NEUR 3001 Unit 3 Flashcards
(240 cards)
1
Q
Process H
A
Homeostatic
2
Q
Process C
A
Circadian, alerting signal
3
Q
General ANS structure
A
Autonomic ganglia connect to the spinal cord and brain stem and mediate simple reflexes
4
Q
Three ANS divisions
A
- Sympathetic
- Parasympathetic
- Enteric
5
Q
Difference in organization of pre-ganglionic neurons in ANS branches
A
Parasympathetic: Craniosacral
Sympathetic: Thoracolumbar
6
Q
Differences in peripheral locations of their ganglia in ANS branches
A
Parasympathetic: close to target organs
Sympathetic: further from target organs in sympathetic trunk
7
Q
Differences in post-ganglionic neurotransmitters in ANS branches
A
Parasympathetic: acetylcholine
Sympathetic: norepinephrine
8
Q
Superior cervical ganglion
A
Sympathetic neurons that control the redirection of blood to muscles
9
Q
Loewi experiments
A
Stimulation of the vagus nerve (parasympathetic nervous system) which results in the lowering of the heart rate
10
Q
Acetylcholine release in a chemical synapse
A
- Acetyl CoA and choline are substrates for an enzyme to form CoA and acetylcholine
- Acetylcholine is released into the cleft via a synaptic vesicle
- Acetylcholine can bind to cholinergic receptors on the post-synaptic membrane
- Acetylcholinesterase breaks acetylcholine into acetate and choline
11
Q
Nicotinic receptor activation speed
A
Fast post-synaptic potential
12
Q
Muscarinic receptor activation speed
A
Slow post-synaptic potential
13
Q
Pre-synaptic α2 receptors
A
Act on the pre-synaptic membrane to provide negative feedback to inhibit further NE release
14
Q
Co-release of neurotransmitters in the ANS
A
Pre-synaptic terminal can co-release 2+ NT types onto the same post-synaptic cell
Example: acetylcholine and VIP
15
Q
Three principles of neurotransmission in ANS
A
- Activation of multiple receptors
- Pre-synaptic and post-synaptic effects
- Co-release of different neurotransmitters
16
Q
Vagus nerve
A
Cranial nerve X
Regulates heart rate, GI motility, pancreatic endocrine & exocrine secretion, hepatic glucose production
17
Q
Inflammatory reflex
A
Pathogens activate TLR4 → cytokines release from macrophages and other immune cells are detected by sensory arm of vagus → activation of efferent vagus regulates immune activation and suppresses pro-inflammatory cytokines release
18
Q
Baroreceptor reflex
A
Decrease in carotid & aortic baroreceptor firing → glossopharyngeal & vagus nerves → increase in sympathetic activation → increase in HR, arterial constriction, venue dilation, & increase in ventricular contractility
19
Q
Transient receptor potential (TRP) channels
A
Act as cellular sensors to perceive and respond to a variety of environmental stimuli (temperature, taste, pain)
20
Q
TPRC5
A
Activated by membrane stretching
Expressed in baroreceptor neurons (remember the diagram with the antibody blocking the TPRC5 neurons and expressed in neurons)
21
Q
Micro-pipette technique
A
- Suction of the cell membrane
- Pulse of cell membrane to rupture the membrane patch
- Future whole cell recording
22
Q
T5E3 antibody
A
Used to image the presence of TPRC5 channels — blocks these channels
After blocking, there is less negative current where is no pressure and less positive current when there is pressure — may indicate the level of pressure with no current indicating small amount of pressure
Similar results where seen with knockout
23
Q
TPRC5 knockout
A
Knockout has lower negative current under no pressure and lower positive current under pressure
24
Q
TPRC5 knockout and mean arterial pressure
A
Higher mean arterial pressure with greater level of variation
25
TPRC5 knockout and heart rate
Higher heart rate with greater level of variation
26
Enteric nervous system
Arrangement of neurons and supporting cells throughout the GI tract from the esophagus to the anus
27
Types of neurons in the ENS
Sensory, motor, and interneurons
28
ENS and other branches of autonomic nervous system
Receives input from the parasympathetic and sympathetic branches
Can operate independent of input from either as well
29
Parkinson’s disease
Progressive neurological disorder with some combination of the following symptoms:
- impaired initiation of voluntary movement
- increased resistance of passive movement
- resting tremor
30
Parkinson’s disease average age onset
50 years
31
Sporadic/idiopathic Parkinson’s disease
Occurs in people with no family history of PD and may be linked to metal exposure
32
Anatomical changes in the substantia nigra in PD
- Loss of dopaminergic cells within the substantia nigra
- Lewy bodies
- Diffuse α-synuclein extracellularly and intracellularly
33
α-synuclein in PD
Spreads throughout the brain (early stages mainly concentrated in the substantia nigra)
34
Leaky gut epithelium
Allows for the uptake in the toxins and luminal factors
Protein pathologies can be detected in the ENS, suggesting that the proteins may have originated in the ENS
35
Vagus nerve and protein pathologies
Allow for the retrograde transport of the pathogen from the efferent fibers and the brain
36
Human findings for Braake hypothesis
Exosome transport α synuclein from cell to cell seen in welders exposed to manganese
37
Braake hypothesis
(1) α synuclein infiltrates the cholinergic and monoaminergic brain stem neurons and the olfactory neurons from exposure via retrograde transport by the vagus nerve
(2) Infiltration of similar neurons in the midbrain and basal brain leads to the motor symptoms of PD
(3) As the disease progresses, Lewy bodies will be found later in the limbic and neocortical brain regions
38
RT-QuIC assay
Normally folded prions are the reagents, and they are fluorescently labeled so that they indicate when they are misfolded
39
Exosomes
These are secreted under both physiological and pathophysiological conditions
Will cause modulations of cellular behaviors and delivery of disease-causing entities
40
Rotenone
Toxin that inhibits the electron transport train (no ATP)
41
Braake hypothesis and rotenone
Three groups: control, rotenone, rotenone + vagotomy
Higher level of α synuclein collection in the substantia nigra for rotenone group and reduced for rotenone & vagotomy
42
Motor learning task and sleep
Improvement after a session of sleep — doesn’t alter based on the number of re-tests
Indicates that sleep is necessary for learning
43
“Sleep is for forgetting” framework
- Targeted erasure of synapses that’s unique to sleep
- Necessary for efficient learning
- Deficits in this process may underlie various kinds of intellectual disabilities & mental health problems
44
Restorative hypothesis
Sleep allows for the reduction of the metabolic rate for brain and increasing the amount of metabolites removed from the brain
“Restoring the balance”
45
Number of hours sleeping
Increased metabolism and smaller size
46
Growth hormone and sleep
Increased release of growth hormone during sleep
More is released at night and is more effective
47
Mitosis and sleep
Increased number of mitosis events at night → supports the restorative hypothesis
48
Ultradian
Biological cycle with a frequency of less than 24 hours
Example: REM sleep
49
REM sleep
Sleep cycle that resembles awake activity with more vivid dreams
50
REM sleep duration
Increases as sleep goes on
51
Physiological changes during sleep
Reductions in eye movements, head movements, & heart rate
52
Clearance of Aβ
Increased clearance of Aβ in sleep and under anesthesia but reduced in awake
Shown with radioactively tagged Aβ
53
CSF influx
Increased CSF influx compared to the awake state
54
Neuromodulation in sleep
Reduction in cholinergic, adrenergic, serotonergic, orexin in NREM sleep
Increased cholinergic activity in REM sleep
55
Chemical system promoting sleep
Buildup of adenosine
56
Melanin-concentrating hormone and sleep
MCH neurons are concentrated in areas that regulate sleep
Antagonist of MCHR1 reduces sleep
Infusion of MCH increases SWS and REM sleep
MCH-expressing neurons are more active during REM sleep
57
MCH and memory
Conditioned fear was used to establish memory
Greater memory seen in mice with MCH ablation
58
Sleep distribution and aging
Reduction in total sleep time
Relative decrease in ratio of REM sleep to NREM sleep
59
Mimosa plant and circadian rhythm
Exhibit a rhythm of opening and closing of leaves
