Unit 1 Flashcards
1
Q
CNS
A
Central nervous system - spinal cord and brain
2
Q
PNS
A
nerves and ganglia outside the brain and SC, including cranial nerves
3
Q
Ramon y Cajal
A
Used the Golgi stain (which stains specific neurons entirely) to determine that the nervous system is contiguous
4
Q
Cresyl Violet staining stains…
A
Cell bodies - nucleolus and ER
5
Q
Groups of cell bodies in the CNS are called _____ while groups of cell bodies in the PNS are called _____
A
Nuclei ;ganglia
6
Q
Layers of neuronal bodies are called ______
A
Laminae
7
Q
Axons traveling together in the CNS are called _____ and in the PNS are called ______. Another name is ______
A
Tracts; nerves; fasciculi
8
Q
What are the four main types of glia?
A
Astrocytes, Oligodendrocytes, Schwann cells, Microglial cells
9
Q
Astrocytes function
A
Form the BBB, maintain the chemical environment around neurons, only in CNS
10
Q
Oligodendrocytes function
A
Make myelin in the CNS
11
Q
Schwann cells functions
A
Make myelin in the PNS - very important in the regeneration of PNS neurons - form a tube distal to lesion and provide growth signals for regenerating axon
12
Q
Microglial cells functions
A
Hematopoietic cells and like macrophages - scavengers and secrete cytokines at site of injury, more microglia increase with injury!
13
Q
How does information travel into and from the nervous system?
A
- Internal and external environment
- PNS - Sensory components (sensory ganglia and nerves and receptors)
- CNS (cerebrum, diencephalon, cerebellum, SC - analysis and integration of motor and sensory information)
- PNS - Motor components (visceral motor system - symp, parasymp, enteric; somatic motor system - motor nerves)
- Effectors: smooth, cardiac muscles and glands (if visceral motor system); skeletal (striated muscles (if somatic motor system)
14
Q
Motors neurons are _____ while sensory neurons are _______.
A
Efferents; afferents
15
Q
Three Motor Components of the Nervous System
A
- Somatic motor system (conscious motor control)
- Autonomic nervous system (visceral, unconscious functions)
- Enteric nervous system (part of ANS that control gastric motility and secretion = small ganglia and lots of neurons in the gut!)
16
Q
Somatic vs Autonomic efferents
A
Somatic: direct connection to muscle
Autonomic: 2 neurons - pre and post ganglionic fibers
17
Q
Parasympathetic vs Sympathetic Divisions
A
Parasymp: Long preganglionic, ACh, short postganglionic, ACh
Symp: short preganglionic, ACh, long postganglionic, NE
18
Q
Synapse direction is usually
A
Anterograde - pre to post synaptic
Exceptions: cannabinoids and some neurotrophic factors
19
Q
Sequence of events involved in transmission presynaptically
A
- AP
- VGCC
- Synaptic Fusion
- Vesicles released!
- Astrocytes help take in excess NT in synaptic cleft!
20
Q
____ is the major excitatory NT and _____ is the major inhibitory NT
A
Glutamate; GABA
21
Q
Amino Acid NTs
A
Glutamate, GABA, Aspartate, Glycine
22
Q
Amines
A
DA, NE, EP, 5HT, histamines
23
Q
Two types of post synaptic receptors
A
- Ionotropic
- GPCRs
24
Q
Ionotropic
A
Ion channels, much faster signals
25
GPCRs
Slower, large effects, NT binds and starts a cascade
26
Gs Cycle
1. NE binds to GPCR
2. Alpha subunit undergoes GDP hydrolysis into GTP via GEF proteins
3. Alpha activate adenylyl cyclase which converts ATP into cAMP that acts on PKA
4. GAP protein deactivates alpha which reassociates with beta/gamma dimer
5. PKA gets dephosphated by phosphotase and phosphodiesterase
6. cAMP becomes ATP in mitochondria
27
_______ and ________ NTs usually only have GPCSRs
Dopamine and NE
28
Aminergic NTs are made in ______ numbers of neurons but are distributed _____ in the brain
small; largely
29
Opiod peptides
Enkephalin, endorphins, and dynorphins
30
Overall process of neuropeptide synthesis
Pre-propeptides are made and then cleaved into several different peptides from one long protein precursor (propeptide)
31
What are two types of atypical neurotransmitters?
