Psychoactive Drugs

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

o Others: kola, guarana, yerba mate
o Most widely used psychoactive drug
o 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: tobacco
o Acts as agonist at nicotinic acetylcholine receptors
Relaxation, alertness, focused attention
o 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-hypnotic
o Low doses: sedative/relaxing effect
o High doses: hypnotic/sleep-inducing effect
o Mild intoxication, impaired judgment and coordination,
grossly impaired movement, loss of consciousness, death
o Barbiturates
Used as medicine at first
Among the first synthetic drug (not coming from
plants) used in medicine
o Benzodiazepines
Librium and Valium: best selling drug in history
o Other: meprobamate, chloral hydrate, sleep-inducing agents
o 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 poppy
o Psychoactive effects: relaxation, pain relief, euphoria
o 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 efficiently
o Methadone: first instance of a completely synthetic opioid
o 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 plant
o 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 attention
o 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 perception
o 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 scolpolamine
o When used in less well-controlled settings, effects are more unpredictable and
negative
o First law against LSD in the US passed in 1966
o 1971: LSD illegal throughout the world
Cannabinoids: plants from genus Cannabis
o Hemp: fiber
o Marijuana, pot, hash, etc: psychoactive/medicinal effects
o THC: delta-9-tetrahydrocannabinol
Hydrophobic molecule
Sticks to lipids and dissolves into phospholipid bilayer membranes
o Cannabinoid receptor: GPCR
o 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 father
o 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 doesnt code for
functional protein
Embryonic stem cells: cells having the capacity to continue dividing and to differentiate
into any type of cell in the body
o 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
birth
o 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 polymersmicrofilaments 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
bodies
o Rotated eyeball 180 degrees see the world upside down and backwards
o 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): neurotrophin
o 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, Robo
o Guidance sometimes involves direct contact between one protein anchored to one
cell and another protein anchored to another
o 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 utility
o Synaptic pruning: elimination of synapses not in use
o 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 membrane

o More neurotransmitter receptors: stronger synapse

o 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 lobe
o Shape of seahorse (same genus name)
Greek hippos: horse; kampos: sea monster
o 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
20
o Myelination needed for cortical neurons to efficiently communicate with one
another
o 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 environment
o 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 cells 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 microorganisms
o Phototaxis: process of moving toward light
o Phototropism: growing/bending toward light
o Increase exposure
o In organisms that dont derive energy directly from light, enables movement
toward a more open region in order to disperse spores/seeds
o Fungus Phycomyces doesnt 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 Nave 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
system
o Interaction of incoming neural signals with vast network of established activity in
the cerebral cortex
o 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, touch
o 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 spectrum

o Karl von Frisch: honeybees have color vision
Can also see UV
o Infrared: too low energy
Vibrations heat
Pit vipers can detect infrared radiation
o Image intensifier amplifies very low intensities of visible light
o Infrared/thermal imager: detects infrared radiation and converts to visible regions
o 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 isnt 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 fields
o Infrasound: frequencies less than 20 Hz
o Ultrasound: very high frequency sound
o 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 sharks 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 poles
o Weakest at equator
o Direction of magnetic field vector points toward the poles and becomes more
steeply inclined nearer to the poles
o Vectors direction is nearly horizontal and parallel to the surface of the Earth
o Humans use compasses for direction
o Birds for migration
Come back to original location
1970: attached magnet onto pigeon
Severely interfered with its ability to navigate home when sun
wasnt visible

Nose and Smell

Perfumery: one of the early applications of alchemy
Olfactory sensory perception begins when odorants (airborne volatile molecules) enter
nasal passages
o 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 months
o 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 GPCRs

o Fish: 100 different olfactory receptor proteins
o Mice: 1300
o Humans: 350 genes coding for 350 functioning olfactory GPCRs
Pseudogenes: nonfunctional genes
o 600 olfactory pseudogenes in humans
Essential oil: oily concentrate of aromatic molecules from a plant
o Latin esse: to be
o Aroma-carrying molecules are hydrophobic
o 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 feces
o Bass note/low note
Geranial: lemon
o Carbon double-bonded oxygen: aldehyde

Geraniol: roses
o OH at end
Thiol: S-H
o Stinky
o Skunk smell: 2-butene-1-thiol, 3-methyle-1-butanethiol, 2-quinolinemethanethiol
o 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 smell
o Due to genetic variation in one of the 350 olfactory GPCRs
General anosmia: loss of sensitivity to a large variety of aromas
o Sometimes a complete lack of olfactory sensitivity
o Caused by nasal congestion, head trauma, etc.
Hyperosmia: increased sensitivity to odors
o Appear transiently
o Migraine headache or pregnancy
Olfactory GPCR receptors are in membrane of olfactory receptor cells in the nasal
epithelium
Activation of olfactory GPCR synthesizes cAMP
o cAMP interacts with a type of cation channel that is gated by the binding of cyclic
nucleotides
o 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 cavity
o Cranial nerve 1: nerve fibers between the nose and olfactory bulb
o Axons form synapses with dendrites of mitral cells (triangular shape) in olfactory
bulb
o Mitral cells send axons to pyriform cortex (interior of brain) and amygdala
(limbic system)
o Pyriform cortex sends axons to the thalamus
o Connections are made to the orbitofrontal cortex of the frontal lobe
Durian fruit: very strong aroma
o From southeast Asia
o King of fruits
o Alfred Russel Wallace wrote about it
o Can evoke robust attractive/repulsive emotional responses
o Propanethiol (oniony), methylbutyrate (pineapple)
White and black truffle mushrooms
o Thousands of dollars
o 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/bear