Even when in darkness, still follow a circadian rhythm — not based on light then
60
Zeitgeber
Any environmental cue that can be used by an organism to align its endogenous rhythm with the external day-night cycle
61
Establishment of circadian rhythms in plants
Photoreceptor proteins → central oscillator → oscillatory rhythms in plants
62
Hirschsprung disease
Disruption of digestion primarily found in newborns
Can be fatal
63
Gut-brain axis
Bidirectional communication between the CNS and ENS, linking the emotional and cognitive centers of the brain with peripheral intestinal functions
64
Clock gene mutations (same gene, different locations)
Arrhythmic, short-period, or long-period irregularities
65
Negative feedback loop for circadian rhythms in flies
TIM and PER are transcribed from tim and per genes
They will dimerize and translocate to the nucleus
They will inhibit the CLK and CYC promoters that drive tim and per transcription
66
Positive elements in flies
CLK and CYC
67
Negative elements in flies
TIM and PER
68
Positive elements in mammals
BMAL1 and CLOCK
69
Negative elements in mammals
PER and CRY
70
Feedback loop in light
Light drives feedback loops in mammals and flies
CRY mediates this in flies
71
Clock gene-mediated circadian rhythms in nocturnal rodents
During “sleeping hours” → less PER2 protein, allowing BMAL1 induction of Per2 transcription
During “waking hours” → reduction in Per2 mRNA due transcription and reduction of BMAL1 activity
72
Neurotransmitters in SCN
- AVP
- GABA
- VIP
73
Intrinsic circadian rhythmicity
Found in diverse classes of SCN neurons (can be AVP, VIP, or neither)
Within a class, can be rhythmic or arrhythmic
74
SCN neurons and circadian rhythms
Small proportion are in sync with rhythm
75
Core (ventrolateral) in SCN
Photo-receptive
Neurotransmitter: VIP
76
Shell (dorsomedial) in SCN
Not photo-receptive
Neurotransmitter: AVP and GABA (connections between core and shell)
77
VL mechanism for photo-reception
Innervated by the optic chiasm
Neurotransmitters: Glu and PACAP
78
SCN target processes (6)
- Sleep
- Wake
- Appetite
- Neuroendocrine
- Local brain clocks
- Autonomic
79
Adrenaline reverse effect
Can bind to β adrenoceptors
Can overpower sympathetic neurotransmission and cause relaxation
80
Bayliss and Starling findings
Motor of intestines occurs even after the complete division of the mesenteric nerves
81
Vasopressin and SCN
Release follows a 24-hr cycle
82
Feedback system in plant circadian rhythms
Feedback auto-regulatory loop
83
Nickname for SCN
Master clock
84
Temperature and circadian rhythms
Increased temperature during awake hours, decreased temperature during asleep hours
85
SCN physiological changes (6)
- Blood pressure
- Blood glucose and triglycerides
- Xenobiotic clearance
- Cognition
- Mood
- Brain homeostasis
86
Phase shift from zeitgebers
Induced molecular changes in the SCN
Seen with jet lag — shift activity from one time to another
87
Neuropathology and circadian rhythms
Neuropathology → abnormal NT release → sleep/circadian disruption → co-morbid pathologies, abnormal light-dark exposure, disrupted social behavior, stress axis activation
88
Autoregulatory system
Modify inputs and outputs to meet certain set point as determined by an error signal which controls negative feedback and positive feedforward
89
Four components of autoregulatory system
1. Input subsystem
2. Regulated compartment with sensor
3. Output subsystem
4. Error signal
90
Baroreceptor reflex (def. 2)
Example of autoregulatory system
Baroreceptor firing modulates vasoconstriction and vasodilation to control blood pressure with comparison to a setpoint via descending vasomotor activity (hypothalamus)
91
6 vital functions regulated by the hypothalamus
1. BP and electrolyte composition
2. Energy metabolism
3. Reproductive behavior
4. Body temperature
5. Defensive behavior
6. Sleep-wake cycle
92
3 sensory signals for fluid balance
1. ANG II (signaling in response to low blood volume)
2. Osmolality/osmolarity
3. Baroreceptors in circulatory system
93
ANG II control system
SFO in hypothalamus detects ANG II and releases ANG II onto MePO, PVN, OVLT, and LHA
