Wijnen - Regulatory Systems Flashcards
(142 cards)
1
Q
What type of bodily functions are regulated automatically by the brain?
A
Breathing, heartbeat, digestion, peristalsis, stress responses, and homeostatic behaviors (e.g., thirst, hunger, excretion)
2
Q
What term describes the brain’s automatic regulation of internal bodily functions?
A
The autopilot system of the nervous system
More formally: the autonomic nervous system (ANS)
3
Q
Is conscious thought required for the brain to regulate heartbeat or digestion?
A
No — these functions are regulated unconsciously by the autonomic system
4
Q
What is homeostasis in the context of nervous system regulation?
A
The maintenance of stable internal conditions (e.g., temperature, hydration, energy balance) via feedback and correction
5
Q
Which brain structure is central to autonomic and homeostatic regulation?
A
The hypothalamus
6
Q
What major divisions make up the autonomic nervous system (ANS)?
A
Sympathetic nervous system: “fight or flight”
Parasympathetic nervous system: “rest and digest”
7
Q
What system monitors the internal state of organs and sends this information to the brain?
A
The interoceptive system
8
Q
What gland works with the hypothalamus to control hormone secretion?
A
The pituitary gland
9
Q
What does the ‘autopilot’ system of the brain do beyond just maintaining status quo?
A
Can initiate corrective responses, e.g.:
- Initiating thirst or hunger
- Triggering stress responses
- Altering heart/gut activity as needed
10
Q
What is the autonomic nervous system (ANS) also known as?
A
The visceral motor system
11
Q
How does the organisation of the ANS differ from the somatic motor system?
A
Somatic system: single cholinergic neuron from CNS to skeletal muscle
Autonomic system: two-neuron chain:
Preganglionic neuron (CNS origin)
Postganglionic neuron (PNS ganglia to target)
12
Q
What are the two divisions of the autonomic nervous system?
A
Sympathetic division
Parasympathetic division
13
Q
Where are the ganglia located in the sympathetic vs parasympathetic systems?
A
Sympathetic ganglia: close to the spinal cord
Parasympathetic ganglia: close to or within target organs
14
Q
What neurotransmitter is used by all preganglionic neurons (sympathetic and parasympathetic)?
A
Acetylcholine (ACh)
14
Q
What neurotransmitter is used by postganglionic neurons in the sympathetic system?v
A
Norepinephrine (noradrenaline)
15
Q
What neurotransmitter is used by postganglionic neurons in the parasympathetic system?
A
Acetylcholine (ACh)
16
Q
What types of tissues are targeted by the autonomic nervous system?
A
Smooth muscle, cardiac muscle, and glands
17
Q
What are the two main divisions of the autonomic nervous system?
A
Sympathetic division (“fight or flight”)
Parasympathetic division (“rest and digest”)
18
Q
What do both divisions of the ANS have in common?
A
Target smooth muscle, cardiac muscle, and glands
Use a two-neuron chain: preganglionic (CNS) → postganglionic (PNS ganglia)
19
Q
Which division has ganglia close to the spinal cord?
A
Sympathetic division
20
Q
Which division has ganglia near or within the target organ?
A
Parasympathetic division
21
Q
Which structures are innervated only by the sympathetic division?
A
Blood vessels, sweat glands, adipose tissue, and the adrenal medulla
22
Q
What regions of the CNS give rise to sympathetic output?
A
Thoracic and lumbar spinal cord
22
Q
What is unique about sympathetic innervation of the adrenal medulla?
A
Direct innervation from CNS (no postganglionic neuron)
Allows rapid adrenaline release
23
What regions give rise to parasympathetic output?
Brainstem and sacral spinal cord
24
What are the key effects of sympathetic activation?
Increased heart rate, increased respiration, pupil dilation, reduced digestion, adrenaline release
25
What are the key effects of parasympathetic activation?
Reduced heart rate, enhanced digestion, increased salivation, pupil constriction, energy conservation
26
What phrase summarises sympathetic nervous system function?
"Fight or flight"
27
What phrase summarises parasympathetic nervous system function?
"Rest and digest" or "Feed and breed"
28
Which forebrain and brainstem structures regulate autonomic output?
Forebrain: Hypothalamus, prefrontal cortex, amygdala, thalamus
Brainstem: Parabrachial nucleus, nucleus of the solitary tract (NTS), autonomic centres
29
What role does feedback play in autonomic regulation?
Enables homeostasis:
Sensory neurons monitor outcomes (e.g. heart rate)
Feedback loops adjust autonomic output to avoid overshooting
30
What is the role of the interoceptive system?
