;; Chapter 1 mentalism: Aristotle, behavior function of immaterial body dualisim: Descartes, ‘’ both mind and brain, mind controlling higher mental functions materialism: Darwin, behavior function of brain humans: family hominidae genus australopithecus: 4-1 million years ago, robustus africanus afarensis aetheiopicus genus homo: habilus: 1.5-2 million years ago, evidence of tool use erectus: 1.6mil-200k, actually walked upright (habilus stooped), migrated to Europe and Asia, brain size larger than any previous hominids (about the same size as modern humans) neaderthalensis: 30k-300k, parallel branch of genus homo, had complex rituals, brain size > sapiens (by a little), found in Europe sapiens: 200k-present, modern humans, thought to originate in Africa, later spread to North Africa and Asia, later Europe, brain size increase about threefold 20th century: about 160 million human deaths due to wars, violent conflicts, etc. encephalization quotient: (/ actual-brain-size expected-brain-size), brain-to-body increase ratio is about (/ 2 3), eg. human and dolphin above average ++ human brain evolution: spurred by rapid climate changes, massive tectonic event ~8 million years ago caused Great Rift Valley split (east “nose” of Africa). West of Valley remained moist, unchanged. To the east, the land became drier, more savanna-like. upright adaptation: more efficient means of locomotion, regulated body temperature better (hominid responses to changing weather) habilus: began walking bipedal, adapted scavenging too erectus: appearance thought to be triggered by lowering of sea levels due to cooling, which opened up bridges to Europe and Asia, massive migrations hypothesis: 1. competition, challenging situations 2. radiator hypothesis: larger brain easier cooling, mutant smaller masticatory muscles allowed for larger size brain 3. neotony: delayed maturation, maintain larger infant-brain-size-growth rate longer, produce more brain cells ;; Chapter 2 the mind is a collection of internal, subjection experiences called mental states the primary functions of the brain: create sensory reality, integrate information, produce behavior sulci: fissures (longitudinal fissure) (lateral fissure (near temporal lobe)) gyri: bumps CNS: brain and spinal cord (bundles of nerves inside CNS: tracts; outside: nerves) PNS: all other nerves, neuromuscular, sensory, enteric (intestines) control, etc. (two divisions) somatic: bodily functions, controlled and monitored by CNS, cranial nerves: 1. olfactory: smell 2. optic: vision 8. auditory vestibular: hearing and balance 10: vagus: heart, blood vessels, viscera, movement of larynx and pharynx autonomic: involuntary (autonomic: two divisions) sympathetic (+): NT: noepinephrine, sympathomimetic (+ to sympathetic), sympatholytic (- to sympathetic, inhibitory) adrenaline: excrete by adrenalin glands to extend and boost effects of sympathetic system, also uses noepinephine parasympathetic (-): NT: acetylcholine, parasmpathominmetic (+ to parasympathetic), parasympatholytic (- to parasympathetic, exhibitory) the brain has two main types of cells neuron (pyramidal cell) : 100 billion cells glia (astrocyte) : 5x-100x neuron cells total: about one trillion cells anatomical directions: anterior: front posterior: back dorsal: upwards ventral: downwards inferior: located below superior: located above lateral: towards side of body medial: towards middle (planes) coronal: side-split (side-side) sagittal: middle-split (front-back) axial: middle-chop (ventral decapitation) skull > dura mater > arachoid > (CSF) > pia mater > sub-arachnoid space > (CSF) mater are made of collagen arteries (anterior, middle, posterior): deliver blood and oxygen to brain ventricles (2 + 1 + 1) : contain CSF, cushion, may help speed up metabolism corpus commissurotomy: cut corpus callosum the brain of a young vertebrae develops into three different regions (which later develop into more complex structures): front brain: olfaction middle brain: vision and hearing hindbrain: movement and balance (spinal cord belongs here) anatomical divisions in CNS: forebrain: (components) cerebral cortex: the stuff that composes the brain (we‘re not talking out the cerebral cortex here, just the cortex in general), the layers of the cortex have distinct characteristics: the density, appearance, and function of each layer varies layers 1-3: integrative tasks layer 4: sensory input layers 5-6: output to other parts of brain basal ganglia: controls voluntary movement limbic system: emotional, instinctual behavior brainstem: relay center (components) diencephalon: (emphasis on integrative task), thalamus, hypothalamus (sits on top of pineal gland) midbrain: (emphasis on sensory processing), visual processing through eyes, tectum, tegmentum hindbrain: (emphasis on motor control), cerebellum, pons, medulla oblongata, rectangular formation (attention) spinal cord: spinal nerves: cervical, thoracic, lumbar, sacral nerves pineal gland: secrete melatonin (hormone to monitor sleep) eight principles of the nervous system: 1. the sequence of brain processing is “in > integrate > out” 2. sensory and motor functions are separated 3. inputs and outputs are crossed 4. brain anatomy with both symmetric and asymmetric 5. the nervous system operates on exhibition and inhibition 6. the nervous system has multiple layers of function 7. brain components operate both in parallel and hierarchically 8. functions in the brain are both local and distributed ;; Chapter 3 Camillo Golgi and Ramon y Cajal were awarded Nobel Prize for medicine in 1906: both stained slices of brain tissue and made elaborate drawings, made conclusions based on drawings: Golgi: nervous system composed of network of interconnected fibers, information flowed throughout like “water” Cajal: nervous system composed of