PVN will drive drinking behaviors
94
Baroreceptor control on PVN
Baroreceptors inhibit the MePO, which will inhibit the PVN
It will prevent further drinking behaviors
95
Optogenetics
Infects specific cells with a virus to cause the placement of an opsin channel on the membrane
The opsin channel will open with light, causing either excitation or inhibition
96
Two possible opsins
1. Channelrhodopsin — opens sodium channel (excitation)
| 2. Halorhodopsin — opens chloride channel (inhibition)
97
Six steps of optogenetics
1. Piece together the genetic construct (promoter to drive expression and gene-encoding opsin)
2. Insert construct into virus
3. Inject virus into animal brain
4. Insert optrode (fiber-optic cable plus electrode)
5. Shine light to open channels
6. Observe behavioral changes
98
Excitation of glutamatergic SFO neurons
Drive fluid intake
99
Inhibition of glutamatergic SFO neurons
Suppress fluid intake
100
Excitation of GABAergic SFO neurons
Suppress fluid intake
101
Osmolality sensors in the hypothalamus
SFO and OVLT
Lack blood-brain barrier → well-positioned for osmoreceptors
102
Hyperosmotic
Greater than reference solution
103
Hypoosmotic
Less than reference solution
104
Vasopressin
Hormone that increases blood pressure and increases reabsorption of water in the kidney
105
4 theoretical mechanisms for osmoreceptors sensing cell volume changes
1. Direct stretch
2. Tethering to cytoskeleton
3. Changes in membrane curvature
4. Interactions with integrins (upstream of cytoskeleton changes)
106
Integrins
Join the cytoskeleton on the side of the cell to the extracellular matrix
Heterodimers of alpha and beta subunits
107
Water restriction
Activation of glutamatergic SFO neurons (will de-activate within 1 minute of drinking)
108
Oral vs. gut infusion water
Oral infusion causes immediate decrease in calcium signaling in SFO, while gut infusion causes a delayed decrease
Must be something involved in perception of water intake prior to osmolarity
109
Gulping
Motor activity of the pharynx and esophagus signals via the vagus to inhibit the drive to drink — anticipatory modulation
110
Temperature of water
Reduces the activity of SFO glutamatergic neurons as temperature decreases
111
Long-term feedforward satiation signal
Osmolality
112
Pre-absorptive inputs (3)
1. Water
2. Fluid taste/temperature/texture
3. Stomach distension
113
Post-absorptive inputs (3)
1. Plasma volume/blood pressure
2. Plasma osmolarity
3. Plasma sodium
114
Hormonal signals (2)
1. Atrial natriuetic peptide
| 2. Angiotensin II
115
G_q DREADDs
Excitatory
116
G_i DREADDs
Inhibitory
117
Prandial thirst
Thirst during or relating to the consumption of food
118
Relative occurrence of prandial thirst
Develops before the ingested food has altered the blood tonicity
119
Prandial thirst proportion of fluid intake
75%
120
Theoretical causes of prandial thirst (4)
1. Facilitation of chewing and swallowing
2. Improving sensory stimulation and taste
3. Reduction of sensations by irritants
4. Anticipation of physiological deprivation
121
Normal drinking behavior
Anticipatory in nature → brain predicts impending changes in fluid balance and adjusts behavior pre-emptively
122
SFO and prandial thirst
Optogenetic inhibition of SFO glutamatergic neurons blocks prandial thirst
123
Key regulator of energy balance
Leptin
124
Site of leptin release
Release from the fat cells
125
Leptin signaling
Inhibits AgRP neurons (hunger) and excites α-MSH neurons (satiety)
126
Hunger neurons
AgRP neurons
127
Satiety neurons
α-MSH neurons
128
Additional signaling beyond arcuate neurons
Occur within lateral hypothalamus and paraventricular neurons
129
Activation of AgRP neurons
Increases anabolic signals (promote energy storage)
130
Activation of α-MSH neurons
Increases catabolic signals (promote use of energy)
131
MC4R receptor location
Located on satiety neurons
132
MC4R receptor agonist
α-MSH
133
MC4R receptor antagonist
AgRP
134
Ghrelin origin
Released from the stomach
135
Ghrelin target
Drives activation of AgRP neurons
136
Ghrelin action
Rapid and powerful but short-term signal to stimulate hunger
