exam 1 Flashcards
scientific method
- observation
- replication
- interpretation
- verification
what drives the scientific method?
hypothesis but discovery research also needed
egypt (5000 years ago)
- knew about the brain but it was not important
- heart was the key to the soul and where memories were stored
hippocrates
brain is the center of sensation and intelligence and epilepsy=brain damage
alcmaion of crotona
described the optic nerve in 500 BC
plato (387 BC)
believes brain is the center of mental processes
aristole (384-322 BC)
thought heart was the center of intelligence and the brain simply cooled the blood
galen (AD 130-200)
a doctor to gladiators that studied the structure of the brain
* had a similar view to hippocrates
what were galen’s beliefs?
- cerebrum felt soft, so sensations and memory formed here
- cerebellum felt hard, so it controlled muscles
- the brain received sensory info
- nerves were tubes
- humors (vital fluids) flowed to the brain ventricles
leonardo da vinci
produced wax cast of ventricles in 1504
andreas vesalius (1514-1264)
produced detailed drawings of the brain
decartes (1596-1650)
believed in fluid-mechanical theory but that humans abilities came from the “mind” which communicated to the brain via the pineal gland
history of neuroscience in the 17th and 18th century
- distinguished gray matter from white matter
- peripheral and central divisions
- every brain has the same pattern GYRI (bumps) and SUCLI & FISSURES (grooves)
grey matter
cell bodies of neurons
white matter
axons of neurons
19th century views of the brain
- brain generates electricity
- nerves are made of bundles of fibers
- each fiber transmission is one way
- sensory and motor nerves in same bundle
Galvani and du Bois-Reymond
showed that electricity can stimulate muscle movement
Bell and Magendie
nerves as bundles, motor and sensory nerves in same bundle
bell (1811)
proposed that motor fibers come from cerebellum and sensory fibers GO TO cerebellum
flourens (1823)
- used experimental ablation to show bell was correct
- though that all parts of the cerebrum contribute to all functions… WRONG
gall (1809)
- phrenology
- brain divided into 35 regions (language, color, hope) shown to be WRONG
broca
believed that different functions localized to different areas
fritsch and hitzig
used dogs and frogs in 1870 to show specific region of the brain controlled movement
ferrier
1881 showed the same thing as fritsch and hitzig with monkeys; removal caused paralysis
munk
showed that occipital lobe was required for vision
evolution of nervous system
1859 Darwin published ON THE ORIGIN OF SPECIES
- nervous systems have evolved and were related
- some animals are better at specific functions
squid and snail
- basic biology of neurons
- synaptic transmission
- plasticity
cats and primates
visual system
rats and mice
neuropharmacological and behavioral studies
alzheimer’s disease
degeneration of cholinergic neurons, dementia, fatal
parkinson’s disease
degeneration of dopaminergic neurons, loss of voluntary movement
depression
15 million experience, major cause of suicide
schizophrenia
2 million affected, severe psychotic illness. delusions, hallucinations, and bizarre behavior
stroke
loss of blood supply can lead to permanent loss of function
epilepsy
seizures due to disruption of normal brain electrical activity
multiple sclerosis
loss of nerve conduction
nervous system uses large amount of…
oxygen and glucose
neurons
- only 10-20% of cells
- 0.01-0.05 mm in diameter
microtome
small slices of neurons needed to study the brain
nissil stain
labels nuclei of ALL cells but also the nissil bodies (rough endoreticulum) of neurons
*franz nissil in 1894
golgi stain
stains ALL parts of neurons but NOT all neurons
- only stains 5%
cajal
neurites not continuous, communicate by contact
is the nervous system an exception to the cell theory?
