neuronal structure and signaling Flashcards
neurons make up what % of CNS cells
10%
do neurons divide or differentiate?
no…terminally differentiated/non dividing
what is the exception to the non-dividing property of neurons
hippocampus neurogenesis (here there is learning and memory which requires continual replenishing of neurons)
the soma contains…
the nucleus (where protein synthesis occurs)
dendrite is the…
major INPUT process. graded potentials occur here.
the axon is the…
OUTPUT process for signalling
axon hillock is where
a.ps start…also called the initial segment
axon terminals are where
vesicles are stored
afferent neurons
are sensory/input neurons that send info to the CNS
afferent neuron cell bodies are located
OUTSIDE the CNS and are called GANGLIA
efferent neurons
are motor/output neurons that send infor to effector cells in the periphery
efferent neuron cell bodies are located
WITHIN the CNS (and project to outside of it)
interneurons
are located WITHIN the CNS and fn as integrators/switches
glial cells make up what % of cells in the CNS
90%
can glial cells undergo cell division
yes
glial cells in the CNS are called
oligodendrocytes
glial cells in the PNS are called
schwann cells
microglia are
phagocytic cells that are in the CNS
astrocytes
cells in the CNS that regulate the ecf (buffering role) and provide neurons metabolically (food) and surround the brain capillaries (forming the blood brain barrier)
schwann cells provide myelin to
one axon (many schwann cells per axon though)
oligodendrocytes provide myelin to
many axons
guillain-barre syndrome
demyelination of peripheral motor axons
unreactive state of microglia
neurons release glycoprotein CD200 to keep microglia (phagocytic cells) unreactive
following neuron injury what rxn takes place between the neuron and microglia
the neuron releases intracellular ATP and induces the motility/chemotaxis of microglial cells (to that area of injury)
movement of materials through axons occur through what component
microtubules w/in the axon
anterograde transport
from cell body to terminal via KINESINS
kinesins are
motor proteins that transport during anterograde transport
retrograde transport
from axon terminal to cell body via DYNEINS
retrograde transport can include the movement of…
growth factors or VIRUSES
herpes virus type I
- transmitted via oral contact
- first, virus transmitted RETROGRADELY to the trigeminal ganglia (and remains LATENT)
- the virus can be activated by fever/sun/stress/trauma/cold and travel ANTEROGRADELY toward the periphery and result in a blister
in infants virus can…
go beyond the trigeminal ganglion and cause encephalitis
damaged CNS neurons
do not regenerate…they “sprout” but never reach their targets
why do sprouted CNS neurons never reach their targets
scar formation
what role do astrocytes have in nerve regeneration
they inhibit it by making chondroitin sulfate proteoglycans
in the PNS, is nerve regeneration possible
yes! some functional recovery can occur which is clinically significant in dental procedures in which nerve injury takes place.
what is the first response (in a timeline) of a nerve to a SEVERE nerve injury
- anterograde degeneration
- terminal degeneration
(peripheral process of neuron lost…approaching the ganglia)
what is wallerian degeneration
anterograde degeneration (from terminal towards the ganglion)
what is transganglionic degeneration
central process of the neuron is lost (plus the ganglia and peripheral process)…this occurs later on in the severe nerve injury
what is transynaptic degeneration
some signal crosses the synapse (where another nerve is synapsing on the one that was injured) to degenerate the adjacent neuron
what is the nerve response to a LESS SEVERE injury
you get both terminal degeneration and anterograde degeneration but also get CHROMATOLYSIS
what is chromatolysis
a physiologic change in which the cell attempts to repair the periphery (via protein synthesis). the cell body swells to have an eccentric nucleus (nucleus pushed to the side?)
