tissue damage if block ability of nociceptors of sending signals can39t get to brain and won39t feel pain similarly cocaine does this o Cocaine plant Refractory Period Upper Limit of AP Frequency About 500 What would happen if we gain the technology to customize special neurons that had ability to generate 2000 action potentials per second the abilities these could create Why is rate important Rate Law refers to frequency of actin potentials that neuron is generating 10 or 50 per second different rates is part of neural coding coding has to do with specific time based features of signal Morse code has to do with tapping that is kind of coding neurons are doing same thing based on patterns for which they become active volley of intense signals can mean different things different ways of encoding signals from environment that will serve as basis for coding intensity domain intensity coded by action potential frequencies sensory receptors the higher the rate of neuron firing the more intense the stimulus seems put tack in finger will cause mildly painful signal if jam knife into it will have more receptors become activated and firing faster intensity domain of what I receive Certain natural toxins block K channels Enhances firing rate of pain fibers nociceptors Bee Venom Apamin and Scorpion Toxins Tamapin and Charybdotoxin the toxin they inject will fool receptros that encountered that highly severe pain the actual damaging stimulus is not that intense in bee venom it enhances firing rate of pain fibers by altering the potassium channels tricking nociceptros of firing high rate of action potentials and experienced as very intense Have axon potential and need to get it to terminals need to get it down their quickly because increases processing speed of brain to have more signals in brain one of solutions that was developed was myelination of neurons Saltatory Conduction will allow us to go from hillock to axon terminals in quick fashion Dominos in unmyelinated axon one set of sodium ion channels causes action potential as consecutive layers of myelin wrap around it goes about 2 miles per hour in unmyelinated axon to 200 miles with heavy myelinated axons myelination allows processing speed of 100 times than in cases where don39t have myelin Most axons in CNS are not myelinated when look at white matter of brain there because of oligdrocyetes and myelin Go from dominos to cheetahs in speed Idea is one of insulation plastic tape that wrap around electrical wires redoubles insulation efforts why want to insulate axons is because of efficiency and interference can have interference of signals and lots of axons are piggybacking one another and don39t want intermingling of signals Nodes of Ranvier unmyelinated segments of axon because action potential will die out quickly under completely myelinated axon Have myelinated segments represented by white stuff and in between is nodes 0 Recharges action potential periodically so when it arrives at terminal it makes it to the end can be about 4 ft long so need mechanism to make sure signal arrives so nodes express more of same thing to make sure process gets started 0 Have high concentration of voltage dependent at axon hillock and high concentration at each of nodes of ranvier o Where action potential gets started voltage dependent and arrive at myelin segment o Threshold set determined by voltage receptors when voltage gated sodium open up As work way from left to right 30 20 0 20 30 Has to end when it gets to point of end of myelinated and get to more nodes before it reaches 55 Calculated length of myelin Gives rise to jumping action potential down the axon jumps from axon hillock to first node and gets regenerated and jumps to next node all the way down Myelinated segments are about 80 times the width of nodes of ranvier so have rapid process that gets us from hillock to terminals 0 We call this Saltatory Conduction jumping the myelinated segments o Nodes of Ranvier recharging the action potential What gets jumped in saltatory conduction Myelinated segments get jumped Propagation the idea that you don39t lose strength down the axon it arrives at full power Really it happens in cell Saltatory Conduction In CNS myelination from Oligodendrocyte don39t do that In PNS myelination from Schwann cells show some ability to reestablish connections over time And Then Effects of Action Potential at the Axon Terminal 0 If don39t get action potential to terminals don39t get exocytosis 0 Last class of ion channel voltage gated calcium channels I They open up same way voltage gated sodium channels but when they open up they don39t allow sodium in they allow calcium in I Importance at axon terminal is not depolarization but the ability of calcium when reaches critical concentration 2nd messenger goes into cell and calcium is signal that causes synaptic vesicles to spill their contents into