Unit 1 Flashcards
ventricles
where cerebral spinal fluid moves through brain
grey matter
cortex
neural cell bodies and dendrites
nonmyelinated
processing and cognition
white matter
glial cells and myelinated axons
transmits signals
action potentials
gyri
ridge in brain
hump surrounded by sulci
sulci
divit in brain
fissure
groove of natural division
phrenology
ancient myth of bumps on skull indicating larger portion of brain- more specialized in that area
“map” on skull
neurons
conduct signals
10% of brain cells
glia cells
help neurons- hold things together
responsible for ion balances
90% of brain cells
experimental ablation method
make lesion on brain then study behavior
aphasia
inability to speak
broca’s aphasia
can understand, but not fluent
hard to GENERATE words
effect of stroke- frontal lobe, left hemisphere
Wernicke’s aphasia
fluent, but don’t make sense
cant CONTROL speech
effect of stroke- left temporal lobe
object agnosia
cannot name an object
distinguishing parts of brain
anatomy- architecture/connection
function- recordings/behavior
fMRI
visualize what parts of brain active during certain tasks
somatosensation
perception based on senses
mice whiskers- more touch brain
bats audiology- more audio brain
why be kind when animal experimenting
stress changes brain chemistry
data inaccurate
similarities between mammal brains
structure- hemispheres, cortex, cerebellum
differences between mammal brains
size
gyrification
size of localized regions
-Ex: mice have larger portion devoted to touch (whiskers)
cortex
outermost covering of brain
memory, perception, attention, awareness, thought, language, consciousness
cerebellum
back of brain
motor control, coordination, precision, timing
Ramon y Cajal
visual system pathway
retinal connections
shape and position of a neuron
origin and destinations in neural network
photoreceptors
cells in retina responding to photons (light)
rods and cones
ganglion cells
provide entire input for vision
influenced by many photoreceptors
visual pathway
photoreceptors -> bipolar cells -> ganglion cells
ganglion axons make optic nerve
cell body (soma)
nucleus and other intracellular organelles
axon
connects cell body to target cells
typically small and hard to see
dendrite
branches upon which incoming fibers make connection
receiving stations for excitation or inhibition
resting potential
inside of cell is negative relative to outside
-65 mV
depolarize
make inside cell less negative
hyperpolarize
make inside cell more negative
graded potential
generated by extrinsic physical stimuli
short spread b/c passive
**decrease in amplitude as travel toward cell body
action potential (nerve impulse)
graded potentials are large enough to reach threshold and depolarize the cell
propagate rapidly over long distances
all or nothing response
**fixed in amplitude and duration
extracellular recordings
put electrode near neurons
signals sent by neurons can be heard
detecting current as neuron delivers output
lots of spikes (represent AP)
intracellular recording
capillary into neuron membrane
clear waveforms
single spike for AP
whole cell patch recording
rupture membrane to record inside cell
clearest technique
receptor field
region of sensory neuron where presence of stimuli will alter firing of that neuron
larger field = more area to detect, but less precision
all or nothing response
once initiate, AP amplitude and duration are fixed
refractory period
after AP is fired
second impulse at same site cannot be competed until first is completed
Action potential path
resting potential -> stimulus causes cell to depolarize (reach threshold) -> AP initiated -> Na rush into cell (inside + now) and K out -> AP propagates along axon to terminal -> transmitter released -> refractory period to repolarize
frequency
indicates intensity of stimulus
limited by refractory period
more effective stimulus -> higher frequency
all AP are the same size, so frequency tells intensity
synapse
structure at which one cell hands its information to the next
synaptic cleft
between pre and post synaptic terminals
contains extracellular fluid
cannot be transversed simply by currents generated in sensory receptor
Synaptic cleft mechanism
- ) photoreceptor terminal releases neurotransmitter from presynaptic vesicles
- ) transmitter diffuses across cleft and interacts with chemical receptor (protein) embedded in membrane of post-synaptic cell
- ) local graded potential spreads to terminals
more neurotransmitter released
