Unit III week 2 Flashcards
1
Q
Light
A
electromagnetic radiation that travels in waves
2
Q
Wave length = ?
Intensity = ?
A
Wavelength = color
Blue = 420 nm Green = 530 nm Red = 560 nm
Intensity (amplitude) = brightness
3
Q
Cornea
A
provides ⅔ refractive (focusing) power for eye, transparent
4
Q
Lens
A
provides ⅓ focusing power, under neural control and allows for focusing of nearby objects, transparent
5
Q
Pupil
A
opening through which light enters
6
Q
Ciliary muscles
A
control size of pupil
Accommodation = contract ciliary muscles, makes lens fatter
7
Q
Retina
A
at back of inner eye - receptive organ of eye
8
Q
Optic disc
A
Output neurons = retinal ganglion cells → group together at optic disc → form optic nerve
No photoreceptors at optic disc = blind spot
9
Q
Photoreceptors
A
(rods/cones): capture light and convert to an electrical signal
Photoreceptors at back of eye - light must pass through all other cells before it reaches the photoreceptors
→ passes electrical signal to bipolar cells and horizontal cells then to ganglion cells
10
Q
Fovea
A
region of most acuity where other cells are swept aside
-In fovea, 1:1 ratio of photoreceptor → bipolar cell → ganglion cell
As you get more out to periphery, the receptive field is larger - many photoreceptors → one bipolar cell → ganglion cell
11
Q
Cones
A
mediate color vision, concentrated in fovea, work well only in bright light
12
Q
Rods
A
color insensitive, work best in dim light
Dominant photoreceptor away from fovea
13
Q
Horizontal cells
A
Mediates receptive field surround
Photoreceptors release glutamate (excitatory) onto horizontal cells
Horizontal cells release GABA (inhibitory) onto neighboring photoreceptors in field center
Modulate vertical flow of information via LATERAL information flow
14
Q
Steps of Phototransduction
A
Light comes in, photon absorbed by Vitamin A (attached to membrane protein)
→ RHODOPSIN = opsin (7 transmembrane spanning protein) + retinal (light sensitive molecule)
→ intracellular cascade, activates TRANSDUCIN
→ cGMP phosphodiesterase
→ decrease in cGMP
→ close Ca2+ channels, and cell hyperpolarizes
Cell at -40mV in dark → in light hyperpolarizes to -70 mV (reversal potential of K+)
Increased intensity → increased hyperpolarization
15
Q
Ganglion cells
A
only cells that make APs - all others communicate by graded changes in membrane potential which alters the rate of exocytosis of NT in a graded fashion
Ganglion cells either have ON center/OFF surround receptive fields or OFF center/ON surround
Get glutaminergic (excitatory) input from Bipolar cells
16
Q
Bipolar cells
A
either have receptors that are excited by glutatmate (OFF center) or inhibited by glutamate (ON center)
Bipolar cells ALWAYS make excitatory synapses on ganglion cells
Determine receptive field property of ganglion cell!
17
Q
On center ganglion cells
A
excited by light shining in their centers, inhibited by light in periphery
18
Q
On center ganglion cells:
Light shone on photoreceptor in center:
→ photoreceptor _________ and releases less _______ onto _______ glutamate receptors of Bipolar cells
→ ______ inhibition of bipolar cells
→ _______ released by bipolar cell
→ ________ of ganglion cell
A
→ photoreceptor hyperpolarizes and releases less glutamate NT onto INHIBITORY glutamate receptors of Bipolar cells → LESS inhibition of bipolar cells → MORE NT released by bipolar cell → excitation of ganglion cell
19
Q
On center ganglion cells:
Light shone on photoreceptors in surround
1) → photoreceptor _______ and releases __________
2) → reduce excitation of _______ cells
3) → horizontal cells __________ and release ________ onto neighboring photoreceptors in field center
4) → center photoreceptors release ______ glutamate NT onto ______ cells with ________ glutamate receptors
5) → inhibition of ______ cells increase when light shines on periphery
6) → ________ bipolar cell excitatory input to ganglion cell
7) → ________ firing rate of ganglion cell
A
1) → photoreceptor HYPERPOLARIZES and releases LESS GLUTAMATE
2) → reduce excitation of HORIZONTAL cells
3) → horizontal cells HYPERPOLARIZED and release LESS GABA onto neighboring photoreceptors in field center (decrease inhibition)
4) → center photoreceptors release MORE glutamate NT onto BIPOLAR cells with INHIBITORY glutamate receptors
5) → inhibition of BIPOLAR cells increase when light shines on periphery
6) → REDUCE bipolar cell excitatory input to ganglion cell
7) → REDUCE firing rate of ganglion cell
20
Q
What are the 4 synapses in determining the receptive field properties of ganglion cells
2 excitatory
1 inhibitory
1 ??
A
2 excitatory =
1) photoreceptor→ horizontal cell
2) bipolar cell → ganglion cell
1 ALWAYS inhibitor =
1) horizontal cell → photoreceptor synapses
1 may be: field center photoreceptor → bipolar cell
-excitatory (OFF center bipolar cell, excitatory glutamate receptor on bipolar cell)
OR
-inhibitory (ON center bipolar cell, inhibitory glutamate receptor on bipolar cell)
21
Q
Rebound Response
A
** after light turned off indicates that light was in the inhibitory part of the receptive field
22
Q
Off center ganglion cells
A
excited by light in periphery, inhibited by light in center
23
Q
Color-opponent ganglion cells
A
- Cones of different color preferences converge in retina to produce ganglion cells with receptive fields partial to particular colors
- Bipolar cells in fovea connected directly to one kind of cone in field center, and indirectly (via horizontal cells) to cones with a different color preference in field surround
→ Red-green opponents (e.g. RED ON-center and GREEN OFF-surround)
→ Blue-yellow opponents
24
Q
Pupillary eye reflex
A
shine light in one eye, muscles in iris contract (pupil smaller) → consensual constriction in other eye
25
Mechanism of pupillary eye reflex (5 steps)
1) Light → AP in ganglion cells
2) → Pretectum gets excitatory input from BOTH eyes
3) → synapse in BOTH Edinger-Westphal nuclei (R and L)
4) → excite ciliary ganglion cells (preganglionic parasympathetic motor neurons)
5) → excitation of muscles in BOTH irises
26
Central visual pathway
optic nerve --> __________ --> ___________
optic tract then synapses in what 4 major regions
Optic nerves from two eyes merge at optic chiasm → axons from nasal half of each retina decussate → continue as optic tract
Optic tract stops at:
1) LGN (thalamus)
2) Pretectum
3) Suprachiasmatic nucleus of hypothalamus
4) Superior colliculus
27
RIGHT optic tract contains axon from where?
Right optic tract contains axons from RIGHT side of each retina which see the LEFT side of the visual world → right LGN
28
Pretectum
important for pupillary eye response
gets input from BOTH eyes and projects to BILATERAL Edinger-Westphal nuclei for pupillary eye reflex
29
Suprachiasmatic nucleus of hypothalamus
One stop of optic tract
important for visceral functions of day/night cycle
30
Superior colliculus
One stop of optic tract
coordinates head and eye movements
31
Lateral Geniculate Nucleus (LGN)
- represents what visual field?
- does it have binocular cells?
- represents termination of what cells?
- how many layers is its cortex?
- sends projects out via what and to where?
LGN represents CONTRALATERAL visual field
**Gets input from both eyes, but eye origin remains separate in LGN layers → NO BINOCULAR INTERACTION IN LGN
After LGN, axons involved in visual processing fan out in OPTIC RADIATIONS to VISUAL CORTEX
Ganglion cell axons end in LGN
LGN composed of 6 layers
32
What layers of the LGN represent the contralateral eye
Layers 1, 4, 6 → contralateral eye (nasal axons decussated at chiasm)
33
What layers of LGN represent the ipsilateral eye
Layers 2, 3, 5 → ipsilateral eye
34
Magnocellular ganglion cells
-in what LGN layers?
-responsible for what?
acuity?
receptive field size?
doesn't do what?
Layers 1, 2
spatial vision, motion and depth
Low acuity, large receptive fields, responsive to motion, no color vision (input from rods)
35
Parvocellular ganglion cells
-in what LGN layers?
-responsible for what?
acuity?
receptive field size?
doesn't do what?
Layers 3-6
object vision, color, form, detail
High acuity, small receptive field, not responsive to motion, color vision (input from cones)
36
The parvocellular and magnocellular systems do what as they go to the visual cortex?