discrete cells that become more complex with age, neuron hypothesis: neurons are the units of brain function neurons: 1-20 dendrites dendrite spine: increases surface area of dendrite, usually the point of dendritic contact with axons (types) sensory: brings information into the CNS (eg. bipolar, somatosensory) interneuron: associate sensory and motor information in CNS (eg. stellate, pyramidal, Purkinjecerebellum) motor: sends signals from brain and spinal cord to CNS, typically have many dendrites, long axons, and large cell bodies) in general, a small cell body means small extensions for a neuron, and vice versa short extensions are for local processing (sensory, for example), while long extensions are for transmitting information (eg. motor, axon) if excitatory input > inhibitory input, neuron activates if excitatory input < inhibitory input, neuron does not activate (input near axon hillock is most potent) glial cells (types) ependymal: small, ovoid, secretes CSF hydrocephalon: buildup of pressure in brain due to blocked CSF astrocyte: star shaped, symmetrical, nutritive and support functions: creates tights junctions in blood vessels to form the Blood Brain Barrier, can also make blood vessels dilate to increase blood flow to brain microglial: small, mesodermically derived, defensive support: phagocytizes foreign matter and debris oligodendroglial: asymmetrical, forms myelin in axons of CNS Schwann: ‘’ peripheral mutiple sclerosis: nervoius system disorder resulting from the loss of myelin around neurons neuron repair PNS (axon repair): microglia first sterilize damaged axon, Schwann cells shrink and divide, creating a path, neuron sprouts an axons to search for that path, once found, Schwann cells wrap around new axon CNS: not repairable Dmitri Mendeleev: developed periodic table chemical composition of elements in human body (and thus brain) by wet weight: (hydrogen #1 in terms of numbers present) (carbon #1 in terms of dry weight) (water % in body is about 55%-70%) 1. oxygen: 65% 2. carbon: 18.5% 3. hydrogen: 9.5% 4. nitrogen: 3.2% 5. calcium: 1.5% 6. phosphorus: 1.0% 7. potassium: 0.4% 8. sulfur: 0.3% 9. sodium: 0.2% 10. chloride: 0.2% molecule: atoms joined together by chemical covalent bonds water: polar, linked by hydrogen bonds hydrophilic: attracts water (lipophobic) hydrophobic: repels water (lipophilic, likes fats) brain consumption of energy: body requires about 700 calories per day brain uses about 60% of this (420 calories) about 36% of total energy (250 calories) required for minimum functioning at rest (to operate Na+/K+ pump) body at rest: ~700 calories, 34 watts brain: 420 calories, 20 watts brain Na+/K+ pumps: 250 calories, 12 watts biological macromolecules: proteins: chains of amino acids linked by peptide bonds (dehydration reaction) > 30 amino acids = protein (normal protein about 200-400 though) amino acids: amino group (NH3), and carboxyl acid group (COOH) (structures) primary: just the sequence secondary: the local structure (eg. alpha helix) tertiary: the whole 3-D blob carbohydrates: made of carbon, hydrogen, and oxygen, sugar and starches, energy source and storage fats and lipids: phospholipids (saturated and unsaturated), highly ordered packaging, irregular packaging, phospholipid bi-layer: hydrophilic head, hydrophoblic fatty-acid tails, protein embedded barrier, impermeable to ions, embedded pumps, ion exchanges, and channels too Na+/K+ Pump: pumps Na+ out pumps K+ in uses ATP (adenoside triphoshate) ratio: 3Na+/ 2K+ uses 1ATP neuronal ion gradients: inside Na+ K+ 45x more ClCa++ outside 8x more 17x more 10K more nucleic acids DNA gene: hereditary material, Darwin (1809-1882) 1859:Origin of Species: natural selection, Schrödinger: What Is Life?, Oswald Avery (1944): suggested DNA were carriers of genetic information, Martha Chase and Alfred Hershey (1952): Hershey-Chase Experiment: radioactive sulfur (proteins), and radioactive DNA, inserted into viruses who invaded bacteria hosts Linus Pauling: alpha helix of protein Rosalind Franklin: X-Ray diffraction image of DNA, confirmed its structure genetic code: the relation between DNA nucleotides and amino acid and proteins: transcription: mRNA into cell nucleus, exits and goes to ribosome in ER for translation translation: tRNA brings amino acids and builds protein three amino acids make one codon important dimensions: diameter cell membrane: 5 nm (nanometers) synapse gap: 40 nm diameter of medium sized protein: 40 nm nerve cell: 5-100 micrometers ;; Chapter 4 electrons flow from negative (source) to positve ends: flow is - to + measuring membrane potential: nerve on a petri dish: electrode measures inside and outside resting potential: -70mV threshold: -50mV, allows Na+ and K+ channels to open peak: +30mV, gates cannot let any more ions pass through anymore refractory period: pause in Na+/K+ pump for recharge (prevents reverse propagation) depolarization (+): “hill”, opens Na+ channels, influx of Na+ ions cause membrane potential to raise hyperpolarization (-): “pit”, opens K+ channels, K+ ions flow out, lowering membrane potential stages of the action potential: resting >depolarization >repolarization >hyperpolarization >Na+ in >K+ out >K+ out >repolarize an action potential cannot occur where the axon is wrapped in myelin voltage-gated ion channels: sodium: typically closed to prevent Na+ entry K+: K+ is free to enter and leave cell (somewhat related: Na+/K+ pump) myelin composition: 40% phospholipid 30% cholesterol 30% protein (to hold phospholipid bi-layer together) myelin increases Na+ channel density per sq. mm unmyelinated: 100 myelinated: 10K myelin increases the speed of nerve impulses via saltatory conduction speed: 10m/s - 100 m/s salutary conduction: action potential jumping from node to node node of ranvier: the part of an axon that