NO
soma
- cell body of a neuron
- 20 um in size
- the nucleus is 5-10 um
mitochondria
widespread throughout the cytoplasm, presynaptic region
neural membrane
- 5 nm thick
- many proteins embedded in the membrane
- protein composition varies from soma, axons, and dendrites
microtubules
- 20 um in diameter
- polymer of tubulin
- not static
- associated with other proteins (MAPS)
- tau found in paired helical filaments seen in alzheimer’s
- involved in axoplasmic transport
microfilaments
- 5 um in diameter
- numerous in neurites
- two thin strands of actin polymers
- not static
- closely associated with membrane
- often seen at synaptic terminals
- dendritic spines
neurofilaments
- 10 um in diameter
- also called intermediate filaments
- strong
- maintains neuronal shape
- form tangle in alzheimer’s
axons
- unique to neurons
- NO rough ER, few ribosomes
- proteins in membrane differ from those in the soma
- 1 mm to over a 1 m long
- form branches or collaterals (some recurrent)
- diameter varies from 1-25 um
speed of nerve impulse depends on..?
diameter, thicker = faster
axon hillock
- beginning of axon
- NO ribosomes or most organelles
terminal
- end of axon
- NO microtubules
- many synaptic vesicles
- protein rich
- many mitochondria
synapse
- two sides (pre and post)
- many drugs and chemicals act here
- malfunctions here are responsible for many mental disorders
synaptic cleft
in-between pre and post synapse sides, no direct contact
synaptic transmission
mediated by chemical neurotransmitters
wallerian degeneration
after axons cut, death distal to injury
axonal transport
- fast axoplasmic (1000 mm/day)
- slow axoplasmic (1-10 mm/day)
anterograde axonal transport
walked down microtubules by kinesin, uses ATP
retrograde axonal transport
dyeing used along microtubules
- fast 50-250 mm/day
dendrites
- come in different shapes and sizes
- covered with thousands of synapses
- some covered with spines; can change structure depending on type
- polyribosomes often under spines
- contain microtubules, fewer mictofilaments
dendritic tree
collection of all branches that extend from the soma
unipolar or pseudounipolar
single process with peripheral branch and central branch
- found in sensory ganglia
bipolar
found in sensory structures
multipolar
many dendrites, single axon
spiny dendrite
ALL pyramidal cells and some stellate cells
aspinous dendrite
some stellate cells
golgi type 1 neurons (projection)
- extend between brain regions
- long axons
- many pyramidal cells
golgi type 2 neurons (local circuit)
- connect to neurons in vicinity
- short axons
- stellate cells
glia
- most of the cells in the brain
- supportive of neuronal function
- support synapse formation
- vasculature
astrocytes
- most numerous glia
- between neurons
- express neurotransmitter receptors
- regulate contents of extracellular space
- remove NTs from synaptic cleft
- regulate extracellular ion levels
- can divide
- source of the majority of brain tumors
myelinating glia
- oligodendrocytes
- schwann cells
ependymal cells
line ventricles, direct cell migration during development
microglia
- remove debris (phagocytosis)
- release cytokines
- may be activated in response to stroke or brain trauma
- may also be involved in pruning or refining circuits
protoplasmic astrocytes
in gray matter close to neurons, involved in blood-brain barrier and metabolism
fibrous astrocytes
repair damaged tissue, may form scars. found primarily in white matter
muller astrocytes
found in retina
oligodendroglia
found in brain and spinal cord; myelinate several axons
schwann cells
found in peripheral nervous system; myelinates single axons, every internode region by one of these
neural membrane at rest
- passive conduction of signal only works for short distance
- need resting potential to generate action potential
- varies between different types of neurons
action potential
conduct signal without loss of strength
excitable cells
- can generate action potentials (nerve impulse)
- at rest have a resting membrane potential (inside negative compared to outside)
how do cells generate a charge difference across the membrane
voltage gated channels
what do you need to generate the resting potential?
- cytosol
- plasma membrane
- membrane proteins
cytosol and extracellular fluid
water is the major component
- polar molecules dissolve in water bc its polar
ions in the cytosol and extracellular fluid
- major charge carrier
- surrounded by clouds of water called spheres of hydration
- Ca2+, K+, Na+, and Cl- are important for neurophysiology
hydrophilic
ions and polar molecules
hydrophobic
molecules with non polar covalent bonds (oils, lipids)
phospholipid membrane
- barrier to water and ions, allows membrane potentials to form
- in the bilayer, hydrophilic head towards water while hydrophobic tail inside towards membrane
amino acids
- 20, properties determined by R group
- chains of these are held together by peptide bonds
ion channels
- have both hydrophobic and hydrophilic regions
- selective
- can be controlled
pumps
transport ions across membranes against concentration gradients using ATP as the energy source
diffusion
random movement from region of high concentration to one of low (concentration gradient) temperature dependent=must have a path through the lipid bilayer (a channel)
electrical current (I)
movement of charge; positive in the direction of positive charge movement
how much current flows depends on…
- electrical potential (voltage, V)
- electrical conductance
voltage
the measure of the difference in charge between anode and cathode. more difference=more current
conductance (g, siemens)
relative ability for a charge to move from one place to another, depends on the number of particles available to carry the charge and how easily these can travel
resistance (R, ohms)
the relative inability of an electric charge to migrate R=1/g
ohm’s law
I=gV
membrane potential (Vm)
- voltage across a membrane
- typical = -65 Mv
- inside of cell is MORE negative relative to outside
equilibrium state
occurs when diffusional and electrical forces are equal and opposite
ionic equilibrium potential
the potential difference that balances the ionic concentration gradient
voltage that balances diffusion
large changes in membrane potential are produced by..
