MCB/Psych C61: Mind, Brain, and Behavior

What is the definition of paleolithic cave art?

Exam 1

Chapter 1: Origins 

­ Paleolithic cave art: Some may represent shamanic connections between the ancient humans and the local animals

­ These drawings show that ancient humans may have had mental worlds of significant complexity

­ Shaman: Healers in their communities that are believed by some to communicate with animals, plants and other elements of nature in ways not explicable within the worldview of contemporary science

­ They are said to be particularly skilled in accessing states of mind that are sources of knowledge and power. Which then can be used in service of others in the community ­ 2001: A Space Odyssey: Hominins find femur bone & use it as a weapon

What is the definition of a shaman?

We also discuss several other topics like What are the steps of the accounting cycle?

­ Hominin: Group of primates that includes modern humans and the ancestors of modern humans ­ Goes back perhaps 5 million years

­ Hominin genera (primary groups): Ardipithecus 4.4 mya, Australopithecus 4­1 mya, and Homo 2.3 mya­present

­ Evolution of Brain/ Skull Size: Part of this substantial increase over time can be partially attributed to an increase in body size

­ Ardipithecus: 350 cubic centimeters (cc)

­ Australopithecus: 500 cc

­ Homo habilis: 650 cc

­ Homo erectus: 1200 cc Don't forget about the age old question of Cocaine and meth are the most dangerous, what?

­ Homo neanderthalensis: 1400 cc

What is the definition of hominin?

­ Homo sapiens: 1400 cc

­ Over the last 2 million years of evolution our brain sizes have increased rapidly. Accompanying the expansion of brain size is the development of ever

sophisticated behaviors: tool use, nuanced social interaction, language,

mathematical skills, complex problem­solving abilities, and a capacity to

construct elaborate explanatory frameworks to aid in understanding our world

­ Violence: The ability to understand the world through physical and mathematical reasoning, has formed a deadly connection with our primal capacity for fear and violence If you want to learn more check out What important characteristics of aspirin did you use to separate it from the other pill components?

­ We also have tremendous capacity for compassion and love

­ Perhaps the strongest and most natural of our behavioral tendencies

­ Mind: The collection of mental experiences

­ Subjective experiences, including thoughts, feelings, perceptions, mental images, and sense of self

­ Consciousness: The capacity to be aware of these mental experiences

­ Mind­body Problem: What is the relationship between our mental experience and the physiology of our body and brain

Chapter 2: Nervous Systems and Brain

­ William James (1842­1910): First official professor of psychology.

­ He studied behavior (psychology) and its biological underpinnings (Neuroscience) ­ Wrote The Principles of Psychology

­ If the nervous communication be cut off between the brain and other

parts, the experiences of those other parts are non­existent for the mind.

The eye is blind, the ear deaf, the hand insensible and motionless.

Conversely if the brain is injured, consciousness is abolished or altered

even though every other organ in the body be ready to play its part

­ Nerve Cell (Neuron): Cellular units of single transmission If you want to learn more check out What kind of epithelial tissue is responsible for secretion and function?

­ There are about 100 billion (10^11)neurons in our brains

­ Glial Cells (Glia):

­ Nervous System Complexity Across Species:

­ Sponges: no nervous system

­ Hydra: Simple nervous system ­ loosely connected network of a small number of cells allowing for simple communication

­ Jellyfish: Simple neural network

­ C. elegans (nematodes): 302 neurons that researchers have been able to map out accurately

­ Planaria (flatworms): Extended network of interconnected neurons & two clusters of neurons at the head end of the worm

­ Some neurobiologists think they could be a primitive brain

­ Vertebrate Brain Structure: Forebrain (cerebrum), midbrain (optic tectum, thalamus), and hindbrain (medulla and cerebellum)

­ Cerebrum: Cerebral Cortex

­ Cerebral Lobes: Frontal, Parietal, Occipital, Temporal

­ Cerebellum: Balance and coordination

­ Brain Stem: Medulla, Pons, and midbrain If you want to learn more check out How is vibration in waves illustrated?

­ Cerebral Cortex: Outer layer of the brain, it’s folded up a lot and if it were stretched out all the way it would be about the size of an unfolded newspaper (2.5 sq feet) Don't forget about the age old question of Do opportunistic pathogens cause disease?