is not covered by myelin summation of inputs: ESPS, ISPS, constructive and destructive interference ;; Addenda Paracelsus said something along the lines of, “Everything is a poison. The difference between a poison and a cure is the dose.” things that mess with nerve conduction: too much water (hypoaetremia: dilute body ions) tetrodotoxin, saxitoxin, local anesthetics, batrachotoxin, ciguatoxin (last two come in varieties, TTX and STX have only one type) TTX/STX: block opened Na+ channels local anesthetics (eg. cocaine): interfere with opening and closing of Na+ channels, only one in this list that can cross BBB batrachotoxin: prevent closing of Na+ channels ciguatoxin: lowers threshold for opening Na+ channels in all cases, nerve signaling fails tetrodotoxin: produced by bacteria that live symbiotically with animals, found in blue ringed octopus, california newt, fugu, etc., does not cross BBB and does not enter human CNS BBB: blood vessels constructed to eliminate pores, only some hydrophilic molecules and some transported molecules allowed to cross tetrodotoxin poisoning: peripheral nerve unable to generate new action potentials symptoms include etc. etc. paralysis death, if it occurs, is from respiratory paralysis TTX resistance ~1-4 mutations in amino acids, which creates for large decreases in the binding affinity of TTX present in animals having TTX saxitoxin: paralytic shellfish poisoning (PSP): shelfish eat dinoflagellates that contain saxitoxin, people who eat shellfish get poisoned, symptoms are very similar to those of TTX local anesthetics: numbs sensations locally anesthetics include cocaine, benzocaine, lidocaine, procaine, etc. cocaine comes from coca plant batrachotoxin uh, comes from frog, next topic ciguatoxin: probably produced by dinoflagellates accumulated by fish most potent Na+ channel toxin ciguatoxin poisoning: most common type of poisoning caused by consumption of fish containing ciguatoxins ~5k cases each year symptoms also similar to TTX ;; Chapter 5 synaptic transmission: action potential > vesicle fusion > neurotransmitter release > receptor binding > inactivation (reuptake transport and enzyme degradation) neurotransmitter release: action potential > opens Ca++ channel > Ca++ ions bind to calmodulin, form complex > complex binds to vesicles and cause them to release their contents ligand: binding sites for transmitter substance, once transmitter binds, the post-synaptic neuron can either be 1) excited 2) inhibited or 3) other neurotransmitter deactivation: 1. diffusion 2. enzyme degradation (acetylcholine) 3. reuptake (dopamine, serotonin) 4. glial cell usurption dendrodentic: dendrites that sends messages to other dendrites axondenitic: terminal synapses in dendrentic spine of another cell ‘’ somatic: axon terminal ends in cell body of another cell etc. Otto Loewi (1875-1981): neurotransmitters are chemical messengers in neuron cells, Nobel Prize 1928. heart experiment: stimulated vagus nerve of frog heart then transferred liquid to another frog heart, found that other frog heart got stimulated too (from liquid) synapses: Type 1 (exhibitory): typically located on shafts or spine of dendries, round vesiscles, denser membranes and wider clefts, and larger active zone than Type II Type II (inhibitory): typically located on cell body, flattered vessles, smaller membranes and more narrow clefts, smaller active zone than Type I EPSP: excitatory post-synaptic potential IPSP: inhibitory post-synaptic potential neurotransmitters: glutamate: amino acid neurotransmitter, primary excitatory transmitter in forebrain and cerebellum GABA (gamma-aminobutyric acid): primary inhibitory transmitter in forebrain and cerebellum, remove a carboxyl (COOH) group from glutamate to obtain this glycine: main inhibitory NT that functions in spinal region, glycine ionotropic receptor (Cl- channel) acetylcholine: quantary amine, nerve > muscle connection, parasympathetic division of PNS, CNS ionotropic receptor: embedded membrane protein with a binding site and pore that regulate ion flow of ions through create rapid change in membrane voltage, usually excitatory in that they may trigger action potentials ligand-gated: ‘’ both NT and voltage metabotropic receptor (protein coupled receptor GPCR): embedded protein with binding site but no pore, linked to a G-protein that can affect other receptors or cellular processes (metabotropic process) neurotransmitter > receptor > G-protein > effects enzyme > 2nd messenger > protein kinase > substrate protein > cellular effects phenylalanine > epinephrine phenylalanine > tyrosine (+ HO) > dopamine (+ HO) > dopamine (- OOH) > noepinephrine (+ HO) > epinephrine (cannot read own notes, insert some comment here as disclaimer) cyclic AMP: “ATP-like” stuff used as a signaling molecule, made from adenylate cyclase protein kinase: attaches phosphorus to stuff, causes them to change (open, close, etc), etc., can also turn genes on and off (transcription factor) “ergic”: something that uses <prefix> (eg. cholinergic is something that uses choline) agonist: molecule that binds to a NT receptor and activates it antagonist: ‘’ blocks it Ach receptors: nicotinic acetylcholine receptor (ionotropic): nicotine/acetylcholine > agonist muscarilic receptor (metabotropic): agonist to muscarilic molecules, CNS > parasympathetic NS, named after mushroom Amanita Muscaria toxins: curare: antagonist at NAChR, can cause paralysis, active component is tubocurare, cannot cross BBB atropine: from plant “Atropa belladonna”, antagonist brain activation circuitry: cholinergic system (acetylcholine): active in maintaining waking electroencephalographic pattern, origin at from midbrain and basal ganglia nuclei, thought to play a role in memory by maintaining neuron excitability, death or decrease > Alzheimer’s disease