Lecture 17; Respiratory Rhythm Generation

Question 1

What is rhythm?

Answer 1

Co-ordinated activity

Question 2

Give an example of processes in the body that are rhythmic?

Answer 2

• Breathing
• Walking
• Heart beating

Question 3

How is walking rhythmic?

Answer 3

Neuronal activity in the spinal cord is the source of rhythm. Switches between left/right, off/on to generate movement

Simple circuit

Question 4

What does activation of the respiratory muscles require?

Answer 4

(Baseline) - Rhythm generator (Firing, deactivation, firing etc (in,out,in,out)

(Modulation) - Patterns of firing (fast,slow…)

(Feedback) - Neuronal inputs to alter activity

Question 5

What can alter respiration?

Answer 5

Feedback can alter at all various levels i.e rhythm generation etc

Conscious control of respiration i.e anticipation

Noxious stimuli alters rhythm i.e sneezing

All these are included in the circuitry that alters burst activity (this is the respiratory network)

Question 6

What are the two groups of respiratory cells in the medulla?

Answer 6

preBOTC

RTN/pFRG

Question 7

Describe the respiratory network;

Answer 7

Rhythm generation

Burst pattern formation

Motor neurons

Co-ordinated activity in respiratory muscles

With afferent chemo and mechanoreceptor feedback mechanisms to the burst pattern formation level

Question 8

What did in vivo studies initially reveal?

Answer 8

Rhythm derived from diffuse network

Also;
Combination of neurons firing to create two distinct events to generate breathing

Question 9

What sort of activity was found at the phrenic nerve?

Answer 9

Augmented activity.

i. e Neuron outputs integrated to increase potential then rapid decline
i. e activity of lots of different nuclie neurons together to generate inhalation exhalation

Question 10

How many respiratory nuclie contribute to rhythm generation?

Answer 10

Lots of nuclie, but integration is key to form a respiratory network

• Can destroy the nuclie and the output becomes altered (i.e waveform) but the rhythm is the same / in sync with respiration
• All fire at specific frequencies, differing firing patterns, but same rhythm

(but if main centre is lost everything is shut off)

Question 11

What does the three preparations of phrenic nerve show you?

Answer 11

Three distinct wave forms;

• Augmented (intact prep)
• Constant (Medullary prep)
• Decreasing (PreBOTC preparation)

Question 12

What is the point of the three preparations?

Answer 12

To demonstrate that all brain regions work together to determine the output and removing them changes this

Question 13

What are the hypothesis’ of pacemaker generation for respiration?

Answer 13

Pacemaker Hypothesis

Network Hypothesis

Hybrid Networks

Question 14

What is the pacemaker model?

Answer 14

Pacemaker cells with inputs altering outputs

Question 15

What is the hybrid model?

Answer 15

Pacemaker cells wont work without Network input

Question 16

What is the role of synaptic inhibition in the network model?

Answer 16

Critical for oscillation: responsible for phase transition

Question 17

What is the role of synaptic inhibition in the hybrid model?

Answer 17

Contributes to phase transition and but not essential for rhythm generation

Question 18

What is the role of intrinsic membrane properties in the network model?

Answer 18

Contribute to bursting behavior of neurons but not essential for rhythm generation

Question 19

What is the role of intrinsic membrane properties in the hybrid model?

Answer 19

Convey voltage-dependent oscillatory properties to pacemaker neurons and these are the source of the rhythm

Question 20

Are networks needed for exhalation?

Answer 20

No they are not needed for passive exhalation only forced

Question 21

What is the browns centre hypothesis?

Answer 21

Initiating stimulus

Reciprocal inhibition (prevents both halves from being coactive)

Terminating signal

Question 22

What is a crucial component of both the network and hybrid models?

Answer 22

Both systems must be able to switch off inhalation or exhalation

note; In the hybrid model inhibitory neurons only needed to switch between exh. and insp. i.e running

Question 23

Describe the firing of the pacemaker cells in the pacemaker hypothesis and the hybrid hypothesis;

In regards to insp. and exp. cell groups

Answer 23

Pace hyp: Continuous firing from pacemaker cells

Hybrid; Continuous firing from all inputs feeding back

Question 24

What exists between exp. and insp. cell groups?

Answer 24

Greater activity wins (reciprocal inhibition)

Question 25

What neurotransmitters are used in reciprocal inhibition?

Answer 25

GABA or Glycine

Question 26

What is evidence regarding inhibition for the hybrid model?

Answer 26

Rhythm persists in vitro in absence of synaptic inhibition

but pattern of firing does change i.e wave form

Question 27

What is the evidence for the hybrid model?

Answer 27

1. Rhythm persists in absence of synaptic inhibition
2. Pacemaker neurons found in preBötzingerComplex
3. Kill Pacemaker cells -rhythm stops in vivo

Question 28

What happened to the pacemaker properties of cells when riluzol was given?

Answer 28

Blocks pacemaker properties of neurons without killing the pacemaker cells -rhythm persists.

But this is because within the pacemaker groups of cells there are different ion channels and therefore the pacemaker activity could continue.

When all ion channels were blocked the pacemaker activity ceased

This gave evidence for the model being both pacemaker and network i.e hybrid model

Question 29

What are the types of pacemaker neurons?

Answer 29

Cadmium sensitive neurons (CS)Calcium-activated cation current.
Blocked by Flufenamicacid

Cadmium in-sensitive neurons (CI)Persistent Na+current.
Blocked by Riluzole

Question 30

Describe the stages of a pacemaker cell;

Answer 30

• Depolarisation
• Burst duration and firing patterns
• Repolarisation
• Interburst interval

Question 31

Describe the ionic conductances of the pacemaker cells during depolarisation (of note);

Answer 31

• Persistance Na conductance

- Low voltage Na conductance (to increase RMP)

Question 32

Describe the ionic conductances of the pacemaker cells during burst duration and firing pattern (of note);

Answer 32

• Persistance Na conductance continues
• High voltage Ca conductance

During this ‘bursting’ window there are many APs firing (this gives the spiking pattern)
- Na and K channels required for these APs

• Ia and Im are two different K channels that fire depending on RMP and alter the rate of AP firing

1 burst = one window of AP activity, burst is change in RMP not APs

Question 33

Why is there bursts of activity within the respiratory rhythm burst?

Answer 33

It encodes how respiration occurs

Pattern = shallow, deep breathing etc

High Hz firing - tetanic contraction
Low Hz firing - Individual contractions

Question 34

Describe the ionic conductances of the pacemaker cells during repolarisation (of note);

Answer 34

• inactivation of persistent Na channels
• K channel activation
• Synaptic transmission

Specific channels drive direction of RMP (neuromodulation)

Question 35

What happens if the inspiration regions are switched off?

Answer 35

Breathing can continue if forced expiration occurs.

Question 36

What did the voltage sensitive dye show?

Answer 36

That exp. cells fire just after/before insp. cells

Question 37

How did they determine the relationship between the preBOTc and pRTN?

Answer 37

The use of opiods (DAMGO) opiod aganist

Question 38

What did DAMGO do?

Answer 38

Made preBOTC function at below threshold
- some of these insp. cells were inhibited too (hyperpolarising where you would expect a spike)

pRTN- change output as network had being altered but rhythm was present.

Question 39

What did the DAMGO study conclude?

Answer 39

two sets of pacemaker cells that interact and inhibit one another to drive insp. and exp.