­ Gyri: Bumps on cerebral cortex

­ Sulci: Grooves are cerebral cortex between gyri

­ Central Sulcus separates frontal & parietal lobes

­ Lateral Fissure separates temporal from frontal and parietal lobes

­ Longitudinal Fissure separates left and right hemispheres

­ Corpus Callosum: Bundle of approximately 200 million nerve fiber that connects the right and left hemispheres of the brain

­ Andreas Vesalius (1514­1564): On the Fabric of the Human Body

­ Dissected human bodies and had professional artists draw many detailed drawings of the nervous system

­ Meninges: Dura, arachnoid, & pia

­ Dura Mater: If one removes the skull bone, this is what they see. Skin­like sheet of tissue covering the brain

­ Arachnoid: Beneath the Dura Mater

­ Pia Mater: Beneath the arachnoid, most delicate layer, closest to brain

­ Between arachnoid and pia layers is the subarachnoid space, contain

cerebrospinal fluid

­ Cerebrospinal Fluid (CSF): liquid that cushions the brain inside the skull and transports soluble substances throughout the CNS

­ Meningitis: Condition that occurs as a result of an infection ­ meninges become inflamed ­ René Descartes (1596­1650): Philosopher & biologist who was interested in connecting the mind with body processes

­ Eyes and perceptual awareness

­ Mind, body pluralism

­ Luigi Galvani (1737­1798): Studied the effects of electrical stimulation on animal muscles ­ He found that dead frog legs twitch when electrically stimulated and he hypothesized that muscles move as a result of internal electrical forces that can be triggered by external electrical stimulation

­ Camillo Golgi (1843­1926) & Santiago Ramón y Cajal (1852­1934): Created a technique for staining neurons to make them eminently visible under the microscope

­ Golgi Stains: The dark crystals of the silver chromatic stain neurons and leave them and all their extra parts completely visible. It only stains about 1% of neurons which actually makes them easier to study because you’re not overwhelmed by seeing 100% of the billions of connections in the brain

­ They disagreed about how the nervous system worked

­ Ramon y Cajal: Focused on individual neurons

­ He dominated the way people have thought about neuroscience

­ Golgi: Things were only understandable in terms of global networks. Must look at a large group of neurons

Chapter 3: Chemistry and Life 

­ Chemistry: Is concerned with the nature of matter and its transformations

­ Investigates the conditions of how these elemental constituents (atoms) interact to form molecules

­ Alchemy: Similar to chemistry, but older, and had an esoteric or occult aspect that was concerned with investigation of the psyche and with transformation of one’s self and the human psychological condition

­ Dmitri Mendeleev (1834­1907): Came up with a way of organizing the known chemical elements into what we now call the periodic table

­ Periodic Table: The identity of an element is determined by the number of protons in the nucleus and this is expressed as a number on the table along with the elements

abbreviated name

­ Elemental Composition of the Human Body: Oxygen, carbon, hydrogen, nitrogen, calcium, phosphorous, potassium, sulfur, sodium, chlorine

­ By weight, top 5 elements are Oxygen (65%), Carbon (18.5%), Hydrogen (9.5%), Nitrogen (3.4%), Calcium (1.5%)

­ Human body is about 65% water

­ Ions: Charged atoms that are formed when atoms either gain or lose one or more electrons. ­ Cations: Atoms likely to give up electrons and become positively charged ions ­ Elements on far left side of table will easily give up electrons and become cations ­ Anions: Atoms likely to take on electrons and become negatively charged ions ­ Elements on the far right side of the table will easily take on electrons and become anions

­ Molecules: Stable configuration of atoms held together in a particular geometric shape by the sharing of electrons between atoms

­ Covalent Chemical Bonds: The sharing of electrons between atoms, this acts as a glue holding atoms together

­ Organic Molecules: Molecules produced by life are composed largely of carbon and hydrogen & are made of lots of atoms

­ Hydrocarbons: Organic molecules made solely of carbon and hydrogen ­ Polarity: Separation of charge between different parts of molecules

­ Water has more of a negative charge at the oxygen and more of a positive charge at the hydrogens

­ Hydrogen Bonds: Slightly negative oxygen molecule of one water molecule is attracted to the slightly positive hydrogen atom of another. Noncovalent because it does not involve sharing of electrons

­ Results in a matrix of water molecules held together loosely by hydrogen bonds, the water molecules can move around easily

­ Hydrophobic/ Lipophilic: Substances that don’t like to be around water and don’t dissolve in water

­ Hydrophilic/ Lipophobic: Substances that like water and dissolve in it

­ Lipids/ Fats: Medium­sized molecules that are composed primarily of carbon and hydrogen atoms in long chains