the synapse process of exocytosis exocytosis is calcium dependent I Reason for having action potential is to enable calcium to infiltrate synaptic region I Calcium initiates cascade of protein interactions Docking when ship pulls up to dock and people get off the boat proteins dock and Fusion fusion of two cell membranes Calcium Mediated Exocytosis Synaptic vesicles contain thousands of neurotransmitters already prepackaged and waiting for calcium levels to increase by the arrival of AP and that is signal to dock and fuse Calcium channels open and cause release of neurotransmitter Simple Version Calcium in and Neurotransmitter out exocytosis is dependent on calcium Detailed Version Ex Families of proteins know what is fusing is the membrane of the synaptic vesicle and cell membrane of axon terminal Proteins allow membrane of synaptic vesicle to join up with cell membrane and get omega shapes and indicate that fusion is taking place and when get fusion get release of neurotransmitters into synapse Botox interrupts interactions with cydocoline get failure of skeletal muscles to contract Certain Natural toxins block the protein interactions required for synaptic vesicle docking and fusing Botulinum Toxin Breaks of proteins required for docking and fusing so AP arrives but exocytosis is not happening and not getting any neurotransmitters When you are getting a botox hope they dilute it enough Part II Intercellular Communication Electrochemical Covered electrical events now we have chemical signal that has been released into synapse neurotransmitters carries signal to postsynaptic They are biochemical body synthesizes them Dealing with amino acids Landmark Studies where neural communication came from Herman von Helmholtz o Conduction Speed establishes connection speed of neurons to be too slow he was able to determine that a simple spinal re ex arc and motor response in withdraw was too slow to be accounted for by continuous neural circuitry and demonstrates with experiments with dogs are there breaks or gaps in system what39s going on with motor responses Charles Sherrington o Synaptic Theory vs Reticular Theory synapse that there are tiny gaps main model was reticular theory or net like prevailing theory was that nervous system worked like circulatory system which is all continuous circuit but he says no nervous system has gaps Otto Loewi o Vagustoff discovered first neurotransmitter first experimental evidence that demonstrates the way neurons work when stimulated is that release chemicals in environment and affects body tissue he has a dream about an experiment that you could conduct to verify that neurons release chemicals and wakes up and takes notes and cant interpret own notes but he has same dream the next night and decides to just go to his lab and takes frogs heart and puts parts in solution in beaker vagus nerve attached to the heart and he decides to stimulate artificially the vagus nerve and finds that the heart slows down insight he has was to add pump that would allow the two electrolyte environments and will share uid from first beaker to the second one first one speeds up then second speeds up providing stimulation to vagus nerve must cause chemical to be released that is responsible for slowing down contraction of cardiac muscle stuff being released from Vagus nerve is vagustoff neurotransmitter known as cydocoline parasynthetic response Not all types of synapses are the same Axon dendritic synapse have dendritic spine axon terminal of first cell causes neurotransmitter molecules to be released and go to spine Also have axosomatic synapses communicating with somacell body region no terminals And have axoaxonic synapses at axon terminal region have axon terminal of a 3rd cell and sends signals to axon terminal and modifies activity of synapse Action can be to stimulate more or inhibit less neurotransmitters o Presynaptic facilitation cell causes to release more neurotransmitters o Presynaptic inhibition inhibits release of neurotransmitters General Schematic Synapse is the gap synaptic gap Presynaptic membrane releases neurotransmitter postsynaptic membrane is like dendritic spine where receptors are going to be Action potential arrives activation of calcium channels and calcium comes in and causes docking and fusion and have omega and release of neurotransmitters in synapse density of mitochondrion synapse is tiny and then have postsynaptic density there because have high concentration of proteins primarily receptor proteins Calcium channel dependent docking and fusion omega symbols What does neurotransmitter binding do to postsynaptic neurons o Can have one or two messengers o Messenger binds to receptor and causes it to open up 0 First messenger neurotransmitter molecule of dopamine or serotonin o Acts on a receptor 0 Binding process ligating process by which neurotransmitter binds to receptor