higher concentration in cleft
larger # activated receptors
larger local potential
excitatory signal
if enough to cause depolarization AP is fired
inhibitory signal
suppresses release of neurotransmitter
electrical synapses
pre and post synaptic membranes are linked by channels that connect intracellular fluids of the two cells and allows electrical potentials to spread directly rom cell to cell w/o a chemical transmitter
integration
neurons take account of influences arriving from diverse inputs to create own new messages with new meaning
Hubel and Wiesel
showed that cortical neurons do not respond simply to light or dark on retina; rather, activation depends on pattern of retinal illuminations
retinal illuminations
specific and distinctive patterns are required and most effective stimuli for different types of cortical cells
Ex: one cell may only fire if detects horizontal light
generation of complex stimulus
progressive integration of information derived from lower order units results in higher order central neurons
transformation of visual information (increasing complexity)
- ) photoreceptor indicates a change in light
- ) signal in ganglion indicates presence of contrast
- ) signal in cortical neuron indicates orientation
columnar arrangement
as you go through the cortical layers (6 of them) processing of a stimuli remains the same
axon hillock
connects cell body to axon
where impulse originates from
if reaches threshold fires AP down axon
charge location relative to membrane
charges congregate around membrane
- inside
+ outside
phospholipid layer and membrane potential
thin so negative charges line inside and positive line the outside
ion channel
protein molecules that span the membrane and form pores through which ions can pass
passive diffusion
ions (K, NA, Ca, Cl) driven through channels by concentration gradients and by electrical potential
transport molecules
- pumps and transporters
- move substances across membrane AGAINST electrochemical gradients
- return ions back to proper side of membrane
- carry glucose and amino acids across
ion channel gate
opens and closes to control ion movement through channel
what causes gate opening
- membrane potential
- binding of ligand
concentration gradient
ions move in or out of the cell based on trying to achieve equal concentrations inside and outside of the cell
how is the resting membrane potential maintained
ion pumps- sodium potassium pump
cytosol of cell in resting membrane
sodium concentration low; potassium concentration high
Na+/K+ pump mechanism
- ) 3 Na+ ions on cytosolic side bind to pump
- ) ATP transfers phosphate group to pump (need energy to move Na+ against gradient)
- ) phosphorylation causes change in pump conformation
- ) Na+ ions released outside cell
- ) pump facing outside cell exposes K+ binding sites
- ) 2 K+ bind to pump
- ) phosphate group released
- ) pump return to original conformation
- ) K+ released inside cell and cycle repeats
inhibition
- big role in generating rhythmic output
- GABA, glycine, and Cl- channel common
- Ex: rhythm of walking inhibiting one leg, while stepping with other
diffusion
- must have a channel and gradient
- each ION has OWN channel
- once reach equilibrium, no net diffusion
Protein channels
- highly specific
- composed of 4-5 subunits
- open or closed conformation
subunits
- strings of amino acids held together in specific structure
- determine what channel is capable of
- often change morphology w/ ligand binding
subunit amino acid residue in membrane
- must be nonpolar
- don’t want to react w/ water, so stuck in place
what causes channels to open
- ) ligands
- ) change in membrane voltage
- ) physical deformation
transmitter gated ion channel
- respond to ligand binding
- ligands can bind inside or outside
- often cause change in subunit conformation
- ACh, serotonin, glutamate, etc
voltage gated channels
- change membrane voltage
- Ex: sodium potassium pump
mechanoreceptors
- responsible for channel opening in response to physical deformation
- Ex: wriggling of hair cells in ears cause channel to open (sound and position of head)
current
movement of charge accomplished by neurons
conductance
- ability to migrate (high conductance -> low resistivity)
- ability of channel to pass current
Ohm’s law
I = gV
- I- current
- g- conductance
- V- potential
patch clamp technique
suction and isolate membrane channel; then put in dish with ions and measure current w/ electrode (ideal for single-channel current detection)
