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- article: first direct evidence that the reponce too alcohol Depends on Genes: dopamine receptors deficiency leads
- suggest that deficiency in dopamine D2 receptors may make people less able to experience normal pleasures and more vulnerable to alcoholism. this is because active d2 receptors inhibit the expression of CB1 gene.
- Endogenous Ligands
-
neurotransmitters, hormones
something made within the CNS body, readily made. - exogenous ligands
- drugs, toxins and mimicking endogenous product.
- agonist
-
initiates same like responce of a neurotransmitter
- antagonist
- interfers prevent action of neurotransmitter.
- muscarine
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mimics ACh at some receptors
causes convulsions death
no effect on CNS - cant cros blood brain barrier
antidote atropine. - walter E. Dixon
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similar actions muscarine and vagus nerve substance
both antagonizzed by atropine. - antropine
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antagonist, prevents ACH from binding to mACHr
result in increase heart rate - Otto Loewi
- role of the vargas nerve and acetylcholine in slowing heart
- how did they determine the body uses chemical messaage
-
1) vargus nerve of frog heart 1 stimulated
2) fluid transferred from first to seocnd containter
3) recording from frog heart shows decreased rate of beating after stimulation
4) as does the recording from the frog heard 2 after the fluid transfer.
conclusion
- - Esterine
-
Ach breaks down almost immediately, Esterine, inhibits esterise from working, stops breakdown.
acts as a cholinesterase inhibitor
Esterase = enzyme that breaks down choline. - Accelerator Nerve:
- speeds up heart rate, unmylinated terves.
- Neurotransmitter
-
chemical released onto a target, excitatory or inhibitory effect
outsid ehte CNS many of these chemicals ciruclate in the blood stream as hrmones. - electrical message
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retina, hypothalamus
most of communication that occurs in the brain is chemical however
electric speed. - chemical synapse
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majority of synapses in mammalian nervous system are chemical
why use chemical synapses
chemical more flexibility in the neuron to neuron communication. - Synaptic Transmission
-
syntheisis: building blocks of a transmitter substances are imported into the terminal
where the neurostransmitter is syntheisesd adn pacakged into vesticles.
release: in responce to an action potential the transmitter is released across the membrane by excoytosis
receptor action: the transmitter corsses the synpatic cleft and binds with the receptor.
inactivation: the transmitter is either taken back into the terminal or inactive in the synaptic cleft. - neurotransmitter release
-
1) when a action potential reaches the terminal, it opens calcium channels
2) incoming calcium ions bind to calmodulin forming a complex
3) the complex binds to vesticles, releaseing some from filaments and inducing others to bind to presynaptic membrane and to empty their contents.
- release of neurotransmitter
-
calcuim
- - release of neurotransmittter
-
influx required for vesticle mobilization and fusion
altering concetrations increaes/ decreaes the release in the vesticles
too low = impar muscles botox
opposate - black widow too much release toxin -
article 2
-
rather than activating all serotonin receptors as SSRI do one could icnrease signalling thorugh one crtical sertonin recetpor that our research shows is important for anti depressant behvoir
boost to 5ht1 receptor - renshaw loop
- the loop made by the axon collateral and the interneuron in teh spinal cords forms a feedback circuit that enables the motor neuron to inhibit itself from becoming overxcited
- dales law
- states that a neuron does the same thing at all synaptic connections to other cells regardless of the cell.
- three groups
-
small molecules transmitter
Ach, amines, amino acids
large molecule transmitters
peptides
Transmitter Gasses - Acetylcholine
-
choline, acetate
Acetyl CoA carries acetate to choline
to form ACh, ChAT transfers acetate to choline
to form ACH - Catecholamines
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Catechalomines (DA,NE,EP)
Phenalal
- comes form diet
tyrosine
L Dopa
Dopamine
Nore-epinephrine
Epinephrine - George Carillo
-
injection of MPTP causes rapid onset of Parkinsonism hence users of mppp developed with mptp will develop these symtpms
MPPP demoral
MPTP attachs sells in the Substania Nigria (selectively
creates onset parkisonism ? -
SMT
Serotnonin -
precursor- tryptophan turkey
dietary sources fight with other large molecules, possible relief from depression - Rate limiting factor
-
restricts pace that chemical is sytheized ?
increasing diet doesnt give you infinate number of transmitters, rate limiting factor prevents that - Glutamate:
- main excitatory transmitter, Aspartate.
- glutamate
- main excitatory transmiter asparate
- Gaba
- main inhibitory transmitter glycine
- Neuropeptides
-
Neurohypophyseals –oxytocin, vasopressin
Opiod peptides
– enkephalin(e) – opiate-like effects
- dynorphin -
Substance P
Many - hormones and transmitters
- neuropeptides 2
-
synthesized from mRNA
do not bind to ion channels
no direct effect on post synaptic membrane voltage (indirect)
degraded by digestive processes. (see text) - transmitter Gases
-
synthesized in cell, as needed
easily cross cell membrane
nitrous oxicide
does not activate recotpors
not stored in vesticles
related to blood flow erection
neuron activity NO relase dialtes vellsel - Ionotropic Receptor
-
embeded in membrane of protein
two parts binding sigh and pore
transmitter binds to binding sight
the pore opens influx or efflux - metabotropic Receptor
-
receptor but no pore
large variety
linked to a G protein
indirect effect on ion channels
second messengers.