and causes it to change 0 Effects on receptor I Induces conformational shift to open position when binds causes 3 dimensional protein to shift and cause something to open up I Initiates second messenger action happening in 2nd or postsynaptic cell First Mechanism Ionotropic Receptors Action requires passage of ions across cell membranes Activating a receptor that allows sodium to come into dendrites ionotropic receptor GABAa is ionotropic receptors Get cellular suppression activate chloride channels and chloride will come in and hyperpolarize the cell Can allow ions out like potassium Sodium in EPSP Potassium out IPSP Chloride in IPSP Calcium in activates enzyme Second Messenger Metabotropic Receptors Single gene products Complex that leaves in and out of cell membrane always 7 times 7TM 7 trans membrane Always one gene product More common in brain Norepinephrine Dopamine Serotonin extracellular area binding site for neurotransmitter but don39t just have direct opening of channel proteins inside G proteins are binding G Protein 0 Attached inside of cell to intracellular part of protein when binds the parts can go into cell and can perform simple actions like ion channel next door opened up w hen alpha subunit goes over and opens it up get ions coming in and changing polarity of the cell 0 More delayed effect takes longer when ionotropic is shorter but stays open for longer periods of time 0 Different possibilities of activating G proteins Brain literally changes when you become addict o ust know basic differences between ionotropic and metabotropic O Modulating NT Release Neuropeptide Action o Not simple amino acids long protein products that take long time to make o Neurons can walk down arrive at axon terminal and get packaged in big vesicles and they contain neuropeptides when these vesicles merge with membrane release norepinephrine and neuropeptide o Neuropeptides eg galanin are released by the same neuron which releases a small molecule NT eg norepinephrine in response to rates of action potentials released from same cell if get bursting rates of action potentials arriving then the docking and fusion will pertain to big vesicles galan helps inhibit the ongoing release of norepinephrine so doesn39t get out of control Autoreceptors o Autoreceptors are expressed on the presynaptic cell and are activated by the neurotransmitter molecules released by that same cell hence the name expressed on same axon terminal as the one that it is being released autoreceptors also have norepinephrine receptors expressed on same membrane exocytosis is happening going to slow down the rate at which cell is releasing norepinephrine Autoreceptors are expressed on the same nerve terminal that is releasing neurotransmitter they are receptors that are being activated by the same cell that is releasing negative feedback loop always inhibition if activate autoreceptor slowing down release of neurotransmitter regulates negative feedback in terms of neurotransmitter release Two different arrangements negative sign negative feedback mechanism and slows down neurotransmitter released neurotransmitters are binding to terminal autoreceptors and initiating IT39S A NEGATIVE FEEDBACK Somatodendritic autoreceptor closer to cell body this one inhibits action potentials if you inhibit action potentials in terms of functional consequence is inhibit neurotransmitter release by inhibiting AP is affect release of amount of neurotransmitter Question A drug acting as an autoreceptor agonist would binding and activating autoreceptors Increase the synaptic activity of the neurotransmitter 0 No Decrease the synaptic activity of the neurotransmitter 0 Yes operating as an antagonist of neurotransmitters Not affect the synaptic activity of the neurotransmitter How is the action of neurotransmitters on postsynaptic receptors terminated 0 Get precise signals will increase capacity for exchange of complex codes which nervous system wants to do two active mechanisms and one passive process that terminates synaptic action of neurotransmitters Terminating Synaptic Action Passive diffusion diffuse away from synaptic cleft over time diminishing synaptic concentrations and get less activation of postsynaptic receptors physical property that is just diffusion Two actions enzymatic inactivation Degradation and Reputake 0 Active mechanisms 0 Enzymatic enzyme that breaks down neurotransmitter molecules Ex Mao is going to serve function of breaking down serotonin norepinephrine and dopamine MAO is enzyme and the action is for it to take serotonin and split in in part and change it into something else and can no longer activate serotonin receptors does same thing to dopamine and norepinephrine can rapidly degrade all three of those 0 Reuptake Accomplished by transporters proteins themselves called transporters Have DAT dopamine transporter and NAT norepinephrine transporter