Neurophyiosology Flashcards
1
Q
Neuro lectures
A
Synaptic transmission
Cortex anatomy
Hippocampus anatomy
Thalamus anatomy
DSA Dennis hypothalmic RF and Limbic systems
PHYSICIAN neurotransmitters, chemical messengers, and excitotoxicity
2
Q
Declarative memory
A
Available to consciousness
-daily episodes, worlds and their meanings, history
3
Q
Non declarative memory
A
Generally not available to consciousness Motor skills Associations Priming cues Puzzle solving skills
4
Q
Working memory
A
Short term
Recollection of a fact or memory for use
Answering a test question
Functions a lot like short term memory
5
Q
Declarative memory
A
Explicit memory
The conscious recognition/recollection of learned facts and experiences
Episodic-events
Semantic-words, language, rules
6
Q
Procedural memory
A
Non declarative memory
Skilled memory
Implicit memory
Reflexive memory
Complex activity repeated over and over again until all of the relevant neural systems work together to autonomically produce the activity
Riding a bike , tying shoes
Basal ganglia-motor skills
Cerebellum-motor skill
Nucleus accumbens-nonmotor skills
7
Q
Neuroplasticity
A
The ability of the brain to form and reorganize synaptic connections, espicially response to to learning or experience or following injury
8
Q
Synaptic neuroplasticity -altering function of synapses
A
Post titanic potetiation (PTP)
Long term potentiation (LTP)
9
Q
Structural neuroplasticity-changing the shape of synapses
A
Gain or loss synapses
Dendritic structural
Soma structural changes
10
Q
Synaptic facilitation
A
An increase in synaptic strength that occurs when two or more action potentials invade the presynaptic terminal within milliseconds of eachther
11
Q
Synaptic potentiation
A
Activity dependent form of plasticity that enhances synaptic transmission due to increase in neurotransmitter released in response to presynaptic action potentials and results from persistent calcium cations within presynaptic terminals
12
Q
Synaptic augmentation
A
Increases the probability of releasing synaptic vesicles during and after repetitive stimulation
13
Q
Post tetanic potentiation
A
Short lived
Results in increased frequency of miniature excitatory postsynaptic potentials or currents with no effect on amplitude in the spontaneous postsynaptic potential
14
Q
Long term potentiation
A
Persistent strengthening of synapses based on recent patterns of activity
Produce long lasting increase in signal transmission between two neurons
15
Q
Bc potentiation acts over a time course of seconds to minutes, it often outlasts the high frequency trains of action potentials that evoke it, leading to __
A
PTP
16
Q
What does PTP require
A
High frequency , brief discharge of the pre-synaptic neuron
Pulses increased neurotransmitter release for 60 seconds
Results in increased probability of action potentials in the post synaptic cell
17
Q
Mechanism of PTP
A
Leading theory depends on abundance of calcium
- action potential opens Ca channels (more enters than can be processed-more vesicular release of NT than otherwise seen)
- Ca causes vesicle fusion and NT release (leads to more activation of receptors than typical)
- receptor channels open Na enters post synaptic cell (leads to more likelihood of action potential in post synaptic cell)
18
Q
Long term potentiation
A
Persistent increase in synaptic strength following high frequency stimulation of chemical synapse
-requires repeated strong stimulation
19
Q
Mechanism of long term potentiation
A
Increased phosphorylation of AMPA receptors and insertion of additional AMPA receptors into post synaptic membrane
Eventually, activation of calcium-calmodulin-CREB mechanism
20
Q
AMPAR
A
Na enters and depolarized cell. This causes depolarization of opening of NMDAR
21
Q
NMDAR
A
Mg leaves cell and Ca enters cell
Open by depolarization from Na entry in AMPAR
22
Q
What happens when ca enters cell STP
A
Binds calcineurin
Binds calmodulin
23
Q
What does ca bound to calcineurin do
A
Increase NOS and production of NO to presynaptic cell which increases cGMP and NT release
24
Q
What happens when Ca binds calmodulin
A
Activates adenylyl cyclase, cAMP and phosphorylation of AMPAR
Increases Na influx in response to future ligand binding
25
What is CREB
CAMP response element binding protein , which is a transcription factor targeting CRE (cAMP response elements)
Well documented roles in memory formation, neuroplasticity, and spatial memory
26
What genes does CREB upregulate the expression of
```
BDNF
Cytoskeleton structural proteins
Synapse and growth formation
Enzymes for NT synthesis
NT receptors
```
27
Long term (declarative/explicit) memory is mediated by four types of processing
Encoding
Storage
Consolidation
Retrieval
28
Encoding
New information is attended and linked to existing information in memory
Attending to new information or facts:
Focus and attention and linked to existing information in memory
29
Storage
Neural mechanisms and sites by which memory is retrained over time
30
Consolidation
Process of taking temporarily stored information and making it stable
31
Retreival
Process by which stored information is recalled
Subject to distortion
32
Short term memory has __ capacity
Limited
33
Long term memory capacity
Unknown
| Unlimited?