Endocannabinoids and NO (nitric oxide)
32
What makes atypical neurotransmitters atypical?
They are released retrogradely (post to pre) and they are calcium dependent
- both diffuse through membranes
33
Three classes of cell signaling molecules
1. Cell impermeant - typical NTs
2. Cell permeant - hormones, anandamide, and NO
3. Cell associated - important in development
34
Activation of G-proteins
1. Receptor binds to g-protein
2. NT binds to receptor
35
Activation of G-proteins
1. Receptor binds to g-protein
2. NT binds to receptor
3. Conformational change in receptor
4. GDP comes off via GEFs, alpha subunit comes off and goes to inhibit/activate effector protein
5. GAP binds GDP back to alpha
6. Alpha associates with beta/gamma dimer
36
How g-protein signals terminate
1. NT/Ligand dissociates from receptor
2. Endocytosis of receptor (think LTD)
3. GTP hydrolysis to GDP (GAP)
4. Phosphodiesterases (PDE) converts cAMP to AMP which then turns into ATP
37
What are short term effects in a cell?
Protein function is changed
38
What are long term effects in a cell?
Gene expression, altered protein synthesis and expression!
39
Types and Functions of GPCRs
1. Trimeric - most common
2. Monomeric - growth factor receptors!
40
How are eukaryotic chromosomes packed?
Chromatin - DNA (negatively charged) plus histones (positively charged) plus other proteins that are important for DNA replication and gene expression
41
Pedigrees analysis
Show a family tree to determine whether a disease may be dominant, recessive, or x-related
42
Mitochondrial inheritance
Mother passes on to all her children
43
Autosomal dominant
Look for vertical inheritance - affected individuals in all generations
44
Autosomal recessive
Look for horizontal inheritance - parents without disease can have children with the disease
45
X-Linked recessive
Female carriers, males affected, daughters are affected only if father is affected and mother is a carrier
46
X-linked dominant
Both males and females are affected, affected father = only daughters are affected, affected mother = both daughters and sons are affected
47
Genetic vs epigenetic inheritence
Genetic: can't change, inherited over generations
Epigenetic: modification of a nuclear gene in an organism - methylation, acetylation, X inactivation, environmental changes!
48
True or False: mutations happen due to pre-existing requisites
False, mutations are random, but can increase with mutagens
49
Types of mutations
1. Gene mutations (nonsense, missense, frameshift, indel, TNREs)
2. Chromosome mutations (large lengths of DNA - deletions, inversions, duplications, translocations)
3. Chromosome numbers (CNV - copy number variants; aneuploids - incomplete sets or extra chromosomes)
50
Monogenic neurological diseases
Huntington's, Fragile X, Rett Syndrome, Early onset AD
51
Polygenic diseases
Most diseases!
Depression, diabetes, heart diseases, epilepsy
52
What kind of studies allow for an estimation of heritability in humans??
Twin studies!
53
What are the three ways of protecting the brain
1. BBB
2. Ventricular system
3. Cranial meningues
54
What is the BBB made from?
Capillary endothelial cells and tight junctions of astrocytes
55
What kind of drugs and molecules can get into the brain through the BBB?
Hydrophobic and non polar ones
56
What is in ventricles?
Cerebrospinal fluid
57
Where is CSF made?
Choroid plexus
58
What does CSF do?
Makes the brain boyuant
59
What are the three layers of the meningues?
Dura mater, arachnoid space, pia mater
60
What is in the subarachnoid space?
CSF!
61
Dura mater
2 layers, has pain receptors (trigeminal nerve!)
62
Arachnoid
Follows dura and doesn't slip into sulci so there is subarachnoid space
63
Pia mater
Closely follows surface of brain and adheres to glia on brain
64
What is the main arterial pathway of blood supply to the brain?
Aorta --> common carotid artery --> internal carotid artery --> anterior/medial/posterior cerebral artery
65
What is the functions of the Circle of Willis?
Block of blood ---> allows backup pathways of blood
66
Four parts of the spinal cord
1. Cervical
2. Thoracic
3. Lumbar
4. Sacral
67
Subparts of the brain
1. Telencephalon
2. Diencephalon
3. Midbrain
4. Cerebellum
5. Pons
6. Medulla
68
What are the 5 names of the brain regions?