dopaminergic system (nigrostriatial and mesolimbic pathways): nigrostriatial: active in maintaining normal motor behavior, origin at from caudate nucleus, decrease > Parkinson’s disease, mesolimbic: dopamine release involved in feelings of reward and punshiment, might be NT system most affected by addictive drugs, origin at substantia nigra noadrenergic system (noepinephrine): active in maintaining emotional tone, decreases > depression, increases > mania, origin at locus coeruleus serotoergic system (serotonin): active in maintaining waking electroencephalographic pattern, increases > OCD, schizophrenia, decreases > depression, origin at Raphe nuclei botox (botulinum toxin) cells uptake the toxin somehow, and it interferes with other vessels, blocks release of NT, comes from bacteria Clustridiura Botulinum) in spoiled food botulinum poisoning: muscle movements > paralysis ;; Addenda seizure: explosive electrical activity in brain, runaway excitation EEG: electroencephalography, method for recording overall electrical brain activity seizure causes: infection, fever, traumatic injury, tumor, stimulant drugs, sedative drug withdrawal, other toxic chemicals aura: sensation or feeling that a seizure is going to occur (effects) motor convulsions, spasms amnesia: memory loss idiopathic seizures: appear spontaneously, not associated with any known cause, genetic and developmental components (causes) intense sensory stimuli trauma sleep deprivation certain drug withdrawal photosensitivity medication for seizures: antiseizure or anticonvulsant medication barbiturate: phenobarbital benzodiazepines: diazepam (Valium)(acute), clonazepam (Klonopin)(chronic) epilepsy: chronic seizure ~2.7 million people in U.S. prevalence ~0.9% ~30% continue to have seizures even with medication surgical treatment: severing of the corpus callosum (rarely done) excision of epileptogenic brain tissue ;; Drugs a drug is an external chemical that has an effect on our body psychoactive drugs affect our mental functioning oral administration of a drug is the most complex (++ barriers, and gets diluted) direct injection of a drug (inhaling, injecting through blood, etc.) is the most quickest and potent pharmacology : a hierarchy of biological science that studies how drugs affect mammals for a drug molecule to pass the BBB, it must be small enough, ionized, and hydrophilic most widely used psychoactive drugs 1. caffeine 2. alcohol 3. nicotine (tobacco) 4. arecoline (betel palm nut) 5. cannabinoids (cannabis, marijuana) ; Addenda lethal injection cocktail 1. thiopental (sodium Pentothal) : barbiturate with a low TI, 5 grams given intravenously 2. pancuronium : nicotinic AChR antagonist (cannot cross BBB), muscle paralysis and respiratory insufficiency, used in some surgical procedures 3. potassium chloride : enhances GABA receptor circuitry, effects K+ and C- balance (first heart and nervous system will stop functioning), then induces cardiac arrest (heart attack) effectiveness: three-drug cocktail : death occurs within ten minutes single barbiturate overdose: death occurs in between 30 to 45 minutes executions in USA since 1976: firing (2), hanging (3), gas chambers (5), electrocution (153), lethal injection (most!) Texas has the highest number of deaths by death penalty (½ of total death penalties given in US) varieties of psychoactive drugs stimulants : caffeine, etc. (caffeine is an inhibitor than blocks adenosine receptors) sedative-hypnotics : increases GABA mediated Cl- flow tobacco and nicotine : agonist ACh receptors opium and opoids : bind to opiod receptors as agonists stimulants : cocaine, amphetamine, blocks pre-synaptic reuptake of dopamine (norepinephrine) caffiene : first isolated from coffee in 1820 blocks CA++ channels and adenosine receptors (see below) effects include arousal, alertness, ++ heart rate, etc. caffeine is an adenosine receptor antagonist (blocks an inhibitor, creates for excitatory responses) adenosine (NT) inhibition : several different GPCR adenosine receptors have been identified, has vasodilatation effects in cardiovascular system tobacco : plant is native to South Africa (Nicotiam tabarum) nicotine : affects receptors in nervous system, agonist at nicotine acetylcholine receptors, induces relaxation sedative hypnotics alcohol : ethyl alcohol (ethanol) barbiturates : used to be prescribed as sleep medication, now mainly used to induce anesthesia before surgery, have a VERY low therapeutic index benzodiazepines : antianxiety agents a common feature of sedative hypnotics is that one develops a tolerance for them (more and more will be needed to maintain the same effect) sedative hypnotics increases GABA mediated Cl- flow : opens Cl- channel resulting in global CNS inhibition alcohol and barbiturates act like GABA, but benzodiazepine just enhances GABA (which is why it is hard to overdose on benzodiazepine) opiods papaver somniferum : opium poppy, to harvest opium, let petals fall, and before the pods inside dry, cut slits in the pod and let the ooze (opium) drip out medicinal properties : analgesia, cough suppression, treatment of diarrhea, and others Friedrich Wilhelm Serturner : 1803 discovered and named “morphine” (isolated contents of opium) opiates from opium : morphine : ~10% odeine : ~1% synthetic modifications of opiates from opium heroin : diethyl morphine : morphine > acetylation > heroin, stronger than morphine (can cross BBB more than morphine can) semi-synthetic opiods hydromorphine, oxycodine, and etorphine (1000 times more potent than morphine) synthetic opiods not related to morphine in chemical structure, includes fentanyl (100 times more potent than morhine), and others opiod peptides in the brain endogenous NTs: endorphins (from “endogenous morphine”), are self-generated, chains of neuropeptides of about 5-31 amino