Two systems established in retina, remain segregated at LGN, and travel in separate, but parallel pathways through visual cortex
Parvocellular and magnocellular pathways project to different LGN layers → different layers in V1 → different layers in V2
parvocellular = color, form --> VENTRAL pathway, stripe and interstripe region in V2
Magnocellular = motion, depth --> DORSAL pathway, thick stripe in V2
37
Visual cortex
area 17
above and below calcarine fissure of occipital lobe
38
Retinotopic map
LGN axons radiate to visual cortex (V1) creating a map
Distorted because tiny fovea region has ½ of visual cortex
39
Hypercolumn
each microregion of V1, about 1mm on a side
Layered 1-6
contains simple cells, complex cells, blobs and ocular dominance columns
40
Input from 10,000 LGN axons, terminate in layer _______ of the visual cortex and create ______ cells that then send axons up and down in same hypercolumn to create ________ cells
Output of each hypercolumn exits layer _____ or _____ to go to higher visual areas
layer 4
simple cells send axons up and down in same hypercolumn to create complex cells
Layer 3 or 6
41
Ocular dominance columns
divide each hypercolumn in half for each eye → ganglion cells in a specific region of retina for each eye sends axons to side-by-side slabs of cortex
Cells at border between two eyes = BINOCULAR - receive input from both eyes
42
Line orientation and the visual cortex
lines in visual field lie in different rays of pinwheels
All cells in a vertical column are sensitive to same orientation
Horizontal rows are a pinwheel of different orientations
--> Orientation column pinwheels spin out over cortical surface, interconnected with neighboring hypercolumns
43
Color information is processed in the visual cortex where?
separated out from spatial information in retina, and handled in central regions of hypercolumns called BLOBS
44
Parallel processing of visual system
requirement that dissimilar dimensions (e.g. color and form) must be analyzed by separate, but parallel, neural systems
For different dimensions of an image(e.g. Shape, color, motion, spatial information) we have analogous systems that use hierarchical processing to construct higher levels of representation in their dimensions
45
Hierarchical processing of visual system
use successive synaptic integrations of highly specific synaptic inputs to construct higher and higher levels of representation of the retinal image until eventually we have cells that respond only to the complete form of an object
46
Dorsal Pathway from V1 goes through _________ --> _________ --> _________
"Thick Stripe" region of V2
Middle Temporal region of V5
Parietal lobe
47
Dorsal pathway is responsible for what?
travels from V1 dorsally to parietal lobe
Spatial vision - Motion, depth perception, WHERE pathway
48
Lesion to the middle temporal region of V5 results in what?
Middle Temporal important for direction and depth
Lesions to MT → impaired motion and depth perception
49
Ventral pathway from V1 goes through _______ and ________ region of _______ --> ________ --> _________
"Stripe" and "Interstripe" region of V2
V4
Temporal lobe
50
Ventral pathway is responsible for what?
travels ventrally from V1 to temporal lobe
Object recognition - color, form, pattern vision, WHAT pathway
51
Blob cells
color only, don’t care about shape, get input from color-opponent neurons
52
V2 stripe and interstripe region receive inputs from what type of cells in V1?
BLOB cells - specific for color
53
If you have a lesion in V4, what happens?
V4 lesions → impairment in color discrimination
54
Cortical simple cells
responsive to lines with certain orientations
Cells with an ON/OFF area that is a narrow line at some preferred orientation that is flanked on each side by OFF/ON areas
Max stimulation by narrow line of light covering all ON areas
Tightly tuned within a few degrees of its best orientation
Cells in the same penetration show same orientation selectivity
Generated by several overlapping LGN and ganglion cells that converge on one cortical cell in area V1 = hierarchical processing
55
How are cortical simple cells an example of hierarchical processing?
several cells with similar but spatially offset receptive fields converge on a higher order cell to create an altogether new type of receptive field (ON/OFF center ganglion cells --> simple cells with lines)
56
Cortical complex cells
receptive fields like simple cells but they abstract for position
Line or edge can be anywhere within receptive field and these cells like to see lines or edges moving across the field
Generated by excitatory synapses onto complex cells by convergence of several simple cells whose positions are slightly offset = hierarchical processing
57
Binocular Cells
receive input from LGN from both eyes
Receptive fields of two eyes are identical in orientation, region of retina, width, and on/off organization
Found at borders of ocular dominance columns
Mediate depth perception - select cells fire when object is certain distance away
58
Photoreceptor:
```
Location?
Diffuse light?
Receptive field shape?
Orientation selective?
Binocularly driven?
Position sensitive?
```
```
Location - retina
Diffuse light - ok
Receptive field shape - tiny spot
Orientation selective - NO
Binocularly driven - NO
Position sensitive - YES
```
59
Ganglion cell
```
Location?
Diffuse light?
Receptive field shape?
Orientation selective?
Binocularly driven?
Position sensitive?
```
```
Location - Retina
Diffuse light - so-so
Receptive field shape - Donut
Orientation selective - NO
Binocularly driven - NO
Position sensitive - YES
```
60
Simple cell
```
Location?
Diffuse light?
Receptive field shape?
Orientation selective?
Binocularly driven?
Position sensitive?
```
```
Location - Cortex
Diffuse light - NO
Receptive field shape - Bar
Orientation selective - YES
Binocularly driven - YES
Position sensitive - YES
```
61
Complex cell
```
Location?
Diffuse light?
Receptive field shape?
Orientation selective?
Binocularly driven?
Position sensitive?
```
```
Location - Cortex
Diffuse light - NO
Receptive field shape - Edge
Orientation selective - YES
Binocularly driven - YES
Position sensitive - NO
```
62
Monocular Deprivation
Normally: binocular cells receive inputs from both eyes with receptive field positions and orientation in two eyes being identical
Monocular deprivation during sensitive period of cortex development causes synaptic connections in cortex from deprived eye to degenerate and disappear
DOES NOT recover if deprived eye is reopened for duration of sensitive period - once connections are lost, they are gone for good
BUT retinal ganglion cell and LGN receptive fields remain intact (normal pupillary reflex)
If one eye is deprived at birth, the bands in LGN change - bands from deprived eye are reduced in size, and normal eye bands are expanded
Showed that you either “Use it or lose it”
63
Binocular Deprivation
Use it or lose it hypothesis would predict that cortex would be silent, with few synapses form either eye...WRONG!
Primary visual cortex was mostly normal (but animals were blind in both eyes), lots of binocularly driven cells
Showed that competition between converging synaptic inputs from two eyes, not disuse atrophy, is the mechanism
64
If left eye was deprived during sensitive period...what happens?
1) if right eye receives normal input
2) if right eye also deprived of vision
If right eye received normal visual input, all cortical cells would be driven by right eye
If right eye was also deprived of vision, then cortex will contain many binocularly driven cells, BUT animals were blind in both eyes (if deprived during sensitive period)
65
Strabismus
deviation of one eye
Normal visual stimuli, but each eye saw a different part of visual world
→ Very few binocular cells!
Almost all cells driven exclusively by one eye or the other (half and half)
No sync, no link - synchronous activity from both eyes is necessary to insure proper synaptic connections form during development in visual cortex
Showed: Cells that fire together wire together
-Done via NMDA receptor plasticity mechanism (AMPA upregulation etc.)
66
Conclusion based on monocular deprivation, binocular deprivation, and strabismus experiments?
NOT a use it or lose it mechanism, there is a competitive interaction between contralateral and ipsilateral eye, that requires normal pattern input spatially and temporally so areas of cortex represent same point in space
67
Sensitive period
2-3 year period of time after birth when connections can be altered by visual experience (corresponds with time babies eyes are moving farther apart)
If visual deficits not repaired soon after birth → irreversible damage to vision
68
Ocular dominance
a measure of relative synaptic input to a cell from each eye
| -can range from only sensitive to ipsilateral eye, only responsive to contralateral eye, to only responsive to both eyes
69
Gross Pathology of Alzheimer's (3)
1. Diffuse atrophy
2. Area around hippocampus (meso-temporal area) disproportionate
3. Status spongiosis - present in any severe neurodegeneration
70
Histology of alzheimer's
must have BOTH neurofibrillary tangles and neuritic plaques
71
Neurofibrillary tangles ion Alzheimers
- Composed of?
- Stained with?
- Where do they begin?
