- On the back of all seizure medications it basically tells you that they dont know exactly how it works

- interact with various parts of the synapse 

interaction with the following to reduce the excitability of the brain: 

- voltage-gated sodium channels 

- voltage-gated calcium channels

- voltage-gated potassium channels 

- GABA receptors

- glutamate receptors 

- other neurotransmitter system 

- antiseizures / anticonvulsant medications

- barbiturates 

- benzoiazepines

surgical procedures for seizure disorders

- Corpus commorrotoy 

(this is how they discovered things about individual sides of the brain)

- excision of epileptogenic brain tissue 

(this is done more often than the other)

- they do this by opening the skull and using ECog

Pharmacology 

- general study of interaction of drugs with the body 

- ology means - "the study of"

- Pharmaco -

ancianet greek word: means medicine and poison at the same time

- A chemical that in relatively small amounts has      some kind of significant impact of physicology 

- Doing something ot the functioning of the body in  small amounts

- comes from an old english words "droog"

- probably means soemthing like dried plant

1. Caffeine 

2. alcohol 

3. nicotine

4. arecolin (betel palm nut)

5. cannabinoids 

a bunch of carbons and hydrogen's and nitrogen's and oxygen's 

- first isolated from coffee in 1820

** one of the first chemical substances to be isolated from a plant and then shown the major effects that the plant had

spearate the properties of a plant into moleculare constituents 

- arousal, alertness, wakefulness

- increased heart rate and blood pressure 

- increased kidney output **diuretic** (have to pee more)

- increased metabolic rate

- powerful stimulant

- has dependence producing quality 

**adenosine receptor antagonist

- has a similiar structure to adenosine

Adenosine

- GPCR receptors 

- inhibitory effect on neuro-signaling

- slows thing down

- wide spread

Caffeine

- also interacts with adenosine receptors but BLOCKS them 

- speeds things up 

- prevents adenosine from interacting with the receptor and slowing it down

- tobacco = native to south america

- cuba = known for production of Tobacco 

- tobacco leaves - picked and rolled and dried and allowed to ferment 

Main effect in nervous system 

Agonist at nicotinic acetylcholine receptors

- CNS effects : stimulation and relaxation 

Ethyl alcohol = ethanol

- both hydrophillic and hydrophobic

**crosses the blood brain barrier

-hydrogen, carbon, oxygen, hydrogen 

- Sedative- hypnotic drug

Sedative-hypnotic Drugs

- produces a kind of calming effect in low doses

- higher doses = passing out / falling asleep 

- inhanse the action of GABA in opening the  chloride channel 

- NOT agonists

- when GABA comes along and binds then the  GABA has a biggere effect at opening the  channel since sedative-hypnotic drugs are bound  to the neurotransmitter receptor 

- many have low TI (very dangerous)

Types of sedative-hypnotic drugs

Alcohol - low TI

Barbiturates - low TI

Benzodiazepines

other pharmeceuticals

general anesthetics - low TI

inhalants 

- slow down brain activity 

- can be useful in the right dosage to control seizures 

- there are a whole lot of "barbiturates" but they all have the same kind of chemical structure

Benzoiazepines

valium and its relatives

all look similar and have the same kind of chemical structure

- a neurotransmitter receptor

- a chloride receptor

Sedative hypnotic drugs all inhance the action of GABA in opening the chloride channels

- NOT agonists 

- bind to the neurotransmitter receptor

- when GABA comes along and binds then GABA has a bigger effect at opening the channel 

- more inhibition

- lethal dose / (divided by) therapeutic dose

- small therapeutic index = very dangerous 

like barbiturates

- there is no units (like grams)

they cancel out so the TI would be something like 10

Cocktail of Thiopental (barbiturate w/ low TI)(slow)

Pancuronium (speeds things up) - AChR antagonist

- major place is the neuromuscular junction

- Paralysis and respiratory failure

Potassium Chloride (really speeds things up)

injected directly into the blood stream

-floods the outside of the nervous system with a bunch of potassium so the action potentials cant work anymore

- induces cardiac arrest

36 states have death penalty 

- all of which have lethal injection 

Coca plant

- South America

- pant is the source of cocaine

- 1% of the dry weight of the plant is this chemical cocaine

- it is a defense mechanism against things that want to eat it

Effects of cocaine on the impact of reuptake transporters / synapse

- sticks to reuptake trasnporters 

dopamine and norepinephrine

- stops them from working

- when signal comes along, the neurotransmitter cant get back in so it stay out in the synaptic cleft longer