34
Encoding memory utilizes what
Perception of something
Focused attention
Linkage to previous knowledge
Emotion enhances encoding
35
What is encoding memory critically important for
How well something is learned
36
For encoding memory to persist, the information must be deeply encoded. What does this require
-attending to the information
Associating the information with knowledge already well established in memory
Even stronger when one is well motivated to remember
REM sleep is important
37
Long term memory storage is associated with the area of the __ that the memory is most associated with
Cortex
38
Long term visual memory
Visual cortex
39
Long term sound memory
Auditory cortex
40
What happens with widespread damage to the cortex
Sig decline in long term memory
41
Is all short term memory turned into long term memory
Nope
| A lot is lost
42
Consolidation of memory
Labels memory is stabilized(making a memory permanent)
43
How does memory consolidation occur
LTP and physical changes in synaptic structure
44
Anatomy of consolidation of memory
Hippocampus, temporal lobes, papez circuit, cingulate cortex
45
__ improves consolidation
Sleep
46
Reconsolidation
Long term memory goes back to short term memory
47
Short term memory is associated with __ synaptic chemical changes
More
48
Long term memory is associated with more ___ changes
Structural
49
What structural changes is long term memory associated with
Increased vesicle release sites (active zones)
Increased number of vesicles released
Increased pre synaptic terminals
Increased dendritic spines
50
Rehersal
Short term memory to short term memory
51
Retreival memory
Act of accessing the long term memory: recollection or using the memory
Brings the memory into working memory
-makes the memory susceptible to modification or deletion
52
What does retreival of memory use
Cortex, parahippocampal gyrus, and hippocampus
53
Memory is reconstructed int he ___
Hippocampus
54
Cortex
Site of memory storage and sends it to the parahippocampal gyrus
55
Parahippocampal gyrus
Brings all the components from the cortical memories into working memory
Sends to the hippocampus
56
Hippocampus
Reassembles the full memory and sends back to the parahippocampal gyrus
57
Parahippocampal gyrus
Prolongs the life of the memory trace and sends back to cortex
58
Cortex
Stores memory again
59
Dentate gyrus
Site of adult neurogenesis
- excitatory principle neuron that adds to mossy fiber circuits between DG and pyramidal cells of CA3
- low turnover of old neurons
60
Function of dentate gyrus
Time stamping new information to distinguish two pieces of information in time
Aka content
61
Working short term memory
Accessing memories and using what you remember
62
Three components of working short term memory
Phonological loop
Visuospatial loop
Executive control process
63
Phonological loop
Wernickes and Broca’s areas (verbal information )
Provide and interpret the auditory information associated with the memory
64
Visuospatial loop
Occipital cortex (visuospatial information)
Provides and interprets the visual information associated with the memory
65
Executive control processes
```
Prefrontal cortex (allocates attention)
Directs, uses and updates memory
```
66
Spatial memory
Place cells in the hippocampus (specialized pyramidal cells in CA1)
Grid cells in enterohinal cortex (works in conjunction with place cells. Spacing and orientation between fields and a reference point)
Encodes the physical space associated with the memory
Believed to act as an anchor to the entire memory
-speed cells-released function guesses speed
67
Good cells
As a person wanders around a new environment, so called “grid cells” within the brain are thought to provide a base coordinate system
68
Place cells
Related “place cells” response to specific locations such as NY Central Park
69
Which of the following is another name for short term memory
Working memory
Sensory memory
Episodic memory
Implicit memory
Idk
70
In each of the following determine whether you would use implicit or explicit memory
1. speaking your native tongue
2. Remembering what present you bought for your aunt
3. Opening a present
4. Writing with pen and paper
5. Remembering that time you fell out of a tree when you were 5
6. Climbing a tree
7. Knowing the work for flower in anoth language
8. Hearing a French speaker and later noticing French food more often wherever you go
9. Knowing the state capital of Missouri
10. Solving a geometry problem
Ok
71
Compare and contract implicit and explicit memory
Explicit-intentionally and consciously recalled (formula for statistics), declarative. Dates for history class
-recall phone number, dates for class, what time meeting a friend
Implicit-not consciously recalled (ride a bike )
Nondeclarative
Procedural swinging a bat
Singing a familiar song, ride bike
72
Two types of explicit memory
Episodic and semantic
73
Episodic memory
Long term memories of specific events such as what you did yesterday’s or your high school graduation
74
Semantic memory
Facts, concepts, names, and other general knowledge
75
A 27 year old man with severe epilepsy, characterized by major convulsions and lapses of consciousness every few minutes, underwent experimental neurosurgery to help relieve seizures. The operation has a significant , beneficial effect not he epilepsy, but led to a devastating memory deficit. He had normal procedural memory, maintained long term memory for events that occurred prior to surgery, and high short term memory was intact, but he could not commit new events to long term memory (loss of declarative memory). Which of the following areas of the brain was bilaterally respected in this patient
```
Cerebral cortex
Cingulate gyrus
Hypothalamus
Parietal lobe
Temporal lobe
```
Idk
76
What cells does the brain (BBB) capillary have apart from the general capillary
Astrocyte
Pericyte=contractile
Endothelial cell
77
Pathways across the BBB
```
Paracellular aqueous pathway
Transcellular lipophilic path
Transport proteins
Endocytosis
Passive discussion
```
78
What agents are transported with paracellular pathway
Water soluble agents (rare)
| Through tight junction
79
What agents cross the transcellular lipophilic path
Lipid soluble agents
80
What sort of agents cross the transport proteins
Glucose, aa, nucleosides, vinca alkaloids, ciclosporin A, AZt
81
What agents use endocytosis
Insulin, transferrin, albumin, other plasma proteins
82
Agents of passive diffusion
