exam 1 Flashcards
how are electrical potentials generated across neuronal membranes
- ion concentration gradients
- selective permeability
what type of transporter establishes ion concentration gradients
active transporters
what type of cell creates selective permeability in the direction of the conc gradients
ion channels
when chemical gradients equals to electrical gradient
electrochemical equilibrium
what ions are more concentrated outside cell
na, cl, ca2+
what ion is more conc inside cell
k+
measures the electrical activity of neurons
electrophysiological recordings
an electrode is placed near the neuron to detect its activity
*only detects temporal patterns of several action potentials (spikes)
extracellular recording
electrode is placed inside the neuron
-detects smaller, graded changes of electrical potential
*detects resting mem potential, receptor potential, synaptic potential, wave form of a single action potential
intracellular recording
due to the activation of sensory receptor neurons by external stimuli
receptor potential
due to the activation of synapses
synaptic potentials
a brief active all or none electrical response of the neuron after stimuli that causes mem potential to meet or exceed stimuli
*ALWAYS SAME SIZE AND ONLY FREQUENCY CHANGES
action potentials
if current inject makes the membrane potential at or more positive than this even, action potential occur
threshold potential
chemical conc gradient that causes k+ ti move inside to outside
chemical force
an opposing electrical gradient (electrical potential) that increasing tends to stop k+ from moving across the membrane
electrical force
electrical potential generated across membrane at electrochemcial equilibrium
-AKA reversal potential b/c the current reverse polarity at this point (inward and outward equal)
-can be predicted by Nernst Equation
equilibrium potential
relation of equilibrium potential to the conc gradient
-MEMBRANE PERMEABLE TO ONE TYPE OF ION
nearest equation
equilibrium potential when the membrane is PERMEABLE to SEVERAL IONS
Goldman equation
what were Hodgkins and Katz conclusions
- membrane of resting neuron is more permeable to k+ in comparison to any other ion
- there is more K+ inside than outside
-changing mem potential to a level more pos than the threshold potential produces 2 effects: an EARLY INFLUX OF NA+ INTO NEURON and DELAYED EFFLUX OF K+
*RESTING MEM POTENTIAL IS LARGELY DETERMINED BY K+ SELECTIVE PERMEABILITY AND K+ CONC GRADIENT
what causes the mem potential of a neuron to depolarize during the action potential
increased na+ permeability
action potential is generated because of ___ conc gradient and transiently increased ___ permeability
Na+
neurons constitute ___ ___ which constitutes neural systems (what is it? )
neural circuits
-neurons –> circuits –> systems
who proposed the neuron doctrine
Santiago ramón y cajal
nerve cells are discrete entities
neuron doctrine
body of the neurons
soma
what sends info
axon
what receives info in neuron
dendrites
the most abundant type of synapse
chemical synapse
the rare type of synapse that is facilitated by the gap junction
-permit direct, passive flow of electrical current from one neuron to another
-transmission of electrical synapses *BIDIRECTIONAL and extraordinarily fast without delay
-PORE OF CONNEXONS are much LARGER than voice –> allowing diffusion of ions, atp, intracellular metabolites, and second messengers
electrical synapse
what are the 4 types off glial cells in the CNS
- astrocyte s
- oligodendrocytes
- microglial cells
- glial stem cells
maintain an appropriate chemical environment for neuronal signaling
astrocytes
lays down myelin around some CNS axons
oligodendrocytes
removes myelin and cellular debris
microglial cells
some glial cells retain the capacity to proliferate and generate additional precursors or differentiated glial and sometimes neurons
2 types:
- astrocytes
- oligodendroglial precursors
glial stem cells
neurons organized into ensembles to process specific kinds of information
neural circuits
the dense tangle of dendrites, axons terminals, and glial cell processes; the region between nerve cell bodies where MOST SYNAPTIC CONNECTIVITY OCCURS
neuropil
nerve cells that carry information from periphery toward the brain or spinal cord
(SENSORY)
afferent / sensory neurons
nerve cells that carry info away from the brain or spinal cord
Efferent neurons / motor neurons
participate only in the local aspects of a circuit
interneurons / local circuit neurons
calcium indicators or genetically encoded calcium sensors
calcium imaging
channelrhodopsin
