Exam 1 Flashcards
What is an electrical synapse and how is it different from a chemical synapse?
In electric synaptic transmission, IONIC CURRENT flows PASSIVELY by diffusion through A PAIR OF GAP JUNCTIONS from presynaptic terminal to post synaptic membrane and directly alter the membrane potential.
VERY RAPID/ CLOSE (few nm) COMMUNICATION
NOT COMPLEX/FLEXIBLE
UNCOMMON in mammalian nervous system
In Chemical synapse, MORE COMMON in mammalian nervous system USE NEUROTRANSMITTERS NO GAP JUNCTION channels Have structural specialization - synaptic vesicles, pre/post synaptic densities LARGER GAP of communication (20-40nm)
How do you determine change in membrane potential for electrical synapse and what directions can electrical synapse go?
Change in V (membrane potential) = I · Rm
SOME electrical synapse - ONE DIRECTION (rectifying- sense voltage differences)- open only when presynaptic terminal is depolarized
MANY electrical synapse - BI-DIRECTIONAL (not-voltage sensitive)
What type of synapse do not allow for much complexity or flexibility in cell to cell communication? Why?
ELECTRICAL SYNAPSE
They do not provide a mechanism for inhibitory synaptic communication
What are the structural features of chemical synapse and their specific functions ?
MITOCHONDRIA - high rate of use of metabolic energy in presynaptic terminal
SYNAPTIC VESICLES- round, sub-cellular organelles found in presynaptic terminal (has many neurotransmitters). Membrane composed of lipid bilateral and integral proteins and transporters
PRE synaptic densities - cluster of proteins where neurotransmitter is released (tethered to filaments which extend from membrane to cytoplasm of presynaptic terminal).
POST synaptic density- neurotransmitter receptors, G-proteins, enzymes, structural proteins
ECM/Basement membrane- at synaptic cleft between pre and postsynaptic plasma membrane. Has AchE that breakdown acetylcholine
The synaptic vesicles in a presynaptic terminal of chemical synapse has a vesicle membrane that contains —
Primary active transporter (H+ -ATPase) - concentrates proton within the vesicle
Proton gradient is used to energize specific neurotransmitter carrier protein ( secondary active transporter)- loads the vesicle with the neurotransmitter
Chemical synapses are found at what 3 different locations on the postsynaptic neuron
axo-dendritic synapses (Shifts and spines)
Axo-somatic synapse (cell body and axon hillock)
Ayo-axonic synapse (pre-synaptic terminal of axon)
What vesicle membrane protein is responsible for mobilization of synaptic vesicles from being bound to cytoskeleton filaments to their release into the active zone of presynaptic terminal? What state is the protein in?
Synapsid
Phosphorylated state (by PKA and CaMK)
Synapsin have high affinity for actin filaments in what sate? Result in what?
low affinity in what state ? Result in what?
High affinity in dephosphorylated state - vesicles for a reserve pool
Synapsin has low affinity for actin filaments in phosphorylated state - result in releasable pool of vesicles mobilized to active zone.
What determines neurotransmitter release ?
High conc of Ca2+ by influx/inward flow
Increased Ca levels - CaMK activated - synapsin phosphorylated - vesicles mobilized from actin cytoskeleton
Name 2 reasons why docking and priming important? What step should this be? What proteins help with this?
1) To position a vesicle at active zone in presynaptic terminal where VGCa channels are located. This reduce delay btw entry of calcium into terminal and elease of neurotransmitter
2) To position vesicle adjacent of plasma membrane. This enables fusion and exocytosis to occur.
Should be first step before mobilization
VSNARE - synaptobrevin
TSNARE - SNAP 25 and syntaxin
soluble/cytoplasmic proteins - regulate snare complex assembly and disassembly
What calcium sensor helps with fusion by influx of Ca binding to it? What happens to this calcium sensor after?
Synaptotgmin
Calcium binding to synaptotagmin increases its lipid solubility which enable synaptotagmin to move into plasma membrane and fuse with the vesicle membrane (stimulate fusion and exocytosis)
2 types of exocytosis/fusion
Kiss and run fusion - fusion pore open briefly and allow vesicle empty its contents (neurotransmitter) into the synaptic cleft but then close after.