How to only get recording for channel of interest during patch
-have to induce blockage of other channels with poison b/c patch often result in sucking multiple channels
tetrodotoxin (TTX)
- from puffer fish
- selectively blocks Na+ channels (occludes pore)
- would allow for recording of K+ channels only
kinetic behavior channel
duration of closed and open states
driving force
- difference between the membrane potential and the equilibrium potential
- higher driving force -> more push
two factors influencing conductance
- ) membrane permeability
2. ) concentration of ions in the region of the channel
channel permeability
ease at which ions can pass through the open channel
open channel
permeability
permeability + ions
conductance
reverse potential for K+ currents
- if cell receives applied negative voltage, the potential outward movement K+ is reduced
- completely retarded if voltage more negative than -80 mV
K+ currents w/ positive applied voltage
if the cell receives applied positive voltage, the potential gradient accelerates the K+ out of the cell (increasing current amp)
equilibrium potential
- where concentration and electrical gradients are balanced (at equilibrium)
- electrical gradient balances tendency for concentration gradient to drive ions into or out of cell
- driving force is 0
- ions diffuse in or out of cell until reach
equilibrium potential K+
- 80 mV
- channel opening hyperpolarizes resting cell
- flow outward to make more negative
equilibrium potential Na+
62 mV
- channel opening depolarizes cell
- flow in to make more positive
equilibrium potential Cl-
- 67.5 mV
- channel opening hyperpolarizes cell (inhibits)
- flow inward to make more negative
equilibrium potential Ca2+
123 mV
- channel opening depolarizes cell
- flow inward to make more positive
Nernst Equation bottom line
- ) Ions diffuse DOWN concentration gradient trying to reach equilibrium potential
- ) passive process
- ) applies to single ion species at a time
- ) point of equilibrium between diffusion and electrical forces for ion
valence for ion species (Z)
- K+ = 1
- Ca2+ = 2
Cl- channel opening
- resting membrane potential is -65 mV
- Cl- equilib potential is -67.5 mV
- Cl- diffuses into the cell to make it more negative (hyperpolarize)
- inhibits
nicotinic acetylcholine receptor (nAChR)
- ligand activated channel
- activated by ACh release from presynaptic nerve terminals
- when activated, open to form channels through which cations can enter or leave post-syntaptic cell
mutations in receptor protein
- some affected ligand binding -> channel inactivation
- some affected ion selectivity
- some affected channel conductance
Proof that M2 helices line open channel pore
- mutations affecting selectivity and conductance were located on M2 helices (line inside of pore)
- replacing serines with alanines reduced channel conductance and binding affinity
hydrophilic amino acids
- serines and threonines
- exposed to aqueous pore
hydrophobic isoleucines
- alanines
- nestled against membrane lipid
electron microscopy
reveals general shape and orientation of receptor in membrane
polar substituents within pore
higher channel conductance
increasing side chain volume in pore
decrease conductance
pore differences in charge selectivity (anions vs. cations)
- related to sign of charged residues along ion pathway
- mutations can chance ion selectivity
voltage-activated channels
- activated by cell membrane depolarization or repolarization
- Na+, K+, and Ca2+ channels
selectivity filter
- four inner channel links combine to form restricted passe responsible for ion selectivity of voltage-activated channels
- filter formed at extracellular opening
selectivity for potassium
- achieved by size and molecular composition of selectivity filter
- pore diameter accomidates dehydrated potassium
- ions that are too small can’t be dehydrated
- ions that are too large don’t fit
why Na+ cannot pass through K+ channel
- in order for K+ to pass it must be dehydrated, which is achieved by exposed oxygen atoms
- Na+ is too small for its hydration shell to make contact with the 4 oxygen atoms simultaneously, so it cannot be dehydrated
how to increase pore conductance
-replace neutral amino acid residues with those that are opposite in charge of the desired ion to pass
voltage-activated gating
occurs when depolarization causes displacement of charges of the pore helices, resulting in conformation changes and opening of conducting pathway from channel pore to cytoplasm
