Psychoactive Drugs Caffeine: coffee, tea, chocolate are best-known plant sources of caffeine

o Others: kola, guarana, yerba mateo Most widely used psychoactive drugo Similar psychoactive effects: theophylline (tea), theobromine (cacao)o Effects

On CNS: increase wakefulness and alertness On cardiovascular system: increase heart rate and blood pressure

o Similar structure: adenine, guanine Caffeine acts as antagonist at adenosine receptors

In heart: slowing of heart rate On blood vessels: opening up of the vessels (vasodilation) In brain: decreasing of neuronal excitability GPCR Caffeine reduces inhibition neurons are more excitable

Nicotine : tobaccoo Acts as agonist at nicotinic acetylcholine receptors

Relaxation, alertness, focused attentiono Poison

Disruptions in heart rhythm, blood pressure, and respiration Alcohol: two-carbon ethyl alcohol or ethanol

o All organic alcohols are poisons Ethanol is the least poisonous to the human body

Formed by metabolic action of yeast on sugars from plants (fermentation)

Sedative-hypnotico Low doses: sedative/relaxing effecto High doses: hypnotic/sleep-inducing effecto Mild intoxication, impaired judgment and coordination,

grossly impaired movement, loss of consciousness, deatho Barbiturates

Used as medicine at first Among the first synthetic drug (not coming from

plants) used in medicineo Benzodiazepines

Librium and Valium: best selling drug in historyo Other: meprobamate, chloral hydrate, sleep-inducing agentso Anesthetics

Loss of sensation Interferes with voltage-gated sodium channels Reduce overall CNS neural activity

Loss of consciousness lack of awareness of sensory experience (pain)

Ethanol diethyl ether other volatile chemicals halothane desfluarane and sevoflurane

Halothane: small hydrocarbon and ether with halogen atoms replacing hydrogen

o Act at ionotropic GABA receptors Facilitate the action of GABA at the receptor Increase inhibition in the CNS by increasing

GABA-induced Cl- flow into cells Low doses: relaxing, anxiety-reducing

(anxiolytic) effects High doses: impaired movement and

memory storage, loss of consciousness, death

Opium and opiods : opium poppyo Psychoactive effects: relaxation, pain relief, euphoriao Medicinal effects: reduce perception of pain (analgesia), suppress cough, slow the

motile muscle action of intestines (treating diarrhea)o Friedrich Wilhelm Sertuner: morphine

First time a chemical substance was isolated from the plant Bayer Company

Acetylsalicylic acid: salicylic acid acelytated (aspirin) Diacetylmorphine: acetic acid + morphine (heroin)

o Twice as potent as morphine Acetyl groups are less polar than hydroxyl groups

crosses blood-brain barrier more efficientlyo Methadone: first instance of a completely synthetic opioido Fentanyl: another synthetic opioid

100x more potent than morphine Wildnil: sedation of large animals

o Endorphins: function as agonists at opioid receptors Endogenous + morphine

Endogenous (made within the body) First of neuropeptides (class of neurotransmitters) Chains of amino acids (polypeptides)

Shortest: 5 aa; longest 31 aa Cocaine : coca plant

o Effects: increased wakefulness, focused attention, decreased fatigue, and increased stamina, decreased appetite, increased positive mood, stimulation of sympathetic nervous system

Increased heart rate, vasoconstriction, opening up of the bronchial airways and nasal passages, dilation of pupils

Poisonous: over-arousal of CNS anxiety, irritability, impaired judgment, psychosis, seizures, cardiovascular stress, stroke, heart attack

Psychosis: discombobulation of the perception of reality and delusions/hallucinations

o Blocks reuptake transporters for the neurotransmitters norepinephrine and dopamine

Excessive activity at all synapses in the nervous system that use norepinephrine/dopamine as a neurotransmitter

Amphetamine-type stimulant drugs o Synthetic pharmaceutical drugs

Amphetamine: Dexedrine, Adderall Methamphetamine: Desoxyn, speed Methylphenidate: Ritalin

o Ephedrine: plants of genus Ephedra Used to treat asthma

o Cathinone: khat planto Causes reuptake transporters for norepinephrine/dopamine to become leaky

Instead of transporting neurotransmitter from the synaptic cleft back into the presynaptic axon terminal after release, neurotransmitter continuously leaks out of the axon terminal and into the synaptic cleft

Overstimulation of neural circuits using norepinephrine/dopamine as neurotransmitter

o Stimulant effects: increased arousal, stamina, and focus of attentiono Sympathomimetic effects: increased heart rate and blood pressure, opening of

nasal and bronchial air passages, pupil dilation Psychedelics

o Effects: intensification of thoughts and feelings, alterations of sensory perceptiono Set and setting

Set (mental set): psychological factors Expectations, memories of prior experiences, mood, etc

Setting: physical environment in which the experience of intoxication takes place

Humphrey Osmond: psychedelic Psyche: mind; delos: visible

Mescaline: peyote, a small cactus Arthur Heffter First psychedelic substance to be chemically identified