bundles of paired helical filaments in cytoplasm of neurons that displace or encircle the nucleus
a. Filaments primarily composed of hyperphosphorylated forms of tau protein (normally involved in microtubule assembly)
b. Silver stain
c. First tangles begin in transentorhinal cortex
72
Neuritic amyloid plaques in alzheimer's
beta pleated sheet configuration
73
Genetics of Alzheimer's (3)
1. APP on Chr21 → early onset for pts with down syndrome, or increased risk with mutation of APP gene
2. Presenilin 1 and 2, Chr14 and 1→ altered AB
3. APO-E4 = highest risk of AD
- APO-E3 and E2, lower risk of AD
74
2 variants of frontotemporal lobar degeneration
primary progressive aphasia or behavioral variant
75
Histology of frontotemporal lobar degeneration
ubiquitin positive inclusions with TDP-43
1.TDP-43 inclusions usually associated with mutations in progranulin (growth factor secreted in response to injury and/or inflammation)
76
Pic Disease
aggregates of tau in the form of pick bodies
77
Pick bodies
Well demarcated, round, slightly basophilic inclusions in neuronal cytoplasm- aggregates of tau proteins
- silver stain darkly stains pick bodies
78
Amyotrophic lateral sclerosis
Degeneration of upper and lower motor neurons (anterior horn cells)
79
Onset of ALS
early middle age - rapid course leading to death (due to respiratory failure) in 1-6 years
80
Clinical manifestations of ALS
1. Lower motor neuron signs: symmetric atrophy and fasciculation
2. Upper motor neuron signs: hyperreflexia and spasticity
81
Pathology of ALS (4)
1. Shrinkage of precentral gyrus in severe ALS
2. Marked depletion of neurons from anterior horn of spinal cord
3. Ubiquitin-immunoreactive neuronal inclusions
4. Loss of corticospinal fibers in pyramids of medulla
82
Pathology of Parkinson's
1. Depigmentation of substantia nigra and locus ceruleus
a. Pigment incontinence and pigmentophagy
2. Lewy bodies: Neurons contain eosinophilic intracytoplasmic round inclusions
83
Genetics of Parkinson's (3)
1. PARK1 - alpha-synuclein (AD)
2. PARK2 - Parkin (AR, juvenile)
3. PARK3 through 11 - some AD, AR, with differing ages of onset
84
Dementia with Lewy Bodies
1; Second most common dementing disorder in late life
- Common to have concomitant AD
- Begins with memory impairment and progresses to movement disorder
2. Parkinson’s and Lewy Body Dementia appear to represent a clinico-pathologic continuum
85
Clinical presentation: Dementia with Lewy Bodies (4)
1. Progressive cognitive decline
2. Fluctuating cognition with pronounced variations in attention and alertness
3. Recurrent visual hallucinations that are usually well-formed and detailed
4. Spontaneous features of parkinsonism
86
Pathology of dementia with Lewy body (3)
1. Cortical atrophy less severe than alzheimer's
2. Significant atrophy of limbic system
3. Lewy bodies present with a-synuclein
87
Clinical characteristics of Huntington disease
1. Delay of clinical abnormalities until 30-40 years
2. Course extends 15-20 years
3. Begins with athetoid movements with progressive deterioration leading to hypertonicity, dementia, and death
88
Pathology of Huntington disease (2)
1. Progressive degeneration of striatum (Caudate and Putamen) and frontal cortex with neuronal loss and gliosis
2. Loss of myelinated fibers
89
Genetics of Huntington disease
1. AD
2. Increased (more than normal 11-34) of CAG trinucleotide repeats within Huntingtin gene on chr 4p
3. Preferentially paternal anticipation is due to greater genetic instability in spermatogenesis as compared to oogenesis
90
Role of frontal lobe (6)
i. Voluntary movement
ii. Language fluency (left)
iii. Motor prosody (right)
iv. Comportment
v. Executive function
vi. Motivation
91
Role of temporal lobe (5)
i. Audition
ii. Language comprehension (left)
iii. Sensory prosody (Right)
iv. Memory
v. Emotion
92
Role of Parietal lobe (6)
i. Tactile sensation
ii. Visuospatial function (right)
iii. Attention (right)
iv. Reading (left)
v. Writing (left)
vi. Calculation (left)
93
Role of occipital lobe (3)
i. Vision
ii. Visual perception
iii. Visual recognition
94
Broca's aphasia
lesion in Broca’s area of left hemisphere (Brodmann areas 45), nonfluent aphasia
95
Motor aprosody
lesion to region equivalent to Broca’s area in right hemisphere
i.Inability to inflect speech with emotion
96
Traumatic brain injury (3)
i. Cortex damaged by direct injury via contusion
ii. Bleeding from damaged blood vessels can also occur → intraparenchymal, subdural, or epidural hemorrhage
iii. Widespread white matter damage called diffuse axonal injury is also typically present
97
Three frontal lobe syndromes
1. Disinhibition
2. Apathy
3. Executive dysfunction
98
Disinhibition:
- Where is the lesion?
- What is it?
orbitofrontal cortex lesions
1. Person can no longer adequately integrate limbic drives into an appropriate behavioral repertoire in the face of social situations where limbic drives are influential and impulse control is critical
2. Irritability, loss of empathy, impulsivity, hypersexuality, hyperphagia, violence
99
Apathy:
- Location of lesion?
- What is it?
medial frontal cortex lesions
1.Loss of motivation
100
Executive dysfuntion:
- location of lesion?
- What is it?
dorsolateral prefrontal cortex lesions
1. Loss of capacity to plan, carry out, and monitor goal-directed action
2. Problems with altering actions in response to changing environmental stimuli
101
4 cognitive disorders of temporal lobe
1. Wernicke's aphasia
2. Sensory aprosody
3. Amnesia
4. Temporal lobe epilepsy
102
Wernicke's aphasia
auditory comprehension is impaired because of lesion in posterior region of left superior temporal gyrus (Wernicke’s area, Brodmann area 22)
103
Sensory aprosody
diminished ability to comprehend emotional inflection in speech - lesion in right hemisphere analogue of Wernicke’s area
104
Amnesia related to temporal lobe
due to removal of hippocampus bilaterally
105
Limbic system is in the ______ lobe
temporal
106
Limbic system
(fight/flight, feeding, sexuality)
1.Circuit of hippocampus, parahippocampal gyrus, cingulate gyrus, anterior nucleus of thalamus, mammillary bodies, fornix = center of human emotional function
107
Temporal lobe epilepsy (TLE)
a. Related to focal cortical lesions in temporal lobe that produce complex partial seizures
b. Many behavioral phenomena can be associated with these seizures → deepend emotionality, hyperreligiosity, philosophical interests, hypergraphia
c. Interictal state of patients with TLE
108
Parietal lobe lesion deficits
produce deficits in tactile sensation, but also cognition → visuospatial dysfunction, inattention to contralateral space (right parietal with left hemineglect), and reading, writing, and calculation disorders (all with LEFT side lesions)
109
Hemineglect
failure to report, respond to, or orient to sensory stimuli that cannot be explained by primary sensory dysfunction
1. Inattention to one side of the body or extrapersonal space
2. Due to RIGHT parietal hemisphere lesions
110
Why is hemineglect due to right hemisphere lesions?
a. Right hemisphere has capacity to attend to both sides of space, whereas left can only attend to contralateral space
b. Thus a right parietal lesion will only permit surveillance of RIGHT hemispace
c. Left hemineglect is more severe and lasting than right hemineglect
111
Occipital lobe lesions lead to what?
visual function → hemianopia, quadrantanopia often
112
Occipitotemporal cortex:
VENTRAL stream, WHAT
113
Occipitoparietal cortex:
DORSAL stream, WHERE
114
Visual field deficits
actually have problems seeing object
115
Visual agnosia
Deficit to occipitotemporal or occipitoparietal cortex causing impairment with recognition - object SEEN normally, but adequately recognized
116
Lesion causing object agnosia
Left occipitotemporal lesion
117
Lesion causing face agnosia (prosopagnosia)
Right occipitotemporal lesion
118
Lesion causing sumultanagnosia (failure to recognize entirety of visual array)
bilateral occipitoparietal lesions
119
Cerebral disconnection
lesion disconnecting one part of brain from another causing behavioral disturbances
120
2 examples of cerebral disconnection
i. Conduction aphasia = linguistic disconnection due to damage to arcuate fasciculus (Wernicke’s area is disconnected from Broca’s area)
ii. Hemispheric disconnection = lesions of corpus callosum
- Surprisingly few effects - get anomia, agraphia, apraxia of left hand
121
Types of eye movements (4)
1) Smooth pursuit
2) Saccades
3) VOR and Optokinetic nystagmus (OKN)
4) Vergence
122
Smooth pursuit
tracking (to keep an object on the fovea)
visually-evoked tracking of movements
Used once object is on or near the fovea
Slower movements to track a moving object
Analyze position, direction of movement, and speed in visual cortex
→ descending command to brainstem conjugate movement pattern generators
Can only maintains foveation at max rate of 50 degrees/sec
Completely dependent on visual input
123
Saccades
rapid, ballistic (to bring an object onto the fovea)
rapid eye movement that brings eyes to a predetermined target or position
Ballistic in character - programmed to foveate a particular target even if target moves after saccade was initiated
Up to 700 degrees/second
124
Vestibular Ocular Reflex (VOR) and Optokinetic Nystagmus (OKN)
combination of pursuit and saccades
125
Vergence
moving the fovea to an object closer (convergence) or farther away (divergence)
126
Lateral and medial recti --> what movement?
Superior and inferior rectus → what movement?
Superior and inferior oblique → what movement?
Lateral and medial recti → horizontal rotation
Superior and inferior rectus → vertical displacement
Superior and inferior oblique → rotation about visual axis, and some vertical movement
127
contains motor neurons for what extraocular muscles?
Oculomotor (III) nuclei
Trochlear (IV) nuclei
Abducens (VI) nucleus
Oculomotor (III) nuclei: medial rectus, inferior and superior rectus, and inferior oblique muscles
Trochlear (IV) nuclei: superior oblique
Abducens (VI) nucleus: lateral rectus muscle
128
Conjugate Movements
eyes move same amount in same direction
EX) VOR: eyeball rotation precisely opposing head rotation
Can be fast (saccades), or slow (tracking movements)
Elicited by visual and vestibular inputs
129
Optokinetic nystagmus
rhythmic pattern of saccades and tracking movements - visually evoked nystagmus due to a moving visual stimulus
130
Vergence Movements
eyes moving in opposite directions
EX) near reflex
131
Near Reflex
both eyes town nasally to focus on near object
Both medial recti contract → pull eyes nasally
Pupils constrict to increase depth of field
-Ciliary muscle contract → lens becomes fatter (for focus on near object)
132
Pattern generator for horizontal saccades
Paramedian Pontine Reticular Formation (PPRF) (near abducens nucleus)
Horizontal saccades driven CONTRALATERALLY - saccade to left driven by activity in right frontal eye field
133
Important control center for saccades (2)
cortex (FEF) and superior colliculus
134
Frontal eye field
anterior to head representation in motor cortex
voluntarily generated saccade
135
Frontal eye field can activate saccades via two pathways
1) Direct to reticular formation
2) Via superior colliculus to reticular formation
- Involves auditory spatial map, retinotopic map, and somatotopic map all superimposed on motor map for the movement resulting from saccade
136
Change in saccades how?