Complete fusion- Fusion pore dilate rapidly and completely leading to complete fusion of vesicle and plasma membrane and release of neurotransmitter into the synaptic cleft
What toxins affect neurotransmitter release?
Tetanus toxin - cleave docking and priming proteins and will prevent neurotransmitter release. Active in axon terminal of inhibitory spinal interneurons. Uncontrolled muscle contractions and spasms - start in JAW
Botulism toxin - (active in axon terminal of motor neurons) cleave docking and priming (SNARE) protein, prevent release of Ach to NMJ- cause paralysis, respiratory paralysis in extreme conditions
Animal toxin - Black widow spider has alpha Latrotoxin - axon terminal membrane- stimulate massive release of neurotransmitter - constant painful muscle contractions and cramps
Cone snails - conotoxin- loss of voltage gated calcium channel- failure of neurotransmitter release
Diffusion of neurotransmitter out of synaptic cleft is a slow way to terminate neurotransmitter action? What are faster ways and how does it work?
Re-uptake - High affinity transporter proteins (specific re-uptake carriers and glial cells) - use secondary active transport -sodium dependent cotransport
Degradation - Enzymatic degradation. Eg extracellular enzyme AchE found in synaptic cleft and hydrolysis ACh to choline and acetate
Clathrin and dynamic are used to recycle vesicle membranes by refilling neurotransmitter and returned to reserve pool o release pool. This process is called
Endocytosis
Differentiate between small and large neurotransmitters
SMALL NTs
Low MW,
E.g A.A (Glutamate, GABA), Ach, Biogenic amines (NE), Purines (ATP)
Synthesized and packaged into vesicles within the cytoplasm of NERVE TERMINAL
LARGE NTs
High MW
Neuroactive peptides
Synthesized and packaged into vesicles within the CELL BODY
Which small neurotransmitter is used at the neuromuscular junction? which is used at the ANS (by pre and para postganglionic neurons) and by brain neurons ?
Synthesized by what enzyme?
Precursors for synthesis?
ACh- Acetylcholine
Choline acetyl transferase (ChAT)
Precursors are CHOLINE (from blood) and ACETYL CoA
3 biogenic amines are catecholamines, serotonin and histamine.
What is pathway of catecholamine synthesis? What is the parent precursor ? Enzymes?
Parent precursor of catecholamines is TYROSINE
Tyrosine - dopa (tyrosine hydroxylase)
Dopa- dopamine (Dopa decarboxylase)
Dopamine - norepinephrine (Dopamine beta hydroxylase)
Norepinephrine - epinephrine (PNMT- methyl transferase)
Dopamine (expressed in substantia Nigra and ventral tegment - project in striatum, amyygdala and frontal cortex
NE - locus ceruleus CNS
Epinephrine- Adrenal medulla (express all enzymes)
3 biogenic amines are catecholamines, serotonin and histamine.
What is the precursor for serotonin synthesis ?
Enzyme?
Where are serotonergic neurons found?
TRYPTOPHAN - 5-HTP (Tryptophan hydroxylase)
5-HTP - Sertonin (5HT) by 5-HTP decarboxylase
2 step process
Serotonergic neuron found in raphe nuclei of brain stem- axons project to CNS
3 biogenic amines are catecholamines, serotonin and histamine
What is the precursor of histamine?
What enzyme?
Functions?
Histidine - Histamine (Histidine decarboxylase)
Synthesized n some neurons of the hypothalamus
Function as neurotransmitter and signaling molecule
3 A.A used as neurotransmitters are glycine, glutamate and GABA.
What are their roles? Inhibitory vs excitatory and what pat of body?
Precursor and enzyme of GABA synthesis?
Glycine- main inhibitory NT in spinal cord
Glutamate - main excitatory NT in CNS
GABA- main inhibitory NT in brain.
Glutamate - GABA ( glutamic acid decarboxylase)
ATP (a small NT) is degraded into what by ecto-nucleotides? This product can them accumulate into the extracellular space as a result of intracellular ATP hydrolysis. What is the function of this product?
Adenosine.
Extracellular adenosine is a signaling molecule that alter neuronal function
Small NT Nitric Oxide (NO) is synthesized by what?
Enzyme?
Is NO stored in vesicles? Why/Why not?