­ Fatty Acid: kind of lipid molecule consisting of a hydrocarbon chain with a carboxylic acid group (­COOH) at one end

­ Phospholipids: Composed of 2 carbon­hydrogen chains joined together at one end by a group of atoms containing phosphorous and perhaps nitrogen

­ They have a highly hydrophilic part (head) and a highly hydrophobic part (tail) ­ Phospholipid Bilayer Membrane: Phospholipids form sheets in three dimensions that can fold to form enclosed surfaces separating two aqueous environments

­ The hydrophobic/philic parts of phospholipids align with each other and create this bilayer

­ Quaternary Amine: In the head of a phospholipid, there is a phosphorous atom, oxygen atoms, and a nitrogen atom that carries a positive charge. The positive charge comes from its electron deficit arising from the nitrogen having four bonds with other atoms, rather than its normal 3

­ Amino Acids: Create proteins by linking together by covalent chemical bonds called peptide bonds

­ Contains an amine group (­NH2) and a carboxylic acid group (­COOH)

­ Polypeptides: A chain of amino acids join together by peptide bonds

­ Only happens under specific catalytic conditions found within the ribosomes of cells

­ Levels of Description for Protein Structure:

­ Primary: Linear sequence of amino acids forming the protein ­ a list of the component amino acids in the order they occur in the polypeptide chain

­ Secondary: Interactions of nearby amino acids to produce patterns of local folding within the protein

­ Alpha Helix: common secondary structure of proteins and is a right hand­coiled or spiral conformation

­ Tertiary: Overall shape of the entire protein molecule, created by all the electrical and geometric properties of the constituent amino acids guiding the folding of the chain of amino acids into a unique 3D form

­ Fold into 3D form

­ Quaternary: Many functional proteins are composed of a complex of more than one polypeptide subunit, with each subunit consisting of hundreds of amino acids

­ Put 3D forms together

­ Carbohydrates: Made of carbon hydrogen and oxygen joined by covalent bonds ­ Nucleic Acids: Largest molecules in living organisms, contain info required for constructing a living cell (genetic info)

­ Deoxyribonucleic Acid (DNA): Double helix composed of 2 long chains of nucleotides ­ adenine (A), cytosine (C ), guanine (G), thymine (T)

­ A forms with T, G forms with C

­ Ribonucleic Acid (RNA)

Chapter 4: Genes and the History of Molecular Biology 

­ Charles Darwin (1809­1882): The great diversity of living organisms can be understood as resulting from processes of variation and selection ­ Evolution

­ Darwinian Evolution says that there must be some underlying source of variation producing variant organisms that can be selected by natural (or domestic) processes ­ Gregor Mendel (1822­1884): Did experiments on inheritance in pea plants ­ He observed that various traits in pea plants parceled out in an orderly fashion during breeding, from one generation to the next. This led to the idea that info that is needed to build an organism is packaged into units associated with specific traits

­ Provided a mechanism to explain Darwin’s phenomena

­ Gene: the fundamental unit of heredity

­ Niels Bohr (1885­1962): Claimed that the acts of observation place fundamental limits on what we are able to know about the universe, and this will necessarily limit the capacity of any physical theory to describe what kind of reality might exist independent of our observations. ­ This is quantum mechanics

­ He said that in order to study the structure and function of living organisms at the subcellular level, it would be necessary to probe the cell with measuring instruments, and that such probing actions would necessarily perturb and disrupt the molecular

components of the cell in profound ways

­ Max Delbrück (1906­1981): Investigated how to study the molecular infrastructure of organisms

­ Proposed that genes are molecules, and the atomic configurations can be rearranged when impacted by high energy electromagnetic radiation, like x­rays

­ Presti was his grad student

­ Used E. coli and bacteriophages (viruses) as a way to investigate the physical properties of heredity

­ Erwin Schrödinger (1887­1961): Wrote What is Life? and was impressed with the notion that pursuing the investigation of life at the most fundamental molecular and atomic levels might lead to the discovery of new physical laws

­ Oswald Avery: Demonstrated that DNA can carry genetic information from one cell to another. He said that his evidence supports the belief that a nucleic acid of the deoxyribose type is the fundamental unit of the transforming principle

­ No one believed them that genes were composed of DNA, because everyone thought that DNA was too stupid of a molecule to carry genetic information