- Telencephalon - cerebrum
- Diencephalon - thalamic structures
- Mesencephalon - midbrain
- Metencephalon - pons and cerebellum
- Myelencephalon - medulla
69
Brain Imaging Techniques
CT
MRI
fMRI
PET
DTI
70
CT
X-rays make a 3D picture, structural
71
MRI
Grey matter structural images, magnetic field that responds to the spin of hydrogen atoms
72
DTI
Type of MRI for white matter
73
fMRI
Functional imaging, detects presence of oxygenated or deoxygenated protons (BOLD changes)
74
PET
Radioactive imaging - uses an isotope that can't be metabolized which are more seen in active neurons
75
Stroke
- cerebrovascular accident disruption of blood flow to brain
- 3rd leading cause of death in US
- learned anatomy stroke by stroke
76
A stroke is less that 24 hours it is...
TIA - transient ischemic attack
77
A stroke is more than 24 hours it is...
a stroke - persistent focal sx
78
Stroke Sx
Alteration in consciousness, headache, aphasia, facial weakness or asymmetry, incoordination, ataxia, visual loss
79
FAST
Face, Arms, Speech, TIME
80
Risk factors of stroke
Age, hypertension, heart disease, diabetes, smoking, alcohol, previous TIA or stroke
81
Types of stroke
Ischemic and Hemmorhagic
82
Which type of stroke is more common?
Ischemic
83
What is ischemic stroke?
Insufficient blood supply - lack of oxygen and glucose to the brain
84
What are the types of ischemic stroke?
Focal and global ischemic
85
What is focal ischemic stroke?
Blockade of blood flow by a clot formed in the vessel (thrombotic) or an embolus made somewhere else (embolic)
86
Global Ischemic Stroke
Global decrease in blood due to another event
87
Thrombolytic cascade
Thrombin activates = converts fibrinogen into fibrin which cross links and forms a clot
88
Pathways of making clots
1. Extrinsic (damaged endothelial cells, bad cholesterol)
2. Intrinsic (blood is exposed to collagen)
89
Hemorrhagic stroke
Bleeding inside skull due to rupture of blood vessels or aneurysm --> bleeding into brain tissue!!!!
90
Diagnosis of Stroke
Acute focal brain syndrome --> presists >24 hours ---> CT high density (hemorrhagic) OR CT low density (ischemic - use MRI)
91
What is another method to determine stroke?
Cerebral angiography - however, it can cause stroke and uses a dye that can cause allergy (insert dye into artery)
92
Penumbra vs Core infarct
Penumbra - region surrounding core infarct region of stroke in which some blood flow remains and tissue is still viable and salvageable - seen in perfusion
Core- permanent destruction, seen in diffusion
93
What is the goal when treating stroke?
To rescue penumbra tissue!
94
What happens when blood flow stops in the core?
Necrosis - rapid cell death due to swelling and inflammation
95
What happens when blood flow stops in penumbra?
Apoptosis - slow cell death - cytochrome c is released from the mitochondria and caspases are activation, leading to DNA fragmentation and cell shrinking (no inflammation)
96
Loss of blood flow means...
Loss of glucose = loss of energy = no energy in cells to use Na/K ATPase = K levels outside rise and depolarize cell!
97
Excitoxicity
The idea that a constant depolarization causes constant Ca2+ influx which leads to constant Glu release which leads to Ca+2 influx postsynaptically which triggers cell death (apoptosis - caspases due to cyt c release = DNA fragmentation)
98
How do glia contribute to excitotoxicity?
Astrocytes use EAAT2 to reuptake glu, but that channel doesn't work if the sodium gradient is disrupted - no reuptake = constant glu release and binding
99
Glutamate is toxic to what other type of glia?
Oligodendrocytes
100
Why is the brain so vulnerable?