optogenetics
neural circuits that process similar types of info make up neural systems
neural system
nerve cell bodies that resides in the PNS
ganglia
bundle of peripheral axons
nerves
how are nerve cells in the CNS arranged
- nuclei
- cortex
local accumulations of neurons that have roughly similar connections and functions
nuclei
sheet like arrays of nerve cells
cortex
gathering of CNS axons
tracts
tracts that cross the midline of the brain
commissures
any accumulation of cell bodies and neuropil in the brain and spinal cord
gray matter
axon tracts and commissures in the CNS
white matter
what is part of CNS
- Brain:
-cerebral hemisphere
-diencephalon (thalamus/hypothalamus)
-cerebellum
-brainstem - spinal cord
cranial nerve ganglia, dorsal root ganglia (spinal ganglia), cranial nerves and spinal nerves
sensory ganglia and nerve
do motor nerves belong to PNS or CNS
PNS
motor neuron cell bodies belong to the CNS
autonomic ganglia and nerves are part of what motor division
visceral / autonomic motor division
small ganglia and neuron through the wall of the gut control mastic motility and secretions
enteric nervous system
during restating state what is more permeable K+ or Na+
K+
technique allows experimenters to control membrane potential and simultaneously measure the permeability changes
voltage clamp method
controls or clamps membrane potential at any desired level
voltage clamp
controls or clamps INJECTED currents at any desired level
current clamp
-pos ions moving into the cells
-depolarization on voltage trace
inward current
pos ions moving out of the cell
-hyperpolarization on voltage trace
outward current
selective Na+ channel blocker blocks early current
tetrodotoxin TTX
selective K+ channel blocker blocks late current
(TEA)
ability for ions to flow across the mem, defined as the reciprocal of the mem resistance (R)
membrane conductance
what prevents backward propagation
refractoriness
the time required for electrical info to travel from one end of a neuron to another
conduction velocity
how does myelination increase conduction velocity
- insulate the axonal mem to increase passive current flow
- saltatory conduction
can measure the currents flowing through single channels
patch clamp method
the currents flowing through single channels
microscopic currents
the currents flowing through a large number of channels
macroscopic currents
-inward
-inactivated during depolarization
single Na+ channel
outward
activated during depolarization
single K+ channel
___ channel has 3 conformations: open (depolarization, ion flow), inactivated (depolarization no ion flow) , close (hyperpolarization, no ion flow)
VNa+
___ channel has 2 conformation: open (depolarization, ion flow) and close (hyper polarization, no ion flow)
VK+
opening channel is influenced by different factors or stimuli
-non gated or leak channel
-voltage gate channels (contains VOLTAGE SENSORS)
-ligand gated channels
– extracellular ligands: many are neurotransmitters
–intracellular ligands : many are 2nd messengers
–an extraordinary ligand : light/photons: channelrhodopsin
gating mechanism
voltage gated Na+ channel genes are coded by what gene
SCN
voltage gated Ca2+ channel genes are coded by what gene
CACNA
-regulated any biochemical signaling processes and release of NTs at synapse
what channel is the largest and most diverse class of VGIC and what gene are they encoded by
K+ ; KCN
voltage gated Cl- channel genes are coded by what gene and what do they do
CLCN: control excitability, contribute to resting potential
ion channel pores account for ion conductance and are formed by:
- transmem PORE HELICES
- PORE LOOPS in btw pore helices
- WATER FILLED CAVITY
- SELECTIVITY FILTER
- CHARGED VOLTAGE SENSORS that account for voltage sensitivity
Na+ and Ca2+ channels can be produced by ___ protein and K+ channel made up of ___ subunits
one; multiple
genetic diseases result from mutation in ion channel genes
channelopathies
don’t directory use ATP but use the electrochemical gradient of other co-transported ions as an energy source
ion exchangers
exchange intracellular and extracellular ions
antiporters
carry multiple ions in the same direction
cotransporters
contain precisely aligned paired channels called CONNEXONS:
made of 6 presynaptic conexiones aligned with 6 postsynaptic connexions to form a pore
gap junction
what are the functions of electrical synapses
- synchronize electrical activity among population of neurons
- coordinate intracellular signaling of coupled cells
what are the functions of chemical synapses