H20, CO2, O2, unbound steroid hormones, lipid soluble stuff
83
GLUT1
Transports glucose from blood through BBB
Not insulin dependent
2 isoforms (45kD and 55kD)
84
NaK2Cl
Transports ions from CSF to blood
Expression tied to endothelium 1 and 3
Endothelium production ties to astrocyte signals
85
P-glycoprotein
Moves drugs that don’t belong that crossed BBB back into blood
Similar to MRPI in GI
Some drugs target this signaling path
86
The BBB and blood CSF layer is not present in _____
Circumventricular organs (CVO)
87
What are the circumventricular organs
Area postrema, OVLY, SFO, and posterior pituitary
88
How does blood CSF barrier work in CVO
Facilitated transport carries necessary molecules across the barrier
Majority of capillaries lack the typical slit pores
89
What are CVE highly permeable to
Water, CO2, O2, and lipid soluble substances
90
What are CVO slightly permeable to
Na, Cl and K
91
What are CVO nearly permeable to
Plasma proteins and non lipid soluble organic molecules
92
What is the posterior pituitary
Secretory, endocrine
93
What is the area postrema
Sensory; initiation of vomiting in response to chemotactic triggers
94
What is the organum vasculosum of the lamina terminalis
Sensory; regulation of total body water and thirst-target of angiotensin II
95
What is the subcortical organ
Sensory
96
What are the sensory CVO
Subcortical organ, OVLT, area postrema
97
What are the secretory CVO
Median eminence, posterior pituitary , pineal gland
98
Metabolic glutamate receptors (mGluR’s)
8 subtypes, GPCR
Modulates synaptic signaling of other receptors
Modulates transmitter release
99
Inotropy glutamate receptors-has a glutamate binding domain
NMDAR’s
| Non-NMDA receptors(AMPAR, KAR)
100
The NMDA receptor is activated by what
Exogenous N-methyl-D-aspartate
| Glutamate and aspartate
101
What happens when NMDA receptor is activated
Allows Ca influx
102
Modulators sites of the NMDA receptor
Glycine binding site
Mg binding site
PCP binding site
103
Activation of the NMDA receptors leads to what
EPSP in post synaptic cell
104
NMDA has a ___ onset and __ duration
Slow
| Prolonged
105
Glycine binding site of the NMDA receptor
Serves as a coagonist
Required for EAA to have an affect
Can’t open the channel on its own
106
Magnesium binding site of the NMDA receptor
Inside the channel
Mg blocks the channel
To open the channel, Mg must leave
Depolarization forces Mg out of channel
107
PCP binding site of NMDA receptor
Inside the channel
Internal to Mg binding site
Blocks the channel
108
Most glutamatergic synapses have both _ and _ receptors
AMPA and NMDA
109
The rise time for NMDA receptor currents are much slower than those of non NMDA receptors
10-50ms
| .2-.4 ms
110
Deactivateion is also much slower for NMDA receptors than non NMDA receptors
10-50 ms vs .2-.4 ms
111
AMPA provides fast cell depolarization and NMDA receptors determine the duration of that deporization
Ok
112
For NMDA receptor, ESPs show longer duration and longer latency. Why
Ca influx is slower
| Takes time to remove Mg
113
Non-NMDA receptors are almost exclusively __ receptors
Post synaptic
Similar to NMDAR
114
Non NMDA receptors cause _ influx and small amount of _ influx
Na Ca
115
Two types of non NMDA receptors
AMPA
| Kainate
116
Activation of Non-NMDA receptors lead to what
EPSP
117
Non-NMDA receptors often co-localize at the same synapses as __
NMDARs
118
Binding sites on non-NMDA receptor : AMPA receptor
```
EAA binding site
Benzodiazepine site (inhibitors response to NT)
```
119
What does the AMPA receptor allow
Na influx
| Small amount of Ca influx
120
When Na enters through the AMPA receptor what happens
Depolarization of cell
121
What does depoaliraztaion of a cell (caused by Na entry from AMPA) cause
Mg out of NMDA and Ca in at NMDA
122
Binding sites on NMDA
Glutamate binding site
| Glycine binding site
123
Both inotropy and metabotropic receptors can be activated by __
Excitatory neurotransmitters
124
What are the inotropic receptors and what do they allow influx of
NMDA Ca influx
| AMPA Na influx
125
Both __ and ___ receptors can be activated by eaa
Inotropic and metabotropic
126
Metabotropic aa receptors
Both pre and post synaptic location
| Presynaptic : controls NT release
127
What are the uptake systems that get rid of EAA
Neurons and glia
- Na dependent secondary active transport
- high affinity
128
Glia uptake system
Converts to glutamine
| Release into ECF
129
Neurons take up glutamine
Converts back to glutamate
130
Glutamate enters glial cell after being release from extrasynaptic NMDARS. What happens
Glutamine synthetase turns it to glutamine
131
Glutamine leaves the glial cell and enters the neuron. What happens then
Glutaminase turns it to glutamate
132
Glutamate is released from the presynaptic neuron. What happens
Binds mGluR (metabotropic),
| kaintae, AMPAR, and NMDAR
Inotropic
133
What happens when neuron is depolarized
ATP levels rapidly fall to 0 inside the neurons
NaKATPase function ceases
Cell depolarizes
Leads to action potential and excessive release of NT (including EAA)
134
Lots of EAA accumulate int he synapse after neuron depolarization
Ok
135
EAA reuptake is _ dependent
Na
*but there is less Na around in synaptic cleft
EAAs accumulate outside the cell
136
What does NMDAR activation from glutamate lead to
Ca influx
137
Increased intracellular Ca initiates
Activation of phospholipase A2
Activation of calcineurin (phosphatase)
Activation of Mu calpain (protease)
Activation of apoptosis pathway
138
Activation of phospholipase A2
Release o arachidonate from membrane and causes physical damage to the membrane
139
What does arachidonte from the membrane do
Acts at Ryan’s dine receptor on ER, which releases Ca from intracelllular stores
- ER:unfolded protein response-stops making protein
- activation of elFa-kinase
- mitochondria: impaired function
140
What happens with u-calpain (protease) activation
Proteolysis
-spectrin (more structural damage to cell)
-elF4G (eukaryotic induction factor 4G-protein synthesis)
Others-metabolic impairment
141
Activation of calcineurin
Phosphatase
Activates NOS
Increases NO synthesis
142
The disruption of mitochondrial and ER function further increases free cytosolic __
Calcium
143
As mitochondrial membranes are disrupted, __ pathways are activated
Apoptosis
Cytochrome C and caspase 9 activate caspase 3
144
Caspase 3
Proteolytic enzyme
| Apoptotic
145
What activates cytochrome C and caspase 9
Bcl2 enzymes
146
What turns on Bcl2 enxymes
Excitotoxicity ????