­ Hershey­Chase Experiment: Showed that it was viral DNA (containing phosphorus) not viral protein (containing sulfur) that was transferred from from virus to bacteria during infection, proving that genes are made of DNA

­ They used a bacterial virus (phage T2). They grew it on two different things: one with radioactive sulfur atoms and one with radioactive phosphorous atoms. Proteins contain sulfur and DNA doesn’t. DNA contains phosphorus and proteins do not. Therefore, the phages that grew on radioactive sulfur would have radioactive protein and the phages grown with radioactive phosphorous would have radioactive DNA. They then allowed the phages to infect E. coli bacteria. Then, they agitated the cells enough to dislodge the virus particles from the from the surface of the bacteria. The resulting solution would be E. coli bacterial cells with viral genes inside and whatever remained of the bacteriophage after they transferred their genes to the bacteria

­ They found that the infections w/phages containing radioactive phosphorous led to the radioactivity being in the pellet, and thus it must have been transferred to the bacteria during the infection. Viral DNA carries genes!!

­ Francis Crick & James Watson: Proposed the famous double­helical structure of DNA ­ DNA Structure and Function:

­ Structure: 2 long strands of DNA. Each strand consists of a sequence of nucleotide bases (A,T,G,C) joined by covalent bonds to a very long backbone of sugar molecules and phosphates. The two strands wrap around one another and are held together by hydrogen bonds between the nucleotides.

­ Function: Molecular basis of the gene and the physical basis for inheritance ­ Nucleotide Codons: 3 nucleotides = 1 codon

­ Genetic Code: The relationship between codons and corresponding amino acids ­ Gene Transcription: DNA → RNA

­ DNA unwinds and one strand is used as a template for synthesis of RNA that is complementary to the DNA (except T is now U ­ uracil)

­ The RNA molecule is a copy of the exact genetic information in the DNA but now represented in a slightly different form

­ Gene Translation: RNA → Protein

­ mRNA moves from the cell nucleus to regions of the cell where protein synthesis takes place ­ ribosomes

­ In ribosomes, molecules of tRNA match nucleotide triplets in mRNA with their corresponding amino acids, according to the genetic code. Amino acids are then enzymatically joined into a linear chain by way of peptide bonds ­ a protein is born

Chapter 5: How Neurons Generate Signals 

­ Diffusion: Particles move apart and distribute uniformly over whatever volume of fluid is available ­ From high concentration to lower concentration

­ Ion Channels: Proteins in the phospholipid bilayer membrane that open and close, allowing specific ions to pass through & cross the membrane when the channels are open. ­ Ion Pumps: Use energy to move specific ions from one side of the membrane to the other ­ One really important one is the sodium­potassium pump that transports Na+ ions out of the neuron and K+ ions into the cell to restore resting state of the cell after action potential ­ This needs energy bc it’s pushing Na+ out of the cell to a place where there is already a lot of Na+

­ For the Na/K pump, one molecule of ATP will power one cycle of the pump, in which 3 Na+ ions are pumped out of the cell and 2 K+ ions are pumped into the cell

­ ATP (adenosine triphosphate): The phosphorous­oxygen bonds in ATP contain a lot of energy that is released when they are broken by enzymatic reactions in a cell. That energy is then available to other cellular processes. ATP is the primary currency for powering cellular processes

­ Energy Consumption by human Brain: ~ 25% (360 calories per day), 60% of that is used to run the Na/K pump

­ Major Ions for Neural Function: Na+, K+, Cl­, Ca++

­ Ion Concentration Differences Inside & Outside a Neuron: More Na+, Cl­, Ca++, outside More K+ inside

­ Membrane Potential/Resting Potential: ­65 mV (inside is more negative than the outside) ­ The voltage across the neuronal membrane will be used to power the transmission of a signal along the cell’s axon

­ Hyperpolarization: Greater separation of charge across a cell membrane (more negative). Opening K+ or Cl­ channels in a neuron at rest produces a hyperpolarizing effect on the cell ­ Depolarization: Decrease in separation of charge across a cell membrane (more positive). Opening Na+ or Ca++ in a neuron produces a depolarizing effect

­ Alan Hodgkin & Andrew Huxley: Studied the axons of squids and recorded action potentials from inside a nerve fiber. They predicted that there were ion channels that were gated by different voltages and that was what caused the channels to open and close.

­ Action Potential: When a signal passes along a nerve cell’s axon, a striking change in membrane voltage occurs, this is action potential. This is the result of electrically charged particles moving across the membrane.