acids cocaine : extracted from Peruvian coca shrub produces increased adctivity at noepinephrine and dopamine systems (blocks reuptake receptors) has sympathomimetic effects can also be used as a local anesthetic side effects : overstimulation of the excitatory system potentially toxic, lethal effects may cause cardiovascular stress : heart attack, stroke, also seizures may cause psychosis : delusions, hallucinations is addictive the coca plant makes cocaine because it is aversive to most insects and predators amphetamine stimulants related to amphetamine speed : methamphetamine mechanism : causes leakage of dopamine and norepinephrine from axon terminals (reuptake transporters work backwards) psychedelics : hallucinogens synthetic : lysergic and diethylamide (LSD) psilocybin, psilocin dimethyltryptamine (PMT) mescaline causes complex effects on mental state four major types of psychedelics: acetylcholine psychedelics : block of facilitate transmission at acetylcholine synapses in brain noepinephrine psychedelics : includes mescaline tetrahydrocannabinol (THC) psychedelics : the active ingredient in marijuana, has detrimental effects on memory serotonin psychedelics : LSD and psilocybin, affect serotonin neurons Albert Hoffman : discovered LSD, identified psilocybin, psilocin Psilocyte cudensis : psychedelic mushroom, contains psilocybin and related molecules Maria Sabina : introduced the world to the ritual ethnobotanical practices of her culture peyote cactus : lophophora williamsii native to central Mexico (Texas area) contains mescaline : the first molecule to be identified as a psychedelic affects serotonin receptors : binds to the receptors and cause agonist effects legal state of all psychedelics : illegal cannabinoids : source of marijuana, hash, etc. Cannabis sativa primary psychedelic chemicals in the genus Cannabis has unique chemical structure, more than 60+ types of delta-9-tetrahydrocannabinol (THC) identified THC: GPCR cannabinoid receptors : the most abundant GPCRs in the human brain endogenous neurotransmitters : anandamide, endocannabinoids cannabinoids receptors at pre-synaptic neurons use “retrograde signaling” ;; Development of the Nervous System humane genome: 23 chromosomes (haploid) 3 billion base pairs 23K distinct genes stages: zygote: fertilization to two weeks embryo: 2-8 weeks fetus: 9 weeks till birth development process: day 1: fertilization day 2: initial cell splitting day 15: embryonic disk day 18: neural plate (primal neural tissue) > neural groove (later) > neural tube (later) > spinal chord (later) day 21: neural grove day 22: ventricles origins of brain cells evolution type depends on where the cell is, it’s environment stem cell > self-renewal > progenitor cell > neuroblast > interneuron > projecting neuron > etc. > glia cell > oligodendroglia > astrocyte > etc. neurogenesis: neuroblasts differentiate into various types of nerve cells (process completed approximately five months after birth), still happens later gliogenesis: “ glio cells nervous system development neurogenesis and gliogenesis occur in tandem (at the same time) with: 1. cell migration 2. differentiation 3. maturation (axon/dendrite branching) 4. synptogenesis (forming synapses) filopodia: a thing at the end of a developing axon that reaches out to search for a potential target or to sample the intercellular environment (guides axon tail growth) cell-adhesion molecule (CAM): a chemical to which special cells adhere, aiding in cell migration how do migration and synptogensis happen? Roger Sperry: the right and left hemispheres of our brain differ because of migratrion/synptogenesis, rewired frog eyballs Sperry Chemoaffinity Hypothesis: neurons use special chemical signals to guide their wiring (migration and synaptogenesis during development) Rita-Levi-Montalcini: co-discovered first neurotrophin (nerve growth factor) neurotrophins: chemical substances produced by the body that promote growth, differentiating, and synptogensis of neurons neuro-growth-factors (NGG): long-range contact cues: concentration gradient of chemoattractants and chemorepellants short-range contact cues: cell grows along path marked by contract (attraction or repulsion) selective cell death: apoptosis (programmed cell death) synaptogen and synapse formation: pruning of synapses, activity-dependent survival, stabilization through use, elimination through disuse myelination in cortex takes years (18+!) different regions of the brain finish myelinating sooner than others (sooner = less complex) plasticity: ability of neural circuitry to alter its properties dendritic and axon branching: dendritic spine and synapse formation, synapse formation and degradation learning and memory: rewiring happens all the time ;; Brain Imaging damage to the brain can cause a change in one’s thoughts, feelings, perceptions, and actions lesion: an injury to the brain circumscribed, or local, lesions are caused by: stroke (blockage of blood to the brain) tumor (abnormal growth of cells) trauma (physical) selected diseases methods of STATIC brain imaging: (used to visualize the anatomical structure of local lesions ) autopsy exploratory brain surgery x-ray photography William Rontgen: discovered x-rays in 1845 Computed Axial Tomography (CAT and CT scans): used x-ray technology Magnetic Resonance Imaging (MRI): developed in 1970s Nuclear Magnetic Resonance Imaging (NMR): derived from MRI, measured the spin energy states of atoms when they are put into a magnetic field ??? Renfield: first used electro-stimulation and recording to map the functions of the brain methods of DYNAMIC brain imaging: (used to visualize the brain at work) surgical recording and stimulation Electroencephalography (EEG): (brain waves) Magnetoencephalography (MEG): measures the magnetic field produced by