147
What does calcium release cause
Caspase 3/9 activation and calpain activation
148
What does caspase 3/9 and calpain activation lead to
Cell death
149
What system is crucial for increasing general excitaability of cortical ceurons
RAS-PBN EAA
150
The ___ system adds to the general excitation
Cholinergic
151
The __ and __ systems move us from being awake to being more generally aware of incoming information
Noradrenergic and serotonergic
152
The __ pathways modulate the activity of noradrenergic and serotonergic systems
Histiminergic
153
The __ system adds to that awareness , particularly focused awareness associated with novel stimuli, but its role is not as well defined
Dopaminergic
154
Alertness
Cognitive, motor, emotion, novel stimuli
DA
Agonists improve cognitive function
155
Awareness
Moving beyond awake into general awareness of environment
NE, 5-HT
Startle and awareness
156
Arousal (wakefulness)
General excitation of cortex
EAA, Ach
Hyperpolarization and memory
157
Dopamine
Substantia Nigra, ventral tegmental area
158
EAA
Dorsal and ventral pathways (to cortex)
159
Norepinephrine
Locus coeruleus
160
Serotonin
Raphe nuclei
161
Acetylcholine
Pedunculopontine tegmetnal and laterodorsal nuclei
162
Histamine
Tuberomammillary nucleus of the hypothalamus
163
Describe the steps of the neuromuscular junction
1. NT in vesicles
2. Action potential
3. Ca enters cell
4. Vesicles fuse
5. NT released
6. Post-synaptic receptors activated
7. Neurotransmission ends
164
The descending systems are __ motor neurons
Upper
165
What are the descending systems (upper motor neurons)
Motor cortex
Brainstem centers
166
What does the motor cortex do
Planning, initiating, directing voluntary movements
167
What does the brainstem center do
Rhythmic, stereotyped movements and postural control
168
What do the descending systems (UMN) get information from
Basal ganglia and cerebellum
169
What does the basal ganglia do
Initiation of intended movement and suppression of unwanted movement
170
What does the cerebellum do
Coordination of ongoing movement
171
What does the descending system UMN send information to
Local circuit neurons and motor neuron pools
172
Local circuit neurons
Sensorimotor integration and central pattern generators (CPGs)
173
Motor neuron pools
Lower motor neurons
174
What do local circuit neurons get information from
UMN and sensory inputs
175
What do motor neuron pools give information to
Skeletal muscles
176
Where are local circuit neurons and motor neuron pools
Spinal cord and brainstem circuits
177
Basic function of cortico and rubrospinal tracts
1. Transmission of commands for skilled movements
| 2. Corrections of motor patterns generated by the spinal cord
178
Reticulospinal tract
1. Activation of spinal motor programs for stepping and other stereotypic movements
2. Control of upright body posture
179
Vestibulospinal tract
Generation of tonic activity in antigravity msucles
180
Premotor cortex
Determines whether its okay to move
Identifies the goal and the motion required to meet that goal
181
Supplementary motor cortex
Postural control
Identifies the specific motor sequence required and plans the motion
Changes tactics if necessary
182
Primary motor cortex
Codes the individual motions. Required to reach the goal and activate muscles
183
Vestibulocerebellum
To vestibular nuclei
| *coordinated balance and eye movement. Postural control for future movements
184
Cerebrocerebellum
To motor cortices
| *planning, coordinating, properly times movement sequences, motor memory
185
Spinocerebellum (medial and lateral)
To descending brainstem and Corticospinal pathways
| *proper execution of coordinated movements, postural control, correct ongoing motion
186
Basal ganglia get input from what
Striatum receives input from nearly all of the cerebral cortex
187
Basal ganglia send output
From GPi and SNpr is inhibitory and projects to motor areas in brainstem and thalamus (releases GABA; then on to cortex)
188
Damage to any basal ganglia structure may cause what
Slowness of voluntary movement, involuntary movement, involuntary postures, or a combination of these
189
Damage to SNpc
Causes tremor at rest, slowness of movement, rigidity, and postural instability, which are the main features of PD
190
Striatum
Caudate
| Putamen
191
Globes pallidus
External segment
| Internal segment
192
Substantia nigra
Pars compacta
| Pars reticulate
193
Subthalmic nucleus
Ok
194
Where does striatum receive most of its information from
Basal ganglia
- from cortex regions (glutamate)
- also receives input from dopaminergic neurons of substantia nigra pars compacts (loss of which—>parkinsons)
195
90% of neurons are striatum
Medium spiny neurons (GABAnergic)
| Output is inhibitory
196
Output from striatum to basal ganglia is ___
Inhibitory
197
Intrastriatal system is ___
Cholinergic and stimulators
198
Subthalamic nucleus receives input form
Frontal lobe
199
Output from subthalamic nucleus
Excitatory (glutamate) to other basal ganglia nuclei
200
Subthalamic nucleus is typically kept under tonic inhibition by ___, disinhibition is seen in __ disease
GPe
| Parkinsons
201
Globes pallidus
Has external and internal segments
| Function
202
Substantia nigra
Has two divisions (pars reticulata and pars compacta)
Dopaminergic neurons project to other basal ganglia nuclei (see nigrostriatal path)
-stimulates D1 (+) and D2 (-) receptors
203
Normally the direct pathway allows _ and indirect pathway prevents __
Motion motion
204
Dopamine helps motion occur by two mechanisms