Lysergic acid diethylamide (LSD) Albert Hofmann Before discovery of LSD, acetylcholine was the only known

neurotransmitter Magic mushrooms

Originally used by Mazatec people Contemporary discovery by R Gordon Wasson and wife Valentina With Hofmann discovered psilocybin and psilocin from the

Psilocybe mushrooms Dimethyltryptamine (DMT)

Can be synthesized by aa tryptophan Occurs in nature in plants and human body

o Ayahuasca (yage): brew with a DMT-containing plant + ayahuasca vine which enhances DMT effects

Lysergic acid amide: seeds of morning glories

Ibogaine: root of Tabernanthe iboga Binds as agonists to serotonin receptor subtypes, dopamine and

norepinephrine receptors Type-2A serotonin receptors

o Non-classical: psychedelic effects but different character of classical MDMA: ecstasy MDA Salvinorin Dissociative anesthetic ketamine Anticholingeric hallucinogens

Atropine and scolpolamineo When used in less well-controlled settings, effects are more unpredictable and

negativeo First law against LSD in the US passed in 1966o 1971: LSD illegal throughout the world

Cannabinoids: plants from genus Cannabiso Hemp: fibero Marijuana, pot, hash, etc: psychoactive/medicinal effectso THC: delta-9-tetrahydrocannabinol

Hydrophobic molecule Sticks to lipids and dissolves into phospholipid bilayer membranes

o Cannabinoid receptor: GPCRo Anandamide: endogenous ligand for the cannabinoid receptor

Sanskrit ananda: bliss First of several molecules to be discovered that appear to function as

neurotransmitters at the cannabinoid receptor Another: 2=arachidonylglycerol (2-AG) Aka endocannabinoids Act as agonists at the same receptor

o Cannabinoid receptors and endocannabinoids found widespread in brain without functions

Cannabinoids: present on presynaptic axon terminals of neurons Endocannabinoid: synthesized and released from postsynaptic dendrites in

response to glutamatergic stimulation. Travels across the synaptic cleft to interact with cannabinoid receptors on presynaptic axon terminals

~backward nature of signaling~ endocannabinoids: retrograde neurotransmitters

Molecules that carry signal info in the direction opposite from the way neural signals were generally thought to move

Dynamic tuning of strengths of synapses: intensity of signal transmission (neuroplasticity)

Neural Development and Neuroplasticity Human genome: 46 chromosomes (23 from each parent)

o Sex chromosome: X from mother, X/Y from fathero Diploid chromosome number: 46

o Haploid chromosome number: 23 Used in reference to distinct genetic material Contains approx. 3 billion nucleotide base pairs

Codes approx. 21000 proteins After fertilization of egg, cell differentiation takes place

o Regulated via transcription factors Proteins that bind to regions of the DNA and regulate the read-out of

genes <3% of human genome codes for functional protein >85% of human genome is transcribed into RNA

o Involved in regulation of gene expression Dark matter of the DNA/junk DNA: >97% of the human genome that doesn’t code for

functional protein Embryonic stem cells: cells having the capacity to continue dividing and to differentiate

into any type of cell in the bodyo In the developing nervous system differentiate into neural progenitor cells

Cells that are on track to become neurons or glia Neurogenesis/gliogenesis

o Takes place in utero Cell migration: as cells differentiate, the move around to occupy specific locations Developing neurons grow out dendrites and axons Synaptogenesis: maturing neurons begin to wire together and form synapses Neural tube: within 3 weeks of conception, a group of cells begins to fold and form a

structure By the third month post-conception, brain growth really takes off Gyri and sulci of the cerebral cortex begin to form during the final two months before

birtho Rapid expansion of the density and connectivity of cells in the cerebrum

Caused by proliferation of neurons and glia from dividing stem cells and growth/branching of dendrites and axons

Ramon y Cajal: tips of growing axons possessed exquisite mechanisms of sensitivity, motility, and guidance

Growth cone progresses via extension of finger-like structures (filopodia)o Propelled by actions of the internal cytoskeletal structure of the cell

Composed of elaborate ordered arrays of protein polymers-microfilaments made of actin proteins and microtubules composed of tubulin proteins

o Functions of microfilaments and microtubules: Growth and movement of cell processes Moving materials around within the cell Insertion and removal of membrane proteins (ion

channels, transporters, neurotransmitter receptors) Roger Sperry: research with amphibians that regenerate after physical damage to their

bodieso Rotated eyeball 180 degrees see the world upside down and backwardso Cut the optic nerve in a frog and it regenerated from the eye to the brain

o Chemoaffinity hypothesis: nerve cells use specific chemical signals to guide their wiring during development and during neural regeneration