­ Action potential occurs when there is a large enough depolarization of the cell. Membrane potential goes from resting potential of ­65 mV to +30 mV and then returns back to resting potential. This all occurs in 4 milliseconds

­ Voltage­gated Ion Channels: Open and close based on membrane voltage

­ Voltage­gated Na+ channels open when membrane potential reaches about ­50 mV. Thus positive charge (Na+) flows into the cell, making the membrane voltage more and more positive. When the voltage reaches +30 mV, the Na+ channels close & K+ channels open, letting potassium flow rapidly out of the cell (bringing positive charge with it). The outflow of K+ causes the membrane voltage to become less positive. Enough K+ flows out to return the cell to resting potential of ­65 mV, this is when the K+ channels close.

­ The Na/K pumps then turn on and reestablish the inside/outside concentration differences ­ Action Potential Propagation along Axon: Once an action potential gets started and voltage­gated sodium channels open, sodium rushes into the axon, making that location in the axon more positive. The Na+ ions rapidly drift away from where they flow in and make the nearby regions more positive as well. This local depolarization triggers the voltage­gated Na+ channels in the adjacent region of the axon to open. This process is repeated over and over again along the whole length of the axon.

­ This is like thousands of people doing the wave at a sporting event

­ Axon Hillock: The place where the axon emerges from the soma of the cell. There is a high density of voltage­gated sodium and potassium channels here. This is where the action potential is initiated

­ Refractory Period: After the voltage­gated Na+ and K+ open and close, they require several milliseconds to return to a state that can be triggered again to open.

­ Myelin: Myelin is formed when particular kinds of glial cells develop large, flattened bodies and wrap around and around the axon. It is largely composed of layers of lipid bilayer membrane, 70% is lipid, the rest is protein to link the layers together, so the myelin doesn’t unravel from the axon.

­ Oligodendrocytes: Glial cells in CNS

­ Schwann Cells: Glial cells in PNS

­ Nodes of Ranvier: Small gaps in the myelin, all of the voltage­gated channel proteins and Na/K pump proteins are jammed together at the nodes

­ When sodium diffuses into the cell there is no voltage gated sodium channels right next to it because of myelin, so it just diffuses until the next one which is in the next Node of Ranvier where it activates the next voltage gated sodium channel

­ Saltatory Conduction: Propagation of action potential from one node of Ranvier to the next ­ The action potential leaps from one node to the next, making the neural signal travel much faster down the ion

­ It is like traveling on an express bus vs. a normal bus

Chapter 6: Synapses, Neurotransmitters, and Receptors 

­ Electrical Synapse (Gap Junction): Built from clusters of proteins that form channels in the membranes of two adjacent cells. A single channel is called a connexon, and each connexon is made of several proteins called connexins. An electrical synapse forms when one or more connexon pairs join together, allowing ions to pass directly from one cell to the next.

­ Communication of ion concentration or membrane potential changes from one cell to another

­ Chemical Synapse: Provides opportunities for additional kinds of regulations, like changes in strength, feedback, and varied effects on different target cells

­ Synaptic Cleft: Narrow gap that separates presynaptic axon terminal and postsynaptic cell filled with H2O & ions

­ Dendritic Spine: A bulge on a dendrite that increases the surface area available for receiving signals

­ Synaptic Vesicle: Small spheres formed of lipid bilayer membrane, each filled with several thousand neurotransmitter molecules. They bind to specific proteins in the boundary membrane of the axon terminal and then the neurotransmitters are released into the synaptic cleft. (These proteins are called the SNARE complex)When

neurotransmitters are released into the synaptic cleft, they bounce around until they bump into all kinds of things. One of these are neurotransmitter receptors in postsynaptic neurons. If the appropriate neurotransmitter makes contact with the appropriate receptor protein, it binds to it (like a key in a lock). The interaction of the neurotransmitter with its corresponding receptor protein changes the shape of the receptor protein, which then passes a signal to the postsynaptic neuron.

­ As soon as the neurotransmitter is released from the presynaptic neuron, processes take place to try to remove it from the synaptic cleft. There are 2 ways this happens, one of which is via reuptake transporter proteins in the membrane of the axon terminal. When a neurotransmitter bangs into its corresponding reuptake transport protein, it will bind to it and be moved from the exterior of the cell, back into it.