what is a schwann cell’s response to regeneration
the cells proliferate and produce LAMININ and NGF
what is the role of laminin in regeneration
schwann cells produce this as a substrate for regenerating axons to grow on
what is the role of NGF
nerve growth factor is secreted by schwann cells and is transported to the ganglion cell body of the adj non-injured nerve (retrograde). here it regulates gene expression and promotes the sprouting of the axons
NGF regulates the gene expression of what
- microtubules/microfilaments (for nerve axon structure)
- n.t
- ion channels
- n.t receptors
collateral sprouting
schwann cells release NGF which is retrogradely transported to nerve adj to injured neuron (?) and causes “collateral sprouts” to branch off towards the area of lost innervation
the older the patient (of nerve injury) the…
less transmedian regeneration/sprouting. negative correlation of age and recovery of function
synaptotagmin
a Ca2+ sensitive docking protein used for vesicle fusion and release in presynaptic neuron (Ca must have entered the axon terminal in order for this to occur)
4 ways what n.t can diffused
- uptake by astrocytes
- diffuse from synaptic cleft
- enzymes in synaptic cleft can degrade the n.t
- reuptake by the presynaptic neuron
synaptic integration
interactions b/w inputs on a neuron influence whether or not there will be an output/a.p by that neuron
temporal summation
adding together of PSP’s from one synaptic contact over time
spacial summation
adding together of PSP’s produced by different synpases
what is a classical neurotransmitter
used for rapid communication (msec)…they act on the postsynaptic cell to produce an excitatory or inhibitory effect
what are neuromodulators
can be co-released with n.ts. can amplify or dampen the synaptic activity. also can act on the presynaptic cell to alter the synthesis/release/uptake/metabolism of n.ts. the actions that they cause occur much slower than n.ts (min to days)
acetylcholine is synthesized by
choline and acetyl co-A
what enzyme makes acetylcholine
choline acetyletransferase
what enzyme stops the action of Ach
acetylcholinesterase diffuses/degrades Ach
what is another way for Ach action to stop
reuptake of choline by presynaptic neuron
what neurons release ACh
- all motor neurons
- those in nucleus basalis and pons
- pregang symp and psymp
- all postgang psymp
what is the ACh receptor type in the CNS
muscarinic receptor…EXCEPT postgang psymp (PNS)
muscarinic ACh mechanism
ACh binds and (INDIRECTLY) causes g protein activation to open or close ion channels
muscarinic receptors are blocked by
atropine
what is the ACh receptor type in the PNS
nicotinic receptors (not many in the CNS)
nicotinic ACh mechanism
ACh binds and DIRECTLY opens the ion channels (channel located in the ACh receptor)
ACh nicotinic receptors are blocked by
curare (like at the neuromuscular jn)
ACh neurons in the nucleus basalis/basal forebrain are for
cognitive fn
ACh neurons in the pontine nuclei are for
sleep regulation
myasthenia gravis
autoimmune disorder. ab made that target nicotinic receptors (ACh receptors). muscle weakness (neuromuscular jn).
myasthenia gravis is treated with
acetylcholinesterase inhibitors to prolong the effect of ACh
alzheimers disease and ACh
loss of neurons in nucleus basalis (which has Ach neurons) which leads to a decrease in cholinergic/Ach activity in cortex (CNS)….can’t be treated by actyl cholinesterase.
biogenic amines are synthesized from
a.a…they include the catecholamines, serotonin, and histamine
catecholamines include
dopamine, norepinephrine, and epinephrine
catecholamines are synthesized from
a.a, tyrosine
catecholamine release is dependent on
Ca2+
termination of catecholamine action is through
- presyntaptic reuptake
2. degradation by MAO (monoamine oxidase)
neurons for biogenic amines are found
in very limited locations
receptors for biogenic amines are found
extensively in the CNS
receptors for biogenic amines are
exclusively G-protein couples receptors
dopamine neurons are found in the
- ventral tegmental area
2. substantia nigra
in the VTA, dopamine is associated with
reward and addiction
cocaine and amphetamine do what
prolong dopamine action at the synapse in the VTA
in the substantia nigra, dopamine is associated with
the motor system
loss of dopamine in the S.N results in
parkinson’s disease
D1 vs D2 dopamine receptors
D1: activate adenylate cyclase–>a.p
D2: inhibit a.c–> hyperpolarization
tardive dyskinesia
drugs that block D2 receptors can cause this.. presented as rhythmic oral movements.
norepinephrine neurons are found
- locus ceruleus
2. brainstem
norepinephrine neurons in the locus ceruleus are responsible for
attention and sleep
norepinephrine neurons in the brainstem are responsible for
autonomic/homeostatic fns
norepinephrine neurons include
postgang symp
noepinephrine receptor type
noradrenergic (alpha and beta types)….g-protein coupled
alpha NE receptors
type 1: release Ca=excitatory
type 2: open K channels/block Ca=inhibitory
beta NE receptors
open Ca channels
depending on receptor, NE effects are
very different
serotonin is synthesized from
tryptophan
serotonin neurons are located in
- rostral raphe nuclei
2. caudal raphe nuclei
serotonin neurons in the rostal raphe nuclei are responsible for
sleep, mood, homeostasis
serotonin neurons in the caudal raphe nuclei are responsible for
sensori-motor fn
histamine is synthesized from
histadine (a.a)
histamine neurons are found
small pop. of hypothalamic neurons
histamine is responsible for
sleep-wakefullness
histamine receptors are
g-protein coupled (H1-H4)
what are the EXCITATORY amino acid n.ts
glutamate and aspartate
excitatory a.a n.ts bind to what kind of receptors
ionotropic receptors and metabotropic receptors
ionotropic receptors for the excitatory a.a n.ts have channels that….
