Lecture 15- Respiratory circuits II

Question 1

Where is the central pattern generator of breathing located?

Answer 1

-in the pons and the brainstem (the bridge part of the brain)

Question 2

Why we need to breathe?

Answer 2

• oxygen uptake and carbon dioxide excretion

- happens in lungs

Question 3

What are the 2 types of respiration?

Answer 3

• external and internal

- external is the lung bit and internal are the cells

Question 4

What is oxygen essential for?

Answer 4

-for ATP production in the mitichondria

Question 5

How is the CO2 and O2 in the blood controlled?

Answer 5

• very tightly
• little fluctuation in O2 or CO2 in the blood will trigger a difference in the pattern of breathing= classic feedback circuit
• changes in partial pressure of CO2 or O2 (PCO2 or PO2) it will immediately be picked up by sensors in the vessels= the carotid body (also aortic)
• another layer of control is central (CNS) chemoreceptors= respond mainly to CO2 (only come into play in very severe conditions= hypoxia)
• constant monitoring of the blood gas concentrations

Question 6

Where is the carotid body and what does it do?

Answer 6

• in the carotid artery and senses the CO2 and O2 concentration in the blood
• the blood is going to the brain
• peripheral chemoreceptor

Question 7

What are the important sensory feedbacks from the periphery for the control of breathing?

Answer 7

1. Arterial chemoreceptors (carotid bodies)
2. Chemoreceptors lungs (irritant receptors-asthma)
3. Stretch receptors lungs= feedback lung volume (Breuer-Hering Reflex)
4. Upper airway receptors= chemo and mechano receptors protective reflexes cough, sneeze, apnoea

Question 8

What is the Breuer-Hering reflex?

Answer 8

• important for the motor pattern of breathing
• stretch receptor is in the lung, when inflate and the receptor gets activated and sends signal to CNS and helps terminate the inspiratory phase

Question 9

What is lung ventilation?

Answer 9

• lung ventilation is a skeletal muscle control= it requires muscle contraction
• 2 phases= inspiration and expiration (but in CNS have 3 phases)
• breathing more complex than locomotion (walking)

Question 10

How does inspiration happen (lung ventilation)?

Answer 10

• main muscle is the diaphragm
• expand the chest wall and lungs expand and the air flows in
• also external intercostal muscles contract

Question 11

How does expiration happen (lung ventilation)?

Answer 11

• passive in terms of muscle contraction
• diaphragm relaxes as do the intercostal muscles
• controlled by larynx= resistance = controlled by CNS
• particularly when exercising it is active, when high metabolic demands need to pump out the taken in air as the volume is much larger

Question 12

What is the breathing system used for?

Answer 12

• breathing
• expressing behaviour
• vocalization

Question 13

What are the movie quotes and what does it mean?

Answer 13

• we breath no matter what (need to breathe all the time, last only 4 minutes without it)
• breath without love, anger or sorrow is just a clock ticking (breathing as a sign of emotions, can judge people by their breathing patterns how you pitch etc can tell in the voice)

Question 14

What is the rat breathing like and how can you monitor it?

Answer 14

• blood pressure recording and phrenic nerve activity
• heartbeat is hardly modulated in
• the breathing is highly modulated as the rat is running around, sniffing and also vocalize (but we cannot hear it as it is in ultrasound)
• even in a 2 second window, lot of modulation

Question 15

Which are the motor neurons that contribute to the breathing pattern?

Answer 15

1. = these are the spinal neurons that have a role in breathing, the pump muscles (mainly the diaphragm and abdominal expiratory muscles, the intercostal muscles) are innervated by nerves that are in the ventral horn of the spinal cord
2. second group are the cranial nerves= IX (Glassopharyngeal) and X(vagus) these target the upper airways particularly the larynx (the nerves in medulla oblongata)
   - in larynx have two types of muscles dilators and constrictors (abductors and adductors) act as a mechanical valve another output is the tongue= very special muscle (brainstem that is where the neurons)

Question 16

Is breathing conscious?

Answer 16

-can be but normally isn’t

Question 17

What is the 3 phase activity of respiration?

Answer 17

• recording from phrenic nerve initial burst of activity in I (inspiration) don’t need much force, flowing contraction (THE PUMP)
• second nerve recording recurrent laryngeal nerve (innervates the key laryngeal muscles) biphasic discharge pattern, some discharge overlapping with the inspiratory discharge of the phrenic and then peak right after the inspiration ends (the P2= post inspiratory phase or early expiratory activity) this is important for airflow control then it is merged into the expiratory phase (THE VALVE)
• then recording of subglottal pressure (pressure changes in mouth) , pressure decrease in mouth, then when the inspiration is terminated then contraction of (twitch) of laryngeal constrictors now get recoil of lungs and pressure rises

Question 18

What does phrenic nerve innervate?

Answer 18

-diaphragm

Question 19

What is expiration like in terms of neural control?

Answer 19

-not passive

Question 20

What does postinspiration sounds like?

Answer 20

• it sounds like an ocean, wave

- go up and then peak, breaks and rolls off

Question 21

What is the significance of postinspiration?

