Lecture 17; Respiratory Rhythm Generation Flashcards
What is rhythm?
Co-ordinated activity
Give an example of processes in the body that are rhythmic?
- Breathing
- Walking
- Heart beating
How is walking rhythmic?
Neuronal activity in the spinal cord is the source of rhythm. Switches between left/right, off/on to generate movement
Simple circuit
What does activation of the respiratory muscles require?
(Baseline) - Rhythm generator (Firing, deactivation, firing etc (in,out,in,out)
(Modulation) - Patterns of firing (fast,slow…)
(Feedback) - Neuronal inputs to alter activity
What can alter respiration?
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)
What are the two groups of respiratory cells in the medulla?
preBOTC
RTN/pFRG
Describe the respiratory network;
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
What did in vivo studies initially reveal?
Rhythm derived from diffuse network
Also;
Combination of neurons firing to create two distinct events to generate breathing
What sort of activity was found at the phrenic nerve?
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
How many respiratory nuclie contribute to rhythm generation?
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)
What does the three preparations of phrenic nerve show you?
Three distinct wave forms;
- Augmented (intact prep)
- Constant (Medullary prep)
- Decreasing (PreBOTC preparation)
What is the point of the three preparations?
To demonstrate that all brain regions work together to determine the output and removing them changes this
What are the hypothesis’ of pacemaker generation for respiration?
Pacemaker Hypothesis
Network Hypothesis
Hybrid Networks
What is the pacemaker model?
Pacemaker cells with inputs altering outputs
What is the hybrid model?
Pacemaker cells wont work without Network input
What is the role of synaptic inhibition in the network model?
Critical for oscillation: responsible for phase transition
What is the role of synaptic inhibition in the hybrid model?
Contributes to phase transition and but not essential for rhythm generation
What is the role of intrinsic membrane properties in the network model?
Contribute to bursting behavior of neurons but not essential for rhythm generation
What is the role of intrinsic membrane properties in the hybrid model?
Convey voltage-dependent oscillatory properties to pacemaker neurons and these are the source of the rhythm
Are networks needed for exhalation?
No they are not needed for passive exhalation only forced
What is the browns centre hypothesis?
Initiating stimulus
Reciprocal inhibition (prevents both halves from being coactive)
Terminating signal
What is a crucial component of both the network and hybrid models?
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
Describe the firing of the pacemaker cells in the pacemaker hypothesis and the hybrid hypothesis;
In regards to insp. and exp. cell groups
Pace hyp: Continuous firing from pacemaker cells
Hybrid; Continuous firing from all inputs feeding back
What exists between exp. and insp. cell groups?
Greater activity wins (reciprocal inhibition)
What neurotransmitters are used in reciprocal inhibition?
GABA or Glycine
What is evidence regarding inhibition for the hybrid model?
Rhythm persists in vitro in absence of synaptic inhibition
but pattern of firing does change i.e wave form
What is the evidence for the hybrid model?
- Rhythm persists in absence of synaptic inhibition
- Pacemaker neurons found in preBötzingerComplex
- Kill Pacemaker cells -rhythm stops in vivo
What happened to the pacemaker properties of cells when riluzol was given?
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
What are the types of pacemaker neurons?
Cadmium sensitive neurons (CS)Calcium-activated cation current.
Blocked by Flufenamicacid
Cadmium in-sensitive neurons (CI)Persistent Na+current.
Blocked by Riluzole
Describe the stages of a pacemaker cell;
- Depolarisation
- Burst duration and firing patterns
- Repolarisation
- Interburst interval
Describe the ionic conductances of the pacemaker cells during depolarisation (of note);
- Persistance Na conductance
- Low voltage Na conductance (to increase RMP)
Describe the ionic conductances of the pacemaker cells during burst duration and firing pattern (of note);
- 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
Why is there bursts of activity within the respiratory rhythm burst?
It encodes how respiration occurs
Pattern = shallow, deep breathing etc
High Hz firing - tetanic contraction
Low Hz firing - Individual contractions
Describe the ionic conductances of the pacemaker cells during repolarisation (of note);
- inactivation of persistent Na channels
- K channel activation
- Synaptic transmission
Specific channels drive direction of RMP (neuromodulation)
What happens if the inspiration regions are switched off?
Breathing can continue if forced expiration occurs.
What did the voltage sensitive dye show?
That exp. cells fire just after/before insp. cells
How did they determine the relationship between the preBOTc and pRTN?
The use of opiods (DAMGO) opiod aganist
What did DAMGO do?
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.
What did the DAMGO study conclude?
two sets of pacemaker cells that interact and inhibit one another to drive insp. and exp.