1. Needs a lot of energy but has no where to store it - relies on blood to bring glucose to make ATP
2. No energy storage (no glycogen)
3. Imperfect blood supply - ICA carries blood to entire brain while the MCA feeds many parts of the cortex
4. Learning and stroke hing on the NMDA-R receptor - the cost of being smart is excitotoxicity!
101
Treatment Options
1. Restore blood flow by removing clot (tPA and mechanical removal)
2. Restore and protect neurons (GABA increase, Glu decrease)
102
How does tPA work?
tPA activated PLG that becomes plasmin, which breaks down fibrinogen and fibrin
103
Downfalls of tPA
- Only works within first 3 hours of sx onset
- Giving to patients on anticoagulants
- Giving to patients with bad blood pressure
104
Neuroprotective treatments
- NMDAR antagonists
- Reduction of Ca2+ with blockers or calcium chelators
- AMPA antagonists
- Inhibitor of ROS
- Hypothermia to reduce glu release and cell death
105
Use of SSRIs in stroke
After a stroke, patients have increased plasticity - SSRIs can lengthen that plasticity window by reducing inhibitory activity so dendrites could resprout in affected areas -- need to act fast after stroke though
106
Components of brainstem
Midbrain, pons, medulla
107
Midbrain components
Superior and inferior colliculi (sight and audio); substantia nigra (motor); PAG (pain), reticular formation (consciousness)
108
Pons - What do they look like?
Stripy fibers, has parts of the reticular formation, large ventricle, descending motor neurons are ventral
109
Medulla Oblongata components and functions
Vestibular control, reticular formation (heart rate and respiration), olives and pyramids (descending motor control)
110
Difference between rostral and caudal reticular formation
Rostral - responsible for consciousness; regulate wakefulness and sleep-wake transitions
Caudal - Coordinates somatic and visceral motor neurons
111
Internal structure of spinal cord
Gray matter = cell bodies, on the inside of the cord
White matter = axons, on the outside of the cord
112
Lumbar vs Thoracic vs Cervical
Lumbar - Thickest gray matter
Thoracic - Grey matter is top heavy
Cervical - Grey matter is bottom heavy
113
Touch Pathway
DRG cell bodies ipsilaterally all the way up to medulla (SYNAPSE and DECUSSATE) medulla to thalamus (SYNAPSE) thalamus to somatosensory cortex (SYNAPSE)
114
Pain and Temperature pathway
Cell body in DRG to dorsal horn (SYNAPSE AND DECUSSATE) ascend contralaterally to medulla (SYNAPSE) medulla to cortex (SYNAPSE)
115
What is the same about the pain and the touch pathways?
2nd neuron crosses the midline
116
_____ information becomes lateral and ______ information becomes medial.
Dorsal; ventral
117
Assessment of TBI can be done using the _____
Glasgow Coma Scale
118
Range of Glasgow Coma Scale
3 - 15, lower = worse
119
Damage to rostral brainstem symptoms
Limbs decorticate (lower limbs extend, upper limbs flex)
120
Damage to caudal brainstem symptoms
Limbs decerebrate (all limbs extend - BAD because it may mean caudal reticular formation damage!)
121
How does the CSF protect the CNS?
Buoyancy - reduces brain mass by a matter of 30
Injury often results in a coup-contre-coup movement
122
TBI Types
Penetrating and non penetrating
123
What happens in TBI?
Swelling of brain causes an increase of pressure, often due to leakage of blood which acts similar to a hemorrhagic stroke and lots of damage
124
Damage at C5/C6
quadriplegic
125
Damage in T or L regions
Paraplegic
126
Damage in S regions
Loss of sensation in back of leg
127
Damage caudal to medulla means
Ipsilateral touch and contralateral pain
128
Damage rostral to medulla means
Contralateral pain and touch
129
What happens most often in SCI?
Demyelination due to shearing
130
True or false: TBI usually causes grey matter injury, while SCI causes white matter injury
TRUE
131
Chronic Traumatic Encephalopathy (CTE)
Mild head injuries adding up, leading to dementia and have hallmarks of AD - tau fibrillary tangles and beta amyloid plaques
132
Is there a causal link between the tau deposits and amyloid plaques?
NO
133
What kind of cells get damaged in trauma
Vasculature, neurons, and glia
134
What happens with the injury of vasculature and neurons?