What is the target/receptor of NO
NOS- calcium - Calmodulin dependent
NO is not stored in vesicles because it is a gas and can diffuse out of the cell . It Is produced when calcium flows into the axon terminal during A.P
Receptor is soluble/cytotoxic guanylyl Cyclase - stimulate GTP- cGMP - activate PKG protein kinase - phosphorylated synapsin.
Differentiate between ionotropic and metabotropic receptors
IONOTROPIC/ DIRECT receptors Receptor DIRECTLY gates an ion channel MORE RAPID synaptic transmission Exist for many small molecule transmitters like Ach, glutamate, glycine Has modulating site for other functions
METABOTROPIC/ INDIRECT G-protein coupled receptors
Receptor indirectly regulates an effector molecule which could be ion channel or enzyme through a G protein.
Postsynaptic potentials are SLOWER
Affect ENZYME ACTIVITY (Adenylyl cyclase and PLC) in addition to ion channel
WHat are the basic receptor types and mechanism for Ach - ACETYLCHOLINE Glutamate GABA (a and b) Glycine
ACETYLCHOLINE
Nicotinic -(ionotropic receptor) -directly open cation channels (Na and K)
Muscarinic (metabotropic M1,M3,M5) - stimulate PLC, close K channels
Muscarinic (metabotropic M2, M4)- inhibit Adenylyl Cyclase, open K channels, inhibit Ca channel opening
WHat are the basic receptor types and mechanism for Ach GLUTAMATE GABA (a and b) Glycine
GLUTAMATE Ionotropic receptors (KA,AMPA, NMDA) - directly open cation channels (Na/K or Na/K/Ca)
Group 1 metabotropic - stimulate PLC
Group 2 and 3 metabotropic - inhibit AC
WHat are the basic receptor types and mechanism for Ach Glutamate GABA (a and b)- GABA a/b Glycine
GABA A
Ionotropic
Directly open CL- channels
GABA B
Metabotropic
Open K+ channels, inhibit Ca2+ channel opening
WHat are the basic receptor types and mechanism for Ach Glutamate GABA (a and b) GLYCINE
GLYCINE
GlyR; Ionotropic
Directly open Cl- channels
The post synaptic response that increase the probability of action potential firing in pot synaptic neuron is called —
Excitatory postsynaptic potential (EPSP)
Depolarize the postsynaptic cel membrane potential towards the threats hold for opening of voltage gated Na+ channels
The change in the postsynaptic ion permeability that DECREASES the probability of action potential firing is called —
Inhibitory postsynaptic potential (IPSP)
Synaptic current flow hyperpolarize the postsynaptic membrane. IPSP can also result from ion permeability changes that reduce ability of cell to reach threshold
How do ionotropic receptors permeable to both Na+ and K+ generate conductance increase EPSPs
The driving force is 5-6times greater for Na+ thank K+ .
Inward Na+ current is several times greater than outward K+ current. This will DEPOLARIZE the neuron.
For depolarization to be excitatory, the equilibrium potential for current flow must drive AP to threshold i.e toward positive. In this case it is -1 (close to 0mV)
What are common ionotropic receptor types that mediate conductance increase EPSPs.
Where are they found?
Nicotine Ach receptors - found at NMJ (initiate muscle A.P which cause muscle contraction), also found in ANS and some synapses in CNS
Ionotropic glutamate receptors - tetramers found at excitatory synapses of brain (marinate, AMPA, NMDA)
***NMDA is permeable to Ca2+ in addition to Na, and K.
The amplitude and direction of the total synaptic current (Isyn) depends on what 2 factors
The NET DRIVING FORCE (difference btw cell membrane potential and synaptic equilibrium potential)
SYNAPTIC CONDUCTANCE (gsyn- directly proportional to the number of open channels)
Isyn = (Vm - Esyn) · gsyn
Synaptic potential Vsyn is dependent of 2 factors?
Vsyn = Isyn · Rm
SYNAPTIC CURRENT
And
RESISTANCE of cell membrane
The lag between the peak of the synaptic current and the peak of the synaptic potential is due to what?
Membrane time constant
Measure of the amount of time required to rearrange the charge in the cell membrane
How do metabotropic (e.g muscarinic Ach) receptors which decrease resting K+ channels generate conductance decrease EPSPs?
