Exam 1 Flashcards
1
Q
Nerve vs Tract
A
- Nerve= collection of axons/white matter in the PNS
- Tract= collection of axons/white matter in the CNS
2
Q
Ganglia (ganglia) vs Nucleus (nuclei)
A
- Ganglion= collection of cell bodies in PNS
- Nucleus= collection of cell bodies in CNS
3
Q
Afferent vs Efferent
A
- Aff= coming in toward the brain (sensory)
- Eff= going out/away from the brain (motor)
4
Q
Grey Matter vs White Matter
A
- Grey= cell bodies, dendrites, and axon terminals
- White= axons
5
Q
Central NS vs PNS
A
- Central= Brain and spinal cord
- Peripheral= nerves
6
Q
Divisions of the PNS
A
- Somatic NS
- Autonomic NS
7
Q
Somatic NS
A
- To and from skin, skeletal muscles, and joints
- VOLUNTARY control of movements
- Tactile sensations, pain, and temp
- Can also include involuntary skeletal muscle reflexes
8
Q
Cranial nerves
A
- part of somatic division of PNS
- 12 pairs (L and R)
- Sensory and motor fxns of the head and neck
- Ex: Vagus nerve= travels through thoracic and abdominal cavities
9
Q
Spinal Nerves
A
-Part of the somatic division of the PNS
-31 pairs (L and R)
-MIXED: contain both sensory (dorsal) and motor (ventral) fibers
8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 cocegeal
10
Q
Autonomic NS
A
- To and from visceral organs throughout body
- Involuntary control over heart rate, sweating, digestion etc
- NO VOLUNTARY CONTROL
- Divisions: Sympathetic and Parasympathetic
11
Q
Sympathetic NS
A
- Fight or flight prep
- Uses norepinephrine
- Short 1st order neuron, long 2nd order
12
Q
Parasympathetic NS
A
- Increases metabolic and other resources during “rest and digest”/”feed and breed”
- NTM= ACh
- Long 1st, short second neuron
13
Q
Divisions of the Central Nervous System
A
-Cerebrum, cerebellum, brainstem, spinal cord
14
Q
Spinal Cord
A
- Contained within the vertebral column
- Continuous with brain and peripheral nerves
- Circuits act independently from the brain to produce spinal reflexes
- Roots= contain only efferent/ventral/motor or afferent/sensory/dorsal info
- Spinal nerves=mixed
15
Q
Brain stem
A
- Composed of midbrain, pons, medulla
- Contains= cranial nerve nuclei, sensory afferents, motor efferents, homeostatic regulatory control centers
16
Q
Cerebellum
A
- Motor: postural balance and gait center
- R controls right side of body
- L controls left side of body
17
Q
Diencephalon
A
- Part of cerebrum
- Thalamus= relay system of senses to and from brain
- Hypothalamus-Key center for homeostasis
- –Circadian rhythms, hunger, body temp
18
Q
Telencephalon
A
- Part of the cerebrum
- Cerebral cortex, cerebral white matter, deep grey nuclei
19
Q
Defining features of coronal section of the brain
A
- Superficial grey, middle white, deep grey
- Ventricles= cavity in the brain that contains CSF made by choroid plexus
20
Q
Cerebral Cortex Lobe Organization
A
- Organized by sulci (valleys) and gyri (bumps) on surface
- Afferent and efferent pathways cross (R controls L, L controls R)
21
Q
Deep Grey Nuclei
A
- Part of the telencephalon
- Amygdala, hippocampus, basal ganglia
22
Q
Soma
A
- Cell body of a neuron
- Contains: Nucleus, ribosomes, ER, golgi apparatus, mitochondria
- Extensions from the soma= axon and dendrites
23
Q
Variety of Neuron Shapes
A
- Unipolar= no dendrites, one axon
- Bipolar= 2 projections coming off of cell body
- Pseudounipolar= one axon that branches into collaterals
- Multipolar= multiple dendrites, one axon
24
Q
Communication of sensory neurons, motor neurons, and interneurons
A
-Sensory activated by stimulus, sends info to interneurons, sends info to motor neurons
25
Dendrites
- Receive signals from other neurons/ outside world
- Axons of presyn cell will synapse to dendritic spines of post-syn cells
- Location of NTM receptors
26
Axons
- Specialized to send electrical signals from one of the cell to another
- Myelinated or unmyelinated
- --Gaps btwn myelin sheath= nodes of ranvier
27
Axon Terminals
- Send signal to outside world or another neuron
- Usually axon-dendritic synapse btwn 2 neurons
- --Axon of pre synapses to dendritic spines of post
28
The synapse