-majority of neuronal connections and mediate most synaptic transmission in nervous system
-gap btw pre and post synaptic neurons called synaptic cleft
-needs to use chemicals called NTs to transmit signals
-mediate ionic signaling
*SLOW and UNIDIRECTIONAL (from pre to post synaptic)
chemical synapse
what is the signal transmission at chemical synapses
- action potential invades the presynaptic axonal terminal
- depolarization of mem potential leads to opening of vg calcium channels
- influx of ca2+ allows synaptic vesicles to fuse with presynaptic mem
- Its released into synaptic cleft via exocytosis
- Nts bind to receptors in postsynaptic mem causing Chanels to open or close
- Nts- induced postsynaptic current increases or decreases the probability that the postsynaptic cells will fire an action potential ( the excitability)
- removal of Nts by diffusion, recycle, glial uptake or enzymatic degradation
when more than 1 transmitter is presented within a nerve terminal, the molecules are called
co-transmitters
what are the 3 criteria that define a NT
- substance must be PRESENT WITHIN THE PRESYNAPTIC NEURON
- the substance must be RELEASED IN RESPONSE TO PRESYNAPTIC DEPOLARIZATION and the release must be Ca2+ DEPENDENT
- specific RECEPTORS for the substance must be PRESENT ON THE POSTSYNAPTIC CELL
a transient depolarization of the postsynaptic muscle fiber elicited by an action potential from the postsynaptic motor neuron
end plate potential (EPP)
spontaneous changes in muscle cell mem potential without stimulation from the presynaptic motor neuron
miniature end plate potentials (MEPPs)
EPP responses occur in units about the size of single MEPPs
EPPs : made of individual units each equivalent to a MEPP
Quantal fluctuations of EPP amplitudes
release of ACH occurs in discrete packets each equivalent to a _____
MEPP
what is the synaptic vesicle cycle in presynaptic terminals
exocytosis – vesicle fuse –> endocytosis
fused vesicle mem is retrieved into cytoplasm of the nerve terminal by ENDOCYTOSIS
Heuser and Resse HRP experiment
coated vesicle –> endosome –> synaptic vesicles
endocytosis
maintain receiver pool by tethering vesicles to each other and to actin
location: vesicles
synapsin
mobilize reserve pool vesicles by phosphorylation of synapsin
location: in cytoplasm near vesicles
CaMKII
organize snare proteins into a complex and is involved in mem fusion
-synaptobrevein
-snap -25
-synataxin
*ALL ARE SNARE PROTEINS
Ca2+ sensor sensing the elevation of ca2+ in terminal and triggering vesicle fusion
location: vesicles
synatotagmin
combine transmitter binding and channel functions into a single molecular entity
*FAST
ionotropic receptors / ligand gated ion channels
movement of ions through a channel depends on interfering metabolic steps, no channel as part of the structure and indirectly affects channels through activation of G protein
*SLOWER
metabotropic receptor / G protein coupled receptors
the macroscopic current resulting from the summed opening of many Ach gated channels on muscle membranes
end plate current (EPC)
the potential where the direction of EPC reverses or the membrane potential at which there is NO NET FLOW OF IONS
reverse potential
for postsynaptic neurons, the reversal potential I the mem potential at which a given NT causes ___ net current flow of ions through that transmitter gated receptor channel
NO
Vm < Erev = EPC is ___
inward
Vm > Erev = EPC is ___
outward
Vm = Erev = EPC is ___
zero
T/F ACh gated ion channels are almost equally permeable to both sodium and potassium
T
currents generated from opening or sometimes closing of ion channels by transmitter binding to postsynaptic rectors in chemical synapses
postsynaptic current
changes of the postsynaptic mem potential due to PSC in chemical synapses
postsynaptic potential
the action of a transmitter always drives the postsynaptic mem potential toward ___
Erev
inward current hyperpolarizes or depolarizes?
depolarizes
outward current hyperpolarizes or depolarizes
hyperpolarization
Erev > threshold –> ___
excitation
Erev < threshold –> ___
inhibitory
EPSPs produced by individual excitation synapses are usually well below the threshold for generating postsynaptic action potentials
sub threshold EPSPs
catecholamines (dopamine, NE, EPI, 5HT, His)
biogenic amines
-ACh
-Neuropeptides
-Endocanabinoids
-Nitric Oxide
-substance P
what is the removal mechanism
enzymatic degradation
Glu, GABA, Gly, catecholamines, 5-HT , His are removed by?
reuptake
NTs are removed through?
diffusion, REUPTAKE, into nerve terminals, or glial cells and enzymatic degradation
neuropeptides are removed through?