Damage superior colliculus →
Damage to frontal eye field →
Damage superior colliculus and frontal eye field →
Damage superior colliculus → saccades less accurate, occur less often, but still happen
Damage to frontal eye field → TEMPORARY loss of ability to generate saccades
Damage superior colliculus and frontal eye field → permanent loss of ability to make saccades
137
“Blindsight response”
occurs with stroke in visual cortex
light flashed in dark room, eyes foveate to light, but the say they didn’t see anything → superior colliculus still drives saccade
138
6th nerve (abducens) deficit --> ?
6th nerve (abducens) → cannot laterally rotate in side ipsilateral to lesion
139
3rd nerve palsy (oculomotor) → ? (3 symptoms)
3rd nerve palsy (oculomotor) → ptosis (drooping eyelid), down and out position of eye (lateral rectus remains intact, but medial rectus not), and mydriasis (pupil dilation)
140
Children with hydrocephalus → what eye exam findings? (3)
setting sun gaze (problems with upgaze) + enlarged pupils + sluggish to react
141
Parietal Eye Field (PEF)
reflexive direction of saccade
→ activate Brainstem Gaze Center (BGC) directly, or indirectly through Superior Colliculus (SC)
142
Dorsolateral Prefrontal Cortex = DLPC
Inhibits reflex saccades, provides advanced planning of saccades
143
Supplementary Eye Fields = SEF
Coordinates saccades with body movement
144
Substantia Nigra (pars reticulata) = SNPR and saccadic movements
Inhibits superior colliculus
145
Caudate Nucleus = CN
| and saccadic movements
Inhibits substantia nigra pars reticulata
CN inhibition of SNPR → activation of SC
146
**Internuclear Ophthalmoplegia
Caused by MLF damage resulting in disconnection in the coordination of medial and lateral recti during horizontal gaze movements
Right sided lesion to MLF → when patient looks left, left eye will go lateral, but right eye won’t medially deviate normally
**When looking to the right, eyes move normally!
**NO defect in convergence!
Common in patients with MS
147
Nystagmus
aka vestibular nystagmus
Sawtooth movement of eyes, slow ramp opposite to head rotation, fast saccade to center of eye position
Head turns right, then eyes counter rotate left - if head continues to turn, eyes slowly rotate left until the limit of eye rotation is reached, then snap quickly back (right) to a new fixation point
Direction of nystagmus defined by direction of rapid saccade
148
Refractive Errors (4)
nearsightedness, farsightedness, astigmatism, presbyopia
When light doesn’t focus properly on retina, causes blurred vision and difficulty performing daily activities
Vision can be corrected with glasses to help focus light rays more precisely in eye and in turn improve vision
149
Nearsightedness
optical power of eye is too large and causes light to focus in front of the retina
150
Farsightedness
optical power of eye is too small and causes light to focus behind the retina
151
Astigmatism
shape of cornea causes light to focus in front or behind retina
152
Presbyopia
results when eye progressively loses ability to focus on near objects
Caused by natural aging as lens becomes less flexible
Around age 40-50 years
Treatment with simple magnifying lenses or bifocals can help improve near vision
153
Basic Eye Exam: (6 components)
1) Visual Acuity: one eye at a time at 20 foot distance
2) Visual Fields: look at nose, cover one eye, old up fingers in visual fields
3) Ocular Motility: follow finger left, right, up and down
4) Pupils: round, reactive to light, equal
5) External exam (eyelids, conjunctiva, cornea)
6) Fundoscopic exam (red reflex, disc, retina)
154
Unilateral Red Eye: (8)
1) Bacterial/Viral conjunctivitis
2) Iritis
3) Corneal abrasions
4) Corneal ulcers
5) HSV keratitis
6) Herpes Zoster Ophthalmicus
7) Pterygium
8) Subconjunctival hemorrhage
155
Bacterial conjunctivitis
2 common bugs that cause it
“Pink Eye”
Inflammation of conjunctiva caused by bacterial infection
Most common = Staph aureus and Strep pneumoniae
156
Bacterial conjunctivitis
Symptoms
Red eye with purulent discharge
-minimal loss of vision
More inflammation of conjunctiva than viral (red)
Purulent discharge (white-yellow color)
Eyelid swollen, almost closed
157
Bacterial conjunctivitis
Treatment
Antibiotic eye drops for one week
Usually self-limiting, but treatment shortens clinical course and reduces person-to-person spread
158
Viral conjunctivitis
More common than bacterial conjunctivitis
Common after URI
Adenovirus most common cause
159
Viral conjunctivitis (3)
Symptoms
Moderate inflammation of conjunctiva (pink)
Associated with watery discharge
+/- preauricular lymph node enlargement
160
Viral conjunctivitis
Treatment
Hand hygiene so it doesn’t spread to contralateral eye
No specific treatment - self-limiting within a week
Cool compresses and artificial tears
161
Iritis
form of uveitis with inflammation of iris
162
Iritis
Symptoms (6)
```
Can have acute onset
Ocular/periorbital eye pain
Photophobia
Blurred/cloudy vision
Redness (near limbus=junction between cornea and sclera)
Irregular shape of pupil
```
163
Iritis
Treatment
- Topical steroid drops
- Dilating eye drops
- Occasionally topical glaucoma drops
**Second recurrence → systemic workup recommended
164
Corneal abrasions + Symptoms (6)
painful scratch involving cornea
Severe eye pain or foreign body sensation with acute onset, tearing, blurred vision, and redness
Exam may show irregular epithelium, slightly cloudy
165
Corneal abrasions
Treatment
Mild → artificial tears, topical abx
Large → abx, patching of eye, oral pain meds
NO topical anesthetic eye drops → delay healing process
166
Corneal ulcers
+ causes?
(bacterial keratitis): infection of corneal stroma
associated with injury/abrasion, contact lens wear
167
Corneal ulcers
Symptoms (8)
acute onset, severe pain, redness, decreased vision, eyelid swelling
White infiltrate seen in cornea
+/- thinning of cornea where infiltrate is present
+/- Hypopyon inside anterior chamber
168
Corneal ulcers
Treatment
Small → 4th gen fluoroquinolone
Large → culture + fortified abx (vanco, tobramycin) - REFER
Slow healing, can require weeks of therapy
**Can leave corneal scar with permanent vision loss
If corneal thinning results in perforation, corneal transplant can be performed
169
HSV keratitis:
viral infection of corneal epithelium
Primarily HSV-1
One of the most frequent causes of permanent vision loss
170
HSV keratitis:
Symptoms (5)
Acute onset with variable symptoms of pain, visual blurring, and watery discharge
```
Unilateral eye redness (can be bilateral)
Pain
Photophobia
Decreased vision
Tearing
```
171
HSV keratitis:
Special test
Fluorescein on ocular surface shows dendritic epithelial ulcer in branching pattern with terminal bulbs
172
HSV keratitis:
Treatment
typically resolves spontaneously
Topical trifluridine
Oral acyclovir
Once healed, may have corneal scar, can cause blurred vision
173
Herpes Zoster Ophthalmicus + Symptoms
reactivation of VZV
Symptoms: prodromal period of fatigue, low grade fever, unilateral rash on forehead, upper eyelid, and nose
Includes dermatological involvement of V1 distribution
Unilateral eye pain, redness, decreased vision, photophobia
174
Herpes Zoster Ophthalmicus
special test
Fluorescein on corneal surface can reveal multiple swollen lesions with staining around them
175
Herpes Zoster Ophthalmicus
treatment
Oral acyclovir or valacyclovir
Neurotrophic cornea may develop
At risk for chronic dry eye and infections requiring chronic artificial tear supplements
176
Pterygium
benign fibrovascular tumor
UV induced
Often becomes inflamed
Treatment: artificial tears, sunglasses, vasoconstrictors (short term), conjunctival autograft with tissel glue
177
Subconjunctival hemorrhage
ruptured blood vessel under conjunctiva
Can happen in absence of trauma, but can happen with sneezing, coughing, excessive eye rubbing, trauma
Usually asymptomatic
No treatment necessary - resolves in one week
178
Bilateral Red Eye (2)
Allergic conjunctivitis
| Dry Eyes
179
Allergic conjunctivitis
| + Symptoms (4)
occurs when allergens irritate the conjunctiva, seasonal
| Symptoms: itching**, eyelid swelling, redness, watery discharge
180
Allergic conjunctivitis + treatment (4)
Avoid offending allergens
Topical antihistamine
Topical mast cell stabilizers
Topical steroids
181
Dry Eyes + symptoms (4)
common disorder of the tear film
```
Symptoms:
Foreign body sensation
Blurred vision
Reflex tearing
Condition worsens towards end of day and activities that require attention (Reading, computer work)
```
182
Causes of dry eye
Body not making enough tears
- Systemic conditions: rheumatoid arthritis, lupus, grave’s disease
- Medications: antihistamines, pain meds, antidepressants
May also occur if they are producing tears, but it’s just evaporating quickly
183
Special tests: for dry eyes (2)
Schirmer's test
| Corneal staining pattern
184
Treatment for dry eyes (5)
1) Artificial tears
2) Flaxseed oil, omega-3 vitamins
3) Medicated eye drops to help improve tear production (restasis)
4) Modification of oral medications, treatment of underlying systemic disease
5) Punctal plugs - tear outflow blocked
185
Angle Closure Glaucoma
risk factors (3)
Risk factors: ethnicity (asian), age (60s-70s), and hyperopia
186
Angle Closure Glaucoma
symptoms (6)
```
Unilateral, severe eye pain
Nausea
Redness
Blurred vision
Halos around lights
**sight threatening glaucoma
```
187
Angle Closure Glaucoma
exam findings (5)
```
Sluggish mid-dilated pupil
Conjunctival injection
Hazy cornea
Shallow anterior chamber
Eye may feel hard on palpation
```
188
Angle Closure Glaucoma treatment
laser peripheral iridotomy