electrical activity in brain using SQUID (superconducting quantum interference devices) Positron Emission Topography (PET): insert something about particle annihilation here, maps which parts of brain are active when one does a certain activity PET isotopes: are unstable and they decay by positron emission name half-life applications fluorine-18 2 hours fluorinated glucose: glucose consumption oxygen-15 2 minutes blood flow to brain oxygen consumption carbon-11 20 minutes receptor locations and densities Single Positron Emission Photography (SPECT) Functional Magnetic Resonance Imaging (fMRI): uses a magnetic field with a strength of 4 teslas (Earth’s geomagnetic field is 0.5; 80,000 times greater) that targets hemoglobin and measures the BOLD (blood-oxygen-level dependent) signal, which represents the changes in that occur in a oxygenated and deoxygenated hemoglobin resulting from blood flow and cell metabolism uranium: 99.3% U-238 0.07% U-235 (only U-235 will undergo fission, U-238 will not) Ernest Lawrence: created the first cyclotron invasive: autopsy, surgery, x-ray, CAT, MRI non-invasive: EEG, MEG, PET, fMRI comparison: DYNAMIC imaging method update) EEG MEG PET fMRI spatial resolution temporal resolution (how quickly the images poor mm cm mm milliseconds milliseconds minutes seconds ; most efficient ;; Sensory Perception sensation: a collection of information from sensory receptors perception: an interpretation of a sensation that leads to an experience sensation in microorganisms (bacteria) chemotaxis: moving in respond to chemical signals E. coli runs in a random walk of “runs” and “tumbles” (tumbles cause a change in direction) chemoreceptor proteins: detect “goodies” (attractants) and “badies” (repellants), a biased swim towards attractants exists (make the microorganism tumble less) complex flagella rotary motor proteins behavioral responses to light: (examples) phototaxis and phototropism (move and grow): bacteria, protists, fungi, plants phycomyces: light-sensitive fungus experiences: present reality, physics of sensory perceptions, processing done by brain, ontology (what exists?), etc. perception is highly transformed and constructed human sensory perception sensory pathways > organ of reception > receptor cells > stimulus > perception vision: eye > photoreceptor cell > photon of visible light > see images audition: ear > hair cells > mechanical vibration > hear sounds gustation: tonge > taste receptors > soluble molecules > taste olfaction: nose > olfactory receptors > airborne molecules > smell odors somatosense: mechano-pressure receptors > mechanical touch or pressure temperature receptors > molecular motion > temperature irritant receptors > irritant chemical or pressure > irritation vestibular: semicircular canals > hair cells > gravity and acceleration > balance proprioception: muscle and joints > stretch receptors > muscle tension > body alignment and coordinated movement five canonical senses: 1. vision > sigh (sensitivity 400-700nm) 2. audition > hearing (sensitivity 20-20,000 Hz) 3. gustation > taste 4. olfactory > smell 5. somatosensory > touch human sensory perception is elaborated, sophisticated, sensitive, and limited Karl von Frisch: studied honeybee vision, and other aspects of animal behavior honeyguides: “landing patterns” on flowers, visible if sensitive to UV region of the electromagnetic spectrum, bees, insects, and some birds have UV sensitive vision electromagnetic radiation: can be polarized honeybees, ants, beetles, and birds, etc. can perceive polarization and use it to navigate pigeons, dolphins, whales, etc. can detect low frequency sounds some bats can hear high frequency sounds above 150,000 Hz (echolocation, biosonar), also moths, other organisms, etc. can too other perceptual worlds: ultraviolet radiation infared radiation polarized light low and high frequency sound electric field detection: sharks: strong detection by the passive electro-receptors (on the head) platypus: passive electro-receptors in bill, detection of bioelectric fields of invertebrate prey magnetic field detection pigeons: magnetic compass (magnetic chemical, FE3O4, in blood, called magnite?) also: turtles, magnetic bacteria the human eye: the fovea contains the most rods and cones rods: night vision, contain protein receptor rhodopsin, most absorption occurs at about 500nm (bluish green colors) cones: receptive to bright light, cone-opsin protein peak sensitivities blue: 419 nm green: 531 nm red: 559 nm has a blind spot (optic nerve) most cones are distributed at the fovea, rods are distributed around the fovea total receptors: 100 million rods 5 million cones trichromatic color vision: 3 cone photoreceptors primates: humans, apes, and monkeys most other animals have dichromatic color vision tricolor vision is thought to be an evolution of nocturnal animals (to support diurnal evolution) some birds are tetrachromatic cone cells contain cone opsin photoreceptor proteins (~350 amino acids) red and green cone opsin genes are located on the X-sex chromosome blue opsin and rhodopsin genes are coded on other chromosomes two variants of red and green opsin genes (in humans) exist: 552 nm and 559 nm genetic changes in color discrimination: color anomalies: impairment in color discriminating, but can still perceive colors prevalence: 6% male 0.04% female color blindness (red and green): impairment in the discrimination between reds, greens, and grays, due to loss of functional red or green cone prevalence: 2% male 0.1% female color blindness (blue and yellow): ‘’ blues, yellows, and grays prevalence: 0.01% (no sex difference) Ishihara: color test retinal achromatopsia: loss of all cone cells: no functional cones, complete colorblindness, extreme sensitivity to light rod photoreceptors cells: each cell has up to 100 million