By decreasing the resting leak potassium permeability (normally the leak channels are open and contribute to negative resting membrane potential). This removes the hyperpolarizing influence allowing the membrane potential to depolarize.
How do metabotropic receptors which increase the resting K+ conductance generate conductance INCREASES IPSPs. (2 ways)
INDIRECT GATING OF K+ CHANNELS
E.g GABA b and muscarinic Ach receptors.
Activate G-protein which In turn open K+ channels which hyperpolarize the neuron lead to postsynaptic neuron INHIBITION
DIRECT GATING OF Cl- CHANNELS
E.g Glycine and GABA A receptors (multimeric)
Cause opening of the Cl- permeable ion channels which will stabilize the membrane potential and reduce ability of cell to depolarize. (Equilibrium potential of Cl must be less/negative to action potential threshold)
How does ionotropic receptors permeable to Cl- generate conductance increase IPSPs
As long as ECl is negative to the action potential threshold, a postsynaptic response generated by glycine or GABA a receptors will be inhibitory.
How does conductance decrease IPSPs
Closure of cation permeable leak channels
Very UNCOMMON
How does LENGTH constant affect dendritic integration through SPATIAL summation
Many neurons of CNS e.g pyramidal cell has large dendritic tree and short length constant. For this, there has to be simultaneous activation of SEVERAL excitatory synapses in order to depolarize the axon to threshold.
The LENGTH CONSTANT determines the the degree to their is SPATIAL SUMMATION to create action potential .
How does TIME constant affect dendritic integration through TEMPORAL summation
The time constant of a neuron determines the speed with which a synaptic current can change the postsynaptic membrane potential.
Short time constant- allow membrane potential to change rapidly but can cause potential to decay back to resting level once current stop flowing
Long time constant - membrane potential not changing rapidly but can persist for a longer period even after the flow of current ends
In temporal summation, same synapse is activated more than once with short period of time, DEGREE OF TEMPORAL SUMMATION DEPEND ON TIME CONSTANT
What happens when both the excitatory and inhibitory synapses are simultaneously active
EPSP and IPSP will add together to affect the membrane potential at the axon
If 2 synaptic potentials are equal and opposite = NO CHANGE in membrane potential will occur.
Neuron will only fire an A.P when the result of the spatial and temporal integration depolarize the axon to threshold
Distant synapse from the axon will have what effect compared to the proximal synapse
Weaker
Presynaptic receptors found on presynaptic axon terminal membrane.
Name the synapses?
Effect of the synapses to neurotransmitter release?
Which effect is more common? What mechanisms/receptors?
Axo-axonic synapses
Facilitate or Inhibit neurotransmitter release.
Inhibition is more common - involves metabotropic GPCR. Which either :
Open K+ channels or inhibit Ca2+ channels from opening
How do autoreceptors of presynaptic receptors function?
They are similar to the inhibitory presynaptic receptors but do not require an axo-axonic synapse. Instead, they are activated by transmitter released from their own terminal.
Negative feedback - Inhibit the release of neurotransmitter
Numerous proteins inside cell can be substrates for protein kinases ad neurotransmitter- stimulated phosphorylation of these proteins can alter cell function but cause NO CHANGE to membrane potential. This type of alteration is called —
Neuromodulation
Spillover of neurotransmitters like NO to non-synaptic extracellular space result in swelling/varicosities. Release of the ranks titer has a diffuse effect on many different cells. This type of signaling is called —
Volume transmission
In infancy (0-1 year) Which senses is the most developed? Which is the least developed?
Touch
Vision
Social smile develop by what age
1-2 months
When do children begin toilet training? When do they have it mastered?
Begin at toddlerhood (1-3)
Mastered by Pre-school (3-6 yrs)
Conservation is mastered at what stage of development
School age (6-11 yrs)
The vertebral column is the core of the body. Name 4 important functions of the vertebral column?
1) SUPPORT BODY WEIGHT - transmit weight to pelvis and lower limb
2) HOUSES AND PROTECTS SPINAL CORD- spinal nerves leave cord btw vertebrae
3) PERMITS MOVEMENT - clinical problems can result from this - back/spine problems
4) PROVIDES FOR MUSCLE ATTACHMENT- muscles of back, head, neck, upper extremity, thorax.
What is the second most common cause of disability? What function of vertebral column is responsible for this? What is the first cause of disability?