Nerve growth factor (NGF): neurotrophino Other: BDNF (brain-derived neurotrophic factor), GDNF (glia-derived

neurotrophic factor), NT3 (neurotrophin-3) Other proteins involved in axon/dendrite guidance: ephrin, netrin, neuropilin, plexin,

semaphorin, Slit, Roboo Guidance sometimes involves direct contact between one protein anchored to one

cell and another protein anchored to anothero Mechanisms of attraction/repulsion are mediated by coupling the activation of

membrane receptors Attraction: extension of an axon in one direction Repulsion: extension of an axon in another direction

More connections between neurons are formed during the first year of life than will be retained

o Connections are assessed for utilityo Synaptic pruning: elimination of synapses not in useo Synapses that are used become stabilized and strengthened

Example of pre-synaptic mechanism to strengthen synapse Prolonging the state of depolarization in the axon terminal

voltage-gated calcium channels remain open longer fusion of more vesicles and increased release of neurotransmitter

o More neurotransmitters released: more signal passed to the next cell stronger synapse

More reuptake transporter proteins: neurotransmitter remains in synaptic cleft for a longer time following release more signal stronger synapse

Post-synaptic mechanism: influence gene transcription Greater/lesser numbers of neurotransmitter receptors are produced

and inserted into the post-synaptic membraneo More neurotransmitter receptors: stronger synapseo Fewer post-synaptic neurotransmitter receptors: weaker

synapse Neurogenesis occurs in adult vertebrate brain esp. in hippocampus

o Bilateral structure located beneath the surface of the temporal lobeo Shape of seahorse (same genus name)

Greek hippos: horse; kampos: sea monstero Formation and stabilization of memories

During early years of life, brain is most susceptible to wiring changes Myelination of axons interconnecting cells within the cerebral cortex continue past age

20o Myelination needed for cortical neurons to efficiently communicate with one

anothero Important to establish during teen years

Good parenting and loving atmosphere during childhood important for brain plasticity

Sensory Perception Sensory perception: nexus between brain, mind, behavior

o Sensation: collection of info from the environment via sensory organs and receptors

o Perception: analysis and interpretation of info by the nervous system, contributing to the experience of mental states of perceptual awareness

Single-celled bacteria detect and respond to physical stimuli in their environmento E. coli and Salmonella swim in runs and tumbles

Runs: straight line for a second; flagella rotate in one direction and form a bundle that functions like a propeller

Tumbles: stops swimming and flops around for a minute; direction of flagella rotation reverses, the individual flagella fly apart, forward motion ceases, tumbles about randomly

o Chemotaxis: amino acids (aspartic acid and serine) interact with receptor proteins located on the bacterial cell’s outer membrane and influence the bacterium to swim toward nutrients

Interaction between nutrients and receptor proteins reduces likelihood of tumbling keeps bacterium moving in direction toward nutrients

Light can influence microorganismso Phototaxis: process of moving toward lighto Phototropism: growing/bending toward lighto Increase exposureo In organisms that don’t derive energy directly from light, enables movement

toward a more open region in order to disperse spores/seedso Fungus Phycomyces doesn’t photosynthesize but has sensitivity to light

Directs growth of its fruiting bodies (sporangiophores) Have stalks At tip of each stalk is a sporangium: contains 100,000 spores

Ontology: study of nature of reality Signals from sensory receptors are manipulated by the nervous system (brain)

o Synaptic connections are impacted by info received via sensory pathways Forms basis of mental experience of the world

Epistemology: how do we know what we know?o Experience of the world is a function of what actually exists, the physics of our

sensory receptors and organs, and the neural manipulation of incoming signals by the brain

o Naïve realism: what we perceive is identical to what actually exists in the world All forms of perception involve elaborate manipulation of signal info by the nervous

systemo Interaction of incoming neural signals with vast network of established activity in

the cerebral cortexo Our perception being a transformed and constructed representation of what is “out

there” The various sensory pathways are associated with organs of reception containing receptor

cells responding to particular kinds of physical stimuli

o 5 primary senses: taste, smell, sight, hearing, toucho Vestibular sense

Organs of reception: semicircular canals of the inner ear Receptor cells: hair cells Physical stimuli: gravity and acceleration Associated perceptual experience: balance

o Proprioception: stretch receptors in the muscles and joints gather info related to muscle tension and joint movement

Used to tune body alignment and coordinated movement Visual pathway in humans responds to a limited range of energies within the

electromagnetic energy spectrum

o Humans only see visible light spectrumo Karl von Frisch: honeybees have color vision

Can also see UVo Infrared: too low energy

Vibrations heat Pit vipers can detect infrared radiation

o Image intensifier amplifies very low intensities of visible lighto Infrared/thermal imager: detects infrared radiation and converts to visible regionso Polarization: vibration of electromagnetic field aligned along specific angles in

relation to the direction of propagation The angled of polarization and the extent to which the light is polarized

varies depending upon where in the sky one looks relative to the sun Human visual system w/o the aid of a polarizing filter isn’t sensitive to

this property of sunlight

Honeybees use sunlight polarization patterns as navigational aid Humans are capable of hearing 20-20,000 cycles of vibration per second (Hertz/Hz)

o Heinrich Hertz: studied vibrating electromagnetic fieldso Infrasound: frequencies less than 20 Hzo Ultrasound: very high frequency soundo Ultrasonic: higher than 100,000 Hz used by bats