photoreceptor proteins 10E16 photoreceptor proteins in the human eye retinal: light absorbing part of the protein, covalently attached to the interior of the opsin protein, local electronic environment of retinal tunes absorption spectrum, retinal comes form retinol (vitamin A) and beta-carotene (found in carrots) light-induced isomerization of retinal in opsins: retinal exists as 11-cis-retinal in the absence of light when it absorbs a photon of light, it gains energy and shape shifts from 11-cis-retinal to all-trans-retinal opsin is a GPCR: rhodopsin and cone-opsin are GPCRs GPCR amplification of a signal from activation of one photoreceptor: one photon of light hitting a photoreceptor can activate 100 G-proteins, each which activate 100 phosphodiesterases, which then hydrolyzes 10,000+ cGMPs per second, cGMP is broken down to GMP, closing a sodium channel, the cell is then hyperpolarized (causes the inhibition of a NT to be released) layers in the retina: retina | ganglion cells (~1 million) > bipolar cells additional cells: amarine and horizontal > rod and cone photoreceptor cells (~105 million) visual regions: retinal | LGN/thalamus > internal geniculate muscles (cross-wire) receptive field of a cell: overlap and blend many different visual regions, each represent a map of the visual world V1: primary gateway to the cortex (everything through here initially) V4: color processing V5: processing of motion posterior temporal lobe: face-recognition lesions: hemianopia: blindness in one hemifield, caused by a lesion in half of V1 scotoma: blind spot or region in visual cortex, V1 lesion cortical achromotopsia: V4 lesion motion blindness: V5 lesion prospagnosia: inability to recognize faces, posterior temporal lobe lesion ;; Sound sound waves: air pressure variation over time properties of sound: frequency: low amplitude soft timbre: simple high loud complex speed of air is roughly 335m/s (~750 miles per hour) light: 3E8m/s (~86 miles per second) velocity = frequency * wavelength Joseph Fourier: Fourier Analysis: decomposition of any sort of vibration into a chart of different frequency components human ear anatomy: hair cells synapse with auditory nerve (8th cranial nerve) middle ear: ossicles, oval window inner ear: cochlea, basilar membrane, hair cells (3,500 hair cells) connectivity from ear to brain basilar membrane: does a Fourier analysis of sound narrow band (thick): high frequencies wide band (thin): low frequencies sound waves with a medium frequency cause a peak bending of the basilar membrane about the middle inner hair cells (on the membrane): auditory receptors, 3500 present outer hair cells: modify the basilar membrane (move it), 12,000 present molecular cables: coupled to K+ receptor channels (3 nm in diameter) connect hair cell cilium (pulls cables, K+ channels open, signal created) auditory pathways: ear > brain > brainstem > midbrain > thalamus > auditory cortex (inside lateral fissure) hearing loss: infection: damage to cochlea genetic impairments of the cochlea: “Connexion 26” gene that codes for channel proteins not present noise-induced hearing loss: acute acoustic trauma: loud, sudden noises chronic: self-explanatory treatment: hearing aids, cochlear implants (does a Fourier analysis, selects optimal frequencies) the vestibule (system): balance semicircular canals auditory nerves semicircular canals: (attached) otricle and saacule (contain hair cells and otoliths) otocania/otoliths (calcium carbonate stones): amplify signals received, help tug on hair cells vestibular neuron signaling: hair cells pull left: hyperpolarization, - - frequency impulse pull right: depolarization, + + frequency impulse ;; Taste taste: cranial nerves 7, 9, 10 microvilli, taste buds stem cell: formation of new taste receptor cels gustatory pathways: tongue > brainstem > thalamus > insula > somatosensory cortex (also) > brainstem > hypothalamus > amygdala flavor perception: salt: ion channel sensitivity to Na+ sour: ion channel sensitivity to H+ bitter: 30 GPCRs sweet: 2 GPCRs sweet (sugars): sugar: medium sized, carbon rings, size fits in GPCR, sucrose synthetic sweeteners: saccharin (1879): 500 times sweeter than sucrose, slightly bitter aftertaste (“Sweet N Low”) acesulfame (1967) aspartame (1969): 180 times sweeter, dipeptide of aspartate and phenylalanine, heat unstable, pH sensitive stability, (“Equal”) sucralose (1976) neotame (2002) Max Delbruck: Principle of Limited Sloppiness: sloppiness allows for serendipitous discoveries, and that was how saccharin was discovered! sugarcane: originated from SE Asia and South Pacific, contains high amount of sugar, many varieties Splenda: most widely used artificial sweetener today, made from sucralose: a chemical structure that actually relates to sucrose! sucralose is about 600 times more sweeter than sucrose in 2004, Equal sued Splenda for deceptive advertising Neotame: 10,000 times stronger than sucrose, similar in structure to aspartame Stevia: powdered extract of Stevia rebaudiana, comes from Amazon jungle, stevioside from the plant is about 300 times sweeter than sucruse almost all of the non-sucrose sweeteners are chemically different from one another umami: “delicious”, responds to GPCR glutamate flavor is a combination of taste, smell, and texture jasmine: some chemical components include jasmone, indole, etc. and many others! oflaction and smell: odorants an be airborne and volatile olfactory epithelium: nasal passage, smell receptors, olfactory bulb in brain is right above the epithelium of the nose olfactory receptors proteins are GPCRPs: mammals: + 11000 genes fish: 100 genes mouse: 1300 genes humans: 350 genes (codes for about 350 functional receptors, ~650 are junk pseudo-genes), ~1300 functional receptors, can smell over 100,000 different odors essential oil: aromatic