137
Most common monogenic forms of human obesity
MC4R mutations
138
Warm food theory
The gut has less work to do to acquire the energy and there is a system in place to let it know
139
Warm food mechanism
Activation of TRPV1 receptors → activate α-MSH neurons → increase satiety
140
Additional rapid-acting satiety signals (3)
1. Potentiates VGLUT2 by increasing the expression of AMPA receptors
2. Combined activation of VGLUT2 & α-MSH neurons required for satiety mechanism to work properly
3. VGLUT2 are hormone-activated (oxytocin) — faster than α-MSH neurons alone
141
Neurocircuitry controlling reward
Begins in the pedunculopontine & lateral dorsal regimental areas, which drives dopaminergic release from VTA
VTA activates the medial PFC and nucleus accumbens
Inhibition includes the medial PFC, nucleus accumbens, and ventral pallidum (GABA)
142
Nucleus accumbens neurons
Dopamine release occurs for pleasurable stimuli from VTA — closer in synaptic spine
Glutamate release is from medial PFC — further in dendritic spine
143
Pursuit of reward
Strengthened by increases in dopaminergic synaptic transmission
144
Reward prediction and dopaminergic neurons
Unexpected reward: increase in DA firing
Predicted reward that occurs: increase in DA firing when anticipating
Predicted reward that doesn’t occur: decrease in DA firing during normal occurrence of reward
145
Optogenetic activation of VTA dopamine neurons
Cause “addiction-like” behavior
146
VTA activation in response to a painful stimulus
Reduced VTA activation
147
cFos
Protein marker for neuronal activity
148
cFos and optogenetic stimulation of VTA
Shows increased activity within the frontal cortex → marked by cFos
149
Frontal cortex and addiction
D2 receptors receive modulation from the frontal cortex enabling goal-directed decision-making
Reduction in D2 receptor availability and glucose metabolism
150
Long-term addiction
Reduction in D2R availability in the nucleus accumbens
Reduced orbitofrontal cortex activity
151
Key effect of addictive drugs
Increased release of dopamine from the VTA
152
Three mechanisms for increasing VTA DA release
1. Interference with dopamine reuptake
2. Indirect disinhibition of dopamine neurons
3. Direct activation of dopamine neurons
153
Top-down inhibition of drug and food-seeking
Depends heavily on the pre-frontal cortex
154
Macroscopic changes in brain anatomy due to cocaine addiction
Loss of frontal cortex gray matter
155
Function of frontal cortex
Adaptive action-consequence decision making
156
Method for measuring action-consequence decision making
Contingency degradation test
157
Contingency degradation tasks
Operant conditioning trains the association between an action and consequence
In contingency degradation task, the action-consequence relationship is degraded by providing the reward independent of the action
A probe test measures if the organism has adjusted its understanding of the action-consequence relationship
158
Mechanism for updating action-consequence relationships
Frontal-cortex-activity-dependent structural remodeling
Shown with inhibitory DREADDs within the frontal cortex during degradation change → exhibit a response pattern indicating no change value for acting the degraded nose-poke
159
Drug use and age
The younger the person is at the onset of illicit drug use → the lower their odds of seeking treatment throughout their lifespan
Impaired action-consequence decision-making abilities due to frontal cortex dysfunction
160
Frontal gray matter during adolescence
Peaks in volume at 11 yo for females and 13 yo for males
Declines steadily with age
161
Dendritic spines in frontal cortex during adolescence
Declines in spine concentration as adolescence progresses
162
Cocaine exposure and frontal cortex
Adolescent cocaine exposure causes dendritic spine loss in the frontal cortex
163
Neurocircuitry controlling drug addiction
Non-addicted brain: healthy frontal cortex regulates the action of the nucleus accumbens and VTA. Actions are goal-directed.
Addicted brain: hypoactive frontal cortex can’t regulate the NA and VTA. Actions are driven by “habits.”