Proteins represented by 2 is reuptake like vacuum cleaner and balls being sucked back into presynaptic axon terminal if gave drug that blocked transporters and kept them from doing job Keeps ability of removing neurotransmitter from synapse have ongoing release of neurotransmitter molecules and get accumulation of synapse of increased concentrations of neurotransmitters One of thing cocaine does cocaine come in synapse and bind to DAT and blocks ability to accomplish reuptake Reuptake by transporters Animals can39t distinguish subjective effects of cocaine from wellbutrim SSRIs reuptake inhibitor ex Prozac antidepressants selective serotonin reuptake inhibitors coming into synapse attaching itself to serotonin receptors and blocking transporter and allow serotonin to accumulate in synapse serotonin agonist drugs Inhibitors of Enzymatic Degradation Example Monoamine Oxidase MAO Inhibitors if dissemble enzyme that blocks degradation increased activity of postsynaptic receptors Old School Antidepressants 0 Specific example Phenelzine Nardil Inhibitors of Reuptake Rls Example SSRIs Second Generation Antidepressants lower risk of severe side effects 0 Specific Examples Fluoxetine Prozac Sertraline Zoloft Citalopram Celexa et cetera Almost always psychotropic drugs both illicit and medicinal work by altering one or more aspect of the synaptic action of neurotransmitters 0 They are not magic pills come in and sway balance in favor of promoting action of system of inhibiting that system just changing the balance of mechanisms already in place 0 Green sign how drugs act as agonist 0 Red signs how drug act as antagonist Brain wants to say something to another part of the body Brain Signal Outputs 1 Send neural signals down the spinal cord directly and through the peripheral nervous system paramatial signals volitional behaviors when decide to send signals and descend spinal cord and cause skeletal muscles to do something 2 Hormonally does by releasing hormones pituitary gland works in conjunction with hypothalamus hypothalamus tells pituitary what types of hormones and how much to be released into blood stream hormones delivered through blood stream use bloodstream to arrive to multiple target sights needed in both males and females released in blood stream and carry throughout body 1 Spinal cord Hypothalamus controls pituitary NT communicate across synapses message relayed specific signals from one cell to another cell hormone is like PA system By contrast hormonal signals is broadcasted and affecting a lot of different norepinephrine is that a neurotransmitter or a hormone It is both depending on how it is activated when released across synapse its neurotransmitter also works in fight of ight response NTs act across synapses while hormones are delivered via blood stream Hormone Actions Peptide hormones activate metabotropic receptors same as NTs G protein 7 transmembrane receptor embedded in cell membrane activated by hormone how norepinephrine acts in periphery Steroid hormones activate nuclear receptors and regulate gene expression steroid cholesterol derived from go through cell membrane don39t have to activate surface receptors and go to nucleus and regulate gene expression Stress Responding HPA Axis Hypothalamus originate in for release of CRH this is released from hypo and travels short distance down to pituitary gland and causes it to release ACTH two biggest areas of focus is stress response and regulation of sex 0 CRH Pituitary ACTH going to go into blood stream and its target is a structure on top of the kidneys called adrenal glands and ACTH is going to act on adrenal cortex Adrenal Cortex to get the release of CORTISOL the main stress hormone and that is going to travel through blood stream throughout body and help increase fight of ight responding increases metabolic output Know two axis have gonads that are undifferentiated after fertilization specializes tissues into gonads and they become either ovaries or testes depending on which signals they get have same tissue talk about regulating menstrual cycle LH and FSH in hypothalamus get release of GnRH Sex Dev amp Regulation HPG Axis Hypothalamus kisspeptidin causes hypo to release GnRH when reaches pituitary causes release of FSH and LH which are released in blood stream and their target are gonads in females it is regulation of when is estrogen and progesterone being released when ovulation occurs regulating the maturation and release of follicle also causing the release of estrogen men have LH and FSH as well when they reach gonads cause testes to release primary hormone testosterone females also have a little testosterone released critical for development of male gametes as well production of sperm depends on hypothalamus is ultimate control cycle for sexual development 0 GnRH Pituitary Gonads
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