It monitors internal organ function and provides feedback to the brain to support homeostatic regulation
31
What is the baroreflex?
A homeostatic reflex that reduces blood pressure when it rises above the set point
32
What type of neurons are responsible for sensing internal organ states?
Visceral sensory neurons
33
Where are the baroreceptors involved in the baroreflex located?
In the carotid sinus of the carotid artery
34
What triggers the baroreflex?
Increased blood pressure stretches vessel walls, activating mechanosensitive ion channels in baroreceptors
35
What is a mechanosensitive ion channel used in baroreceptors?
Piezo2
36
How does the baroreflex reduce blood pressure?
Decreases cardiac output (via reduced heart rate)
Dilates blood vessels (reduces peripheral resistance)
Both actions lower arterial pressure
37
Why is the circulatory system described as a "closed system"?
Because blood volume and pressure are regulated internally without external loss or input
Pressure changes must be managed by adjusting volume distribution or cardiac output
38
What brainstem nucleus receives visceral sensory input via cranial nerves like the vagus and glossopharyngeal nerves?
Nucleus of the Solitary Tract (NTS)
39
What structures provide sensory input about blood pressure to the brain?
Carotid sinus and aortic arch baroreceptors via cranial nerves IX and X
40
What type of ion channel is key in baroreceptor mechanosensation?BARORECEPTOR FUNCTION
Piezo2 (mechanosensitive ion channel)
41
What triggers activation of Piezo2 in baroreceptors?
Mechanical stretch caused by elevated blood pressure
41
What physiological responses follow baroreceptor activation?
Decrease in heart rate (bradycardia)
Decrease in blood pressure (vasodilation & reduced cardiac output)
42
What is the function of baroreceptors in homeostasis?
To maintain blood pressure at a set point by initiating reflexive parasympathetic responses when pressure is too high
43
What is Channelrhodopsin-2 (ChR2)?
A blue light-activated cation channel originally from microorganisms, used in optogenetics to activate neurons with light
44
How was ChR2 used in this baroreceptor experiment?
Genetically expressed only in Piezo2+ baroreceptor neurons
Blue light was used to directly activate these neurons and simulate stretch
45
What happened when blue light was applied to region 2 (aortic arch branch)?
Strong decrease in heart rate and blood pressure
Indicates functional baroreceptors that normally respond to mechanical stretch
46
What does optogenetic activation of baroreceptors reveal about their role?
Confirms their causal role in reducing heart rate and blood pressure when mechanically activated
47
What was the effect of light stimulation in control (non-ChR2) mice or inactive regions (e.g., vagus trunk)?
Minimal or no change in heart rate or blood pressure
Demonstrates specificity of response to targeted baroreceptor neurons
47
What type of afferent neurons monitor airflow in the lungs?
Stretch-sensitive sensory neurons expressing Piezo2
48
What happens to lung nerve activity when airflow increases in wild-type mice?
Increased stretch → Increased afferent activity (via Piezo2)
49
What is the effect of knocking out Piezo2 in pulmonary afferents?
Loss of stretch sensitivity
Disrupted coupling between tidal volume and respiratory rate
50
Why is the ability to detect lung inflation important for breathing regulation?
It allows the body to adjust respiratory rate based on air exchange efficiency (deep breaths reduce breathing frequency)
51
What is Olfr78 and where is it expressed?
An olfactory receptor expressed in glomus cells of the carotid body
52
: What does Olfr78 detect to infer tissue oxygen levels?
Lactate, a byproduct of anaerobic metabolism
53
Why is lactate used to sense hypoxia?
Lactate levels rise when oxygen is low, making it a proxy for hypoxia
54
What is the physiological response when Olfr78+ cells detect lactate?
Neurotransmitter release → Stimulates respiration
May also enhance circulation to increase oxygen delivery
55
What are the two interoceptive feedback mechanisms for respiratory control discussed?
Piezo2: Detects lung stretch to modulate respiration
Olfr78: Detects hypoxia via lactate to stimulate breathing
56
What is the role of these interoceptors in homeostasis?
They help the brain monitor and maintain respiratory set points, triggering corrective responses when needed
57
What is GCaMP2 and what is it used for?
A genetically encoded fluorescent calcium sensor
Used for in vivo imaging of neural activity
58
What does an increase in intracellular calcium typically indicate in neurons?
Increased neuronal activity, often linked to action potential firing
59
How does GCaMP2 report calcium levels?
Contains GFP, calmodulin, and an M13 peptide
Ca²⁺ binding to calmodulin causes a conformational change that increases GFP fluorescence
60
What does ΔF (delta F) represent in calcium imaging?