­ Otto Loewi (1873­1961): Got the idea for an experiment in a dream. He had already been studying the vagus nerve in the hearts of frogs and had found that when it was stimulated, the heart slowed down. In his new experiment, he allows fluid, released when the vagus nerves slows down the heart, to go into another container with another beating frog heart, and he found that the mere movement of the fluid from on jar to another was enough to slow down the other heart. He concluded that some chemical substance must be released when the vagus nerve is stimulated, and it’s this chemical substance that mediates the signal from the vagus nerve to the heart to slow its beating. He called this substance vagusstoff and it is known recognized as acetylcholine

­ Ionotropic Receptor (ligand­gated channel receptor): One major type of neurotransmitter receptor on the postsynaptic neuron. They are channel proteins that let specific ions across the cell membrane when they are open. They open by the binding of a specific neurotransmitter molecule to a particular location on the receptor protein. This causes the receptor protein to shift shape, opening the channel and letting neurotransmitter in.

­ Glutamate: Most abundant neurotransmitter in the human brain. It is the primary excitatory neurotransmitter in the human brain. (aka glutamic acid)

­ How does glutamate communicate an excitatory signal between neurons? ­ Large numbers of glutamate receptors are on ionotropic receptors that are Ca++ and Na+ channels. Thus, the binding of glutamate to ionotropic receptors initiates a flow of Na+ and Ca++ from outside the cell to inside the cell. This produces a depolarization which gets the cell closer to the threshold for triggering the

opening of voltage­gated Na+ channels and the resulting generation of an action potential & a neural signal.

­ GABA: The major inhibitory neurotransmitter in the human brain

­ Large numbers of GABA receptors in the brain are ionotropic GABA receptors that are Cl­ channels. The binding of GABA to ionotropic GABA receptors allows Cl­ to flow from outside the cell to inside the cell. This produces a hyperpolarization. The membrane potential moves further away from the threshold for triggering the opening of

voltage­gated Na+ channels and the resulting generation of an action potential

­ EPSP: Excitatory postsynaptic potential. If there is enough EPSPs, there will be a depolarization in the cell & it will initiate an action potential

­ Produced by Na+ or Ca++ flowing into cell

­ IPSP: Inhibitory postsynaptic potential. If there is more IPSPs, there will be a hyperpolarization in the cell

­ Produced by Cl­ flowing into cell or K+ flowing out of the cell

­ Glutamic Acid Decarboxylase (GAD): Enzyme that makes GABA from glutamic acid ­ Spatial and Temporal Summation of Neuronal Input:

­ Metabotropic Receptor (GPCR): Affect the chemistry inside the cell. Binding of a neurotransmitter to a metabotropic receptor does not directly open an ion channel but can cause a variety of different things to happen: ion channels could open and close, enzymes may be activated or inactivated, gene transcription may be turned on or off, etc.

­ GPCR Signaling: Neurotransmitter binds to metabotropic receptors. This causes the receptor to shift shape and make it able to bind another protein called a G­protein. The G­protein attaches to the receptor and becomes activated. The G­protein interacts with the effector enzyme (adenylate cyclase). This causes the intracellular cAMP concentration to change. The cAMP molecules move around inside the cell and interact with various proteins, altering their enzymatic activities. Some of these proteins that are altered are protein kinases. This change in protein kinases causes channels to open or close, or genes are turned on or off, and so forth.

Chapter 7: Neuroanatomy and Excitability 

­ Acetylcholine acts on both ionotropic receptors and GPCRs

­ Neuromuscular Junction: Ionotropic AChRs mediate communication between nerves and skeletal muscles in humans and other vertebrate animals. This is called the neuromuscular junction.

­ CNS: Brain and spinal cord

­ PNS: Autonomic nervous system, neuromuscular nervous system, sensory nervous system, enteric nervous system (digestive systems)

­ Cranial Nerves: Connections between CNS/PNS enter and exit the brain at several points in the brainstem

­ Autonomic Nervous System: Regulates various body organs and internal functions like heart rate, blood pressure, respiration, and digestion. Most of this is outside of our awareness. ­ Sympathetic: Neural fibers of the sympathetic nervous system emerge from the spinal cord & form connections with clusters of nerve cells just outside the spinal cord all along its length (sympathetic ganglia)

­ Increases heart rate, dilates lung airways, dilates pupils, inhibits salivation, inhibits bladder from voiding, decreases intestinal motility

­ Fight or flight

­ Parasympathetic: For the upper and middle body, neural fibers connect with CNS via cranial nerves 3, 7, & 10. For the lower body the connections are via the lower end of the spinal cord. These fibers connect with clusters of neurons called parasympathetic ganglia.