Allow aqueous to gain access to anterior chamber and opens trabecular meshwork
189
Open Angle Glaucoma
+ risk factors
Progressive disease of optic nerve
Associated with elevated IOP
-Elevated IOP causes stress on optic nerve → nerve cell damage, enlargement of optic nerve
Risk factors: age, ethnicity, myopia, family history
190
Open Angle Glaucoma
Symptoms
Symptoms: Usually do not experience symptoms - slowly causes damage to peripheral vision
191
Cataracts
| + symptoms
- gradual clouding of eye’s natural lens
- Purpose of lense is to focus light on retina
- Causes progressive decline in vision as it obstructs light from entering eye
-Symptoms:
Vision like looking through dirty window, color desaturation, or night-time glare and halos
-Develops with age as lens proteins breakdown
```
-Can occur in younger patients with:
Poorly controlled diabetes
Steroids
Trauma
Radiation
```
192
Treatment of cataracts
Cataracts develop to point that patient’s vision cannot be corrected with glasses, interfering with daily activities → surgical intervention
- Phacoemulsification: lense removal using ultrasound probe through small incisions
- Cataract replaced with artificial lens
- Necessary to allow for functional vision post-op
193
Symptoms of orbital floor fracture
pain, ecchymosis, edema, proptosis, enophthalmos, emphysema, nausea/vomiting, bradycardia, diplopia, double vision
194
Basal Cell Cancer of eyelid
Commonly involves lower eyelid
Tx = excision with margin control (Mohs surgery) and reconstruction
195
Thyroid Eye Disease
Primary inflammatory disease of orbital soft tissue
Get huge swollen eyes due to EOM hypertrophy, hyaluronic acid overproduction, and immune cell proliferation
Autoimmune disease: target is orbital fibroblast
196
Autoimmune mechanism behind thyroid eye disease
Autoimmune disease: target is orbital fibroblast
- Orbital fibroblast expresses TSH-R and ILGF-R
- Stimulatory autoantibodies (TSI) stimulate orbital fibroblast to produce proinflammatory cytokines and recruit inflammatory cells into orbital soft tissue
- Leads to production of hyaluronan (glycosaminoglycan, GAG)
- Lymphocyte infiltration, GAG production, and orbital fibroblast proliferation (adipogenesis) causes EOM hypertrophy
Associated with autoimmune thyroid disease (Graves)
-Dysthyroidism is NOT the cause
197
Treatment of Thyroid Eye Disease
1) Typically self-limited disease
2) Immunomodulators during active phase (lasts 18-36 months)
3) Surgery during quiescent phase - make orbit bigger via decompression surgery (take out medial part of orbit so fat, muscles, etc can expand into nose
198
Nasolacrimal duct obstruction
blockage in lacrimal duct (below lacrimal sac)
- Chronic NLDO → epiphora (overflow of tears onto face), chronic dacryocystitis
- Acute NLDO → Dacryocystitis (infection of lacrimal sac)
Treatment: Dacryocystorhinostomy (DCR)
199
Macula
-region in retina = fovea and foveola, central vision
```
Fovea = central 1.5 mm, sharp central vision
Foveola = central 0.35 mm, small depression in retina
```
200
Peripheral retina is responsible for what?
peripheral and night vision
201
Ora serrata
anterior termination of retina (just behind lens and pars plana)
202
Pars plana
posterior ciliary body (right behind lens)
203
Retinal pigment epithelium (RPE)
- Provides support for photoreceptor metabolism and provides tight blood-retina barrier
- Potential space between neurosensory retina and RPE --> fluid/abnormal waste products can collect there
204
Vasculature of retina:
Central retinal artery
Central retinal vein
Capillaries
Central retinal artery
- Branch of ophthalmic artery from internal carotid artery
- Blood to inner ⅔ of retina
- Smaller than veins, lighter color
Central Retinal vein - drains blood supply from eye
Capillaries = form inner blood-retina barrier
205
Choroid
middle layer between sclera and retina
vascular supply, metabolic and nutritional support
Vascular layer with highest blood flow per tissue weight (provides blood to outer ⅔ of eye)
206
Possible pathologies of choroid (3)
1) Uveitis: inflammation of choroid/uveal tissue
2) Choroidal nevus
3) Tumors - mets (melanoma)
207
Sclera
outer layer, white, fibrous covering
208
Vitreous
main volume of posterior eye (water, hyaluronic acid, collagen)
209
Vascular supply for optic nerve: _______ and _________ branching from ___________ artery
possible disease of optiv nerve (CN II)
Vascular supply: ophthalmic artery → posterior ciliary artery branches to optic disc and pial capillaries
Diseases: glaucoma
210
Sub-retinal hemorrhage
between retinal pigment epithelium and sensory retinal layer
211
Dot-Blot hemorrhage
common in what disease?
common in diabetes, middle layer of retina
-can be present in Non-proliferative diabetic retinopathy (NPDR)
212
Flame hemorrhage
common in what disease?
common in HTN
follows nerve fiber layer, inner layer of retina
-can be present in Non-proliferative diabetic retinopathy (NPDR)
213
Preretinal hemorrhage
boat shaped
obscures retinal vessels
in front of retinal layer
214
Vitreous hemorrhage
common in what disease?
diffuse bleeding into vitreous cavity
obscures retina
common in diabetes
215
Lipid/Exudative disease in the eye
common in what disease?
Lipids leak from retinal vessels → common in diabetes
-can be present in Non-proliferative diabetic retinopathy (NPDR)
216
Drusen
hallmark of what disease?
yellow circular deposits underneath retina
hallmark of macular degeneration
217
Cotton wool spot
common in what diseases?
fluffy white areas, capillary ischemia → common in diabetes and HTN
218
Choroidal nevus
benign pigmented neoplasm, asymptomatic, incidental finding
219
Diabetic retinopathy
risk factors (4)
#1 cause of blindness in working age adults
Risk factors: duration of diabetes, glycemic control, blood pressure, pregnancy
220
Pathophysiology of diabetic retinopathy
Microvascular injury to small vessel capillaries → retinal hemorrhage, capillary leakage → ischemia
→ Neovascularization: eye trying to compensate for ischemia, but areas where new vessels are cause problems
Two types: Non-proliferative diabetic retinopathy (NPDR) and Proliferative diabetic retinopathy (PDR)
221
Non-proliferative diabetic retinopathy (NPDR)
Early changes in eye, may be asymptomatic
Includes: Microaneurysms, flame hemorrhage, dot-blot hemorrhage
Diabetic macular edema - retina gets swollen
#1 cause of vision loss in DM
Hard exudates - lipoprotein leakage from capillaries
222
Proliferative diabetic retinopathy (PDR)
More severe, vision threatening
Neovascularization - around optic disc and peripheral retina
Fibrovascular proliferation that pulls on retina
223
Complications of Proliferative diabetic retinopathy (PDR) (3)
1) Vitreous hemorrhage - blood vessels leak into vitreous cavity causing complete loss of vision
2) Tractional retinal detachment - fibrovascular tissue pulls neurosensory retina detaches from back wall of eye and Retinal pigment epithelium
3) Neovascularization of iris → neovascular glaucoma because neovascularization of iris blocks egress of fluid from eye
224
Management of diabetic retinopathy (4)
1) Glycemic and BP control, screening eye exams
2) Laser photocoagulation
3) Anti VEGF injections
4) Pars Plana Vitrectomy (with vitreous hemorrhage)
225
Hypertensive retinopathy causes what two vascular changes
1) Vasoconstriction → arteriolar narrowing
2) Arteriosclerosis → copper and silver wiring, arteriovenous nicking
- When wall of artery gets thick
226
Acute hypertensive retinopathy (3)
1) Retinal hemorrhage
2) Macular edema and exudate
3) Optic disc edema (Papilledema if bilateral), especially with acute, severe HTN
227
Central retinal vein occlusion
→ extensive retinal hemorrhage and edema
Often related to HTN
Dilated veins, extensive hemorrhage
228
Central retinal artery occlusion
→ cherry red spots
“Stroke” to eye
229
Age-related macular degeneration is a disease of the __________
risk factors (4)
disease of choroid
Risk factors: age (>75 years), race (caucasians), gender (females), tobacco
230
Dry (nonexudative) Age-related Macular Degeneration (3)
1) Drusen - lipoprotein deposits
2) RPE changes - atrophy and hyperpigmentation
3) Geographic atrophy - severe vision loss if in fovea
231
Wet (exudative) Age-related Macular Degeneration
more vision loss, less common
- Blood vessels start to leak and bleed in back of eye
- Choroidal neovascularization (CNV) = vessels growing out from choroid into retina → subretinal hemorrhage, macular edema, scarring
232
Treatment of Wet (exudative) Age-related Macular Degeneration
Anti-VEGF intravitreal injections every 1-2 months
- First treatment to improve vision in wet AMD
- Regression of CNV
- Improved macular edema
233
Optic neuropathies (2)
Glaucoma and Papilledema
234
Glaucoma
most common optic neuropathy
Damage to nerve fiber layer and optic disc resulting in visual field loss - insidious onset of visual field loss
235
Risk factors of glaucoma (6)
age, elevated IOP, race, central corneal thickness, family history, myopia
236
Findings in glaucoma exam (4)
Elevated IOP (not in all)
Enlarged Cup/Disc or asymmetry
Optic disc hemorrhage
Visual field defects
237
Treatment of glaucoma
*Screening - asymptomatic until end stage
* Lower IOP
- Meds → decrease aqueous humor production or increase outflow
- Laser
- Surgery - drain fluid from eye to allow fluid to move from inside to outside of eye
238
Papilledema
bilateral optic disc swelling due to elevated ICP
| → Blurring of disc margin, sometimes flame hemorrhage on margin
239
Anisocoria
unequal size of pupils
can be physiological if it is the same in light and dark
240
Interrupt parasympathetic pupillary fibers --> ?