The change in fluorescence intensity, indicating changes in intracellular calcium levels
61
What is the nodose ganglion?
A visceral sensory ganglion of the vagus nerve
Integrates sensory input from organs like the stomach, lungs, and intestines
62
What kinds of visceral inputs are detected in the nodose ganglion?
Stomach stretch, intestinal perfusion, and lung inflation
63
How was calcium imaging used in nodose ganglion neurons?
Neurons were labeled with GCaMP2
Fluorescence increased in response to organ-specific stimuli (e.g., food in intestine, stomach inflation)
64
Why is the nodose ganglion considered a hub for interoception?
It integrates signals from multiple organs and relays them to the CNS for homeostatic regulation
64
What does distinct activity in different nodose neurons during stomach vs. intestinal stimulation demonstrate?
Functional specificity of nodose ganglion neurons for different interoceptive modalities
65
What is the primary role of the hypothalamus in the brain?
Acts as an autopilot center for homeostatic regulation (e.g., hunger, thirst, temperature, stress)
66
How is the hypothalamus structurally organised?
Contains multiple nuclei, each with specialised but interconnected functions
66
What is the basic model of hypothalamic regulation?
Receives interoceptive input → compares to a set point → generates output to restore balance
67
What does the lateral hypothalamus control?
Feeding, drinking, locomotion, arousal
Lesion → aphagia, adipsia, reduced activity, hypothermia
68
What happens when the ventromedial hypothalamus is damaged?
Hyperphagia, obesity, insulin resistance, reduced energy expenditure
69
What is the function of the arcuate nucleus?
Regulates appetite and metabolism
Lesion → obesity, energy imbalance, glucose dysregulation
70
What does the paraventricular nucleus control?
Feeding, autonomic tone, stress
Lesion → obesity, high parasympathetic tone, stress dysregulation
71
What is the role of the dorsomedial hypothalamus?
Aggression, metabolic rhythms, feeding
Lesion → changes in circadian patterns and emotional responses
72
What does the suprachiasmatic nucleus (SCN) regulate?
Circadian rhythms
Lesion → arrhythmic behaviour, sleep disruption, metabolic disturbance
73
What function is associated with the mammillary bodies?
Memory consolidation
Lesion → memory defects
74
What does the posterior hypothalamus control?
Thermoregulation and arousal
Lesion → hypothermia, hypersomnia
75
Why are lesion studies in the hypothalamus limited in resolution?
Lesions affect multiple overlapping neuron types, obscuring cell-type-specific roles
76
How can we improve specificity beyond lesion studies?
Use genetic tools to target excitatory or inhibitory neurons selectively
77
How does the hypothalamus communicate with the rest of the body long-term?
Via hormone secretion through the pituitary gland
78
What are the two main routes of hypothalamic–pituitary signalling?
Direct: Neurons from hypothalamus release hormones via posterior pituitary
Indirect: Hypothalamus releases releasing hormones to anterior pituitary → secondary hormone release
79
Name examples of hypothalamic–pituitary target axes.
HPA axis (hypothalamic–pituitary–adrenal): Stress response
HPG axis (hypothalamic–pituitary–gonadal): Reproduction
HPT axis (hypothalamic–pituitary–thyroid): Metabolism
80
Outline the HPA axis stress hormone cascade.
1. CRH (Corticotropin-Releasing Hormone) from hypothalamus
2. Stimulates ACTH (Adrenocorticotropic Hormone) from anterior pituitary
3. ACTH triggers cortisol release from adrenal cortex
Final outcome: Systemic stress response and energy mobilisation
80
How can a hormone like vasopressin regulate both water balance and social behaviour?
Vasopressin (ADH) acts on different receptors in different tissues:
Kidneys: Promotes water reabsorption for osmotic balance
Brain: Influences social bonding, aggression, and pair bonding via distinct neural pathways
81
What is an example of a hypothalamic hormone with both social and physiological functions?
Oxytocin:
Physiological: Stimulates milk ejection and uterine contractions
Behavioural: Involved in maternal behaviour, trust, pair bonding
82
Why do hypothalamic systems often include both stimulatory and inhibitory pathways?
To allow fine-tuned, bidirectional regulation (like an accelerator and brake)
Enables precise homeostatic balance in response to changing internal states
83
What is the ventromedial hypothalamus (VMH) responsible for in feeding behaviour?
Acts as a satiety center
Lesions in VMH → hyperphagia, obesity, and increased fat deposition
84
What did the classic parabiosis experiments demonstrate?