- this is an increase in activity in these synapses 

- Sympathomimetic effects

-increased heart rate

-increased blood pressure

-dilation of pupils, airways, nasal passages

- Anxiety. irritability 

- impaired judgment

-stimulant psychosis (delusions, hallucinations)

-chromic psychosis

- seizure (over activity of the brain)

- cardiovascular damage, heart attack, stroke 

(overactivity of the sympathetic nervous system)

addiction

- mechanisms of amphetamine and its realitves effect the same things as concaine (dopaine and norepinephrine) but in a slightly different way 

- mechanism: sticks to the reuptake transporter and causes it to LEAK out of the axon terminal 

- instead of going in it is going out 

- leaks out into the synaptic cleft

comes from opium poppy flower

- cultivated for thousands of years for its medicinal purposes 

- gathered from poppy by slitting the pod and collecting the mikly stuff that comes out (has the highest concentration)

- most legal opium comes from india

- Analgesia 

means releaf from pain (ex aspirin)

-Cough suppression

- treatment of diarrhead

(slows down intestines so more water can be absorbed in the body)

-discovered the name "morphine"

-first time the medicinal properties of a plant were associated with a specific chemical

-pharmacist assistant

interested in how medicines worked in the body

Named morphoine after the greek god Morpheus the Greek god of sleep

-tested it by eating it and found that its effects were the same as those from opium only much more powerful 

SIMPLE Chemical modification of morphine or codeine that makes it DIFFERENT

- Heroin

* Bayer was the first to patent heroin

- made something so potent than mophine so you could take less of it

*Oxycodone (oxyCotin) , hydrocodone (vicodin) hydromophone etorphine

Toxicity of opioids 

-depression or respiratory control centers in brainstem

- high addictive potential 

- act on reward centers of the brain

Opioid peptides in the brain

- Endorphins

-endorphins 

from "endogenous morphine" - made within the brain

- about a dozen in our brains

- block signals of pain 

- all MADE FROM AMINO ACIDS

**- first neural peptide to be discovered

first example of a chain of amino acids acting as a neurotransmitter

Psychedelic - means mind revealing or mind manifesting

Hallucinogens - means generating hallucinating

LSD

psilocybin, bsilocin (mushrooms)

DMT

Mescaline

* have complex effects on mental state

* effect things in the menal realm ( ex thought)

* produce an exaggeration, amplification, and or distortion of this

*bring up memory in new and or interesting ways

*have been used for thousands of years for medicinal purposes

*all schedule one drugs

**agonists at certain serotonin receptors found through the cortex and made in the raphé nuclei

discovered LSD

"LSD my Problem Child"

DIDNT get Nobel prize because LSD was such an issue

- lsd is not found in nature ( it is a derivative of something that comes from a fungus that grows in grains)

- shaman

- introduced the modern world to the ritual practices of her culture

- from oaxaca mexica

reviled the secret practice of muchroom ceremonies to an outsider with a russian wife who liked mushrooms

- this guy wrote about it in the magazine LIFE

- this is how the wider public became aware of this powerful substance

THC = delta-9-tetrahydrocannainol

- primary psychoactive chemical in cannabis 

Unique chemical structure found nowhere else 

- more than 6 identified in Cannabis 

GCPR cannabinoids receptors

- most abundant GPCRs in the brain

- made within the brain

- first to be discovered - Anadamine  (Ana = bliss)

- released by the postynaptic cell (different from most)

- one of the effects of this is to trigger the synthesis and release of an endocannabiniod

**RETROGRADE SIGNALING

- this bangs around in the backwards direction and bangs into the pre-synaptic cell 

- a pattern on compulsive use of a drug (including  compulsive behaviors) which results in adverse  effects in the person's life

- Reward-reinforcement pathway 

Ventral tegmentum (VTA) to nucleus accumbens? then to frontal cortex

- Chemically:

the neurotransmitter dopamine

- drugs haveing abuse potential facilitate increated dopamine activity in the reward pathway

- this can change the synaptic strength 

so now what used to feel good to a person no longer feels that goo 

Learning in rats 1954

- studied how memory works on rats by having rats with electrodes in their brains run around mazes

-stimulated various parts of their brain and tried to see if rats could learn more effectively when vertains regions were stimulated

- he found an area that did this

- when rat was allowed to press a bar to receive electrical stimulation he would not stop pressing the bar

-chose stiumlation over food and pain 

- pathways that were stimulated where from the brainstem 

- reward-reinforcement pathway 

ventral tegmentum (VTA) to nucleus accumbens then to frontal cortex

Injury to the brain

Causes or circumscribed / localized lesions

- stroke

-tumor

-traumatic injury

-certain brain disesase 

  (like parkinson's and alzheimer's)