Answer 21

• physiologically
• it is expressed in the laryngeal constrictor muscles, and also in one part of the diaphragm
• the diaphragm is pierced by the esophagus and around this area is where the crural diaphragm is
• crural diaphragm has postinspiratory activity
• this is used in many activities e.g. the ejection phase of vomiting requires relaxation of the crural diaphragm

Question 22

Can you learn how to breath?

Answer 22

• yes
• yogins, belly breathing and chest breathing
• also in opera singers= they are champions of muscle control of upper respiratory pathway muscles (up to 1 minute without a breath during singing)

Question 23

Where is the respiratory central pattern generator?

Answer 23

• saggital section of brainstem
• the white dots in single column from caudal to rostral= the respiratory central pattern generator
• central pattern generator = a neural network that can generate a motor pattern that can generate the motor activity without any sensory feedback

Question 24

What are the separation of the column of neurons= the central pattern generator?

Answer 24

-sub-aspects
=have caudal and ventral respiratory
-pre Brotzinger complex= rhythm generator
-from medullary area to the facial motor nucleus and up to the pons
-this network is bilaterally formed and generates the breathing movements
-integrates higher commands like when want to vocalize etc.

Question 25

What is the central and sensory control of postinspiration?

Answer 25

2 pathways

• 1 is the Breurer Hering reflex, the stretch receptors, they fire more and more as you stretch the lungs and send to nucleus of the solitary tract (sensory relay for visceral feedback) and give signal to terminate the inspiratory activity (protective mechanism)
• 2 is via nucleus Koliker-Fuse nucleus that is the inspiratory offswitch and initiates the expiratory and integrates the cortical function and sensory

Question 26

What are some details about pre-Boetzinger complex?

Answer 26

• supposedly generates the rhythm of breathing (like a pacemaker in the sinus node)
• pacemaker activity is generated without synaptic input (the cell fires automatically) but that is NOT how we breathe
• it is not a constant clock signal in the brain, would have to override it all the time to allow for the modulation in vocalization etc.
• so its role is questionable

Question 27

What do you modulate?

Answer 27

-the expiration part is the dynamic part

Question 28

What is the new view on the rhythm generation of breathing?

Answer 28

• complex oscillators between lot of different cells
• post inspiratory cells, late etc.
• all wired together in a huge network
• lot of inhibitory and excitatory connectivity
• when one neuron is most active it provides maximum inhibition to the antagonistic muscle group (oscillation)

Question 29

What is the Galley model?

Answer 29

• hierarchical organisation
• 1. nucleus of the solitary tract= gets info from chemoreceptors, stretch receptors
     
     2. also have lot of neurons that project from these area to the neurons themselves the respiratory muscles and respiratory pre motor neurons, project to activate the motor neurons, must generate the muscle force, pre motor neurons and interneurons generate the patterning and phasic activities (like in the koliker-fuse, the midbrain and periaquadactal grey)
• the periaquadactal grey and limbic systam is the behavioural and emotional command for the muscle
  3: pre botzinger complex= generates the rhythm of the motor activity

Question 30

What is important for healthy breathing?

Answer 30

• the full integrity of the entire central pattern generator
• not a single component can generate and compensate for others
• huge network of neurons that is required to control and modulate the complex activity like breathing
• Every part of the CPG serves a specific function and is of importance
• In case of failure (stroke) other intact parts of the CPG take over (Network redundancy, degeneracy)

Question 31

What are some breathing disturbances when issues in centrally generated disorders?

Answer 31

• rapid shallow breathing= in hypoxia and heart failure, intoxication
• apneusis= cerebral hypoxemia, pathological expansion of inspiration, no time to remove air
• chyene-strokes breathing= arythmyia
• forced breathing= hypoxemia
• ataxic breathing
• gasping

Question 32

What is the Rett syndrome?

Answer 32

• only girls (boys dead)
• central breathing disorder
• normal development to about 1 or 2 years and then everything goes backwards
• X-linked mutation
• record from different parts of the body, breathing arrests for 3 minutes, they are adapted to it but sometimes collapse and get blue
• all those breath holds are generated by the brain, they close their larynx
• overshoot of the neurons, too much excitation during the postispirational phase (the adductors and the folds close too much)

Question 33

How did they research the Rett syndrome?

Answer 33

• transgenic mouse models
  1. Mecp2 (transcription factor) knockout mouse for the autism spectrum neurodevelopmental disorder Rett syndrome and can study
• record the central activity and can analyse in half rat preparation, cut it in half and remove all the cortex etc, only keep the brainstem to have the respiratory network
• all consciousness is removed
• then profuse the preparation via the aorta, oxygenation is provided by the passive diffusion into the tissue
• then test it as if it works normally
• then breath for 4-5 hours
• can see how it works

Question 34

What happens in the Mecp2 knocout mouse?

Answer 34

-impaired resistance in the postlaryngeal nerve, so the larynx closes off

Question 35

What happens in the TAU-P301L knockout mouse?

Answer 35

-model for neurodegenrative diseases like alzheimer’s, parkinson and dementia= have also respiratory problems
-often cause of death in elderely pations= swallowing and breathing discoordination
=massive secondary pulmonary infection= usually lethal