→ mydriasis (enlargement), and abnormal reaction to light
Parasympathetic → sphincter constriction (light)
241
Interrupt sympathetic pupillary fibers --> ?
→ miosis (constriction), and abnormal reaction to dark
EX) Horner syndrome
Sympathetic → radial dilation (dark)
242
“Light-near dissociation”
tonic pupil, dilated pupil that does not respond to light but will constrict during near reflex
243
Left inferior quadrantanopia is a deficit where?
lose left lower quadrant in both eyes = homonymous field loss
244
What happens if you damage the optic chiasm?
→ lose retinal vision from each eye, get tunnel vision = bitemporal field loss (NOT homonymous)
245
Left optic radiations “Meyer’s Loop” lesion
→ lose upper right quadrant in both eyes = Homonymous field loss
246
Homonymous field loss
same part of the field with respect to left to right in each eye loss of visual field
247
Left occipital lesion inferior to calcarine sulcus
lose upper right quadrant in both eyes = Homonymous field loss
below sulcus → lose vision in upper half of contralateral field
248
Calcarine sulcus lesion, above sulcus
above sulcus → lose vision in lower half of contralateral field
249
Posterior vs. anterior region of calcarine sulcus represents what regions of visual field
More posterior = more medial part of visual field
250
Optic nerve lesion/optic neuropathy results in what deficits
monocular vision loss, color vision impaired
Afferent pupillary defect = hallmark of optic nerve or optic tract disturbance
251
Afferent pupillary defect (APD)
problem prior to synapse in LGN
Hallmark of optic nerve or optic tract disturbance
EX) shine light in right eye, both pupils constrict, shine light in left eye, and it dilates = left APD
252
What four questions should you ask to determine source of diplopia
1) Is it binocular or monocular?
2) Is it horizontal or vertical?
3) Is it worse left, right, up, or down?
4) Is it worse near or distance?
253
Oscillopsia
appearance of movement of visual world, eyes not steady
EX) Nystagmus
254
Types of nystagmus (3)
1) Pendular: slow-slow
2) Jerk: fast-slow
3) Mixed: slow-slow + fast-slow
255
Routes of systemic absorption for topical drugs of eye (3)
1) Corneal route of absorption
2) Nasolacrimal route of absorption
3) Conjunctival-Scleral route of absorption
256
Corneal route of absorption
tears → cornea → aqueous humor → iris → systemic circulation
257
Nasolacrimal route of absorption
tears → systemic circulation
258
Conjunctival-Scleral route of absorption
tears → conjunctiva → sclera → ciliary body
259
Appearance of drug in aqueous humor is dependent on ______________
passive diffusion through cornea
260
Anterior Chamber of Eye
pathway for secretion and drainage of aqueous humor
Humor secreted slowly, continuously by cells of epithelium covering ciliary body → drains into canal of Schlemm
261
Primary open angle glaucoma
nerve damage, one of most common preventable causes of blindness
Associated with increased IOP
262
Drug targets in glaucoma (especially open angle)
PGs = increase aqueous humor outflow
B1 and B2 = increase aqueous humor production
Bicarb increases aqueous humor production
263
Treatment of Primary open angle glaucoma (4 types of drugs)
1) PG analog (monotherapy initially)
2) Good response to PA but short of target → add B-BLOCKER or CARBONIC ANHYDRASE INHIBITOR or A2 AGONIST
3) Poor response to PA → discontinue PA, substitute another class (B-blocker or carbonic anhydrase inhibitor)
264
Closed Angle Glaucoma
aka ACUTE congestive, narrow angle glaucoma
Less common
Pathophysiology: mechanical blockage of trabecular meshwork by peripheral iris → extreme fluctuations in IOP - requires emergent treatment
265
Goal of treatment with closed angle glaucoma
drugs with rapid onset to reduce pressure at time of attack until surgery (iridectomy/laser iridotomy) can be performed
266
Closed angle glaucoma drugs to treat (4) and their mechanism
1) Pilocarpine (cholinergic agonist) → induce miosis and contraction of ciliary muscle → free entrance to trabecular space from blockage by iris tissue, increase outflow
2) Apraclonidine and Timolol: given with pilocarpine to synergistically reduce IOP (reduce aqueous humor production)
3) Acetazolamide (Carbonic anhydrase inhibitor) → block formation of humor
4) Mannitol or glycerol → osmotic diuresis → intraocular dehydration
267
________ and _________ can precipitate closed angle glaucoma attacks
anticholinergics
| decongestants
268
Latanoprost
mechanism and use
Prostaglandin analogs
First line medical therapy for treatment of open angle glaucoma
Mechanism: Topical PGF-2a prodrug
Lowers IOP by facilitating aqueous humor outflow through accessory uveoscleral outflow pathway
269
Side effects of prostaglandin analogs (3)
brown discoloration of iris, eyelash lengthening and darkening, ocular irritation
270
Brimonidine, Apraclonidine
use and mechanism
Alpha-2 adrenergic agonists
Add on second or third line therapy of open angle glaucoma
Mechanism: topical selective a2 agonist
- Increases uveoscleral outflow of aqueous humor
- Inhibits formation of aqueous humor
271
A2 agonist side effects for eye administration (3)
red eye, ocular irritation, CNS depression
272
Timolol (use for eyes) use and mechanism
Beta-adrenergic antagonist
Common treatment of open angle glaucoma
Mechanism: preferential B2 in eye
- Reduces aqueous humor production via block of B-receptor pathway
- Decrease ocular blood flow → decrease ultrafiltration required for production
273
Side effects of B-agonists used in glaucoma (3)
systemic absorption → bradycardia, heart block, bronchoconstriction
(avoid with asthma, bradycardia, COPD)
274
Dorzolamide
mechanism and use
Carbonic anhydrase inhibitors
Add on second or third line therapy of open angle glaucoma
Mechanism:
Inhibit carbonic anhydrase in ciliary body epithelium → reduce formation of bicarb ions → reduce fluid transport and IOP
275
Dorzolamide (carbonic anhydrase inhibitor)
side effects (3)
bitter taste, fatigue, kidney stones
276
Pilocarpine
mechanism and use
Cholinomimetics
Used to treat open angle glaucoma
Mechanism: Lower IOP by causing contraction of ciliary muscle → facilitates outflow
277
Pilocarpine side effects (3)
ciliary spasm → headaches, myopia, dim vision (small pupil)
SLUDGE side effects for muscarinic agonists
278
Direct pathway, D1 vs. Indirect pathway, D2
Direct pathway, D1 → coupled to Gs → INCREASES excitatory outflow
Indirect pathway, D2 → coupled to Gi → DECREASES inhibitory outflow
279
Parkinson's is a primary loss of what dopamine pathway? what are the consequences?
Parkinson’s is a primary loss of D1 input, so “foot is off the gas” and “foot is still on the brake”
Decreased striatal DA release and leads to loss of DA “go” signal → decrease motor function
280
Antipsychotic drugs - block D2 receptors → ?