Inflammation, glutamate excitotoxicity, axonal sprouting and demyelination (chronic - happens after trauma), all of which lead to cell death
135
BBB damages causes
Excitotoxicity and fluid leakage
136
PNS Regeneration
- Regenerate really well
- Proximal stumps form growth cones that grow along old path which is stimulated by diffusible factors secreted by Schwann cells and other organs
- Synapses form back in original places
137
CNS Regeneration
- Not good
- All types of glia are activated which seem to act as inhibitory signals to growing axons
- Oligodendrocytes: make Nogo-A that binds to NgR1 on neurons which causes collapse of growth cones
- Astrocytes: form glial scar and act as a physical barrier
- Neurogenesis is very rare in CNS
- Oligodendrocytes have multiple axons to bind to!
138
Treatment of TBI
- ABCs - airways, breathing, cardiac function
- Imaging
- Steriods and NSAIDs
- Monitoring intracranial pressure
- Anti-convulsants
- Avoid fever (hypothermia)
- Oligodendrocyte replacement
- Rehabilitation
139
Treatment of SCI
- Same as TBI
- Could also use GABA agonists for spasticity due to UMN damage so there may be a lot of contractions
- Rehabilitation
140
Clinical Trials for TBI and SCI
- NMDAR antagonists to prevent excitoxicity
- Masking NogoA
- Blocking rho A (collapse of growth cones)
- NSAIDs and levels rho decrease
- Stem cells (including bone marrow and olfactory epithelial cells)
- Estrogen (more SCI in men)
- Robotic rehabilitation
141
Differences between active transporters and ion channels
Active transporters: move selected ions against concentration gradient with the use of energy
Ion channels: ions diffuse down concentration gradient and are selectively permeable to certain ions
142
What is the role of Na/K ATPase pumps?
Use the energy of ATP to pump K into the cell and Na out of the cell
143
What happens to the Na/K ATPase when [ATP] decreases?
Less Na outside the cell, less K inside the cell = depolarization
144
What do exchanger sand co-transporters use as energy?
Gradients of ions
145
Types of Ion Channels
1. Voltage-gated channels
2. Ligand gated channels
3. ASICs (activated by heat, pain, and temp)
4. Mechanically activated channels
146
How are synaptic potentials encoded?
By amplitude - higher amplitude means larger EPSP
147
How are action potentials encoded?
By frequency - more APs means more active neuron
148
What does the electrochemical equilibrium rely on?
Probability of an ion encountering a channel and going through it
149
Nerst equation
58/Z (charge of ion) log(xout/xin)
150
Membrane potentials summary
1. Neuronal membranes tend to have resting potentials of -50 to -70 mV
2. Resting membrane potential depends up the concentration gradients of the ions and the permeability of the membrane to K (at rest K channels are open)
3. Hyperpolarize means membrane potential is more negative, depolarize means membrane potential is more positive
4. When ions move across the membrane to affect the membrane potential, usually only a few ions are involved and the overall cellular concentrations of ions are relatively unchanged
151
Action potential phases
1. Resting potential: maintained by Na/K ATPase and K+ leak current
2. Depolarization to threshold and Na+ channels open - Na+ rush into cell and depolarize the cell
3. Repolarization: K+ channels open, sodium channels inactivate, K+ rushes outside, membrane potential hyperpolarized back to resting
4. Hyperpolarization: can get overshoot
5. Refractory period: Na+ channel still inactivated and cell is hyperpolarized
152
Current flow of a particular ion is a combination of...
conductance (how open the channel is) and how far the membrane is from equilibrium potential of that ion
153
Why don't Na and K voltage gated channels open at the same time?
Na+ open immediately, but K+ open more slowly and Na+ channels inactivate with prolonged depolarization (when K+ channels open)
154
True or false: APs can happen at any depolarization
False, they are only generated when a cell membrane is depolarized to a threshold
155
EPSP vs IPSP
Excitatory vs inhibitory post-synaptic potentials - can summate in order to reach threshold (or prevent threshold!)
156
Why do APs need passive conductance?
Passive conductance leads to decay over distances, but as long as sufficient depolarization reaches a voltage Na+ channel, the AP will continue!
157
Myelin's role in APs
Think of this as the insulation of a wire; AP travels by saltatory conduction because ions can't leak out of myelin = increases passive conductance = ensures enough depolarization reaches the next node!
158
What happens when axons are demyelinated?
Membrane is leaky = APs can't keep going because there is not enough depolarization to reach threshold at the next path of Na+ channels
159
Channelopathies
Mutations in ion channels
160
AP reaches presynaptic terminal - now what?