- Presynaptic neuron has synaptic vessicles-> contain NTMs
- Postsynaptic neuron has receptors
* Can also be how neurons communicated to non-neuronal tissue= neuromuscular Jon
29
Convergence
-Several presynaptic neurons synapse with one post-synaptic neuron
30
Divergence
-One presynaptic neuron synapses with many postsynaptic neurons
31
Glia
- Structure and support for neurons
1. Astrocytes
2. Microglia
3. Oligodendrocytes
4. Ependymal cells
5. Schwann cells
32
Astrocytes
- CNS
- Maintain chemical and ionic balances in environment surrounding neurons @ nodes or ranvier and @ synapses
- Send signals to surround environment (neuron guidance, survival)
33
Microglia
- Macrophages
- PNS and CNS
- Clean up debris after injury, programmed cell death
* *Many problems if malfunction
34
Oligodendrocytes
- Myelinating glia
- CNS
- Reach out and wrap myelin around axons of multiple neurons
* If damaged, multiple neurons are affected
35
Ependymal Cells
- Line ventricles
| - Produce CSF
36
Schwann Cells
- Myelinating glia
- PNS
- Wrao myelin around axons of a single neurons
- --One neuron has multiple Schwann cells around its axons
37
Determinants of Ion Movement
1. Chemical conc.
2. Electrical conc.
3. Permeability
38
Ion Channels
- Allow for passive flow of ions from high concentrations to low concentrations
- Doesn't require energy
39
Active Transporters
- Actively move ions against their concentration gradient
| - Requires energy
40
Ions in a human neuron
1. Potassium- high inside cell
2. Sodium- high outside cell
3. Chloride- high outside cell
4. Calcium-high outside cell
41
Resting Membrane Potential
- Largely determined by K+ because cell is most permeable to it
- RMP is -65 to -70mV
42
How does a neuron respond to a stimulus?
- Injecting a neg current hyperpolarizes
| - Injecting a pos. current depolarizes relative to size of the current
43
What causes rapid depolarization in the cell?
1. Na+ rushing into cell due to depolarization increasing its permeability in the cell
- --Na+ permeability is zero at rest
44
The flow of ions
- If current is negative- ions flowing into cell
- If current is pos- ions flowing out of cell
* Small depolarizations cause small neg currents followed by small positive currents
- --Once a cell is depolarized, cell will eventually return to resting membrane potential (-65mV)
45
Sodium in the cell
- Sodium is high out of the cell, and likes when the cell is positively charged (~+50mV).
- If given the chance (permeability increase), sodium will flow down it’s concentration gradient, into the cell, bringing it to a depolarized state.
* *Quick depolarization caused by Na+ entering cell
46
Potassium in the cell
- Potassium is high in the cell, and likes when the cell is negatively charged (~-75mV).
- If the cell becomes positively charged, potassium can flow down it’s concentration gradient, out of the cell, and bring the cell back to a negative charge.
* *Delayed depolarization of the cell due to K+ leaving
47
Transmembrane Proteins
- Act as channels
- Composed of multiple subunits
- Selective to specific ions/ has a filter
- Some always open, some only open after a conformation change
1. Potassium leak channels (always open).
2. Voltage-gated sodium channels (only open when the cell is depolarized).
3. Voltage-gated potassium channels (only open when the cell is depolarized).
48
Voltage Gated Na+ Channels
- Composed of 4 subunits
- -Each subunit has 6 transmembrane domains
- Btwn S5 and S6- pore loop
- -Combo of 4 pore loops creates a pore
- -Closed at rest
- S4= voltage sensor
- -When cell is depolarized, channel undergoes conformation change to open pore
49
Voltage Gated K+ channels
- Composed of 4 subunits, where each subunit has 6 transmembrane domains
- -Come together to create a pore (closed at rest)
- Outer edges of each subunit has a voltage sensor domain
- --Voltage sensing wings are positively charged, push away from inside of cell when cell becomes positive
- ----Conformational opens pore
50
Potassium leak channels
- Transmembrane proteins that act as a channel
| - Always open
51
If we open channels at the same time, what happens?