164
Dendritic spines and integrins
Binding of integrins to ECM proteins supports intracellular signaling pathways that promote dendritic spine stability
165
Arg
Inhibition of a protein (ROCK2) to stabilize the cytoskeleton
166
Fasudil
Inhibits the ROCK2 protein
Is used to treat stroke
167
Knockdown of β1 integrin
Accelerates operative response for cocaine and energizes cue-induced reinstatement of cocaine seeking
168
Adolescent onset loss of Itgb1 within oPFC
Accelerates acquisition of stable cocaine self-administration and energizes cocaine-seeking
169
Depression
A mental health disorder characterized by persistently depressed mood or loss of interest in activities, causing significant impairment in daily life
170
Depression prevalence
17%
171
Factors increasing risk for depression (4)
- Experiencing stressful events in your life
- Difficult childhood
- Certain personality traits
- Family history of depression
172
Hypoactive brain centers in depressive patients
Frontal and temporal (hippocampus) areas
173
Hyperactive brain centers in depressive patients
Amygdala
174
VFT frontal cortex activation
Improvement in depressive symptoms
175
Shift in signaling pathways under stress
Normally pre-frontal cortex regulates striatum, hypothalamus, amygdala, and brainstem emotional reflexes
Under stress conditions, loss of prefrontal regulation, causing the amygdala to take control
176
HPA axis
CRH (hypothalamus) → ACTH (anterior pituitary) → cortisol (adrenal cortex)
Negative feedback of cortisol on anterior pituitary and hypothalamus
177
Cushing’s syndrome
Increased release of cortisol
Co-morbid with depression
178
Early life stress
Reduced birth weight and gestational time
Alterations in development and behavioral disorders (including depression)
179
Stress hypothesis of depression
Stress increases glucocorticoids which activate GRs to decrease BDNF, CREB, and TrkB activity
Decreases monoaminergic NTs & growth factors
180
Glucocorticoids and spine stability
Frontal cortex has reduced spine concentration with increasing GC levels
181
Anhedonia
Inability to feel pleasure from typically rewarding events
182
Measuring anhedonia
Sucrose consumption test — rodent has a choice between water or sucrose solution
183
Elevated GC experiment in rats (depression)
Decrease in dendritic spines in the frontal cortex & decreased sucrose consumption
184
Genetic manipulations with GC elevations
Over-administration of glucocorticoids in mice with heterozygosity of cytoskeletal supporting genes leads to significantly reduced sucrose consumption and reduced dendritic spine concentration
185
Heterozygosity
Expect 50% reduction in protein
186
Subthreshold
Dosing that doesn’t cause behavioral deficits in healthy animals
187
Serotonin hypothesis of depression
Proposes hat diminished activity of serotonin pathways plays a causal role in the pathophysiology of depression
Amine-depleting drugs, like reserpine, cause depression-like behaviors
Drugs that potentiate the effects of serotonin at the synapse alleviate depression
188
Mechanisms of anti-depressant drugs (4)
- Stimulation of autoreceptor agonist
- Stimulation of receptors as partial agonist
- Inhibition of MAO
- Inhibition of reuptake
189
SSRI effect onset
6 weeks
190
Ketamine effects on synaptic function
Ketamine at low doses selectively binds to GABAergic neurons (instead of glutamatergic neurons)
Causes disinhibition of excitatory glutamatergic neurons in frontal cortex → glutamate burst
191
Ketamine effect onset
Within hours
192
Autism prevalence
1 in 54 children in the US
More males than females
193
DSM criteria for autism spectrum disorder
- Difficulty with communication and interaction with other people
- Restricted interests and repetitive behaviors
- Symptoms that hurt the person’s ability to function properly in school, work, and other areas of life
194
Sally Anne test
Sally put her ball into the basket and leaves & Anne moves the ball to her box — where will Sally look for her ball?
