;; 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!