Echolocation, biological sonar Electroreception: detection of electric fields generated by living organisms

o Every living creature is surrounded by electric fields produced as a result of the movement of charged ions within the organism

o Sharks can locate fish well-camouflaged on the ocean bottom Electroreceptive structure: ampullae of Lorenzini on shark’s head

o Platypus finds prey in muddy bottoms of aquativ environments Electroreceptors on bill

o Fish use to communicate Different species have different frequencies and patterns

Magnetic fields: generated by large-scale movement of magnetic atoms in the molten interior of the planet

o Strongest at north and south poleso Weakest at equatoro Direction of magnetic field vector points toward the poles and becomes more

steeply inclined nearer to the poleso Vectors direction is nearly horizontal and parallel to the surface of the Eartho Humans use compasses for directiono Birds for migration

Come back to original location 1970: attached magnet onto pigeon

Severely interfered with its ability to navigate home when sun wasn’t visible

Nose and Smell Perfumery: one of the early applications of alchemy Olfactory sensory perception begins when odorants (airborne volatile molecules) enter

nasal passageso Some molecules are caught in the nasal/olfactory epithelium

Moist and mucousy tissue lining the interior of the nasal passages Within the epithelium are stem cells

Cells w/ enough flexibility to differentiate into the various different types of olfactory receptor cells

Replace receptor cells every 1-2 monthso Direct exposure of the receptor cells to potentially toxic

substances from the environment results in accumulation of cellular damage

o Molecules come into contact with cilia of olfactory receptor cells

Olfactory receptors are GPCRso Fish: 100 different olfactory receptor proteinso Mice: 1300o Humans: 350 genes coding for 350 functioning olfactory GPCRs

Pseudogenes: nonfunctional geneso 600 olfactory pseudogenes in humans

Essential oil: oily concentrate of aromatic molecules from a planto Latin esse: to beo Aroma-carrying molecules are hydrophobico Prepared by distillation: heating an extract of plant and concentrating the more

volatile components Aroma and aromatic come from Greek word for spice Plant aromas have many different chemical components Christopher Columbus: allspice in America

o Similar to peppercorn seeds, cinnamon and clove aroma In roses: citronellol, geraniol, nerol, etc

o Similar molecular shape Linear chain of eight carbons with one or two double bonds, two methyl

(CH3) side groups, and a hydroxyl group (OH) Jasmine: indole

o Aromatic quality in feceso Bass note/low note

Geranial: lemono Carbon double-bonded oxygen: aldehyde

Geraniol: roses

o OH at end Thiol: S-H

o Stinkyo Skunk smell: 2-butene-1-thiol, 3-methyle-1-butanethiol, 2-quinolinemethanethiolo Asparagus pee: methanethiol, dimethylsulfide

Not found in asparagus Result of digestive chemical transformation of asparagusic acid

Specific anosmia: loss of sensitivity to a specific kind of smello Due to genetic variation in one of the 350 olfactory GPCRs

General anosmia: loss of sensitivity to a large variety of aromaso Sometimes a complete lack of olfactory sensitivityo Caused by nasal congestion, head trauma, etc.

Hyperosmia: increased sensitivity to odorso Appear transientlyo Migraine headache or pregnancy

Olfactory GPCR receptors are in membrane of olfactory receptor cells in the nasal epithelium

Activation of olfactory GPCR synthesizes cAMPo cAMP interacts with a type of cation channel that is gated by the binding of cyclic

nucleotideso Result: influx of Ca++ and Na+ ions depolarizing cells and contributing to

signal generation Olfactory receptor cells send axons into olfactory bulb of the brain

o Located immediately above and adjacent to the nasal cavityo Cranial nerve 1: nerve fibers between the nose and olfactory bulb o Axons form synapses with dendrites of mitral cells (triangular shape) in olfactory

bulbo Mitral cells send axons to pyriform cortex (interior of brain) and amygdala

(limbic system)o Pyriform cortex sends axons to the thalamuso Connections are made to the orbitofrontal cortex of the frontal lobe

Durian fruit: very strong aromao From southeast Asiao King of fruitso Alfred Russel Wallace wrote about ito Can evoke robust attractive/repulsive emotional responseso Propanethiol (oniony), methylbutyrate (pineapple)

White and black truffle mushroomso Thousands of dollarso Can evoke strong, generally very positive, emotional reactions

Pheromones: chemicals that carry signal info related to social communications between members of the same species

o Greek pherein: to carry/bearo Mate attraction, territorial marking, signaling danger

o Vomeronasal system: distinct olfactory sensory structure and neural pathway that responds selectively to pheromone molecules found in vertebrate animals