tiny changes in ionic concentration (0.00001mM)
net difference
occurs at the inside and outside surfaces of the membrane (5nm thick), the membrane acts like a capacitor (stores charge)
rules for generating a electrical potential difference
ions move across the membrane at a rate proportional to the difference between the membrane potential and the equilibrium potential (Vm-Eion). for each different ion is the ionic driving force, move in the direction that moves the cell toward the Eion
nernst equation
- ions have their own equilibrium potential
- charge and concentration difference determines whether inside of cell is positive or negative at equilibrium for each ion
what is the equilibrium potential of potassium, K+?
-80 mV
what is the equilibrium potential of sodium, Na+?
+62 mV
what is the equilibrium potential of calcium, Ca2+?
+123 mV
what is the equilibrium potential of chloride, Cl-?
-65 mV
ion pumps
work against the concentration gradient
sodium-potassium pump
uses ATP for energy source, exchanges internal Na+ for external K+, used 70% of brain ATP
calcium pump
transfers Ca2+ out of the cell, other proteins and channels help as well
goldman equation
relative permeability to multiple ions can be factored in
*if cell 40x more permeable to K+ than Na+, then Vm= -65mV
K+ channels
- key to determining a neurons resting Vm
- first cloned in fruit fly
- mutations here lead to severe neurological problems or death
external K+ must be carefully regulated
- membrane potential close to K+ due to high permeability of the cell
- changing K+ outside can change membrane potential
- can cause cell to depolarize
- blood-brain barrier
- death by lethal injection
hodgkin and katz (1949)
used manipulation of the external K+ concentration to show that resting potential is mostly set by K+ permeability of neuron
other names of action potential
spike, discharge, or nerve impulse
stages of action potentials
- resting
- rising
- overshoot
- falling
- undershoot
generator potential produced by…
entry of positive charge into cell
properties of action potentials
- all or none mechanism
- firing frequency can reflect size of inout current
absolute refractory period
- Na+ channels inactived, can’t be deinactivated until Vm is more negative
- maximum rate 1000Hz, 1 msec
relative refractory period
- Vm hyperpolarized until K+ channels close
- more current required to fire action potential
what controls the firing frequency of action potential?
amount of depolarization
*more stimulation=more firing
hodgkin and huxley
- used voltage clamp to determine ionic permeability changes during the AP
- early inward current is carried by Na+
- late outward current carried by K+
- membrane voltage changes are time and voltage dependent
action potential theory
- depolarization caused by influx of Na+ ions
- depolarization by efflux of K+ ions
- rising phase due to inward Na+ current
- falling phase due to outward K+ current
I=g(Vm-Eion)
change in Na+ channel
-65mV closed to -40mV opened
voltage-gated sodium channels
- open and closed by changes in membrane potential Vm
- one long protein
- 4 domains of 6 transmembrane helixes
- association with water important for selectivity
- segment S4 contains voltage sensor
tetrodotoxin (TTX)
from puffer fish, blocks channel
saxitoxin
from dinoflagellate, occurs in clams, shellfish, mussels
bactrachotoxin
from frog, channels open at more negative voltages and stay open too long
scorpion and sea anemone toxins affect…
channel inactivation
voltage-gated K+ channels
- falling phase of AP also due to opening of K+ channels, NOT just Na+
- delayed opening after depolarization
- delayed rectifier channels
threshold of AP
voltage at which Na+ channels open, more permeable to Na
rising phase of AP
Na+ ions enter cell due to large driving force
overshoot of AP
voltage approaches equilibrium of Na+, greater than 0mV
falling phase
Na+ channels inactive, K+ channels open, large driving force for K+ to leave the cell
undershoot
voltage moves toward equilibrium of K+. hyperpolarizing the cell, little permeability to Na+
gradients maintained by…
Na-K pump
action potential conduction
- moves down axon in ONE direction
- can be started at either end
- 10 m/s, lasts 2 msec
orthodromic
AP starting from cell body
antidromic
backward AP
synapses (person)
sherrington 1897
electrical synapses
furshpan and potter 1959
chemical synapses
loewi and vagusstoff 1921
katz
motor neuron to muscle
eccles
central nervous system
bidirectional synapse
cells are electronically coupled, fast
- common in mammalian CNS, glia, cardiac muscle cells, smooth muscle, epithelial cells, liver cells
is the synaptic cleft empty?