1. turn on/amplify the direct pathway
| 2. turn off/dampen the indirect pathway
205
In parkinson disease, the __ input is abolished resulting in a loss of dopaminergic tone in the basal ganglia..characterized by bradykinesia
SNPC
206
What are the effects of loss of dopaminergic tone
1. Direct pathway becomes difficult to activate (but it still can due to the presence of excitatory glutamatergic and cholinergic circuits in the striatum)
2. The indirect pathway becomes overactive (due to loss of D2 mediated inhibitory tone
Therefore difficulty in initiating motion
207
In __ disease, the indirect pathway is abolished, resulting in excessive movement
Huntington
208
Why is there excess movement in Huntington disease
Ach activates GABAergic input in those local intrastriatal loops
When active and functional, this inhibits motion
Therefore the loss of Ach tone results in excess motion
209
Following deflection of stereocilia, _ ions enter cell and depolarize it
K
210
Describe the steps of depolarization of hair cells
1. Ion channels (TRPA1) on stereocilia tips are opened when the tip links joining the stereocilia are stretched
2. Entry of K depolarize the hair cell which opens voltage gated calcium channels
3. Incoming Ca leads to the release of glutamate from synaptic vesicles ,which then diffuses to the postsynaptic afferent neuron from the spiral ganglion
211
Adelta peripheral nerves
Afferent type III, 1-5 micrometer diameter, 5-30 m/s conduction velocity, skin mechanoreceptors, thermal receptors, and nociceptors
212
C peripheral nerves
Type IV
.2-1.5 micrometer diameter
.5-2 (slow)
Skin mechanoreceptors, thermal receptors, and nociceptors
213
Location of pain
Somatic or cutaneous pain
Muscle pain
Deep pain
Visceral pain
214
Modality of pain
Thermal, mechanical, chemical
Many subtypes of each
Can be polymodal (respond to more than one modality)
Silent nociceptors are related to the phenomenon of phenotype switching
215
Cutaneous pain
Skin, superficial structures (cutes, burns, bruises
Fast pain (sharp) and slow pain (dull and achy, throbbing)
216
Deep pain
Periosteum ligaments, bone
Usually dull and achy
Associated with muscle spasm
217
Muscle pain
Injury of ischemia
Both fast pain and slow pain
218
Visceral pain
Internal organs:GI tract, stomach, bladder, prostate, reproductive tract, kidneys, heart
Poor localization, very sensitive to stretch. (Distension). Associated with referred pain
219
Free nerve endings
Lacks specialized receptor cells or encapsulateions
Characterization can further be broken down by various molecular markers
220
Peptidergic free nerve endings
Expresses neuropeptides
- substance P
- CGRP(calcitonin gene-related peptide)
```
Responsive to NGF (nerve growth factor)
Most visceral afferent
Half cutaneous afferent
-chronic inflammation
-visceral pain
```
221
Non-peptidergic free nerve ending
Does NOT express these neuropeptides
Responsive to GDNF
Half cutaneous afferent
-diabetic neuropathy
222
Sensing noxious stimuli with __ receptors
TRP
| Transient receptor potential family
223
TRPVI
Capsaicin , heat
224
TRPAI
Mustard
| Cool
225
TRPM8
Menthol
| Cool
226
Ligand gated non-selective cation channel is permeable to _, _ and _
Ca Na K
227
Nav1.7
Mechanosensitive sodium channel
- I type off mutation results in pain insensitive individuals (rare)
- other mutation results in paroxysmal extreme pain disorder (channel doesn’t inactivate properly)
228
Other signaling modalities
```
Nav1.7
ATP receptor
Acid-sensing channel-activated by H+
SP and CGRP
Histamine
Minions (bradykinin)
```
229
Referred pain
Brain requires some experience to localize pain, visceral pain is not experienced often enough in early development ot train the brain to localize it
Afferent converge in the dorsal horn
Antidromic signaling further diffuses visceral pain across multiple organs
230
Central processing of pain is done by what
Cortex, thalamus, raphe nuclei, insular cortex
231
Information cortex
- pain inputs widely distributed
| - damage to these areas may impact perception of pain, but not the emotional processing associated with the pain
232
Cortex details
SI and PTO-receive initial input and also involved in higher processing
233
Thalamus information
-damage to thalamus would greatly impact perception of pain-damage to a specific nucleus would impact some but not all features of pain
234
Thalamus details
Nociceptors inputs do synapse in the thalamus, intralaminar nucleus in particular
235
Raphe nuclei information
Descending pathway
236
Raphe nuclei details
Serotonergic signaling results in opoid Eric signaling in dorsal horn
237
Insular cortex information
Relays nociceptors input to Limbic system
| -damage decreases emotional component of pain
238
Details of insular cortex
Emotional component of pain
239
Membrane potential: seizure disorders
Held stable at a negative Vm compared to the outside of a cell
240
Nerve and muscle relationship
The bigger the nerve and muscle, the more negative
Skeletal-large neurons are usually listed as -70,-90 mV
Smooth muscle-small neurons -50mV
241
How is the membrane potential maintained
Na/K ATPase
- electrogenic (pumps three sodium out for every 2 K in)
- creates the concentration gradients for sodium and potassium (this is critical to Vm in large muscle and nerve cells)
242
How is membrane potential maintained
By selective permeability of the membrane (ions don’t cross readily without a channnel)
-twoions cross at rest bc they have channels that allow it
K leak channel
Chloride ClC1 channel
243