1) transmitter binds to receptor in both types
2) the binding of tranmitter triggers the activation of G protein in both types of Reactions
3) the alpha subunit of the G proeitn binds to a channel causing structural change in channel that allows ions to pass through it.
or the alpha subunit combines to a second messagner the seconmessanger can activate cellularar processes. -
what does a metapotropic recetpor do for a living
-
communicates within the cell
examples
alter ion flow in a membrane channel
formation of new ion channels
production of new proteins. - activating system
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cell bodies brainstem nucleus
wide spread activation, means of synchronization
mediate rather than causation
abnormal activation = abnormal Beauvoir
aberrant activation often cited with neuropathology - Schizophrenia
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delusions, hallucinations, disorganization of speech, bluntd emtion, agitiation, immobility and other symptoms
invovles dopaminergic sytem. - Alzheimers Disease
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degenerative brain disorder that frists appears as a progressive memory loss and later developed into generalized dementia
involves the cholinergic system. - Obsessive Compulsive Disorder
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characterized by compulsively repeated acts and often unpleasant thoughts obsessions.
involves the serotonin system -
article 3
psychopaths brains wired to seek reward and disregard the consequence s - consistent with what we thought, we found people with high levels of psychopathic traits had almsot 4 times the amount of dopamine responce to amphetamine.
-
article 4
Economic Status, Genetics Together Influence Psychopathic Traits - Researchers studying the genetic roots of antisocial behavior report that children with one variant of a serotonin transporter gene are more likely to exhibit psychopathic traits if they also grow up poor
- habituation
-
weaker responce with repeated stimulus
aplysia Californica
with habituation the influx of calcuim ions in responce to an action potential dereaeses
2) resulting in less neurotransmitter relased at the presynaptic membrane. - Stenitization
-
serotonin reduces k+ efflux through potassuim channels prolonging an action potential on the siphon sensory neuron.
prolongued action potential results in more ca influx and icreased transmitter realsed
causing greater depolarization of hte membraine. - AMPA
-
normally responce to glutmate
- NMDA
-
double gated channels normally blocked by magnesuim ions
- LTP
-
depolarization of post synaptic membrane displaces MG from Pore
resulting in more stronger second habituation.
activation by glumate from the presynaptic neuron
NMDA receptors open
- - NMDA receptors open
-
ca enters the post synaptic neuron
increaes ampa recptor responsivenss
increae glutate realse from teh presyanptic - corsi block tapping test
- short term recall of spatial position
- Mirror Drawing Task
- Procedural Memory
- recent Memory task
- challenges assumptions about memory
- morris swimming task
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place learning
rat must find platform using external cues
matching to place learning platform is in the same location each trial but a different location each day
landmark version - platform is identified by some cue on the wall. - skill reaching task
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rats are trained to reach through a slot and obtain food
movements can be broken down into segments, which are differentially affected by different types of neurological pertubation - brain lesion
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developed by KarlLashley
Ablation: removal or destruction of tissue
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steoreotaxic apparatus
- surgical instrument that permits the research to target a specific part of the brain
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FASD - Fetal Alchol Spectrum Disorder
FAS
PFAS
-
leading preventable cause of mental redtardation
Narrowing of forehead, upper lip flatten, folds between eyes short
FAS: Don’t need confirmation from mother
Partial: some facial deformities, but need to have confirmation that there was alcohol exposure from mother
No sign of deformity, hardest to diagnose, more subtle, behavioural deficits (ADD)
Social problems: ignore people when they don’t play the same way you play, find other people who play like you play, people with FASD don’t understand social rules, feelings get hurt, express hurt by acting out in anger
Motor deficits: no eye-hand coordination
Primary disorder but not expressed/developed
Without sound mind, shouldn’t be held accountable in judicial system
Everything shifts, don’t stand alone, different distribution
A lot of individual variability
- Wisconsin Card Sortin Task
- WCST: ability to move from one rule to another without information, won’t tell you if you’re doing it right but will tell you if you’re doing it wrong, FASD individuals have hard time switching to new rule (perseveration
- Iowa Gambling Taks
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IGT: emotional component, personal gain and loss, don’t know rules, need to figure out the rules, learn that some decks will give you long-term gains; FASD individuals will go to high amounts, need to use emotion, 16 year olds did better than undergraduates
- FMRI
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changes in elements such as iron or oxygen are measured during performance of a specific behvoir
measures cerebral blood flow during behvoir or resting
pateitns must lie motionless -
Positron Emission Tomography (PET)
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Imaging technique that detects changes in blood flow by measuring changes in the uptake of compounds such as oxygen or glucose
Used to analyze the metabolic activity of neurons
Radioactive molecules are injected into the bloodsteam
Very expensive
- Iowa Gambling Test for ratns
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food is motivator
Put into box and nose poke to start trial
Vary on amount of rewards depending on which light they turn on
Rats do learn this task, will go for hole that gives them largest rewards
By blocking certain receptors, there is relationship to neurotransmitter availability and how well you can perform this task
- Benifits of creating animal models of disease
-
Some disorders are easy to model (e.g., stroke)
Behavioral disorders are more difficult
Attention-Deficit/Hyperactivity Disorder (ADHD)
Developmental disorder characterized by core behavioral symptoms of impulsivity, hyperactivity, and/or inattention
FASD - developmental disorder caused by the teratogenic effects of alcohol during ???? stage of development.
- fMRI FASD and simple WCST
-
Look at brain activation in different individuals
FAS individual has increased activating: too much brain at work, imbalance of excitatory and inhibitory impulses, no refined connections, end up using less of the brain, become hemispheric, bilateral hemisphere activation
Using different areas and connections less refined
fas
partial FAS
control