Antipsychotic drugs - block D2 receptors → can cause “Pseudoparkinson’s” because you can’t inhibit your inhibitory pathway (can’t take foot off brake) → drug induced movement disorder
281
Testing of CN II (4)
Ocular Nerve
1) Visual acuity: use best corrected vision
2) Visual fields
3) Direct ophthalmoscopy
4) Pupillary exam (size, shape, equality, reactivity, convergence)
282
Direct ophthalmoscopy
Check red reflex, then focus on red reflex to focus on optic fundus (disc + cup in middle of disc + Macula + arteries and veins)
283
Oculomotor nuclei/nerve
seen in upper midbrain (next to Edinger-Westphal Nucleus)
- III runs between PCA and superior cerebellar artery
- Does all EOM except for LR (6) and SO (4)
- CN III palsy → down and out, mydriasis (unopposed sympathetic)
284
Horner's syndrome (3)
sympathetic dysfunction, worse in dark
Ptosis (droopy eyelid), miosis (small pupil), and anhidrosis
285
Trochlear nuclei
lower midbrain
Eyes of creepy bald man - MLF = circles under guy’s eyes
Nerve exits DORSALLY (only motor nerve that exits dorsally)
Innervates contralateral SO muscle
People tend to tilt head to compensate for IV palsy
286
VI Abducens Nucleus and Nerve
Nucleus seen on pontine section
exits at ventral midline at junction between pons and medulla → innervates LR
Vulnerable to hydrocephalus 6th nerve palsy → eye deviates medially and is unable to abduct beyond midline
Send axons to ascend in contralateral MLF to III nerve nuclei (medial rectus adductor)
287
Trigeminal Nuclei (4)
1) Motor nucleus
2) Principal Sensory Nucleus
3) Spinal Trigeminal Nucleus
4) Mesencephalic nucleus
288
Motor nucleus of trigeminal
motor for muscles of mastication (medial to sensory nucleus)
Mouth/tongue may deviate to affected side
289
Trigeminal nerve enters/exits at what level of brainstem
enters at level of middle cerebellar peduncle
290
Principal Sensory Nucleus
fine touch and vibration sense of face (more lateral to motor) → contralateral VPM
V1 - includes tip of nose and forehead
V2 - Maxilla and upper lip
V3 - Lower lip and chin
291
Spinal Trigeminal Nucleus
(located in medulla) → contralateral VPM
Continuous with substantia gelatinosa in spinal cord
Spinal trigeminal tract travels down spinal cord
292
Mesencephalic nucleus
proprioception from muscles of mastications → synapses in motor nucleus
→ Jaw Jerk Reflex
293
VII: facial nerve
Motor structure, exits ventral to vestibulocochlear nerve
Travels up/around abducens nucleus before exiting brainstem
Controls muscles of facial expression
Taste of anterior ⅔ of tongue via chorda tympani nerve, terminates in nucleus solitarius
294
Divisions of facial nerve
Rostral → upper half of face
-Innervated by contralateral AND ipsilateral face motor cortex
Caudal → lower half of face
-Only gets innervation from contralateral face motor cortex
295
EX) stroke in L motor cortex of face region causes what facial features on upper vs. lower face
stroke in L motor cortex
→ R rostral face will be OK because still get motor innervation from ipsilateral side
--> R caudal (lower) face will droop
= CENTRAL FACIAL PALSY
296
EX) Bell’s palsy, peripheral nerve damage (cut facial nerve), or damage to facial nucleus itself causes what facial features on upper vs. lower face?
→ ipsilateral UPPER AND LOWER half of face will be droopy
= PERIPHERAL FACIAL PALSY
297
IX: Glossopharyngeal responsible for what? (3)
1) Pain, temp of post ⅓ of tongue → trigeminal nucleus
2) Taste post ⅓ of tongue → Nucleus solitarius
3) Gag reflex: afferent limb of gag reflex via IX
298
Dorsal motor nucleus of vagus responsible for what?
→ parasympathetic outflow to thoracic and abdominal visceral
299
XII: hypoglossal
exits where?
UMN vs. LMN damage causes what?
Exit between olive and pyramid
Damage to hypoglossal nerve/nucleus → tongue will deviate toward damaged side (LMN)
Damage to motor cortex will point away from side of lesion (UMN)
300
KNOW LOWER PONS AND UPPER-MID MEDULLA SECTIONS!!!!
look at the lab slides!
| DO IT
301
Ageusia vs. Anosmia
Ageusia = loss of taste
Anosmia = loss of smell
302
Smell receptor cells are _________________ and project via CN ____ (#) to ___________ (primary sensory nucleus in CNS)
ciliated bipolar neurons
CNI
Olfactory bulb
303
Taste receptor cells are _________________ and project via CN ____ (3 #'s) to ___________ (primary sensory nucleus in CNS)
Modified epithelial cells (that synapse onto nerve fiber from cranial ganglion cell)
CN VII (facial, ant 2/3), CN IX (glossopharyngeal, post 1/3), and CN X (vagus, epiglottis and oropharynx)
Nucleus of solitary tract
304
Chemesthesis receptor cells are _________________ and project via CN ____ (#) to ___________ (primary sensory nucleus in CNS)
Free nerve ending of cranial ganglion cell
CN V (mostly)
Spinal trigeminal nucleus (pain pathway for face)
305
Taste
provides information to brain on chemical composition of food
306
Two types of channels for taste transduction
What do they sense?
1) Ion channels (sour/pH, salty): ions can permeate ion channels directly to depolarize cell
2) Second messenger systems (bitter, umami, sweet)
- Umami detects glutamate
307
Tastebuds
4 kinds of tastebudes
consist of 50-100 taste cells
1) Fungiform papillae
2) Circumvallate papillae
3) Foliate papillae
4) Filiform papillae
308
Taste cells
Taste cells have limited lifespan (10-30 days) undergo continuous replacement by specialized basal stem cells
Taste cells individually sensitive to just ONE class of taste stimuli
CNS extracts info from POPULATION of afferent fibers activated by a particular chemical stimulus to determine sensory characteristics
-Individual afferent neurons innervates several receptor cells
309
Mechanism of taste particle activation of taste
Depolarization of taste cells (Ca2+ and Na+) → release NT from basal part of cell
ATP acting on P2X receptors on nerve fibers - crucial for taste info transmission
310
Fungiform papillae
located on anterior ⅔ of tongue
Innervated by chorda tympani branch of facial nerve
311
Circumvallate papillae
located on posterior part of tongue
Innervated by glossopharyngeal nerve
312
Foliate papillae
located on sides of the tongue
313
Filiform papillae
non-taste papillae, tactile organs
314
Posterior taste buds
oropharynx and epiglottis
more involved in consummatory reflexes (swallowing, choking) than with conscious appreciation of taste quality
innervated by vagus nerve
315
Central taste pathway:
Primary afferents from tongue run through:
_______ (anterior ⅔ of tongue)
__________ (posterior ⅓ of tongue)
_______ (epiglottis and oropharynx) nerves
→ synapse on second order neurons of ______________
Primary afferents from tongue run through
FACIAL (VII) (anterior ⅔ of tongue)
GLOSSOPHARYNGEAL (IX) (posterior ⅓ of tongue)
VAGUS (X) (epiglottis and oropharynx) nerves
→ synapse on second order neurons of IPSILATERAL NUCLEUS OF SOLITARY TRACT (NST)
316
Nucleus of solitary tract
receives ipsilateral input from VII, IX, and X for taste
Organized orotopically - map of oral cavity in nucleus so anterior parts of mouth represented anteriorly in nucleus
projects to BILATERAL VPM THALAMUS
317
Central taste pathway:
Nucleus of Solitary Tract --> ___________, ____________ and ___________, and ____________
Bilateral VPM of thalamus
Bilateral Hypothalamus and Amygdala
Reflex nuclei of brainstem
318
VPM of thalamus gets taste info from ______ and projects taste info to ________ for what?
Nucleus of solitary tract
Insula (taste cortex)
conscious appreciation of taste
319
Hypothalamus and amygdala get taste info from ________ and is responsible for what aspects of taste?
Nucleus of solitary tract
subconscious reactions to taste and control of appetite, etc.
320
Reflex nuclei of brainstem get taste info from ___________ and are responsible for what 3 actions?
Nucleus of solitary tract
1) Nucleus ambiguus (gagging)
2) Nucleus ambiguus and hypoglossal nucleus (swallowing)
3) Superior and inferior salivatory nucleus (salivation)
321
orbitofrontal cortex
“Flavor” cortex
Gets projections from primary gustatory area (anterior insula) and from olfactory areas of insula
Responsible for integration of taste and smell → perception of FLAVOR
322
Olfaction
inform brain (via olfactory bulb) of quantity and odorous quality of volatile chemicals that enter the nose
323
Olfactory neuroepithelium
covered with thin layer of mucous in which odorants dissolve and interact with olfactory receptor proteins on cilia
324
Olfactory neurons
Bipolar neurons: send single, thin, unmyelinated axon towards olfactory bulb as part of olfactory nerve (CN I)
Exposed to external environment, subject to bacterial attack, viruses, and environmental toxins
Continually undergo neurogenesis and replacement → vulnerable to mitotic inhibitors used in cancer treatment
325
Olfactory receptors
seven transmembrane spanning regions, G-protein coupled receptors, dendrites bind odor molecules
- Each olfactory receptor neuron predominantly expresses one olfactory protein receptor
- Each odorant can stimulate a number of receptors
326
Olfactory transduction
1) Odorant binds receptor protein → associated with _______ → activate _____ → local ______ generation → open _________ channel, allowing _____ and ______ ions in (does NOT cause depolarization on its own)
2) Local increase in [____] → open adjacent ________ channels → _____ flows ____ of cell → further depolarization → cell driven to threshold, AP is fired
1) Odorant binds receptor protein → associated with G protein → activate AC → local cAMP generation → open cAMP gated ion channel, allowing Na+ and Ca2+ in (does NOT cause depolarization on its own)
2) Local increase in [Ca2+] → open adjacent Ca2+ gated chloride channels → Cl- flows OUT of cell → further depolarization → cell driven to threshold, AP is fired
327
Olfactory glomeruli
Axons of olfactory neurons penetrate ethmoid bone (cribriform plate) → converge on glomeruli at outer layer of olfactory bulb
Glomeruli contain input from 1000 axons (1000 olfactory neurons)
-Olfactory receptor neurons expressing the same olfactory receptor protein project axons to SAME glomerulus
328
How are different odors represented in the olfactory bulb?