­ Decreases heart rate, constricts lung airways, constricts pupils of eyes, stimulates salivation, stimulates bladder to void, stimulates intestinal motility

­ Rest and digest

­ Autonomic Neurotransmitters:

­ Norepinephrine: Neurotransmitter in sympathetic nervous system.

­ Acetylcholine: Neurotransmitter in parasympathetic nervous system. Slows heart rate. ­ The receptors for both of these are GPCRs

­ Sympathomimetic: Stimulating effects on the sympathetic nervous system ­ Sympatholytic: Decrease the effects of the sympathetic nervous system ­ Parasympathomimetic: Stimulating effects on the parasympathetic nervous system ­ Parasympatholytic: Decrease the effects of the parasympathetic nervous system ­ Agonist: Activates a neurotransmitter receptor when it binds to it. Like the wrong key opening a lock.

­ Antagonist: Binds to a neurotransmitter molecule and blocks action of the neurotransmitter at the receptor. Like blocking the right key from opening the lock.

­ A neurotransmitter is an agonist at its own receptor

­ Acetylcholine: Is produced and released by a relatively small number of neurons clustered into several regions deep in the brain’s interior called the basal forebrain nuclei and the midbrain pontine nuclei. These are cholinergic neurons. The molecular precursors to ACh are acetate and choline. Only nerve cells that use ACh as a neurotransmitter have the capacity to make ACh from these precursors.

­ Choline acetyltransferase: Enzyme that catalyzes the synthesis of ACh from acetate and choline. The gene coding for this enzyme is expressed only in cholinergic neurons ­ Acetylcholinesterase (AChE): Enzyme responsible for the rapid cleavage of ACh back to acetate and choline after its release at axon terminals. Only cholinergic neurons express the gene to make AChE. This is how acetylcholine is removed from the synaptic cleft, rather than reuptake transporters

­ Another group of neurotransmitters in the brain are the monoamines. They possess an amine (nitrogen containing) group located at the end of a short chain of carbon atoms. They include: serotonin, dopamine, norepinephrine, epinephrine, and histamine.

­ They are involved in feelings of alertness and arousal, wakefulness and sleep, attention and memory, and selection and initiation of behavioral actions.

­ Serotonin: Is biosynthesized in two steps from the amino acid tryptophan. In the 1940s serotonin was found to have effects on constriction and dilation of blood vessels. Serotonin receptors are located on blood vessels throughout the body. Later it was also found to be a neurotransmitter in the brain.

­ Serotonergic neurons in vertebrate animals are located in the raphe nuclei, which is on the brainstem

­ Biosynthesis of Monoamine Neurotransmitters: Dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) are made from the essential amino acid phenylalanine. ­ Phenylalanine → tyrosine → DOPA → dopamine → norepinephrine → epinephrine ­ Dopamine: Dopaminergic brainstem nuclei are the ventral tegmentum and the substantia nigra ­ Norepinephrine: Nearly all the norepinephrine­producing (noradrenergic) cells in the brainstem are located in the locus coeruleus in the pons. The epinephrine­producing cells are located here as well, although there are very few of them.

­ Peptide Neurotransmitters (Endorphins): Composed of polypeptides. These are the opioids, collectively called the endorphins.

­ So basically, there are several categories of neurotransmitters:

­ Amino acid neurotransmitters: glutamate and glycine and GABA

­ Neurotransmitters made directly from amino acids: serotonin, dopamine, norepinephrine, epinephrine, histamine

­ Acetylcholine

­ Polypeptide neurotransmitters: neuropeptides, endorphins

­ There are 2 kinds of neurotransmitter receptors: ionotropic receptors and GPCRs ­ Ionotropic Receptors: glutamate, GABA, and acetylcholine (and glycine)

­ There is one serotonin receptor that is ionotropic (5HT3)

­ GPCRs: All other neurotransmitter receptors (there GPCRs that interact with glutamate, GABA, and acetylcholine)

­ Seizure: Too much excitation and not enough inhibition may set off a kind of explosive chain reaction called excitation. One manifestation of this is runaway neural activity in the brain called a seizure

­ Idiopathic seizures have not been associated with any identified causes

­ Causes of Seizures:

­ Tumor could produce unbalanced excitation, brain infections, high fevers,

traumatic head injuries, drugs that increase brain neuronal excitability (stimulant drugs), etc

­ Epilepsy: Condition of recurrent seizures

­ About 2.7 million people in the U.S. suffer from it. Of those, 30% still have seizures while on medication

­ Antiseizure Medications: Something that reduces the amount of excitation, or enhances the amount of inhibition in the brain.

