Lecture 18; Rhythm Generation 2 Flashcards
Describe the updated model;
RTN (exh.)
preBOTc (insp)
- these two areas interact
- Lung inflation is +ve feedback to RTN and -ve to preBOTc
- Lung deflation is +ve feedback to preBOTc and -ve to RTN
Is rhythm generation static or dynamic?
Dynamic
- preBOTC are sensitive to noradrenalin and seratonin
What is subthreshold activity? - in regards to DAMGO activity?
There is synaptic current and changes in RMP but not AP are elicited. No burst activity therefore no mechanical consequence
What are the types of noradernergic receptors?
Two receptor sub types a1and a2
a1 is excitatory and a2is inhibitory
What are a1 and a2 coupled to?
a1 is coupled to G protein q/11 using the PLC and IP3 system
a2is coupled to G protein i/0 using the cAMPand PKA system
What causes the noradernergic excitatory and inhibitory effects?
Excitatory effect due to increase in Ca2+and activation of Ca2+activated cation conductance.
Blocking resting K+conductance also postulated.
Inhibitory effect due to blocking of Ihcurrent
What are the seratonin receptors?
Three receptor subtypes suggested 5-HT2A, 5-HT2C and 5-HT1A
What are the functions of the different seratonin receptors?
5-HT2A and 5-HT2C have excitatory effects and increase frequency 5-HT1A has inhibitory effect and decreases frequency
What are the seratonin receptor pathways?
Converging second messenger pathways, share pathways with noradrenergic receptor mechanisms.
What are the pre-natal respiratory movements in humans?
Fetal breathing movements (FBM) rare before 20 weeks
FBM episodic with long apnea in 21-25 weeks
FBM more stable in frequency in 28-39 weeks
At late development has sleep rhythm and inhibited by hypoxia
Describe the state of the neural respiratory networks prior to birth;
- All neural networks must be developed prior to birth
- fetal breathing movements allow for the lungs to be exercised, for these circuits to develop more and to exercise the muscles.
What happens at birth?
There is a huge flux of opioids to prevent the baby from feeling pain. This also inhibits preBOTc function.
However this is functional.
What happens post natally?
Circuits continue to develop, increased inputs.
As does modulation, functionality i.e muscle groups, increased lung capacity, decreased resistance
Therefore there must be enough development to allow breathing at birth.
What do ST and NE act on?
Rhythm generation
Pattern formation
What are the predominant neuromodulators?
ST and NE are the predominant neuromodulators.
Describe the development of breathing rhythm in the fetus;
1 every five hours FBM. (E-16)ish
Becomes more episodic until rhythm is generated. (E18ish)
Networks, feedback i.e chemo,mechano receptors develop late on
Circadian rhythms develop therefore rhythm variation
How does hypoxia influence FBM?
Inhibited by hypoxia as no circuitry yet to initiate the increased resp. rate. therefore preterm must have controlled environment i.e temperature, oxygen, PaO2
Describe the plethysmography in pre and post natal mice;
E16 - periodic FBM (infrequent)
E18- episodic FBM (frequent but not stable (no rhythm)
P4 - Stable breathing rhythm (circuits in place)
Describe the phrenic nerve preparations firing in pre natal mice;
Medullary preparations; (network)
E16 - Have resp. bursts that correlate with insp.
E18 - Increased, more periodic and stable
brainstem slices; (Rhythm cells)
E15 - More stable, reproducible and continuous than p measurements
What is the mechanism that leads to the recordings in the brainstem and medullary samples?
- The PBC rhythm develops in line with FBM in Rats and Mice
- Early gestation (E 15-E17.5) first sign of rhythmical activity (prebotC hence E15 trace)
- Initial PBC activity not sensitive to hypoxia or NE
- But very sensitive to 5-HT
- By E20 in rats the RTN responds like in neonates
Why are the pre-natal mice not sensitive to hypoxia or NE?
Not sensitive = Networks yet to develop
- Hypoxia may utilise NE for response
- Hypoxia may not utilise 5HT
Therefore all systems must develop in parallel but delayed
At what stage are preBOTC active?
E15.5 = Rhythmic activity E14.5-15.5 = preBOTc spontaneously start firing.
When does respiratory rhythm activity start?
Two distinct areas.
- Some activity ~14.5 (rostral) then Caudal (preBOTc) later.
What are the nerves involved in respiration?
Hypoglassal = Upper airway
Phrenic nerve = Diaphragm, thoracic.
Describe the changes in firing of the phrenic nerve over time and why;
Decrementing -> Continuous -> augmented
Decrementing; Base Rhythm only
Continuous; Networks / Medullary inputs form, firing pattern changes
Augmented; External sources added (chemo, mechanoreceptors)