The action potential is involved in what
Seizure disorders, MS and other demyelination diseases
244
Fast action potential
- rapid depolarization-opening of voltage gated sodium channels
- repolarization(inactivation of sodium channels, opening of voltage gated K channels)
- at completion-both sodium and k Channels are closed
- activity of the NaK ATPas returns concentration gradients
245
Refractory periods
Lots of cardiac drugs affect these
246
Absolute refractory period
Can’t elicit an AP
Voltage gated Na channels are open or inactive
Occurs during an on going potential
247
Relative refractory period
- requires greater stimulation to produce an AP
- at least some voltage gated Na channels are closed (others are in inactive state-that’s why its harder)
- occurs during repolarization and a bit after the on going AP has completed
248
Voltage inactivation (depolarization block)
- neuron(or muscle cell) forced to remain in a depolarized state for too long
- sodium channels end up struck in the inactivated state (or the open state, depending on exactly what happened0
- cell is depolarized but can no longer generate action potentials (in the inactive state, depolarization no longer opens the Na channels. If the channel is held open, the gradient for Na and/or K is abolished )
- regardless of cause: although NT release was triggered by the initial depolarization, depolarization block prevents the cell from releasing NT once the block has occurred
- essentially stuck in the absolute refractory period
249
Salvatore conduction (MS)
Occurs in myelinated neurons
250
What is the source of myelin
Central:oligodendrocytes
Peripheral:Schwann
251
Action potentials jump from node of ___ to node
Ranviee
252
Salvatore conduction _ conduction velocity
Increases
253
The myelin sheath prevents the _ from leaving the cell, so the depolarization travels quickly to the next node
Na
254
Nodes have __ channels, that the rest of the axon does not have
Voltage gated channels
255
What disease are associated with the synapse/neuromuscular junction
Myasthenia gravis, botulism, tetanus
256
Describe the presynaptic cell
Lots of mitochondria
Presynaptic voltage gated calcium channels
Vesicles containing NTsynaptic docking proteins
257
Describe the postsynaptic cell
Post synaptic densities-likely NT receptors
- ionotropic(ion channel), metabotropic (second messenger)
- may be on the dendrite but cell body and axon hillock is common too
258
Describe release of NT
- depolarization of terminal by AP causes the voltage gated calcium channels to open
- influx Ca
- Ca binds to docking proteins
- docking proteins have vesicles associated with them-the calcium binding triggers a conformational change that brings the vesicle into contact with the membrane
- fusion of vesicular with cell membrane creates opening
- NT released in synaptic trough
- NT diffuses to post synaptic cell and binds to this receptor
- triggers some AP in post synaptic cell
259
Inotropic Ca Na
Cell depolarized and an EPSP
260
Inotropic Cl K
Cell hyperpolarized and an IPSP occurs
261
Metabotropic
Gs (AC)
Gi (inhibit AC)
Gq (activate IP3/DAG)
262
How is NT removed from the synapse
Reuptake
| Enzymatic destruction in the trough
263
Monoamines from tyrosine
Dopamine-clinical relevance relevance: parkinson disease/mood/affect/emotional experience
Two metabotropic receptors
Cetecholamines
-epinephrine (adrenalin)-sympathetic ANS
-NE (noradrenalin)-sympathetic AMS
Receptors-both alpha and beta adrenergic
Removed via reuptake enzymes and enzymatic destruction
264
Monoamine NT from histidine
Histamine
Waking up
H1 and H2 receptors
265
Monoamine NT from tryptamine
Serotonin (5HT)-clinical relevance mood/affect/arousal
-multiple receptor subtypes
1 inotropic-triggers vomiting (found in area postrema)
-rest metabotropic
266
Acetylcholine NT
chloride entrance into he cell
Two receptor
GABA-a ionotropic (chloride)
GABAb-metabotropic
Higher in CNS
Clinical relevance-general anesthesia and activation to reduce speciality
267
Excitatory aa
Glutamate and/or aspartate
| Non-nmda receptors and NMDA receptors
268
Non NMDA receptors
Na influx
| Typical ionotropic response
269
NMDA receptor: calcium influx
With excess activation after seizure/stroke/TBI
| Influx of calcium excessive
270
Two divisions of the PNS
Somatic and autonomic
271
Somatic nervous system
Motor efferent to skeletal muscle
Sensory fibers going to the spinal cord or brain (includes the sensory fibers from the viscera as well as cutaneous and muscle afferent
272
Autonomic nervous system
Efferent fibers to the viscera, glands
273
What makes CSF
Choriod plexus and membranes lining the ventricles
274
Describe CDF
Starts as filtrate of plasma, but modified
Low protein, glucose, and K compared to blood
Mg is higher than plasma
275
Clinical relevance of CSF
Hydrocephalus
276
BBB two components
Tight junctions between capillary endothelial cells
Podocytes from glial cells cover the capillaries to reduce surface area
277
What does BBB do
Prevent or reduce movement from blood to CSF
278
Glucose transport across BBB
Need ransporter insulin INDEPENDENT
279
NaK2Cl BBB
Moves all four ions out of the CSF
Activation tied to K levels
280
P-glycoproteins -(permeability or pump glycoproteins):
Moves many drugs/other substances from CSF to blood
281
What can damage BBB
High bp
282
Clinical relevance of BBB
Ability of drugs to penetrate CNS; hydrocephalus
283
What circumventricular organs
Regions BBB not complete
| Tight junctions between capillary endothelial cells are not present.