Tongue and Taste Taste buds: clusters of receptor cells in the mouth

o Mostly on the tongue but also upper palate and pharynxo Approx. 10,000 taste buds in the human moutho Each taste bud has ~100 taste receptor cellso 1 million taste receptor cells in our mouth

Pore exposes receptor cells to interior of the mouth o Saliva dissolves the molecular components of food and drinko End of receptor cells composed of microvilli

Filamentous structures that increase the surface area exposed to tasty substances

Within the phospholipid bilayer membrane: taste receptor proteins Acts as cilia in olfactory cells

Smaller than cilia and have an internal cytoskeletal structure consisting largely of actin

Cilia’s internal cytoskeleton: microtubules Bulk of gustatory receptor cell: cell body with DNA-containing nucleus, mitochondria,

etc. o At base: contact point (chemical synapse) with nerve fibers that respond to

neurotransmitter molecules released by the taste receptor cells, initiating a signal that goes to the brain

o Fibers carrying signals form taste receptor cells to the brain are part of the system of cranial nerves (7, 9, 10)

There are stem cells adjacent to the taste receptor cellso Differentiate into various types of taste-receptor cellso Turnover rate: 2 weekso Olfactory and gustatory receptor cells have direct contacto Visual and auditory receptor cells shield from direct contact, don’t have stem cells

Salto NaCl breaks down into Na+ and Cl- ionso Proteins on taste receptor cells allow sodium ions to flow across the membraneo Ingestion of some amount of sodium and other related cations: essential for

survival Sour

o Acidic: release of hydrogen ionso Positive charge flows through channels

Bittero GPCRs

More than 30 different GPCR proteins distributed over receptor cells associated with bitterness

o Serve as warning for poisons Plant alkaloids (caffeine, cocaine, morphine, quinine)

o Common in nature

Sweeto Sugar: small molecules composed of rings/chains of carbon atoms with oxygen

and hydrogen atomso GPCRs

Two linked together by non-covalent interaction to form functional receptor

Not common in natureo Non-nutritive: sweet but have little or no caloric or other nutritional value;

synthetic Artificial sweeteners First: saccharin

300x sweeter than sucrose Slightly bitter taste

Cyclamate, aspartame, and acesulfame found on accident Max Delbruck: principle of limited sloppiness

Situations in experimental research with accidental discoveries due to sloppiness of scientist

Aspartame: most widely used 200x swetter than sucrose Dipeptide Neotame: derivative of aspartame formed by adding 6-carbon

branched chain onto aspartic acido 50x sweeter than aspartameo 10,000x sweeter than sucroseo carfentanil: morphine; neotame: sucrose

“Diet foods” Sucralose/Splenda

600x sweeter than sucrose Replaced 3 hydroxyl groups with chlorine atoms

o Steviol: sweet-tasting components from Stevia rebaudiana leaves Stevioside: steviol + 3 glucose molecules

300x sweeter than sucrose Found in highest concentration in the plant

Umamio Kikunae Ikeda: glutamate produced a distinct taste perception

MSG: monosodium glutamate Umai: delicious; mi: taste

o Savory, meaty, mushroomyo Metabotropic GPCRo Glutamate: amino acid

Taste sensory info cranial nerve fibers lower brainstem cells in nucleus solatarius 1) thalamus insula somatosensory cortex in parietal lobe 2) hypothalamus amygdala

Hotness/spiciness/pungency enter brain differentlyo Enter brainstem via 5th cranial nerve (trigeminal nerve) and are received by

regions of the brain closely associated with the perception of paine

o Chili: native to S. America Member of Solanaceous family of plants along with tobacco Hotness: capsicin Capsaicin binds to receptor proteinshape-shift occurs ion channel

opens ion channel opens calcium ions flow from outside the cell to inside depolarize the cell neural excitability

Thermal heat activates capsaicin-sensitive proteins Increasing temperature of protein

o Capsaicin/thermal receptor proteins not just in mouth but all over the body Type of ionotropic channel protein TRP channels: transient receptor potential

Electrical response of fruit fly eye to lighto Capsaicin receptor: TRPV1

Ion channel opens to capsaicin, 43-50 degrees C, and piperine Found in black peper

o Signaling pathway for cold: ionotropic receptor protein found in mouth and body Calcium channel opens in response to binding of menthol

Found in mint plants Temperatures under body temperature produce a shape-shift of protein and

open the channel Same as heat but instead cold TRPM8

o Pungency (mustard, horseradish): isothiocyanates Sulfur, carbon, nitrogen Ionotropic Ca++ channel (TRPA1): activated by binding of

isothiocyanatesneural signals Flavor: taste, texture, smell

Eye and Vision Visible light: energy range 400-700nm Electromagnetic energy can be conceptualized as photons Light and other kinds of electromagnetic energy: simultaneously both a wave-like field

and particle-like photon More energetic radiation (shorter wavelength): interactions w/ molecular and cellular

structures are likely to be damagingo Chemical bonds break and molecules fall aparto Free radicals form

o DNA is damagedo Cell membranes become leaky

Lower energetic radiation (longer wavelength): interactions w/ molecular and cellular structures might not be energetic enough to generate a reliable neural signal