Surgically linked circulation of two rats to allow molecule sharing
VMH-lesioned rat: became obese
Normal yoked rat: became underweight, suggesting the presence of a circulating satiety signal
85
What conclusion was drawn from VMH-lesioned and yoked rats both sharing blood?
The normal rat provides a satiety hormone (now known as leptin)
VMH-lesioned rat doesn't respond properly → suggests a defect in the brain’s ability to respond, not in hormone production
The yoked rat becomes leaner, suggesting satiety signals from the obese rat impact it strongly
86
What did studies of the ob/ob and db/db mice reveal?
ob/ob mouse: lacks leptin (the signalling hormone)
db/db mouse: lacks leptin receptor (the responding component)
Both develop obesity, but for different reasons
87
How do we know which gene encodes the signal and which encodes the receptor?
When ob/ob mice are yoked to normal or db/db mice → they lose weight
- Conclusion: they respond to leptin, but can’t produce it
When db/db mice are yoked to others → they stay obese, while their partner becomes underweight
- Conclusion: they overproduce leptin but can’t respond to it
88
What happened when a db/db (diabetic) mouse was yoked to a wildtype mouse?
db/db mouse: gained weight (lacks receptor, insensitive to signal)
Wildtype mouse: lost weight and starved
Interpretation: db/db overproduces leptin, which suppresses feeding in the yoked wildtype mouse that can sense leptin
89
What happened when ob/ob was yoked to db/db?
ob/ob: lost weight
db/db: remained obese
Interpretation: db/db produces excess leptin but can’t respond, while ob/ob responds to leptin and loses weight
89
What happened when an ob/ob (obese) mouse was yoked to a wildtype mouse?
ob/ob mouse: lost weight
Wildtype mouse: slightly gained weight
Interpretation: ob/ob lacks leptin, but can respond to it → leptin from the wildtype suppresses its feeding
90
Where is leptin produced?
In white adipose tissue (WAT)
Acts as a signal of fat reserves and satiety
91
How does leptin affect feeding and weight?
Injecting leptin reduces food intake and body weight in animals
Works only if the animal/person can respond to leptin
92
Why does leptin injection not help most obese humans?
Most obese individuals already have high leptin levels
They are leptin-resistant — injecting more has minimal effect
93
In which cases does leptin therapy work in humans?
Rare genetic leptin deficiency (e.g. LEP mutation)
Patients experience dramatic weight loss upon leptin injection
94
What are the two main populations of hypothalamic neurons involved in feeding regulation?
POMC neurons (Pro-opiomelanocortin) → promote satiety
AgRP/NPY neurons (Agouti-related peptide / Neuropeptide Y) → promote hunger
95
Where are both POMC and AgRP/NPY neurons located?
Arcuate nucleus of the hypothalamus
96
How does leptin affect AgRP/NPY neurons?
Inhibits them, reducing hunger signalling
96
How does leptin affect POMC neurons?
Activates them, increasing satiety signalling
97
What happens to POMC and AgRP neuron activity upon feeding (first bite)?
POMC activity increases
AgRP activity decreases
98
What happens if you ablate AgRP neurons using diphtheria toxin?
Mice lose weight due to reduced hunger drive and decreased food intake
99
What is the effect of optogenetic activation of AgRP neurons?
Increases feeding, even if the animal is not hungry
Effect persists after stimulation ends
100
What receptor do POMC and AgRP neurons act through?
MC4R (Melanocortin-4 receptor)
101
What ligand does POMC use to activate MC4R?
α-MSH (α-Melanocyte Stimulating Hormone)
102
What does AgRP do at MC4R?
Antagonises α-MSH → inhibits satiety signalling
103
What is GLP-1 and how does it influence appetite?
Glucagon-Like Peptide-1 is a gut-derived hormone
Activates POMC neurons → promotes satiety
104
Q: What are GLP-1 receptor agonist drugs?
Semaglutide (Ozempic, Wegovy), liraglutide, etc.
Mimic GLP-1 to reduce hunger and induce weight loss
105
Q: What are the key satiety-promoting targets of POMC/MC4R neurons?
VN)
Parabrachial nucleus (PBN)
Dorsal motor nucleus of vagus (DMX)
Paraventricular nucleus of hypothalamus (P
106
: Name two other feeding-promoting neurons aside from AgRP.
Htr2a-positive neurons (central amygdala)
PKC-δ-negative neurons (inhibit satiety circuits)
107
Q: What hormones provide long-term feedback about energy status?
Leptin (from white adipose tissue)
Insulin (from pancreas)
108
What hormones provide short-term satiety signals?