284
What regions are CVO
Area postrema-at opening of 4th ventricle
OVLT and dubfornical organ-around the third ventricle (AV3V)
Posterior pituitary
285
Purpose of CVO
Require exposure to plasma constituents to do their job
286
Area postrema
Elicits vomiting in response to certain chemicals in the blood
287
OVLT/SFO
Uses plasma osmolarity to trigger thirst/ADH release
288
Posterior pituitary
ADH and ocytocin release when triggered
289
Consequence of CVO
More sensitive to damage due to toxins int he blood
| Drugs will cross the BBB in these regions
290
Cerebral blood flow is under __ control
Local
291
Cerebral blood flow has more blood flow under what conditions
More active neurons
More metabolites
More blood flow due to vasodilation
292
What conditions cause less cerebral blood flow
Less activity
Less metabolites
Less blood flow
293
__ is a potent vasodilator of cerebral blood flow
NO
294
__ dilates and cerebral blood vessel directly and indirectly
Hypoxia
295
If system blood pressure goes too high what happens
Activation of alpha adrenergic receptors on cerebral vasculature
Vasoconstriction
Prevents the high blood pressure from damaging the capillaries
The capillaries are where the BBB is-so this effect protects the BBB as much as possible
296
What happens if brain blood flow is compromised
Brain will activate pressor regions in medulla
Drive systemic pressure up to force blood through to the brain
297
The vasculature in the brain is innervated with ___ (pretty much the only place in the body)
Nociceptors
298
When is pain perceived from vasculature in the brain
Distended
Torqued/twisted/equilivent
Headache
299
Clinical relevance of cerebral blood flow
Intracranial bleeds can have dramatic effect on bp
| Increased intracranial pressure CNA lead to tremendous increases in systemic bp as the brain tries to maintain perfusion
300
Awake
Sleep/wake cycles are apparent
| Volition/consciousness may not be present
301
Aware
Different levels
| Minimally conscious->full consciousness
302
Core of system
To get to awake requires two components
Medullary reticular activating system and parabrachial nuclei
-glutamate
-both through the thalamus (dorsal path) and bypassing the thalamus (ventral path0
Pedunculopontine tegmental nucleus and laterodorsal nerve (Ach, ditto-dorsal and ventral path)
303
Serotonergic, noradrenergic, and dopaminergic are required for full awareness/consciousness
Ok
304
Clinical relevance of brain arousal mechanisms
Coma vs. persistent vegetative state vs. minimally conscious vs conscious
305
Cutaneous senses
Receptors(specialized, bare nerve endings, generally bare nerve endings have the highest threshold)
Paths to the brain
Dorsal columns (generally fine touch)
-spinothalamic tract
306
Processing in the brain
Regardless of pathway-synapses allow the signal to be refined or lost
- both related to strength of stimulus-strong stimulus=lots of AP=high probability of getting through
- prior to the cortex, most of what happens is related to making the signal as clean as possible
307
Once in the cortex what happens to the signal
S1 for initial processing-identify the characteristics of what activated the receptors
S2-stereognosis (ability t recognize an unseen object by touch, compare two. Objects, ties to memory)
308
PTO
Association complex
| Naming objects
309
Clinical relevance of brain processing
Strokes can produce disruptions in sensory processing leading to numbness
310
Nociceptors
Peripheral mechanisms
Spinal processing is different for the C fibers
Central processing of painful inputs
311
Peripheral mechanisms nociceptors
```
Bare nerve endings
Slightly myelinated (a delta fibers) or unmyelinated (C fibers)
```
The peripheral ending can be activated by numerous chemicals, including bradykinin and substance P
312
Importance of peripheral mechanisms
Leads to sensitization of the nociceptors and increased activation with similar stimulus-the pain perceived increases
313
Spinothalamic path
Likely for fast/sharp pain (a delta)
314
Spinoreticulothalamic path
Likely for slow/dull pain (C fibers)
315
Why is the spinoreticular path important
Bc there is a synapse in the spinal cord at the level where the afferent enters the spinal cord
316
Synapse in spiral cord at the level where the afferent enters the spinal cord
- gating mecahnism (gate theory of pain)-non nociceptive input from abeta fibers (cutaneous) inhibits painful inputs via presynaptic inhibition
- descending opoid inputs via the raphe nuclei also act to decrease transmission at this synapse
- prescribed opoids work to reduce pain transmission by activating this circuit
317
Central processing of painful inputs
Widespread distribution-lesioning in the brain will not block the perception of pain, although it will change it (it may be less well localized )
Insular cortex
318
Why is the insular cortex important
Coordinates autonomic responses
Damage produces pain asymbolia-painful inputs are recognized as painful, but not perceived as unpleasant
319
Chronic neuropathic pain
Results from changes in periphery
- sensitization of the nociceptors themselves
- changes in spinal cord sensitivity to nociceptive input
320
Cornea
Most refraction of light, but constant
321
Lens
Variable refraction
322
Round lens
More bending, required for something close to us
323
Flatter lens
Less bending far vision
324
Cataract
Cloudiness in lens interferes with light passages
325
Presbyopia
Inability to change shape of the lens (stiff)
326
Retina
Rods and cones
327
MOA photoreceptors
Light hitting photoreceptor causes it to hyperpolarized
| Reduces glutamate relase
328
Bipolar cells