enzymatic degradation
what kind of vesicle do small molecule transmitters have
small clear core vesicles
what kind of vesicles do peptide transmitters have
large dense core vesicles
location: NMKs
functions: CHOLINERGIC TRANSMISSION AT NMJs and ganglionic synapses
removal: enzymatic digestion by acetylcholinesterase
AChE
Agonist ligand : nicotine
-receptor type: ionotropic receptor
-function: ligand gated nonselective cation channel
postsynaptic response: fast excitatory
structure: protein complex consisting of 5 subunits
distribution: most cholinergic synapses except those in the brain all in the PNS
nicotinic ACh
Agonist ligand : muscarine
-receptor type: metabotropic receptor
-function: GPCR
postsynaptic response: slow excitatory or inhibitory
structure: SINGLE PROTEIN, 7 helical transmem domains
distribution: most cholinergic synapses in the brain
muscarinic Ach receptor
all GPCRs are a single protein containing ___ transmem domains
7
all ionotropic receptors at fast acting synapses Are comprised of several ___ ___ to form a ligand gated ion channel
receptor subunits
*most important excitatory transmitter
location and function: nearly all excitatory CNS neurons are glutamatergic
*removal: uptake by excitatory amino acid transporters into gilal cells
glutamate
damage or death of neurons caused by excessive release of glutamate + excessive stimulation of the glutamate receptors
excitotoxicity
the cycle of glutamate synthesis from glutamine and glutamate removal between glial cells and presynaptic terminals
-functions: to main an adequate supply of glutamate for synaptic transmission and to terminate postsynaptic glutamate action
glutamate-glutamine cycle
agonist: AMPA
channel type: glutamate gated cation channel for Na+ and K+
post synaptic response: excitatory; EPSCs are large and faster
function: primary mediators of excitatory transmission in the brain
structural properties: protein complex of 4 subunits
AMPAR
agonist: NMDA
channel type: glutamate gated cation channel for Na, K, Ca**
postsynaptic responseL excitatory EPSCs are smaller, slower and long lasting
function: use ca2+ as a second messenger to activate intracellular signaling cascades mediate some forms of synaptic info storage
structural properties: voltage dependent block of the channel pore by Mg2+: Mg 2+ blocks the NMDAR pore at the hyperpolariation while postsynaptic depolarization pushed Mg2+ out of the pore opening of NMDARs require co-presence of glutamate and postsynaptic depolarization**
NMDAR
both AMPAR and NMDAR are comprised of ___ protein subunits. they are tetrameric proteins
4
postsynaptic response:
- slow or
- excitatory or inhibitory
GPCRs: 7 helical membrane spanning domains
metabotropic glutamate receptors
-most inhibitory synapses in CNS use either ____ or ___ as NTs
GABA & Glycine
location: mostly found in local circuit interneurons
____ is found almost exclusively in GABAergic neurons
loading into vesicles: transporter
Removal: uptake by co-transporters in neurons and glia
GABA
GAD___ is found almost exclusively in GABAergic neurons
location and function: distribution is more localized than GABA, half of the inhibitory synapses in spinal cord use ____, most other inhibitory synapses use GABA
loading into vesicles: transporter
removal: uptake by co-transporters in neurons and glia
glycine
GABA receptors are ionotropic or metabotropic?