CCK (from small intestine)
Ghrelin (from stomach; stimulates hunger)
Stomach stretch signals (via vagus nerve)
109
What brainstem structure integrates visceral feedback?
Nucleus of the Solitary Tract (NTS)
110
What are the three main hypothalamic structures involved in thirst regulation?
SFO: Subfornical Organ
MnPO: Median Preoptic Nucleus
OVLT: Organum Vasculosum of the Lamina Terminalis
110
Why are SFO and OVLT outside the blood-brain barrier?
To directly sense blood osmolarity and angiotensin II levels, allowing real-time detection of dehydration or hydration states.
111
What is the effect of optogenetic stimulation of the SFO?
Triggers immediate drinking behavior (high licking rate)
Stops when light stimulation stops
112
How do SFO excitatory neurons respond to water access in thirsty mice?
Activity drops rapidly upon drinking (within seconds)
113
How do MnPO GABAergic neurons respond to water access?
Activity increases during water intake → likely act as inhibitory feedback on thirst
114
What are the two types of neurons in the MnPO and their roles?
Excitatory MnPO neurons: Promote thirst/drinking
GABAergic MnPO neurons: Inhibit thirst/drinking
114
What effect does lesioning excitatory MnPO neurons have?
Reduces drinking, confirming their role in promoting thirst
115
Which hormone regulates water retention, and where is it released?
Vasopressin (ADH)
Released from posterior pituitary
Promotes water retention by kidneys
115
Which hypothalamic nuclei produce vasopressin?
Paraventricular nucleus (PVN)
Supraoptic nucleus (SON)
115
Full Thirst Circuit Flow
Dehydration detected by SFO/OVLT via osmolarity and angiotensin II
Signals relayed to MnPO
- Excitatory MnPO neurons → trigger drinking
- Inhibitory MnPO neurons → limit overdrinking
Signals also go to PVN and SON → release vasopressin
Vasopressin from posterior pituitary → kidneys retain water
Feedback from NTS/PBN via vagus nerve adjusts the system
116
How does the body provide feedback to thirst circuits?
Visceral afferents (e.g. vagus nerve) →
Signal to nucleus of the solitary tract (NTS) and parabrachial nucleus (PBN)
These then project to the lamina terminalis, helping adjust thirst signals
117
What does the drive reduction theory suggest about hunger and thirst?
Hunger and thirst are aversive internal drives
Motivation to eat/drink is driven by the desire to reduce these unpleasant states
118
Which experimental result supports the drive reduction theory in thirst?
Mice trained to associate MPO stimulation (thirst neurons) with thirst learn to press a lever to turn off stimulation, even when hydrated
Shows MPO activation is aversive
119
How does MPO activity behave during drinking?
Immediately decreases upon drinking
Suggests real-time feedback and drive satisfaction
120
What does the incentive salience theory propose?
Food and water are rewards
Hunger and thirst increase the perceived reward value of eating and drinking
121
Which experimental result supports the incentive salience theory in hunger?
Mice self-stimulate HRP or GABAergic LH neurons after associating them with feeding, even if not hungry
Shows stimulation of hunger circuits can become rewarding
122
What's the difference between classical and operant conditioning?
Classical: Passive association (e.g., bell = food → salivation)
Operant: Action-dependent learning (e.g., press lever = water reward)
123
How was operant conditioning used to study thirst motivation?
Mice were trained to press a lever to access water
Later, when MPO neurons (thirst) were stimulated, lever pressing increased even if water-sated
124
What do HRP (AgRP) neuron stimulation experiments show in hunger?
Mice avoid areas where HRP neurons are stimulated during hunger (aversive)
But do not reliably press a lever to stop HRP stimulation — suggesting weaker aversion than thirst
124
What do optogenetic experiments show about MPO neurons in thirst?
Stimulation triggers drinking (even when sated)
Inhibition (via feedback or reward) reduces activity, showing strong homeostatic control
125
How do GABAergic LH neuron stimulations affect feeding?
Mice begin feeding even if not hungry
Self-stimulate these neurons after associating them with food → reward-driven behaviour
126
Which theory is better supported for thirst?
Drive reduction theory
MPO neuron activity = aversive
Mice press levers to turn it off
127
Which theory fits hunger behaviour better?
Incentive salience theory
Mice self-stimulate hunger circuits if linked to food rewards
Aversive motivation is weaker
128
What do these findings suggest about hunger and thirst motivation?
Thirst may be experienced more as aversive, needing relief (drive reduction)
Hunger can be reward-based, especially when food is available (incentive salience)