NO but it contains extracellular matrix proteins
postsynaptic density
receptors and associated proteins
chemical synapses
presynaptic and possynaptic with a 20-50 nm cleft
CNS synapses
- various sizes and configurations
- axodendtritic, axosomatic, axoaxonic, dendrodentritic
gray’s type 1
asymmetrical membrane thickness at synapse, usually excitatory
gray’s type 2
symmetrical, usually inhibitory
neuromuscular junction (NMJ)
- between motor neurons and muscle
- similar to CNS synapses
- easier to study than CNS synapses
- fast, large, reliable synapses
principles of synaptic transmission
- neurotransmitter synthesis
- load NT into synaptic vesicles
- vesicles fuse to presynaptic terminal
- binds to postsynaptic receptors
- biochemical/electrical response elicited in postsynaptic cell
- removal of NT from synaptic cleft
neurotransmitter synthesis and storage
- various transmitters have distinct synthetic pathways
- in all cells (amino acids)
- specific enzymes in neurons which synthesize unique transmitter
- some neurons make multiple NTs
neurotransmitter release
- opening of voltage gated Ca2+ channels, large influx of Ca2+
- exocytosis, occurs rapidly, fusion of synaptic vesicle with membrane of active zone
- some vesicles may be already docked
- vesicle membrane recycled by endocytosis, multiple ways for this
- peptides not released at active zone, slower time course, generally respond to higher Ca
neurotransmitter receptors
- 100 different ones
- gated or ligand-gated
- g-protein coupled
- nAChRs
transmitter-gated channels
- pore usually closed until ligand binds
- 4-5 subunits, change conformation after ligand binds, channel opens within microseconds
- not as selective as voltage-gated channels
- ACh gates Na, K, Ca, excitatory, EPSPs
- Cl gated, IPSP, glycine, GABA
G-protein coupled receptors
- slower acting
- amino acids, amines, peptides
- also called metabotropic receptors
- autoreceptors are often linked to this
neurotransmitter reuptake and degradation
- NT must be destroyed or removed from synaptic cleft to terminate signaling
- diffusion
- desensitization
reuptake is done by..
specific transporters
degradation is done by..
enzymes, blockade can result in death
neuropharmacology
many chemicals, diseases, and drugs can affect each of these steps
curare, cobra venom are…
antagonists
nicotine is an….
agonist
botulinum toxin
blocks transmitter release
black window venom
increases ACh release
synaptic integration
process in which these multiple inputs combine within one neuron, output then determined
integration of EPSPs
- thousands of channels
- number that opens depend of quantity of NT released
- amplitude is multiple of mini-amplitude
quantum
number of transmitter molecules in a vesicle (several thousand)
quantal analysis of EPSPs
- compare miniature and evoked potentials to decide how much NT is released
- at NMJ 200 vesicles, -40mV needs to work every time
dendritic cable properties
- electrically passive calls
- currents will dissipate over a distance
Vx=Vo /e^(x/), e=2.718
V=0.37 (Vo)
lamda
- length constant, where depolarization is 37% of original current
- gives some idea how far away from axon hillock depolarization can occur and still get AP
what does lambda depend on?
internal resistance and membrane resistance
internal resistance depends on
diameter and electrical properties of cytoplasm (constant in mature neuron)
membrane resistance
depends on synaptic activity and how many ion channels open
