Central neuronal circuits controlling respiration Flashcards
Define: eupneic
normal breathing
Where does the phrenic nerve arise from and run to ?
arises from the cervical spinal cord
runs from C3-C5
What does the phrenic nerve do ?
it is the driver of respiration - respiration requires the brain to enable its function
the phrenic motor neurones innervate the diaphragm which when it is active it contracts to open up the rib cage to help pull air into the lungs
What have recordings from the phrenic nerve enabled?
the extracellular recordings of action potentials from this nerve has helped researchers identify changes in the activity of the respiratory cycle and assign functional roles to neurones in the central respiratory network
What happens to the phrenic nerve in normal activity ?
in normal breathing phrenic nerve increases its activity- the activity ramps up in intensity
What are the sequences of breathing ?
3 essential phases
1) inspiration = phrenic nerve activity- action potentials coming down nerve
2) post inspiration = passive relaxation- no more breathing in
3) expiration = active muscular movements
each phase involves contraction of specific muscle groups and respiration requires functioning of many nerve and muscle structures including brainstem and respiratory muscles
What happens in the proper 3 phase rhythm?
- augmenting shape of phrenic nerve bursts
- preinspiratory onset of hypoglossal nerve bursts (50-100ms before onset of phrenic nerve burst) = purpose is to move the tongue out of the way to enable breathing
- prominent stage of decrementing postinspiratory discharge in cervical vagus nerve - big peak post inspiration
What brainstem regions are contributing to respiration ?
rVRG, cVRG, pre-Botzinger complex, botzinger complex and many regions in the pons
DRG- less studied as its less prominent in rats but it does project to the phrenic nerve
VRG- nearly continuous column in lateral rhombencephalon
What is a key point about the rVRG?
rVRG is the source of excitatory drive to the phrenic motor neurones and so for inspiration
BUT the VRG cells dont have a rhythm of their own
How did they know that the BotC, pre-BotC and VRG neurones were involved in respiration ?
these areas contain neurones that have neurones firing with a similar pattern to respiration- therefore firing pattern is related to respiration
Why is the working heart-brainstem prep good?
it doesn’t require anaesthetic to be injected which is important when recording respiration because anaesthetic will alter breathing
- enables recordings from the BotC, pre-BotC and rVRG
- can also record from phrenic, cervical vagus and hypoglossal nerves
What experiment did they do to decipher which areas of the brain are involved in the rhythm of respiration?
sliced off little bits of the brain until they got no activity to determine where the rhythm comes from
What happened when sliced off all the way down to the medulla (cVRG and rVRG)?
once they were down just to the medulla there was no rhythm indicating that the drive cannot come from neurones in VRG alone
What happened when the pre-BotC and medulla were present?
once the pre-BotC was added a rhythm was present but it was a 1 phase rhythm because it was decrementing - not quite the normal rhythm
- detected cervical vagal activity at the same time as phrenic which is NOT normal so rhythm was not proper
- hypoglossal and phrenic were also firing at the same time
What happened in the medullary preparation with BotC, pre-BotC and VRG neurones?
a 2 phase inspiratory-expiratory rhythm pattern occurred
1) non-ramping square-wave motor profile
2) onset of activity synchronised in all nerves and by a lack of post- inspiratory discharge in cVN
still not a proper normal rhythm
What are the neurons like in the BotC?
inhibit expiratory neurones
provide inspiratory-expiratory alterations during normal breathing
What are the neurones like in the pre-BotC?
excitatory glutamate neurones, they are the primary source of inspiratory drive
does have some GABA cells too which may inhibit expiratory cells during inspiration
What are the neurones like in the rVRG?
excitatory and they project to the spinal cord to drive inspiration in the phrenic motor neurones
they are excited by the pre-BotC in inspiration and inhibited by BotC in expiration
What are the neurones like in the cVRG?
excitatory cells which shape patterns of excitatory drive to spinal motor neurones in expiration
What is endogenous bursting activity based on ?
expression of persistent sodium channels
excitatory interactions within the population
What happens when you record the activity in the pre-botzinger complex?
the activity relates to the activity of the phrenic nerve - fires in a rhythmic patter onto rVRG which projects to the phrenic motor neurones
What happens when the pre-BotC is ablated and how did they do it ?
it disturbs respiration
noticed that the cells contained lots of substance P receptors - NK1R - they were fairly restricted to the pre-BotC complex
took antibody for receptor and tagged it with a poison saporin to kill the cells and it completely abolished respiration
What was seen when recording from control and pre-BotC abolished mice?
the control rats breathing room air would spontaneously generate an occasional sigh followed by an extended expiratory pause which was absent in the pre-BotC abolished mice
they breathing movements weren’t occurring like normal
What happened to the control and pre-BotC abolished mice in 5% co2 ?
normal animal had increased breathing rate and depth
whereas the abolished rat didn’t respond well, breathing didn’t increase