odor (flower components of plants) cardamon: a spice that originated in India these molecules smell like: jasmone: jasmine geranial: lemon geraniol: rose skunk spray: 2-bufene-1-thiol 3-methyl-1-butanethiol 2-uinolinemethanthio “thio” : contains sulfer “thiol” : contains sulfide stereoisomers: molecules with the same chemical composition but have different structures “asparagus smell” in urine is consists of methanethiol and dimethylsulfide (not found in asparagus, but found in the urine of those who have ate it, a possible precursor is asparagusic acid) anosmia: a lack of a specific or general smell olfactory neural pathway: olfactory bulb thalamus olfactory frontal cortex amygdala hypothalamus temporal cortex pheromone: chemicals used for intraspecies social communication insects, vertebrates: territorial marketing, sex, social status, identity, and mate attraction, etc. rodent nasal cavity: vomernasal organ and pathway: pheromone detection capsaicin: “hot” substance from chili peppers capsaicin receptors: Ca++ channel, depolarization, activated by heat (temperatures 109-122 F, opens Ca+ channels), are everywhere (tongue, skin, brain, ?_?, etc.) capsaicin receptor terminology: two types of receptors: 1. TRPV1(“transient receptor potential”) : 43-50 C, responds to capsaicin 2. TRPV2: greater than 50 C, does not respond to capsaicin menthol: menthol receptors: Ca++ channel, depolarization, activated by cool menthol receptor terminology: CMR1 (“cold and menthol receptor”): 46-82 F isothiocynates: “pungent” chemicals, mustard family allylisothiocynate: found in mustard, horseradish, and wasabi activates a different type of receptor: TRP ~ ANKTM1 somatosensory receptors: touch, pressure, pain, temperature parietal lobe: sensory Wilden Renfield: neurosurgeon, electro-stimulation and recording, developed the cut-parts-of-the-brain seizure treatment method primary somatosensory cortex: anterior parietal lobe, contralateral projection from body etc., homunculus (body) map central sulcus: primary somatosensory cortex (S1), anterior posterior lobe lesion in S1 results in a loss of sensation primary somatosensory cortex receives data > sends to secondary somatosensory cortex (S2, S3, etc) P2 lesions result in neglect syndromes, and other weirdness mouse somatosensory cortex: “whisker barrels”, whiskers are most sensitive whisker amputation: barrel “expansion”, rewire (neuroplasticity in action!) humans: bodily amputation, “phantom arm” perception > rewire (homunculus map reorganization) VS Ramachandran: “Phantoms in the Brain”, suggested rewiring of nerves of phantom limbs controls on movement: primary motor cortex (M1, posterior frontal lobe) motor: body, homunculus map, lesion in M1 causes paralysis supplementary (secondary) motor areas: anterior (prefrontal, secondary) frontal motor area active druing planning of movement prefrontal plans movement > premotor cortex organizes sequence of actions > motor cortex executes supplementary lesions: apraxia: problems with organizing movement vast interconnectivity between secondary somatosensory areas and prefrontal motor area! frontal lobe mirror neurons: active during movement and during observation of movement frontal-parietal lesions: paralysis, somatosensory weirdness left hemisphere lesions affect right side of the body, and vice versa, but right hemisphere lesions also induce anosognosia (denial) Freudian psychological defenses: denial, rationalization, projection, humor, etc.; anosognosia exhibits exaggeration of defenses left hemisphere: contains psychological defense mechanisms RH stroke: depression uncommon LH stroke: depression common neurology of human language aphasia: disorder of language Paul Broca: Broca’s Aphasia: affects speaking, writing production, associated with a frontal lesion, is a type of agnosia Broca’s Area | areas for facial expressions and speech movements A1 (for sounds heard) Wernicke’s Area | aphasia cerebral lateralization of language: Wada test: barbiturate sedative hypnotic immobilization of one hemisphere (to study the effects), is injected through carotid arteries other tests: examine stroke lesions, fMRI language lateralization in which hemisphere(?): Hemisphere RH (right-handers): L: 97% R: 3% LF (left-handers): L: 70% R: 15% Both: 15% processing: sounds > auditory cortex (A1) sounds that sound like language > A1, Wernicke language with meaning > A1, Wernicke, and Broca’s Area William Burough: “Language is a virus.” corpus callosum: ~700 million axons Roger Sperry also studied L/R brain lateralization, and split-brain patients (those with cortical callosotomy(sp.?)) right hemisphere is spatially superior hemispheres: L: language, calculation, visual detail R: nonverbal linguistics, 3-D dimensional-spatial aspects, visual gestalt, harmony, timbre Thomas Harvey: performed autopsy on Einstein in 1955 Marian Diamond got slices of Einstein’s brain, analyzed glia to neuron ratio Sarah Witelson: discovered that Einstein had an expansion in the postcentral lobe reductionistic explanation of understanding: neurocscience, physics, etc. math porque consciousness exists? 1. by-product of neural complexity, circuitry 2. evolutionary advantages or/and 3. it’s a fundamental property of the universe what does it take to have consciousness? 1. do computers have a mind, etc? 2. mirror/self-recognition? (chimps, gorillas, okay!) neural correlates of consciousness (NCC): which nerves create consciousness? William James: first true neuroscientist, “Principles of Psychology”, suggested three approaches to study the mind: 1. behavior 2. neural correlates of behavior 3. direct study of the neural phenomena themselves scientific revolutions: physics: Copernicus, Newton, Einstein, Quantum Theory, etc. biology: Darwin cognitive science: none yet, but hopefully in the due future!