- Futile cycle- nothing happens
| * Kinetics and timing are important
52
In cell's response to depolarization, the order of events are as follows:
1. Depolarization triggers the opening of Na and K channels
2. Na open much faster than K, so cell is more permeable to Na than K at first
3. After a short delay, the Na channels will inactivate-- at the same time K channels open, making cell more permeable to K+
4. Both channels close, returning cell to baseline
53
Sodium Inactivation Gate
1. Triggered by large depolarizations of the cell
2. Ensures that the cell's permeability to Na+ will increase, allowing the cell to become more permeable to K+ and repolarize
3. Ensures that the cell will be able to fire another AP since it can go through depol-repol- circuit again
- Order: Resting (closed), open (active), inactivated (closed)
54
How are action potentials graded?
- Frequency
| - The bigger the stimulus, the more frequent the AP will fire
55
K2.1 and K4.1 channels
- If we depolarize the cell, we see two types of K channels at play
- K2.1- remain open for prolonged time to allow the cell to return to baseline
- K4.1- quickly close so K+ permeability isn't too much for Na+ to overcome if cell wants to fire another AP
56
Phases of an Action Potential
1. Rising Phase – Nav open, Na+ rushing into the cell, causing the cell to become more positive.
2. Overshoot – Nav channels inactivate, Kv channels open (2.1 and 4.1).
3. Falling phase – Nav channels are still inactivated, Kv 4.1 channels close, Kv 2.1 channels stay open.
4. Undershoot – Kv 2.1 channels start to close.
57
What happens when you depolarize an axon?
- When a positive charge comes into the axon, it is surrounded by a negative environment.
- Moves towards more negative environments (think about the electrical gradient here).
- The charge will move down the axon until it reaches the next set of voltage-gated channels to activate.
- At which point fresh charges will come in
58
Role of Myelin
1. Insulate axon, helping charge move down axon faster and further
2. Create nodes where receptors are located so we only have to create a few APs
59
Electric Synapses
- Gap jxns
- 6 connexins combine to create one connexion
- 2 Connexons from each cell combine to create a gap jxn
- Always open, non-selective pore connecting one cell to another
- Communication=Instantaneous, dependent on each other
- Great if you only need the cell to do one thing, not if cell needs to be flexible
60
Chemical synapse
1. Must have chemical (NTM) in stock ready to go to vesicles
| 2. The electrical AP signal must translate into something that can help release the chemical signal
61
Synapsin
-Binds multiple vesicles together in a reserve pool
62
CaMKII
- Dissociates vesicles from synapsin
| - Allows vesicles to move toward the membrane
63
Vesicles moving toward the membrane
- Once free from reserve pool, individual vesicles can move toward the membrane associate w it
- Association accomplished by SNARE proteins
64
SNARE proteins
- Involved in the fusion of the vesicles w/ the membrane
- V-SNARE: Vesicle SNARE
- --Synaptobrevin and Synaptotagmin
- T-SNAREs= target SNARE
- -Snap-25 and Syntaxin
65
Ca2+ Mediated Vesicle Release
1. When the vesicle reaches the membrane. synaptobrevin will bind to Syntaxin and SNAP-25, holding the vesicle in place
2. Synaptotagmin binds to complex
3. Ca2+ comes in via voltage-gated Ca2+ channels, binds to synaptotagmin
4. Synaptotagmin associates with other SNAREs, the complex pulls the vesicle towards the membrane, causing it to fuse
66
Voltage-Gated Calcium Channels
- When an action potential reaches the axon terminal, it will open Ca2+ channels
- By this time, SNARE complex has already formed, Ca2+ just needs to bind to synaptotagmin in order to twist the complex
- Calcium is only involved in exocytosis of vesicles, not vesicle priming
67
What happens when if Calcium doesn't enter the cell after an AP is fired?
-NTMs cannot be released
68
Vesicle recycling
- Clathrin= pulls vesicles back into the cell
- --Triskeleton shape creates a sphere as more proteins associate with each other--> reforms the shape of the vesicle from the flat surface
- Dynamin- designed to pinch off the vesicle sphere created by clathrin
* Once off the membrane, the vesicle sheds the clathrin
69
When do vesicles go when recycled?