Eye: receptor organ for human visiono Similar to camerao Vitreous humor: transparent gelatinous fluid in the interior of eyeballo Lens, cornea, and pupil focus light onto photosensitive retina at the rear of the

eyeball Retina: layer of light-sensitive photoreceptor cells and several layers of

interconnected nerve cells Crisscrossed with blood vessels Latin rete: net

Light coming from center of visual field is focused by lens onto center of retina (fovea or macula)

Latin fovea: pit Latin macula: spot Fovea: density of photoreceptor cells is highest visual acuity is

best Rods: very numerous, sensitive to small amounts of lights

o Rhodopsin: absorb light and initiate process of transformation of the light energy into a neural signal

o Black and whiteo Sensitive to low light and nighttimeo 100 milliono Throughout the retina

Cones: mostly located at fovea, responds to higher intensity than dim

o Cone-opsins: sensitive to bright light and daylighto 5 milliono Concentrated in foveao SML wavelength absorbing cones

Blue, green, redo Color

S: violet/blue M: green/yellow L: orange/red

Colors do not exist in the world; mental experiences related to nervous system’s response to electromagnetic radiation having different energies

Trichromatic color vision: there differenty types of cone photoreceptors with different light-sensitivity ranges

o Non-primate mammals have only 2 cone photoreceptor tipeso Birds have tetrachromatic color vision

Human opsin proteins: 350 amino acidso Genes for M and L opsins are on X chromosome

Females can have L-opsin variants and be tetrachromats Males can’t have more than trichromatic color vision

o Genes for S opsin and rhodopsin are on non-sex chromosomes (7) Color anomalous: light-absorbing properties in ospin protein is altered hard to

discriminate different colorso More likely for males (6%)o Females: 0.4% because both parents must have the gene

Red-green color blindness: one entire type of functional cone receptor cell (M/L) is losto Significant loss of ability to distinguish between various shades of color in green-

yellow-red region of color spectrumo Males: 2%; Females: <0.1%o On X chromosome

Blue-yellow color blindness: genetic variation in S cone-opsin geneo Loss of ability to discriminate between colors in blue-green-yellow region of

color spectrumo Rare: occurs <0.01% of population

Retinal achromatopsia: genetic or developmental anomaly resulting in loss of all functional cone cells

o No experience of color; black, white, grayo Gradients of contrast, shadow, and texture

Blind spot: a small region of the retina with no photoreceptors; axons bundle together (optic nerve), exit the eyeball, and move to brain

o Different for each eyeo Visual system gathers info to fill in blind spot

Rod cells: one hundred million rhodopsin moleculeso 100 million rod cells in retina ten quadrillion rhodopsin molecules in each

retinao Each rhodopsin/cone-opsin is composed of ~350 aa joined into a long chain by

covalent chemical bonds The chain is embedded in lipid-bilayer membrane in outer segment of a

photoreceptor cell and winds itself back and forth across the lipid bilayer seven times

In sections where the polypeptide chain crosses the membrane, alpha-helical structures that are more hydrophobic made from amino acids form

Retinal: molecule covalently attached to protein (not aa) Absorbs light and begins neural signal Made from vitamin A and carotenoids

o Vitamin A (retinol): aldehyde alcohol with addition of Ho Carotenoids: beta-carotene (orange in carrots)

11-cis isomer of retinal: retinal binds to protein in ospins where carbon chain is bent/kinked

light-induced isomerization (photoisomerization): absortion of a photon of light triggers change in shape and straightens out

Opsin proteins: GPCRs (pg 28)

o Enormous amplification: an activated rhodopsin can bind to 100 Gproteinsactivate cGMP-phosphodiesterase enzymehydrolyze hundreds of molecules of cGMP

o One single photon of light can produce an intracellular decrease of more than 10,000 molecules of cGMP

Different aa sequences in various opsin proteins produce different electronic environments altering molecular energy levels in attached retinal

Three major layers of cells in the retina: photoreceptor cells, bipolar cells, ganglion cells

o Rods and cones form synapses with bipolar cellso Bipolar cells form synapses with ganglion cellso Neural signals flow from photoreceptors to bipolar cells to ganglion cells to braino Axons of ganglion cells bundle together to form the optic nerveo 100 million photoreceptor cells in each retinao 1 million ganglion cellso 1 million axons make up each optic nerve

o ganglion cells wait for coincidences of several signals from one or more photoreceptors

increases the min number of photons necessary to generate an action potential from a ganglion cell that is passed along the optic nerve to 5-10

melanopsin: photoreceptive retinal-opsin protein discovered in light-sensitive cells in skin of frogs

o found in certain ganglion cellso send axons into regions of the brain involved in regulation of pupil size and

synchronization of circadian rhythms receptive field: region of space from which a stimulus elicits a neural response

o all neural cells in retina have visual receptive fields optic chiasm: two optic nerves intersect and divide into two new groups