- visualizing anatomical structure and locating lesions

- autopsy 

- surgery 

- x-ray

- CAT

- MRI

William Röntgen discovered x-ray technology 

- x-rays were first used to fit shoes in 1950

~10,000 devices for this in USA

- 1940s - 50s also appreciated that there were useful applications for x-rays to take pictures of the insides of bodies 

- considered invasive? (strange)

1970s

taks a number of x-ray photos from various angels and then uses a computer to reassemble that information into a 3D picture of that part of the body 

- computer was the innovation that made the CAT scan possible 

NMR - nuclear magnetic resonance 

 - uses nuclear spin (proton doesn't actually spin just behaves mathematically as if it were)

- people invented the NMR with the idea that you could trow a molecule into a magnetic field and then make it change its direction

- MRI was first called Nuclear Magnetic Resonance Imaging Scanner but when people heard the word Nuclear they freaked out because they thought it had to do with radioactivity 

Invasive : autopsy, surgery, x-ray, CAT, surgical recording, PET

noninvasive : MRI, EEg, MEG, fMRI

Invasive- a procedure that invades the body that has a tozic or poisonous or destructive effect

-first measurement of EEG

-adapted the EEG to build the first human EEG machine 

-German Physician

- originally into astronomy but went into the army and had an accident and sister had a premonition 

- this made him switch his studies to medicine 

Spatial Resolution 

poor 

Temporal resolution 

milliseconds 

- attaching elecrtodes to the outside of the scalp

Magetoencephalograph 

- measures magnetic fields outside of the body 

- has an advantage over EEG because it doesnt get distorted over the tissue of the subject'

- magnet fields are really weark compared to EEGs

- SQUID technology 

- superconducting quantum interference devise 

- has to be kept as extremely low temperature

Positron Emission Tomography 

- can be done on any part of the body 

- a bunch of slices of the brain laid out with colors

on the side and difference slices have different colors with them 

- scale in the colors to show the level of activity 

- a whole bunch of detectors around a persons brain 

- there are radioactive byproducts 

- the picture is a way of measuring glucose consumption

spatial resolution okay 

temporal resolution minutes

Fluorine-18

first to be employed in the PET scan 

half life of about 2 horus

fluorinated glucose looks like gluocose but isnt so body take it up. then you can tell which cells are consuming more glucose

Oxygen-15

half life ~2 minutes

oxygen consumption: makes a watermoleucle that replaces the stable oxygen in the water with this unstable one

then regions of the brain that are more nerual-ly active need more blood flow to cary glucose to them

- by looking where it is going you can see the areas that are using more blood

Carbon-11

- number refers to the sum of the number of protons and the number of neutrons total 

looks exactly like the MRI scanner but it collects the date differently 

- there are lots of warning about not cominginto the room if there is any metal on your body

 measures BOLD
- Blood Oxygen Level Dependent signal 

- represents changes in oxygenated and deoxygenated hemoglobin from blood flow and cell metabolism

- the most widely used (besides EEG ) of the functional brain imaging 

- spatial resolution mm 

- temporal resolution seconds 

Magnetic field strength 

1 tesla = 10,000 gauss 

4 tesla = 80,000 x geomagnetic field 

Geomagnetic Field ~ 0.5 gauss 

= 0.5 x 10 ^ -4 tesla

= 50 x 10^-6 tesla

Blood oxygen level dependent signal 

- represents changes in oxygenated and deoxygenated hemoglobin from blood flow and cell metabolism

- with the first cyclotron 

- got the Nobel prize in physics

a way of accelerating particles around so that you can bang them into things and sometimes if you bang them into toher atoms then they will produce something

- this device was exploited to make the isotopes used for PET scan 

- the device got bigger and bigger

Sensation : collection of information from the environement  via sensory receptors and organs  

Perception: a mental experience; analysis and interpretation of this information by the nervous system, leading to the experience of a particular mental state

the way bacteria like e.coli respond to chemicals in their environment

- run and tumble

- when there is something yummy they tumble less

causing their motors to spin the flagella so it doesnt reverse as often 

Phototaxis - moving toward light 

Phototropism- moving toward light in some way (bending or turning)

- many examples of behavioral responces to light among bacterial , plants, animals, etc.