- The endosome
- "Refurbishing center" for vesicles
- Makes sure vesicles are functional, have all their proteins, etc
- Fresh vesicles bud off this, are refilled, and bind back to membrane
- Filling is done via diff proteins depending on the NTM
70
Classes of Neurotransmitters
- Small molecule
| - Peptides/Neuropeptides
71
Small Molecule Neurotransmitters
- Composed of 1 AA or a small number of molecules
| - ACh, AAs, purines, amines
72
Peptides/Neuropeptides
- Larger and composed of 3-36 AAs
| - Enkephalin, substance P
73
General life cycle of NTMs
1. Synthesis
2. Packaging
3. Release
4. Binding
5. Clearing--> transport & degradation
74
Vesicle Transporters vs Transporters
- VTs= proteins that put NTMs into vesicles
| - Transporters- proteins that bring NT or substrates into presynaptic cell and/or glia
75
Transporters
- Tend to be cotransporters
| - Use an ions gradient to push a second molecule againat its gradient
76
Amino Acids
- Glutamate (stems from glutamine)
- GABA (Stems from glutamine)
- Glycine (stems from serine)
77
Glutamate
- Primary excitatory NTM in CNS
- --Found almost everywhere
- Taken up by EAAT into--> presynaptic neuron and glia cells
- Broken down into glutamine before next use
78
GABA
- Considered the main inhibitory NTM in brain
- --Popular among small interneurons
- Composes almost all inhibitory synapses in the brain and 1/2 in the spinal cord
- Taken up by GAT in glial and presynaptic cells
79
Glycine
- One of the other primary inhibitory NTMs in the brain
- --Popular among small interneurons in SC
- Mostly found in SC
- Taken up by GT in glial and presynaptic cells
80
Acetylcholine
- Provides a variety of fxns in brain and body
- -Brain= attention networks
- -Body= muscle, autonomic
- Broken down in cleft by Acetylcholinesterase
- --Acetate+ choline
- Choline is taken back up into presynaptic cell
81
Catecholamines
- Tyrosine is a precursor to all
- Order:
1. Dopamine
2. Norepinephrine
3. Epinephrine
82
Dopamine
- Involved w/ reward-related processes and motor control
- Ventral segmental area= projects into frontal cortex; reward processing
- Substantia nigra= projects into basal ganglia for motor control
83
Norepinephrine
- Can be released as NTM or hormone
- Produced in Locus Coeruleus in brain, adrenal glands in body
- Seen used in sympathetic NS
84
Epinephrine
- Released as NTM or hormone
- Produced in medulla in brain, adrenal glands in body
- Used in autonomic NS
85
Clearance of Catecholamines
- Taken up by neurons and glia by transporters and then broken down OR just broken down in cleft
- Broken down via
1. COMT
2. MAO
86
Histamine
- Amine
- Fxns: sleep/wake cycle, vasodilation, BP regulation
- Used as a NTM and immune cell
- Produced by tuberomammilary nucleus (NTM only)
87
Serotonin
- Amine
- Fxn= mood-regulating NTM
- --Prefrontal and limbic projections
- Produced by raphe nucleus
- Reuptake by serotonin transporter
88
Signaling pathway
- Signaling cell--> signal--> receptor--> effector molecule--> response
* *We want signal to be amplified
89
Activation of Signaling Pathways
1. Cell-impermeant molecules
2. Cell-permeant molecules
3. Cell-associated molecules
90
Receptor activation
1. Binding of substance to the receptor that causes a change in the receptor
2. Intracellular signaling that is caused by binding of the receptor
- -Can be an increase in ions, cascade of proteins that lead to more pronounced cellular changes, or both
91
Categories of Receptors
1. Channel-Linked receptors
2. Enzyme-linked receptors
3. G-Protein coupled receptors
4. Intracellular receptors
92
Channel-Linked Receptors
- Ionotropic
- Protein(s) make a channel that is closed in resting state
- When ligand binds to binding domain, undergoes conformational change, allowing channel to open
93
Example of Channel-Linked Proteins
- Amphiphatic-Tunnel Transmembrane Proteins
- Multiple subunits passing the membrane, 4+ of which are amphipathic (hydrophobic & hydrophilic)
- In an amphiphatic helix- one side of cylinder is lipophilic, and other is hydrophilic
- --Concentric hydrophilic sides create a tunnel through the membrane
94
Enzyme-Linked Receptors
- The receptor is an enzyme that causes a change in something else on inside of cell