o left half of visual space going to right half of the braino right half of visual space going to left half of the braino 10% of optic nerve axons go into part of the midbrain called the superior

colliculus responds to sensory stimuli in ways that are rapid and do not involve

awarenesso 90% of optic nerve axons head to thalamus in diencephalon

enter lateral geniculate nuclei (LGN) LGN cells send axons into the rearmost region of cerebral cortex, the

posterior occipital lobe and form synapses with cortical neurons Contralateral connectivity: crossing over of info between spatial

environment and brain Analysis of visual info: occipital lobes + posterior regions of temporal lobes (visual

cortex)o V1 (visual area number one): edge of objects; shapeo V4: specific colorso V5: movement; speed and directiono David Hubel and Torsten Wieselo Studied people who suffered brain lesions and functional brain imaging

Visual scotoma: lesion in V1o Blind spot in a specific region of spaceo Mild case: unnoticeableo Severe case: complete loss of vision for an entire half of the visual field

(hemianopia/hemianopsia) Disruption of color vision: lesion in V4

o Cortical achromatopsia: washed-out/faded color perception – complete loss of color awareness

Akinetopsia: lesion in V5o Motion blindness: unaware of movement in some region(s) of visual space

Seems like series of snapshots Prosopagnosia: difficulty/complete loss of ability to recognize faces

o Caused by lesions in inferior and medial temporal lobeo Specific type of agnosia: neurological syndrome

Visual agnosia: difficulty recognizing all visual objects Lesions in region where occipital, parietal, and temporal lobes

come together

Ear and Hearing Sound: mental experience and physical vibration Sound wave moves through air with approx. speed of 1,100 feet/second (335 m/s)

o Velocity=frequency of variation*wavelengtho Air pressure variation oscillating at 200 Hz (distance of one

cycle/wavelength)=5.5 ft Higher frequency=shorter wavelength Speed of light > speed of sound

o 186000 mi/s human auditory system is sensitive to air-pressure variations in the range of 20-20,000Hz Higher frequency=higher pitch Amplitude: magnitude of the pressure variation; loudness of a sound

o High amplitude=louder volume Timbre: complexity of the sound waveform

o Simple sinusoidal variation in pressure with single frequency: pure tone

o Most air pressure variations are complex waveforms Joseph Fourier: waveform vibration can always be a sum of sine waves with various

frequencies and amplitudes Pinna: most external structure of the ear

o Funnel/antenna: collects and focuses vibrations of air pressure into ear canal Ear canal terminates at the tympanic membrane (ear drum)

o Ear drum: small drumskin-like piece of tissue set in vibration by the air molecules striking it

Forms boundary between outer ear and middle ear External ear: pinna, ear canal, ear drum Middle ear: ossicles (three small interconnected bones)

o Hammer, anvil, stirrup Malleus, incus, stapes

o Eardrum vibrates hammeranvilstirrupoval window Oval window: boundary between middle and inner ear

Inner ear (bony labyrinth): cochlea, semicircular canals o Cochlea: coiled structureo Vestibular fenestra: location of membrane of oval windowo Cochlear fenstra: location of membrane of round window

Allows fluid inside cochlea to move by bulging in/out as sound vibrations move through cochlea

o Interior filled with fluid and the vibration of oval window sets fluid inside cochlea into vibration

o Structure of ossicles transfers vibrations in air into fluido Basilar membrane: thin tissue length of cochlea down the central core of spinal

interior Thickest at end nearest oval window: higher frequencies Variation in thickness causes different regions to be set into vibration by

different frequencies (resonance) Hair cells: bundle of hairs/cilia

o Vibrate and swoosh in fluid in basilar membraneo Hair cell forms chemical synapses with fibers of auditory nerve (cranial nerve 8)o Spiral ganglion: cluster of cell bodies for nerves (1/ear)o Bipolar neuron: single myelinated dendrite receiving signal from hair cell and a

myelinated axon carrying the signal into the brainstemo In brainstem’s medulla, axons of auditory nerve synapse with cells in cochlear

nucleus Neurons of cochlear nucleus send axons to cells in pons (superior olive

and lateral lemniscus)o Various brainstem auditory centers send axons into inferior colliculus in midbrain

Projects to nearby medial geniculate nucleus of thalamus (MGN) MGN sends axons to temporal love of cerebral cortex (primary

auditor cortex A1)o 3,500 inner hair cells per cochleao 12,000 outer hair cells per cochlea

contain protein prestin: elongates/contracts as a function of membrane-potential changes

Direct vibration of bones of the skull that surround the cochlea can make soundo Vibration of tympanic membrane, ossicles and cochlea

Loss of hearing due to damage of hair cells, genetic anomalies in cochleao Gene coding for a connexion ion-channel protein: form electrical synapses

between neurons and glia Maintain ion flow between various chambers of cochlea Mutation in connexion-26: abnormal ion balances within cochleadeaf

o Most common cause: acoustic trauma; exposure to loud soundso Decibel (dB): unit to measure sound intensity of loudness