­ They interfere with voltage­gated sodium, potassium, and calcium channels; facilitate the inhibitory action of GABA; and reduce the excitatory action of glutamate

­ You want to blunt excitability enough so that seizures are prevented, but not so much that the normal functioning of the brain is impaired.

­ Excitotoxicity: Overexcitation of neurons by glutamate is a toxic phenomenon that can cause death.

Charged particles (ions, acetylcholine) are hydrophilic

Things that have OH groups are HIGHLY polar ­ will not cross blood brain barrier too hydrophilic

Chapter 8: Poison, Medicine, and Pharmacology 

­ Drug: Chemical that in small amounts has a significant effect on body function ­ Pharmacology: Scientific study of drugs: their origins, compositions, and effects on the body ­ Paracelsus (1493­1541): Swiss physician and alchemist that said: “Everything is a poison. The difference between a poison and a medicine depends on the dose”

­ Tetrodotoxin (TTX): Blocks voltage­gated sodium channels so that sodium can’t get into the cell when the channel opens. This prevents the neurons from sending signals. Numbness occurs bc signals from sensory neurons in the skin don’t reach the brain, and signals from the brain don’t reach the muscles, there is muscle weakness, difficulty moving, and paralysis (including the muscles controlling breathing). So if someone dies from TTX poisoning, it is because of respiratory paralysis.

­ Heart doesn’t stop beating and the brain is not affected ­ because TTX doesn’t actually enter the brain (blood­brain barrier) because it is not hydrophobic enough

­ Comes from puffer fish, blowfish, fugu

­ Blood­brain Barrier: Refers to how the blood vessels are constructed within the CNS to regulate the passage of materials from the blood, into the brain, and vice versa. The cells forming the walls of the blood vessels are tightly joined together, with no gaps, no pore, no holes between the cells. ­ There are two ways that molecules can cross the blood­brain barrier

1. Via transporter proteins that shuttle specific molecules across the membranes of the cells forming the barrier.

a. This is how glucose and some amino acids get across

2. By dissolving right through the blood vessel cell walls

a. A molecule must be highly hydrophobic (lipophilic) to do this

b. This is how oxygen, other small gaseous, and all drug molecules known

to have an effect on brain functions get across

­ TTX Resistance: May result from mutations that change only a single amino acid in the voltage­gated Na+ channel. This happens in animals harboring TTX.

­ Saxitoxin (PSP): Paralytic shellfish poisoning ­ Does all the same things as TTX it is just more common because it occurs in shellfish with STX

­ Batrachotoxins: BTXs also mess with voltage­gated sodium channels, but in different ways than TTX & STX. They interact with the channels and prevent them from closing. This also prevents action potentials from firing because Na+ never stops flowing into the cell. Nerve signaling doesn’t work and the same things result as with TTX and STX

­ Local Anesthetics: Chemicals that produce a loss of sensation only in the region of the body near where they have been applied. When the chemical drifts around, enters the bloodstream, and reaches other parts of the body, its concentration is too low to have any effects

­ Cocaine: First local anesthetic to be appreciated by modern medicine

­ They work by binding to voltage­gated Na+ channels and disrupt the ability to open and close in a normal voltage­dependant fashion. They do not block the channel, they just interfere enough to alter the generation of action potentials, resulting in a reduction in signals from neurons sending sensory info to the brain

­ Nicotinic AChRs: AChR activated by binding nicotine. This AChR is blocked (antagonized) by the molecule tubocurarine. This is the neurotransmitter receptor at the neuromuscular junction, and is also present in the brain

­ Now recognized as an ionotropic receptor

­ Muscarinic AChRs: AChR activated by the molecule muscarine, from mushrooms. This AChR is antagonized by atropine. This is found in the parasympathetic neural connections with target organs as well as in the brain

­ Now recognized as a GPCR

­ Atropine (Atropa belladonna): The deadly nightshade plant. It is a parasympatholytic and will therefore slow intestinal motility. This makes it a useful medicine to treat diarrhea, spastic colon, and other gastrointestinal problems

­ Psychoactive Drugs: Top 5

1. Caffeine

2. Ethyl Alcohol (ethanol)

3. Nicotine

4. Areca nut (Betel nut)

5. Cannabis

Neuromorphic Engineering