Common sense theory of perception

- the idea that what we see is really what is there. we are experiencing the world exactly as it is 

- example of why this is not 100% true is the thing with the spinning circles that don't actually move 

- electromagnetic Spectrum 

- range of human sensitiviy ~400 nm to ~700 nm 

first person to realize that it was stupid to think that humans were special in the amount of color they could see compared to other animals

- the experiment with the honeybees 

- showed that they were responding to color 

- got the nobel prize (only time it was given for something that is not a cellular or molecular thing)

- also discovered things about their dancing behavior

- showed that honeybees could see down to the ultraviolet specturm of the color vision 

Honeyguides : "landing patterns" on flowers

- the dark part toward the center of the flower when viewed in UV light 

- visible only in ultraviolet region spectrum 

- does not go through the eye 

- used to hunt in conditions of totaly darkness

- right under the eye (just like vision but not vision)

- humans can use things similar to this for night vision 

Electromagnetic radiation can be Polarized 

- things vibrate in different directions (up down, left right)

- when we talk about these planes of direction of vibration this is the notion of polarization

- light can be polarized (its interaction with amtter can alter that)

- when light comes out of the sun it is random but when it impacts the earth's atmosphere it becomes polarized by bouncing off air molecules

- animals can navigate by using polarization patters of the sky 

- range of human sensitivity ~20 to ~20,000 hertz 

- hertz (vibrations per second)

- very low frequency detection <10 hz

elephants, pigeons, dolphins, whales

-very high frequency detection > 50,000 hz

bats dolphins whales moths

sonar = sound navigation and ranging

- dolphins, killer whales , bats

Electroreception 

- the test with the shark trying to find the flounder

- electroreceptor organs are found all over the shark's body 

- helpful if it is in the water because the static electric field is transmitted through a medium (Water)

- platypus have these receptors in their bills

animal is passively detecting thigns in the envrionment 

- most perception is passive 

**except ecolocation 

- fish producing electric field from their body 

- monitor how this field around their body is distorted by stuff that is around them

- changes depending on whether there is something else around them that produces electricity (like animals) or not (like rocks)

- also used as a form of communication

- detection of geomagnetic field

- the earth has an enormous magnetic field around it 

- used as navigation 

birds, fish, sea turtles, honeybees 

- detection of magnetic field vector changes in its angle depending on where you are 

- more intense near the poles than near the equator by a factor of 2

- lots of blood vessels

- Dark spot in the center 

- Macula - "spot"

- Fovea - "pit"

-light spot

- the blind spot

- it is bright white because there are a lot of axons passing through refelcting the light very strongly

- this is the optic nerve exit

- there is no room for any photoreceptors beause of the fact that there are so many htings passing through the region

Cones and Rods 

- rods ae more pointy and cones are my cylindrical

- one type of ROD cell and 3 or 4 types of CONE cells

- a bright spot

- it is bright white because there are a lot of axons passing through refelcting the light very strongly

- this is the optic nerve exit

- there is no room for any photoreceptors beause of the fact that there are so many htings passing through the region

contain a protein called RHODOPSIN

- this is a detector protein

- this is what interacts with the light

- more sensitive to dim light

- operate in night / dim-light vision

~ 500 nm absorption maximum 

- peaks  in the green region of the specrum 

- falls off in the violet and yellow but still presonds to the whole range of colors

- most sensitive to blue and greens

-CONE-OPSINS photoreceptor proteins

- sensitive to bright light

- operate in day / bright light

- short wave-lenght cones ( s or blue cone)

- medium wave-length cones (m or green cone)

- long wave-length cones (l or red cones)

but not really in the red zone

- THERE IS NO COLOR IN THE VISUAL SPECTRUM, IT IS SOMETHING WE CONSTRUCT OUT OF OUR MINDS

there are a lot of rods everywhere but most of the cones are in the center

- a lot more rods than cones

~100,000,000 rods and ~5,000,000 cones

results from cone photoreception

- there are 3 of them and from those you can make all of the colors that we can see 

three cone photoreceptors

- primates : humans, apes, monkeys

- most other mammals have dichromatic color vision

s

red and green cone opsin genes are X sex chromosomes

there are sex difference mutations

(blue cone opsin and rhodopsin genes are not)

- 2 varients of red opsin genes in humans

- 559 nm and 552 nm 

- because its on the X chrom. males can only have one or the other but females may have both because they have 2 x chroms. 

- if you have both you have tetrachromatic color vision

- impairment in color discrimination between reds, greens and grays

= loss of function of red cone or green cone

- sex difference?

males prevalence : 2%

female prevalance: < 0.1 %

Sex difference?

none because the short wavelenght cone is not on the x or y chrom.