- Not allowing anything to pass through, doesn't need another protein for activation
- Ex: Tyrosine Kinase
95
Structure of Enzyme-Linked Receptors
- Extracellular binding domain
- Intracellular kinase domain
- Dimerizes to become functional
- When activated, the kinase domain can phosphorylate itself and other proteins, leading to intracellular signaling
96
G-protein Coupled Receptors
- Metabotropic receptors
- G-protein is NOT part of the receptor
- G-protein= Guanine nucleotide binding protein
- --If GTP= active, if GDP= inactive
- 7-pass/ serpentine proteins= common
- No pore, undergoes conformational change upon ligand binding on extracellular side, leading to changes inside the cell
- Changes cause G-protein associated w/ receptor to become activated
97
Heterotrimeric G-Proteins
- G-protein consists of 3 subunits
- --Alpha, beta, and gamma
- Alpha binds to guanine-based nucleotide
- --GDP-> Allows alpha to associate w/ beta and gamma in inactive form
- -GTP--> Alpha dissociated from beta and gamma, activating 2nd messenger protein(s)
98
How Heterotrimeric G-Proteins Work
- When a ligand binds to the receptor, GDP+ alpha, beta, gamma trimer bind to receptor
- Trimer binding to receptor causes alpha to exchange GDP for GTP, which initiates the dissociation of alpha from beta and gamma
- Alpha goes on to activate a 2nd messenger protein
- --Beta and gamma can do the same
99
Monomeric G-Proteins
- G-protein= Ras
- Bound to the receptor is an adaptor protein + a GEF
- --GEF= Guanine Nucleotide Exchange Factor
- When ligand binds to the receptor, it activated GEF, which exchanges GDP to GTP on the G-protein, activating the G-protein
100
Regulating G-Protein Activity
- When a ligand binds to GPCR, it activates a G-protein
- --Mechanism accomplished by exchange of GDP for GTP
- To stop the activity of the G-protien, we must hydrolyze GTP back to GDP
- --Done using GAPs
101
Intracellular Receptors
- Activated by cell-permeant (lipophilic) molecules
- Found in the cytoplasm and nucleus
- Lead to production of new mRNA and protein within the target cell
- Bound to inhibitory protein in its inactive state
- --Once activated, inhibitory protein dissociates to exposE DNA-binding domain
102
Order of events after G-Protein Activation
-Another "effector protein" is activated--> increase in 2nd messenger---> activates later effectors--> acts on targets
103
If alpha activates nucleotide cyclases...
1. NTM binds, causing G-protein to exchange GDP for GTp, and alpha dissociates (G-protein)
2. Alpha goes over and activates adenylyl cyclase or guanalyl cyclase (Effector protein)
3. The cyclase creates cyclic AMP from ATP, or cGMP from GTP (2nd messenger)
4. Go on to bind to and activate PKA (if cAMP) or PKG (if cGMP) (Later effectors)
104
If alpha activates phospholipase C
1. NTM binds, causing G-Protein to exchange GDP for GTP, and alpha dissociates (G-Protein)
2. Alpha activates phospholipase C (Effectors)
3. Phospholipase C cleaves PIP2 into DAG and IP3 (2nd messenger)
4. DAG activates PKC, IP3 binds to Ca2+ channels (DAG=late effectors, not IP3)
105
Gs
- Stimulates
| - Activates either adenylyl cyclase or guanalyl cyclase pathway
106
Gi
- Inhibitory
| - Inhibits adenylyl cyclase or guanalyl cyclase pathway
107
Gq
-Activates phospholipase pathway
108
How does the alpha subunit know which pathway to activate?
- GPCRs, along with their different neurotransmitters, can activate multiple different pathways.
- Gs vs Gi vs Gq
109
Tyrosine Kinase signaling
- Involved in nerve growth factor signaling
- When NGF binds to TrkA, the tyrosine kinase domains on intracellular space will cross-phosphorylate
- Phosphorylated tails act as enzymes to activate other proteins inside the cell
- Important pathways: phospholipase C, RAS
110
Tyrosine Kinase PLC pathway
-Same as Phospholipase C pathway
111
Tyrosine Kinase RAS pathway
- Similar to monomeric G-protein pathways
- G-protein= RAS
- RAS (through a number of steps), is going to activate MAPK
- MAPK is an important protein for gene modifications
112
What is the purpose of having TRK?
-Both Gq and TRK can stimulate PIP2-->IP3 + DAG pathway
-Both Monomeric G and TRK can stimulate RAS--> MAPK pathway
Why?-- Variability, diff cells have diff receptor expressions