Answer for children on spectrum → box
Answer for children not on spectrum → basket
195
ASD neuroanatomy (4)
- Frontal cortex
- Fusiform gurus
- Superior temporal sulcus
- Amygdala
196
Frontal cortex & ASD
Social deficits
197
Fusiform gyrus & ASD
Face processing
198
Superior temporal sulcus & ASD
Perception of living organisms moving
Have a role in the perception of intention of actions
199
Amygdala & ASD
Emotional processing
Stops developing at about 8 yo in ASD boys (18 yo typically)
200
Frontal and parietal attentional brain systems
Facilitate orientation to social stimuli appear to exert less top-down control in autism
201
Autism risk factors (4)
- Having a sibling with ASD
- Having older parents
- Very low birth weight
- Having certain genetic conditions (e.g. Down syndrome or fragile X syndrome)
202
Neuroligins
Involved in tethering the post-synaptic terminal to the pre-synaptic terminal
203
Neuroligin knock-in and social interest
Equal interest in empty and stranger compartments of the apparatus
Assesses relative interest in socialization
204
Neuroligin knock-in and somatosensory cortex
No change in EPSCs but increased number of IPSCs
Enhance inhibitory response to GABA
205
Neuroligin knock-out and inhibitory feedback
Doesn’t affect inhibitory input
206
GI tract and serotonin
90% 5-HT made in gut
Intrinsic primary afferent neurons
207
Hyper-serotonemia
Due to enhanced serotonin transporter activity
208
Double heterozygous of serotonin transporter and integrin genes
Integrin and serotonin transporter het increase V_max significantly more than control or each single mutation
209
Co-morbidities of ASD (5)
- Epilepsy
- Chronic GI disorders
- Chronic sleep problems
- Depression
- Schizophrenia
210
Positive symptoms
Additional sensory/motor/affects
Example: hallucinations, delusions, disorganized speech, thought disorder, disorganized behavior
211
Negative symptoms
Reduced sensory/emotional/motor
Example: alogia (speech deficits), flat affect, poor attention, avolition (loss of motivation), anhedonia (lack of pleasure), loss of social interests, attentional deficits
212
Schizophrenia neuroanatomy (3)
- Reduced activity in the dorsolateral PFC
- Exaggerated loss of gray matter
- Enlarged lateral ventricles
213
Schizophrenia genetic support
Increased likelihood for monozygotic twins and in descending order with other family members
214
Schizophrenia gene x environment
Early trauma interacts with genes causing developmental delays, behavioral problems, stress vulnerability → leads to lasting epigenetic changes
215
GAD1
Associated with increased risk for childhood-onset schizophrenia
Significant decrease in the GAD1 promoter-enhancer interaction frequency & overly repressive histone marking in schizophrenic patients
216
Copy number variation
Type of structural variation where you have a stretch of DNA which is duplicated in some people
217
Donezepil
Cholinesterase inhibitor improves cognitive performance in AD patients
218
Pharmacotherapy for AD
Ach is critical in cortical areas for attention, learning, and memory functions
Significant loss of cholinergic cells within nucleus basalis for AD
Cholinesterase inhibitors — popular choice
219
Visualization of Aβ deposits
Radioactively labeled bezothiazole binds to Aβ deposits and can be visualized using PET
220
Mutations in γ-secretase
Higher plasma Aβ than controls
221
Early-onset familial AD
Mutations in human APP and γ-secretases
Perfect correlation between offspring who inherited the full mutation and AD
222
APP role in vivo
Helps direct movement (migration) of neurons during early development
223
Production of amyloid β
Cleaved from amyloid precursor protein (APP) through a process involving 3 different secretases
224
Amyloid plaques composition
Primarily of Aβ plaque
225
Tau in AD
Is hyperphosphorylated causing it to separate from the microtubule and aggregate into tangles
226
Tau
Supports the stability of the microtubule
227
Location of plaques
Occipital language areas
228
Location of tangles
Temporal lobe (memory areas)
229
Diagnosis of AD
Confirms the presence of tangles and plaques — can only be post-mortem
230
Tangles
Located intracellularly
Affects approximately 1/3 of neurons
231
Plaques
Located extracellularly
Disrupt localization of dendrites and dendritic spines
232
Disagreement in AD field
Primary contributor to AD deficits — plaques or tangles?
233
Genetic mutations and AD
Only seen with plaques — not with tangles
234
Imaging with silver-staining (Golgi) in AD
Amyloid plaques and neurofibrillary tangles
235
Neurodegeneration in AD (5)
- Cerebral cortex
- Entorhinal area
- Hippocampus
- Neocortex
- Nucleus basalis
236
Prevalence of AD
1 in 20 people by age 65
6th leading cause of death
237
Prognosis of AD
Can live 4-8 years after diagnosis
But can be up to 20 years depending on lifestyle choices
238
Late Alzheimer’s
Patients requires around the clock monitoring
Loses awareness of recent experiences as well as of their surroundings
239
Middle Alzheimer’s
Requires caretaker
Feels moody or withdrawn, especially in socially or mentally challenging situations
240
Early Alzheimer’s
Still functions independently
Experiences increased trouble with planning or organizing