ON center (light hitting the center of the receptive field turns the cell on)
OFF center (light hitting the center of the receptive field turns the cell of)
The difference is due to different glutamate receptors not he different cells
329
Ganglion cells
On and off centers
Dictated by bipolar cells
330
Pathway to the brain
Optic nerve->optic chiasm->lateral geniculate body->primary visual cortex->V2, V4, dorsal and ventral visual pathway
331
Optic chiasm
The fibers fromt he nasal retina on either side cross
| Thus information from either the left of the right visual field goes to the appropriate side of the brain
332
Lateral geniculate body
Eye movements-so disruptions in the lateral geniculate body disrupt the ability of the eyes to move together
- also focus
- in addition-detectionof motion and initial processing (what’s the interesting stuff here_
333
Primary visual cortex
Initial processing
Columns devoted to orientation of the lines in the visual field
Job:create a contour map of the visual field
Blobs:initial color processing
334
V2
Depth perception
335
V4
Color perception
336
Dorsal visual pathway
Use of visual information in motion
337
Ventral visual pathway
Higher cognitive processing using visual information
338
Consequence of having a dorsal and ventral visual pathway
The ability to name an object can be divorced fromt he ability to copy the object
339
Cochlea endolymph
Surrounds the hair cells
| High K low Na
340
Cochlea perilymph
Similar to plasma/ECF
| High Na low K
341
Basilar membrane
Hair cells arise from the organ of corti
342
Tectorial membrane
Top of hair cells insert into this
343
Basilar membrane
Bends based on wavelength of sound
- high pitched sounds (short wavelength) cause maximal bending close to the oval window
- low pitched sounds (low wavelength/low frequency) cause maximal bending at the helicotrema (away from the oval window
344
Pathway to brain auditory
Superior olive->inferior colliculus_.primary auditory cortex->auditory association cortex
345
Superior olive
Localization of the source of the sound
- medial detect intra-aural time differences
- lateral detects intra-aural volume differences
346
Inferior colliculus
Suppresses information from echoes
347
Superior colliculus
Creates 3D map of where the sound is
348
Primary auditory cortex
Tonotopic map of the sound, loudness
349
Auditory association cortex
Complex map of sound, including harmonies
350
Vestibular (vertigo/dizziness)
Detection of linear and angular acceleration
351
Linear acceleration (straight paths in either the horizontal or vertical dimension)
Utricle-horizontal
| Saccule-vertical
352
Angular acceleration (curved lines)
Semicircular canals
-horizontal aka lateral-turning in circles
Anterior canals-falling forward
Posterior canals-falling backward
353
As with hearing, the binding of the hair cells creates __
AP
354
Reflexes controlling eye movement when we fall/rotate are major actions
Central processing is related to suppressing the reflexes
355
Motor control clinical relevance
Spacicity, parkinson, Huntington
356
Myotactic reflex
Muscle spindles-sensitive to length of the muscle
| Stretching muscle=stretching muscle spindle-> contraction of stretched muscle
357
Parts of the muscle spindle
Middle (sensory portion)
-nuclear bag, nuclear chain fiber, afferent neurons (1a length and rate of change, II length)
End
- contractile (myosin and actin)
- efferent neuron (gamma motoneuron-behaves just like alpha motoneuron, but only influences the muscle spindle)
- role: control the sensitivity of the muscle spindle to stretch (more activity=more sensitivity, less activity=less sensitivity)
- activity of the gamma-motoneuron is controlled via the brainstem(brainstem facilitatory region-activates the gamma motoneurons, is spontaneously active)
- brainstem inhibitory region(inhibits gamma amotoneurons, requires activation by cortex, spasticity results from damage to the cortical regions that activate the brainstem inhibitory area)
358
Golgi tendon organ reflex (inverse myotatic, auto genie inhibition reflex)
Too munch force in contracting muscle could tear the tendon
- golgi tendon organ detects the force being developed
- causes strong inhibition of contracting muscle that stops the contraction
359
What works in voluntary motion
Primary motor cortex
Supplementary and premotor cortex
Cerebellum
Vestibulocerebellum
360
Primary motor cortex
Relat the desired action to the lower motoneurons to activate the muscles
361
Supplementary and premotor cortex
Planning of motions, postural control
362
Cerebellum
Spinocerebellum (medial-postural control, lateral-correct ongoing motion)
Cerebrocerebellum(planning of complex motion; motor memory
Vestibulocerebellum (eye movements/postural movements for future motions)
Basal ganglia (mother may I)
363
Direct pathway basal ganglia
- dopamine from substantia nigra
- binds to striatum neurons expressing the D1 receptos
- activates them
- dopamine allows motion (activation of the direct pathway allows motion)
- clinical relevance-Parkinsonism results from loss of dopaminergic inputs and is characterized by bradykinesia
364
Indirect pathway basal ganglia to activate
Ach activates GABAergic input
| When active, the indirect pathway inhibits motion
365
Indirect pathway basal ganglia to allow motion,
Must be inhibited at the same time the direct pathway is activated
- dopamine from nigrostriatal neurons
- binds to striatum neurons that express the D2 receptos
- D2 inhibits the neuron
- leads to inhibition of the indirect pathway
366
Huntington disease
Loss of indirect pathway results in excess motion