ionotrobic and are GABA gated anion channels for CL so activation of thees causes an Cl influx and inhibits postsynaptic cells
ionotropic glycine receptors are what
pentamers and ligand gated Cl channels
T/F all catecholamines are derived from a common precursor, threonine
F
TYROSINE
function: coordination of body movements ***
loading into synaptic vesicles: transporters
removal: uptake by Na+ dependent dopamine co transporters (DAT) in neurons and glial cocaine and amphetamine inhibit DAT
-inhibitors of MAO and COMT are antidepressants
receptors: EXCLUSIVELY GCPRS
dopamine
what are the receptors for NE and EPI
alpha and beta adrenergic receptors; both are GPCRs
function: sleep and wakefulness
many antipsychotic drugs act on serotonergic pathway
removal: SERT
many antidepressant drugs are SSRIs or SNRIs
catabolism: MAO
receptors: implicated in emotions
receptors
all synaptic vesicles contain ATP, which is co-released with ___ NTs
classical
P2X receptors are trimeric and nonselective caption channels mediating excitatory postsynaptic responses
ionotropic purinergic receptors
many peptide transmitters are ___
hormones
functions: modulate emotions
-substance P and the opioid peptides are involved in the pain perception
removal: enzymatic degradation
receptors: virtually all peptide receptors are GPCRs
peptide NTs
propertied precursors can give rise to more than one species of attic neuropeptides and multiple active peptides can be released rom a single vesicle therefore peptidergic synapses often elicit ___ ____ responses
complex postsynaptic
-Brain and gut peptides
-coney pain and temp info of C fiber in PNS
-its release can be inhibited by opioid peptides thus the suppression of pain by opioid
substance P
endogenous compounds that mimicked the actions of morphine
endorphins
bind to postsynaptic receptors activated by opium
3 classes: endorphins, enkephalins, and dynorphins
function: depressants
opioid peptides
ability of synapses to strengthen or weaken synaptic transmission in response to neural activity over time
synaptic plasticity
changes last for a few mins or less
short term synaptic plasticity
increased synaptic strength due to enhanced NT release: _____ ____ ____ ____
synaptic facilitation, augmentation, and potentiation
changes last for more than 30 mins or longer
long term synaptic plasticity
long lasting increase (strengthening) of a synaptic strength induced by a brief (few secs) continue high frequency patterned stimulus eating hours or days
increased synaptic strength due to **increased AMAP receptors it the postsynaptic cell surface
long term potentiation (LTP)
decreased synaptic strength due to **reduced AMAP receptors in the postsynaptic cell surface
*induced by longer (10-15) mins continue low frequency patterned stimulus
long term depression (LTD)
rapid increase in synaptic strength that occurs when 2 or more action potentials invade the presynaptic terminal within a few milli secs of each other
duration: lasts for ten of millisecond
mechanism: calcium builds up by several action potentials arriving close together in time – prolonged elevation of presynaptic calcium levels –> more NTs to be released by subsequent presynaptic action potential
synaptic facilitation
rapid decrease in synaptic strength during sustained synaptic activity
duration: hundreds of millisecond
mechanism: depletion of the readily releasable pool (RRP) of synaptic vesicles –> declined NT release
synaptic depression
after synaptic activity, increase in synaptic strength over LONGER TIME SCALE than synaptic facilitation
duration: few secs and potentiation acts over tens of secs to mins
synaptic augmentation and potentiation
elevation of presynaptic calcium levels –> increased NT release
mechanism of augmentation + potentiation
an increase in the synaptic strength of a given stimulus at a given synapse after a tetanic stimulus
Post tetanic potentiation (PTP)
drank the duration of short term synaptic plasticity
facilitation < augmentation = depression < Potentiation
precess that causes the animal to become less responsive to treated occurrences of a stimulus
habituation
process that allows an animal to generalize an aversive response elicited by a noxious stimulus to a variety of other non noxious stimulus
sensitization
how do you have a bit long term
increase protein phosphorylation (post translational modification)
how do you have long lasting term
increase gene expression and protein synthesis
how do you have short term plasticity
increase calcium conc -> increase calcium binding protein activity to promote vesicle fusion –> Increase transmitter release
LTP occurs only when pre and postsynaptic neurons are active (they both fire action potentials)
coincidence detector
if there is no magnesium will LTP occur?
no
NMDA receptor channel can open only during _______ of the postsynaptic neuron formats normal resting potential plus the binding of ___ to the receptor
depolarization ; glutamate
Ca2+ entry through NMDARs leads to ___
LTP
when LTP is induced by activation of one synapse, it does not occur in other inactive synapse that contact the same neuron
specificity
if one synapse is weakly activate at the same time that a neighboring synapse onto the same cell is strongly activated , both synapses undergo LTP
associativity
induction: brief high frequency stimulation
receptor recruitment: NMDAR
postsynaptic ca3+ signal: large and fast rise
ca2+ action: activate kinases
require gene expression and protein synthesis
LTP
induction: longer low frequency
receptor recruitment: NMDAR
postsynaptic ca3+ signal: small and slow rise
ca2+ action: activate phosphatases
require gene expression and protein synthesis
LTD
what is in common btw hippocampal and cerebellar LTD
REMOVE AMPAR FROM THE SURFACE
AMPAR INTERNALIZATION
what is the difference btw hippocampal and cerebellar LTD
hippocampal:
Ca action: activates PHOSPHATASES & uses NMDAR as coincidence detectors
Cerebellar:
Ca action: activates KINASES
and use mGluR/VCa2+ channels for calcium entry