inactivate
- many voltage-sensitive channels inactivate following activation
- cytoplasmic residues move to mouth of pore, blocking channel access
how can you change the AP of a living cell
-make the amp higher by adding Na+ to extracellular environment
why need electrolytes during exercise
-have to replenish Na+ levels, so AP can continue to be fired
Botox
- degrades SNARE protein, which prevents ACh release at neuromuscluar junction
- prevents presynaptic membrane vesicles from fusing with postsynaptic membrane
neuromuscular junction reliability
- ) large synapse
- ) located peripherally
- ) lots of synaptic vesicles full of ACh
- ) lots of surface area
organophosphates and sarin
nerve gases that disrupt AChE at neuromuscular junctions
neuropharmacology
-method of studying receptors by observing how ligand binding impacts receptor
antagonist
works against the receptor
agonist
natural ligand for the receptor
ionotropic receptor
- receptor with an ion channel attached
* nicotinic and glutamate receptors
2 types of cholinergic (ACh) receptors
- ) nicotinic
2. ) muscarinic
nicotinic receptor
- transmitter gated ion channel
- ionotropic receptor
- nicotine is agonist
- curare is antagonist
metabotropic receptor
- G protein coupled receptor
- binding of ligand releases G protein, which stimulates other proteins down the line (may or may not be channels)
- muscarinic receptor
muscarinic receptor
- muscarine- agonist
- altropine- antagonist
- does not contain a channel- metabotropic receptor
temporal summation
- neuron receives increased frequency of impulse from a single location (multiple inputs from same presynaptic cell)
- results in greater stimulation than single input
spatial summation
-neuron receives inputs from multiple presynaptic cells, resulting in greater AP
membrane resistance
- walls of a hose
- increase membrane resistance -> increase conductance b/c harder for charge to escape
- Achieved through myelination (reduces capacitance)
internal resistance
- resistance in the direction of flow
- increase internal resistance -> decrease AP conductance
3 criteria for a cell to remain stable
- ) intracellular and extracellular must be electrically neutral- charges balanced
- ) cell must be osmotically balanced
- ) no net movement of any ion into/out of cell
model cell
- impermeable to Na+ and internal anions
- permeable to K+ and Cl-
- Na+ and Cl- in highest [ ] outside
- K+ and anion highest [ ] inside
- membrane permeable to K+ and Cl-
membrane as a capacitor
- as K+ ions diffuse out of the cell, the anions line up along the inner edge of the membrane and are attracted to the K+ ions extracellularly
- the membrane acts as a capacitor between the mutual attraction, separating and storing charge
mechanism for ACh receptor channel
- when channel is closed (gated), pore is occluded by ring of M2 helices
- channel activation (2 ACh binding) -> M2 helices swing outward and open pore
Equilibrium potential elaborated
Potential at which there is no net flux of a particular ion into or out of the cell
RMP is closest to equilibrium potential of K+, so k+ conductance dominates
During AP, K+ overwhelmed by Na+, so Na+ dominates and membrane potential brought to Na+ equilibrium potential
maintaining neutrality of internal and external environments
- charges from Cl- cancel out charges from Na+ extracellularly
- Charges from anions cancel out charges from K+ intracellularly
- If K+ flows out, form as cations on outer edge, attracting the counteranions to membrane and keeping center of cell neutral
why doesn’t messing w/ Cl- change RMP much
- when intracellular leaves, lose same amount of K+
- since tons of K+ in cell, losing some doesn’t do much to cell
Main points of resting membrane potential
- ) large changes in membrane potential can be due to minuscule concentration changes in ions
- ) RMP isn’t changed much by manipulating Cl-
- ) Differences in charge is at the membrane itself
- ) membrane capacitance- takes time for charge to build up
Messing with extracellular Na+
-doesn’t make changes like K+ would b/c membrane isn’t permeable to Na+ like it is K+
Goldman-Hodgkin-Katz
- take natural log of permeability of concentration out over concentration in gives RMP
- tells RMP for a given CELL
saltatory conduction
- propagation of AP along myelinated axons from one node of Ranvier to the next
- increases velocity of AP w/o having to increase diameter