Back and spine problems is second cause of disability
Vertebral column permits movement
Arthritis is first cause of disability
Match the anatomical positions
1) toward midline
2) away from midline
3) front of body (2 names)
4) Back of body (2 names)
5) toward top of head (2 names)
6) toward bottom of feet (2)
1) Medial
2) Lateral
3) Anterior/ventral (NOSE IS ANTERIOR)
4) Posterior/Dorsal
5) Superior/Rostral
6) Inferior/caudal
Name the anatomical positions
7) closer to trunk or origin of structure
8) away from trunk
9) palm side (2)
10) back side of hand
11) top of foot
12) sole of foot
7) Proximal
8) Distal
9) Palmar/ volar surface
10) Dorsal surface of hand
11) Dorsal side of foot
12) Plantar surface of foot
Match the 3 anatomical planes
1) Divides the body in RIGHT and LEFT parts? Right and left halves
2) Transverse plane/ Cross section - divides body into TOP and BOTTOM parts perpendicular to long axis of body
3) Divides body into FRONT and BACK parts
1) SAGITTAL PLANE /Median SAGITTAL Plane
2) HORIZONTAL PLANE
3) CORONAL PLANE
Spinal nerves leave vertebral canal via —
INTERVETEBRAL FORAMINA - btw pedicles of vertebral arch bordered by superior and inferior vertebral notches
5 parts of a typical vertebra (thoracic by convention)
1) Body (anterior position, transmits body weight)
2) Vertebral arch - pedicles and lamina
3) Spinous and Transverse processes (posterior and lateral projections from arch for muscle and ligament attachment)
4) Intervertebral foremen (spinal nerves leave vertebral canal from here)
5) Superior and Inferior articulation process/facets (orientation determines movement btw vertebra)
5 regions of Vertebral column and the location and number of vertebra for each.
1) CERVICAL (neck) 7 vertebrae C1-C7
2) THORACIC (Chest) 12 V. T1-T12
3) LUMBAR (lower back) 5. V L1-L5
4) SACRAL (pelvis) 5 fused vertebrae S1-S5
5) Coccygeal (Tail) 3-5 V. Co1-Co3
Name the vertebral type Has Foramen Transversarium Bifid/divided spinous processes Articulate facets angles superiorly and medically (for flex-extend, lateral flex and rotate movements) Small bodies Most mobile
CERVICAL VERTEBRA
Different between C1 (Atlas), C2 (Axis) and C7 of Cervical Vertebra
C1- Atlas
- No body/only ring of bone
- Anterior and posterior arch with bumps (tubercles)
- Superior articulate facet- flex-ext (head nod/say YES)
C2- Axis
Odontoid process/DENS
PIVOT joint -rotation- say NO- hanging
C7- Vertebra prominens
Small foramina transversaria
Spinous process -long NOT BIFID - PALPABLE
Which cervical vertebra transmit only vertebral veins and not artery? Why? Which transmit artery?
C7- vertebra prominens
Has small foramina transversaria
C1-C6- transmit vertebra artery
Name the vertebrae
-BODY- Heart shaped
-COSTAL FACETS for ribs on - body (facet for heads of ribs) and Transverse process (facet for articulate tubercles of ribs)
-Spines of thoracic vertebra -long and inclined posterior and inferior
-CORONAL PLANE- Articular process oriented here
-Articular process in coronal plane cause NO FLEX, EXTEND, SMALL ROTATION
LEAST MOBILE (House heart and lungs)
THORACIC VERTEBRA
Name the vertebrae
- HEFTY/LARGE body
- Stout pedicles, thick lamina, broad spinous process
- Articular process in SAGITTAL PLANE
- can FLEX-EXTEND , NO ROTATION
- help you tie you shoes
LUMBAR VERTEBRA
Name the vertebra
-5 fused Vertebra
-Anterior and posterior sacral foramina - intervetebral foramina
-Medial crest- fused spinous process
Sacro-lliac joint- transmit weight from vertebrae to pelvis (innominate bone)
-NORMALLY NO MOVEMENT
SACRUM/ SACRAL VERTEBRA
Name the Vertebra
3-5 fused vertebrae
RUDIMENTARY TAIL BONES
NO MOVEMENT
COCCYX
Coccygeal vertebra