Names after Alexander Graham Bell 0: approx. threshold for humans 10 dB: 10^1 increase in loudness 20 dB: 10^2 increase in loudness

o hair cells cannot be repaire or replaced die from over-stimulation

hearing aids: microphone and amp that sits behind/within pinna and a small tube into ear canal

cochlear implant: surgically inserting an array of electrodes into innear ear that electrically stimulate auditory nerve in spatial locations corresponding to particular regions of sound frequencty spectrum

o tiny microphone attached to external ear to pick up sound vibrationso frequency analyzer performs crude Fourier analysiso conveyed to inside of school by radio

utricle and saccule: bulbous cavities in bony labyrinth along with semicircular canalso vestibular system: detects orientation relative to gravity, maintains balance,

coordinate movementso not conscious awarenesso vertigo: condition in which one feels dizzy or in motion when sitting or stillo utricle and saccule have receptor cells that detect movement of fluid in

semicircular canals o vestibular hair cells have otoliths (ear stones)

suspended in fluid above hair cells inertia of stones contributes to bending of hairs generate and amplify sensory signals that allow us to maintain balance

Skin, Touch, and Movement skin: largest sensory organ dendrites of somatosensory neurons terminate in top layers of skin and membranes of

nerve fibers contain receptor proteins o receptors: mechanically-gated ion channels similar to hair cellso receptors responsive to temperature same as TRP (in taste)

dorsal root ganglia (DRG): cell bodies for these fibers are located in clusters of cells near spinal chord

o nerve fibers innervating the skin are contiguous with axons that send signals into CNS

peripheral dendrites contain voltage-gated sodium and potassium channels that are myelinated

o physical stimuli activates sensory receptor proteins generate action potentials that propagate toward the DRG, bypass the cell body continue along axon into CNS

o DRG dendrite functions just like an axon except action potentials propagate toward the cell body instead of away from it

Somatosensory neurons have spatial receptive fields: regions of skin within which a physical stimulus elicits activity in the specified neuron

o In DRG sends axons into CNS and synapse with cells in spinal cord with cells in the medulla of brain stem thalamusanterior parietal lobes in cerebral cortex

Primary somatosensory cortex (S1) contains topographic representation of somatosensory space (surface of one’s own body)

o Receives signals from contralateral side of the bodyo Lesion in S1: loss of sensation in particular region of body related to lesion

Wilder Penfield: somatosensory body mapso Electrically stimulated various regions of cerebral cortex on patients

Body is represented anatomicallyo Exceptions: genitals are on foot; face is not attached to neck; tongue is not on face

Cortical map doesn’t have same relative scale between various body regionso Fingers and hands are same size as rest of bodyo Lips and tongue are much largero Somatosensory sensitivity

Lips and fingers: most sensitive Arm/back/leg: poor somatosensory acuity Measured by two-point discrimination test

Lesions in S2: associated with various kinds of somatosensory weirdness (somatosensory agnosias)

o Neglect syndromes: touch sensation is intact but ignored or not recognized unless one’s attention is specifically drawn to it

Organization of somatosensory context learned by studying miceo Mice use whiskers for everythingo If whiskers were cut off, nearby whiskers would become more sensitive

Neuroplasticity example Phantom limb: feel presence of amputated arm/leg

o VS Ramachandran Primary motor cortex (M1): body map of neurons that send out signals that initiate the

contraction of skeletal muscles involved in movements of our bodyo M1 neurons fire signals from spinal cordsynapses of muscles

(neuromuscular junctions NMJ) acetylcholine releasedcontraction of muscle fibers

o Right posterior frontal lobe’s M1 controls movement of left side of bodyo Lesions in M1: inability to move muscles associated with corresponding part of

body map (partial paralysis)o Supplementary motor areas/premotor areas: other areas involved in control of

body movement Lesions don’t result in paralysis but apraxias

Disorder of organization Apraxias:movement; agnosias:sensory perception

Interconnectivity between diverse regions of cerebral cortex

o Communication between sensation and movement Mirror neurons: neurons that fire when action is being observed

o For example: watching someone move arm in a particular way will make neurons in your arm fire in a similar way

o Used in language, empathetic connection Cerebellum: wraps around brainstem and is very densely packed with neurons and nueral

connectionso 50 billion nerve cells: more in cerebellum than in the rest of the braino Purkinje cell: type of cerebellar neuron; has several hundred thousand dendritic

spines receiving input from other neuronso Involved in timing and coordination of movemento Damage impairment in ability to smoothly execute movements timing

affectedo Experienced on side of body contralateral to side of brain affected

Posterior frontal lobe damage: paralysis Anterior parietal lobe: loss of body sensation and other somatosensory

weirdnesso If right hemisphere lesion, denial that there is anything wrong (anosognosia)

In book The Man who Mistook his Wife for a Hat by Oliver Sacks Patients make up excuses why they cant move