Odor-related map of glomeruli present in olfactory bulb
Olfactory receptor neurons expressing the same olfactory receptor protein project axons to SAME glomerulus
Odor epithelium has receptor cells with common receptor scattered throughout epithelium, but odorants can activate more than one receptor type
--> Identification of odor entails recognition of the PATTERN of activity across all glomeruli of olfactory bulb
329
Central olfactory pathway:
Olfactory bulb --> _________ tract --> what 4 regions?
Lateral olfactory tract
1) Piriform cortex (primary olfactory cortex in lateral olfactory gyrus + uncus)
2-3) Olfactory tubercle and Amygdala
4) Entorhinal cortex
330
Piriform cortex gets ________ info from _______ and projects it to _____________
olfactory
olfactory bulb
Orbitofrontal cortex directly or via MD nucleus of thalamus
331
Olfactory tubercle and amygdala get ______ info from _________ and projects it to ________ for what purpose?
olfactory
olfactory bulb
Hypothalamus
Visceral reactions, homeostasis
332
Entorhinal cortex gets _______ info from _______ and projects it to _______ for what purpose?
olfactory
olfactory bulb
Hippocampus
Memories
333
PROP receptors for taste
detect propylthiouracil, people differ in sensitivity to PROP
Differences in sensitivity → diet preferences and tolerance for bitter tasting medicines
Higher bitter sensitivity → eat less veggies, more nutritionally related diseases
334
PROP receptors and respiratory bacterial disease
“Bitter” receptors located in nasal cavity, trachea, and bronchi can detect bacterial signaling molecules → detect presence of lots of bacteria, and epithelial cells mount local defense and alert innate immune system
Same receptor used to detect PROP (propylthiouracil)
→ People unable to detect PROP have higher incidence of respiratory bacterial disease
335
Hypothalamus and limbic system
hypothalamus connection with limbic system allows for initiation of motivated behaviors and integration of emotional expression with sensory and environmental cues
336
Fornix connects _______ with ________
connects hippocampus with mammillary bodies
337
Stria terminalis:
connects _______ with ____________
connects amygdala with hypothalamus
338
Medial forebrain bundle: connects _________ with _________ and ________
connects hypothalamus with prefrontal cortex and septum
339
Mammillothalamic tract sends info from ___________ to ___________
info from mammillary bodies of hypothalamus to anterior nucleus of thalamus (efferent neural pathway)
340
Limbic system
responsible for modulating emotional expression such that it is appropriate to the situation
341
Sham rage
dissociation of rage response from appropriate environmental context
Observed when hypothalamus disconnected from higher brain areas, but hypothalamic connections to brainstem/spinal cord remain in tact.
Ventromedial nucleus opposes Dorsomedial nucleus and balance between the two results in coordinated response
342
Hypothalamus
coordinates endocrine, autonomic, and somatic motor responses in order to achieve homeostasis in a broad range of physiological parameters including body temperature, blood pressure, fluid and electrolyte balance, and body weight
Role in reproduction and emotional expression
Located at floor of third ventricle, and is ventral-most part of diencephalon
Interconnected with autonomic nuclei of brainstem and spinal cord
Regulates pituitary gland
343
Hypothalamus compares what input to biological set point --> generate output signal via visceral and somatic motor, neuroendocrine, and behavioral responses
INPUT:
Contextual information (cerebral cortex, amygdala, hippocampal formation)
Sensory inputs (visceral and somatic sensory pathways, chemosensory and humoral signals)
344
Location of preganglionic:
sympathetic neurons
parasympathetic neurons
Preganglionic sympathetic neurons: located in intermediolateral column T1-L3
Preganglionic parasympathetic neurons: located in brainstem nuclei (III, VII, IX, X) and S2-S4
345
Hypothalamic neurons innervate upper motor neurons in _______________ → UMN then project to LMN that innervate skeletal muscle
what actions does this region mediate?
brainstem reticular formation
Organizes/initiates complex activities that require both somatic and autonomic responses (vomiting, laughing, crying, facial expressions) and motor activities required for maintenance of homeostasis (chewing, swallowing)
346
Neuroendocrine function of hypothalamus
both direct and indirect via posterior and anterior pituitary
347
Anterior pituitary
indirect
Hypothalamus synthesizes and releases hormones into hypothalamo-pituitary portal circulation that regulates release of hormones from glandular cells of ant. Pituitary
NO dilution of hypothalamic hormones in general circulation
348
Posterior pituitary
DIRECT
Hormones of posterior pituitary (vasopressin/ADH, oxytocin) made by neurons in supraoptic (SON) and paraventricular nuclei (PVN) of hypothalamus and transported down axons of neurons to post. Pit.
Hormones stored in axon terminals until AP signals their release DIRECTLY into general circulation
349
The hypothalamus receives afferent visceral sensory information from baroreceptors, gastric/cervical stretch via what tract?
Nucleus of solitary tract
350
Circumventricular organs (4)
Regions of hypothalamus lack BBB, have fenestrated capillaries - crucial for humoral afferent input to hypothalamus
1) Organum vasculosum of lamina terminalis (OVLT)
2) Subfornical organ
3) Median eminence
4) Posterior pituitary
351
The __________ nucleus of the hypothalamus controls circadian rhythms and gets input via the _____________ tract
Suprachiasmatic
retinohypothalamic tract
352
Suprachiastmatic nucleus
hypothalamic region that gets light information from specialized retinal ganglion cells
“Central Clock”
Important for entraining our endogenous circadian rhythms to environmental light/dark cycle
Can generate rhythms without exogenous info, but light input “entrains” clock to daily environmental light-dark cycles
Peripheral clocks (e.g. liver) entrained by central clock
353
Hypothalamus role in water balance:
Sensory input to hypothalamus telling you are thirsty from where (2)
1) Hypothalamic osmoreceptors - OVLT and SFO (circumverential regions) monitor osmolality
2) Baroreceptors monitor cardiovascular volume
354
Hypothalamus role in water balance:
What does the hypothalamus do when it is notified you are thirsty? (2)
1) Release ADH from SON and PVN into POSTERIOR pituitary
| 2) Make you drink water!
355
Hypothalamus and body weight/food intake regulation:
Ventromedial nucleus/Paraventricular nucleus vs. Lateral hypothalamus
Ventromedial nucleus = satiety center
Lateral hypothalamus = hunger or feeding center
356
Ventromedial nucleus of hypothalamus and appetite:
lesion --> ?
Stimulation --> ?
Ventromedial nucleus = satiety center
Lesion → increase food intake, marked obesity
Stimulation → inhibit urge to eat
357
Lateral hypothalamus and appetite:
Lateral hypothalamus = hunger or feeding center
Lesion → anorexia, starvation, decreased responsivity to food
Stimulation → induce food intake
358
What are some ways our body increases heat production (4)
1) Basal metabolic rate
2) Exercise
3) Shivering
4) Non-shivering thermogenesis
359
Non shivering thermogenesis (NST)
infants have lots of brown fat
Can increase heat production by increasing catabolic activity of this tissue
----------(below this line is less important, but good to read)----------
Due to release of NE onto brown fat cells by sympathetic nerve fibers → signal activation of thermogenin (uncoupling protein 1) in brown fat
Thermogenin = H+ ion channel in inner mitochondrial membrane, expressed exclusively by brown fat cells
Allows dissipation of proton motive force as heat without producing ATP = uncoupling oxidative phosphorylation
360
How does our body increase heat loss?
1) Heat flow to skin (sympathetic control of blood flow to skin)
2) Sweating (sympathetic control)
361
Thermoreceptors in preoptic anterior hypothalamus (POAH)
Excitatory input from where?
Inhibitory input from where?
what happens if you lesion this area?
specialized receptor neurons within POAH that generate APs at frequency proportional to local temperature
Increase firing with increased temp at POAH region→ induce heat loss mechanisms (panting, sweating, vasodilation, cooling behavior)
Get inhibitory synaptic input from cutaneous cold receptors and excitatory input from cutaneous warm receptors → both weak inputs
Lesion → hyperthermia
362
Temperature regulation in posterior hypothalamus
Excitatory input from where?
Inhibitory input from where?
what happens if you lesion this area?
Excitatory input from: cutaneous COLD receptors
Inhibitory input from: cutaneous warm receptors
DO NOT directly monitor local brain temp (like POAH does)
Excitation of these neurons induces heat gain mechanisms (shivering, vasoconstriction, seeking warmth)
Lesion → hypothermia
363
Interaction of POAH and posterior hypothalamus
Cells in POAH are tonically active at normal body temp, and their activity inhibits cells of posterior hypothalamus
Temp drops below certain threshold → POAH drops firing rate → release posterior hypothalamus from inhibition
364
Fever:
induced by _______ to increase __________ of the thermoregulatory system --> causes what physiological responses?
Induced by pyrogens (fever producing agents) → increase “set-point” of thermoregulatory system
→ activate physiological responses normally evoked by cold (vasoconstriction, shivering, etc. until core body temp rises to a new level
365
What happens when pyrogens are injected directly in POAH region?
What about when pyrogens are injected into posterior hypothalamus?
Fever develops when pyrogens injected into POAH region, but NOT when injected into posterior hypothalamus, pons or cerebral cortex
366
_________ are released by the immune system --> ____________ (circumverential organ) to induce local production of _________ in the hypothalamus.
This then acts directly on __________ (region of hypothalamus) to increase temperature set point → vasoconstriction, shivering, blanket
Cytokines (IL-1)
OVLT
PGE2 made in hypothalamus
PGE2 acts directly on POAH cells of hypothalamus