o 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 pharynx
o Approx. 10,000 taste buds in the human mouth
o Each taste bud has ~100 taste receptor cells
o 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 drink
o 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
Cilias 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 cells
o Differentiate into various types of taste-receptor cells
o Turnover rate: 2 weeks
o Olfactory and gustatory receptor cells have direct contact
o Visual and auditory receptor cells shield from direct contact, dont have stem cells
Salt
o NaCl breaks down into Na+ and Cl- ions
o Proteins on taste receptor cells allow sodium ions to flow across the membrane
o Ingestion of some amount of sodium and other related cations: essential for
survival
Sour
o Acidic: release of hydrogen ions
o Positive charge flows through channels
Bitter
o 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
Sweet
o Sugar: small molecules composed of rings/chains of carbon atoms with oxygen
and hydrogen atoms
o GPCRs
Two linked together by non-covalent interaction to form functional
receptor
Not common in nature
o 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 acid
o 50x sweeter than aspartame
o 10,000x sweeter than sucrose
o 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
Umami
o Kikunae Ikeda: glutamate produced a distinct taste perception
MSG: monosodium glutamate
Umai: delicious; mi: taste
o Savory, meaty, mushroomy

o Metabotropic GPCR
o 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 differently
o 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 light
o 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 damaging
o Chemical bonds break and molecules fall apart
o Free radicals form

o DNA is damaged
o 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 vision
o Similar to camera
o Vitreous humor: transparent gelatinous fluid in the interior of eyeball
o 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 white
o Sensitive to low light and nighttime
o 100 million
o Throughout the retina
Cones: mostly located at fovea, responds to higher intensity than
dim
o Cone-opsins: sensitive to bright light and daylight
o 5 million
o Concentrated in fovea
o SML wavelength absorbing cones
Blue, green, red
o Color
S: violet/blue
M: green/yellow
L: orange/red
Colors do not exist in the world; mental experiences related to nervous systems 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 tipes
o Birds have tetrachromatic color vision

Human opsin proteins: 350 amino acids

o Genes for M and L opsins are on X chromosome
Females can have L-opsin variants and be tetrachromats
Males cant 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 colors
o 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 lost
o Significant loss of ability to distinguish between various shades of color in greenyellow-red region of color spectrum
o Males: 2%; Females: <0.1%
o On X chromosome
Blue-yellow color blindness: genetic variation in S cone-opsin gene
o Loss of ability to discriminate between colors in blue-green-yellow region of
color spectrum
o 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, gray
o 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 eye
o Visual system gathers info to fill in blind spot
Rod cells: one hundred million rhodopsin molecules
o 100 million rod cells in retina ten quadrillion rhodopsin molecules in each
retina
o 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, alphahelical 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 H
o 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
o
o
o

Rods and cones form synapses with bipolar cells

Bipolar cells form synapses with ganglion cells
Neural signals flow from photoreceptors to bipolar cells to ganglion cells to brain
Axons of ganglion cells bundle together to form the optic nerve

100 million photoreceptor cells in each retina

1 million ganglion cells
1 million axons make up each optic nerve
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 cells
o 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 brain
o right half of visual space going to left half of the brain
o 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
awareness
o 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; shape
o V4: specific colors
o V5: movement; speed and direction
o David Hubel and Torsten Wiesel
o Studied people who suffered brain lesions and functional brain imaging
Visual scotoma: lesion in V1
o Blind spot in a specific region of space
o Mild case: unnoticeable
o 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 V5
o Motion blindness: unaware of movement in some region(s) of visual space
o
o
o
o

Seems like series of snapshots

Prosopagnosia: difficulty/complete loss of ability to recognize faces
o Caused by lesions in inferior and medial temporal lobe
o 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*wavelength
o 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 structure
o Vestibular fenestra: location of membrane of oval window
o 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 fluid
o 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 membrane
o 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 brainstem
o In brainstems 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 cochlea
o 12,000 outer hair cells per cochlea
contain protein prestin: elongates/contracts as a function of membranepotential changes
Direct vibration of bones of the skull that surround the cochlea can make sound
o Vibration of tympanic membrane, ossicles and cochlea
Loss of hearing due to damage of hair cells, genetic anomalies in cochlea
o 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 sounds
o 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 vibrations
o frequency analyzer performs crude Fourier analysis
o conveyed to inside of school by radio
utricle and saccule: bulbous cavities in bony labyrinth along with semicircular canals
o vestibular system: detects orientation relative to gravity, maintains balance,
coordinate movements
o not conscious awareness
o vertigo: condition in which one feels dizzy or in motion when sitting or still
o 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 cells
o 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 ones own body)
o Receives signals from contralateral side of the body
o Lesion in S1: loss of sensation in particular region of body related to lesion
Wilder Penfield: somatosensory body maps
o Electrically stimulated various regions of cerebral cortex on patients
Body is represented anatomically
o Exceptions: genitals are on foot; face is not attached to neck; tongue is not on face
Cortical map doesnt have same relative scale between various body regions
o Fingers and hands are same size as rest of body
o Lips and tongue are much larger
o 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
ones attention is specifically drawn to it
Organization of somatosensory context learned by studying mice
o Mice use whiskers for everything
o 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 body
o M1 neurons fire signals from spinal cordsynapses of muscles
(neuromuscular junctions NMJ) acetylcholine releasedcontraction of muscle
fibers
o Right posterior frontal lobes M1 controls movement of left side of body
o 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 dont 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
connections
o 50 billion nerve cells: more in cerebellum than in the rest of the brain
o Purkinje cell: type of cerebellar neuron; has several hundred thousand dendritic
spines receiving input from other neurons
o Involved in timing and coordination of movement
o Damage impairment in ability to smoothly execute movements timing
affected
o 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
weirdness
o 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