< 0.1 % for both males and females

Clinical test of color vision 

- shinobu ishihara ~1917

- loss of all cone cells

- all photoreceptors taht person has are rods 

- this means there is NO color vision

- all gray scale

- extreme sensitivey to light

- because rods are really sensitive to light

- treatment, dark glasses 

- treatment: filter on their eyes to filter all the short wave-length light out 

contain proteins 

 up to 100,000,000 (10^8) photoreceptor pproteins per cell 

~100,000,000 photoreceptor cells in the human retina

- 10 ^ 16 photoreceptors in each eye

- rhodopsin and cone-opsins are chains of amino acids

- retinal ( light-absorbing part)

- not an amino acid

- attatched by covalent chemical bond to the interior of the opsin protein

- we dont make it, we have to consume it

Opsin is a GPCR

- rhodopsin and cone-opsin 

huge amplification

one photon of light is one rhodopsin

> 100 G-proteins

Ganglion cells - from optic nerve to the brain 

~1,000,000 ganglion cells and optic nerve axons

bipolar cells

Photoreceptor cells -Rod and cone

- if the retinal cells went the opposite way there would be no blind spot 

- thickness of the retinal is 100 micrometers ( = 0.1 mm)

2 other kinds of cells in the retina 

- find out more 

Lateral Geniculate Nucleus 

- Retina --> LGN / thalamus 

- there are 2 LGNS

one on the right half and one on the left half

- left visual field info that comes into both eyes goes into the right LGN
- right goes into the left LGN

Occipital, posterior parietal, posterior temporal lobes

- occipital lobe first receives information from the eyes

- anatomical connectivity of neurons in the brain's visual areas 

- pretty much everything is connected to everything else 

- the reigon of space from which a stimulus elicits a neural respnose 

- when there is a stimulus in that space, it was cause that cell to respond

Scotoma = blind spot/ region 

- this is a blind spot that has been produced by a lesion and it may be rather large and quite noticable 

- if all ov v1 was whipped out on both parts of the brain there would be a complete loss of vision

- skotos = dark

loss of vision in an entire half of the visual field

- v 1 primary visual cortex damage 

- v4 down near the temporal occipital boundary 

- involoved in color percepton problems

- (Corotical) achromatopsia

- mostly respond to changes in color 

- people with lesions here have problems with color perception

- this is a washing out of color rather than 100% loss

- this may only occur in regions of visual space 

- will produce problems with motion detection

- MOTION BLINDNESS

- sees the world as if a series of still images

Cells in monkey IT

- respond to complex visual stimuli

in particular, things that look like faces

- the more something looked like a face the more firing there was of these cells 

- suggested that this area was possibly tuned to face perception 

Lesion in the human posterior temporal love 

- face-recognition problems

- they are not blind, they hust dont recognize faces, even if they know the person well 

blind spot as a result of a rather large lesion in the V1 aread

- there is some ability to see things in their blind spot at some level 

- they dont KNOW they can see anything though

- this phenomena is called blindsight

-** the thought is that in addition to the main pathway from the retina to the brain there is a another pathway 

--> Retina > LGN> Prima Visual cortex (v1) ~90%

--> Retina > superior colliculus (in midbrain) > v4 or v5 but not v1 

~10%

- before you are even consciously aware of some new stimuli you know some how that something is going on

it appears to come though the superior collliculus 

sound : if sound is defined as a physical stimulus then the physical stimulus that is being produced is a compression of the air molecules

- this is an increas in pressure and as it backs off they spread apart again

- this goes on in a loop so you can get a vibrating wave of more and less pressure 

- this physical stimulus owuld be physically there whether  or not anyone was around to detect it 

- the perceptual experience of sound depends upon our nervous system 

speed of sound in air ~335 meters / sec

~750 miles / hour

~ 3 seconds --> 1 km 

20 - 20,000 hertz (audible sound)

- there is no sound in a vacuum 

Humans - pretty broad range 

dogs- higher

bats- go off the scale

frogs- can only hear in very limited region of the auditory frequency 

- sounds have complex waveforms composed of a combination of frequencies

- all natural sounds are mixtures of a lot of different frequenceis at the same time

- quality of sound is called the TIMBRE

- there is a measure of the ocmplexity of sound

- comes from the fact that any normal sound comes from a bunch of vibrations at the same time

Sound power spectrum of middle C on the piano

- when you play a middle c on different instruments you hear different sounds even though they are the same note

- the phenomena of being able to represent a complex sound in terms of a number of different components of frequency vibrations 

- FOurier analysis : decomposing a wavefrom into a sum of simplier sinusodial frequency components

- complex waveform from clarinet

- component from clarinet : fundamental + overtones

- bond conduction of sound

- when you speak it sets your whole head into vibration so your whole head is vibrating

- also sets the things in your ear vibrating so that you when you hear yourself talk the sound you hear is coming from the vibration from your own body