are permeable to cations (which allow for a depolarizing/excitatory effect): Na, K, Ca
metatropic receptors are
g-protein coupled
the NMDA receptor is what kind of receptor
ionotropic
properties of NMDA receptors
- involved in fns that last
- can be responsible for excitotoxicity (excessive excitation)
the NMDA receptor is the synaptic mechanism for
long term potentiation
what is long term potentiation (LTP)
- before the LTP the stimulus is subthreshold
- tetanic stimulation of a neuron occurs (high fq of stimulation of a neuron) causes…
- an LTP…which is a long lasting increase in excitatory receptors in the post synaptic membrane and sensitivity of those receptors/cell to the excitatory n.t
describe NMDA receptor mediated potentiation
- high fq a.p at presynaptic terminal
- glutamate (excitatory a.a) is released into cleft
- glutamate binds to both the AMPA receptor and NMDA receptor
- glutamate + AMPA-r= Na entry and post synaptic depolarization
- post synaptic depolarization causes the extracellular Mg-block to be RELEASED from the NMDA receptor allowing Ca INTO the postsynaptic cell through the NMDA receptor
- Ca that has just flowed into the postsynaptic cell activates 2nd messenger systems
- this cascade eventually causes the long term potentiation (or long lasting increase in glutamate receptors in the post synaptic cell and sensitivity to glutamate)
- this cascade (2nd messenger system) can also synthesize molecules that can be transported RETROGRADE to the presynaptic cell to increase glutamate synthesis
- 7&8 lead to the long lasting increase in signalling b/w these 2 cells
how does phosphorylation of the NMDA receptor influence LTP
phosphorylation permanently removes the Mg block on the NMDA receptor….which allows Ca to flow into the post synaptic cell
how does Ca entry into the post synaptic cell (through the NMDA receptor) effect LTP
allows the second messenger system to be activated which can synthesize NO (nitric oxide). NO can then be retrogradely transported to the presynaptic cell to FACILITATE GLUTAMATE SYNTHESIS AND RELEASE
what is the astrocytes role in the glutamate pathway
reuptake
what is the glutamate reuptake pathway
- glutamate is released
- glutamate binds to the postsynaptic cell
- glutamate uptake by an ASTROCYTE
- the astrocyte converts the glutamate to glutamine
- glutamine is released from the astrocyte into the ecm
- neurons uptake the glutamine
- the neurons can then convert glutamine back to glutamate (to reuse)
what are the inhibitory a.a n.ts
GABA (modified form of glutamate…in the CNS) and glycine
what are the 2 receptors for GABA
- ionotropic receptor (GABA-a)
2. metabotropic receptor (GABA-b)
what channel does the GABA-a receptor open
Cl-…which HYPERPOLARIZES THE CELL
what channel does the GABA-b receptor open
K+….causing K+ to flow out of the cell (down its [ ] gradient) which will HYPERPOLARIZE the cell
huntinton chorea is linked to what deficiency
GABA…since this is an inhibitory n.t, have trouble suppressing inhibitory effects on muscles (uncontrolled excitability) which= motor spasticity
glycine (inhibitory n.t) opens what type of channels
Cl-
the effects of glycine are inhibited by what
strychnine
peptide neuromodulators are typically
released with other n.ts
properties of peptide neuromodulators
- synthesized in stroma and must be transported to be released (which takes more time than with n.ts)
- their actions can last a long time
actions of peptide neuromodulators are terminated by
- proteolysis
2. diffusion
by what is NO synthesized
L-arginine–> NO by nitric oxide synthase
is NO stored in vesicles
nope! its a gas so it freely diffuses across the membrane (doesn’t require a synapse)
NO acts to
modulate other n.t release
-also plays a role in brain fns like LTP
how does ATP act as an n.t
usually excitatory and co-released with other classic n.ts