VGCC open, let calcium in, vesicles fuse and Nt gets released
161
Relationship between AMPA and NMDA receptors
Both are ionotropic glutamate receptors; AMPA opns faster, allowing Na+ influx which depolarizes the membrane. This causes the Mg2+ plug to be released from the NMDA channel and then NMDA receptors allow Na+ and Ca2+ to flow = important for plasticity and learning!
162
GABA
an inhibitory NT
163
Drugs that act on GABAa channels
1. Barbiturates (agonists)
2. Benzodiazepines (positive allosteric regulator = safer bc it needs GABA to work with it)
3. Alcohol (facilitates GABA's ability to open channels)
4. Anesthetics (prolong GABAa channel opening)
5. Antagonists (CAUSE seizures E:I ratio)
164
GAT
Mops up excess GABA from a synapse
165
Seizures
Uncontrolled synchronous firing of neurons in brain that cause behavioral abnormalities
166
Epilepsy
Clinical syndrome with recurrent and spontaneous unpredictable seizures (chronic seizures for no reason)
167
How is epilepsy diagnosed?
EEG - 21 electrodes placed in a defined pattern; summation of 100s of neurons firing (looking at synchrony of neurons firing)
168
Ictal
seizure
169
Interictal
between seizures
170
Normal EEG
EEG activity is low
171
EEGs during a seizure
Bigger, more synchronous rhythmic activity of neurons that correlates with behavioral effects
172
MRI and CT in seizures
Can be used to find the location of a scar or damaged brain tissue
173
MTLE
Medial Temporal Lobe Epilepsy; most common type of epilepsy that causes hippocampal damage (hippocampus has a sepcific pattern of firing and in epilepsy this pattern can get stuck)
174
Types of seizures
Generalized - across both hemispheres
Focal - Small part of the brain, but can become a generalized seizure
175
Generalized seizures types
- Tonic clonic: rigidity (tonic) then twitching (clonic)
- Absence: non-convulsive, brief loss of consciousness (Ca2+ channel blockers)
- Myoclonic: Twitching or jerking due to motor cortex
- Atonic seizure: loss of muscle tone
176
Focal seizures types
- Simple: short lasting seizures without loss of consciousness
- Complex: impairment of consciousness
177
Status epilepticus
Frequent, long lasting seizures without regaining consciousness between seizures
178
Causes of seizures
- Stress
- Lack of sleep
- Flashes of lights or sounds
- Low blood sugar
- Fever
- Alcohol withdrawal
- Hormones
- Hyperventilation
179
Why are babies more prone to seizures?
Direction of Cl- transport makes GABA either excitatory or inhibitory. In children GABA is excitatory and depolarizes through the NKCC1 receptor = more E = seizures are more often
180
Genetics and epilepsy
50% of epilepsy, especially in children is caused by genetic disposition (usually channelopathies)
181
Acquired Epilepsy
- Most common in adults
- Head injuries
- Brain tumors
- Stroke
- Pre-natal
- Infection
- Vascular abnormalities
- Autism
- Febrile seizures
- Mild TBI
- Drugs
- Sleep deprivation
182
Epileptogenesis
things that may change the E:I ratio, thus leading to seizures
- Increased glu, decreased GABA
- Receptor, dendrite, synapse, astrocytes, ion transporter, signal changes
183
Pyramidal cells and epilepsy
Cortical pyramidal cells fire at once due to gap junction coupling
184
Basket cells
Interneurons that usually synapse on multiple pyramidal cells so that an individual interneuron can control the firing of many pyramidal neurons
185
More inhibition from basket cells leads to ____ excitation
Less
186
What can a mutation in a basket cell lead to?
Affects E/I balance
187
Plasticity and epilepsy
Seizures can cause plasticity, so plasticity and neurogenesis is not helpful
188
Treatment of Epilepsy - Drugs
Attempt to enhance GABA action or block Na+/Ca2+ (like barbiturates and benodiazepines)
- Valproate (blocks Na an dCa2+ and increases GABA)
- Topiramate (same as above)
- SSRIs (plasticity?)
- CBD
189
Treatment of Epilepsy - Surgery
Temporal lobe surgery, corpus callosotomy (split brain), and hemispherectomy
