Flashcards in Can the spinal cord generate locomotor or autonomic activity? Deck (38):
What is the most sophisticated spinal cord motor reflex?
- it involves activation of nociceptive cutaneous receptors driving local circuits and limb withdrawal - the extension of the contralateral limb provides compensatory postural support
Why are spinal cord reflexes so important?
one of there important functions is to help maintain balance
what does the spinal cord do to assist movements?
it can generate a complex rhythmic motor output that underpins walking, running or swimming
How do you get rhythmic movement at the spinal level ?
through neuronal circuits called "central pattern generators" - it is defined as an oscillatory local circuit
- made up of spinal interneurones and motoneurones which working together give rise to rhythmic motor activity
What are CPGs responsible for during limb movement?
they are responsible for alternating flexion and extension h limb in a rhythmic pattern - it is constantly activating this alternating pattern while walking
What did experiments in cats demonstrate about the central pattern generators?
demonstrated that there are adapted patterns
for example acceleration from walking to gallop is subject to higher control
- by isolating the spinal cord they showed that the pattern needs to be able to adapt so movement occurs at the appropriate speed and in coordination as well as ensuring alternation occurs
How did they prove that the central pattern generators are localised to the spinal cord?
cut the spinal cord and dorsal roots to remove any sensory input (central and afferent responses removed)
then they recorded the electrical activity of flexors and extensors and the alternation between left and right and this demonstrated that the basic rhythmic pattern of limb movement isn't dependent on sensory input or on input from higher brain centres
it proved there is an oscillatory spinal cord local circuit e.g the CPG that is involved in alternating flexion and extension
How does the spinal cord generate rhythmic patterns of activity?
neuronal rhythms arise due to
- neuronal intrinisc properties= pacemaker neurones
-an emergent property of the network that is dependent upon synaptic properties and patterns of connections between neurones
What is one theory of gaining rhythmic activity?
by specialised pacemaker neurones
- neurones with intrinsic membrane properties that impart pacemaker or oscillatory activity
What is the concept behind pacemaker neurones and follower neurones?
the follower will fire randomly when it is uncoupled from the pacemaker neurone
the follower neurones will follow the activity of the pacemaker neurones when they are coupled
How are intrinsic oscillators activated or altered?
by activity of other brain structures and by afferent inputs
What is a common model used for testing locomotion?
- jawless parasitic fish, no fins and body is made up of segments
How do lamprey move?
They move by contraction and relaxation of each muscle segment in sequence creating a sinusoidal motion
What was shown when they isolated the lamprey spinal cord?
after isolating the spinal cord they maintained it and recorded its activity- as it was isolated it wasn't receiving any supra spinal or afferent inputs
- the locomotor pattern generated from the isolated spinal cord was similar to that of an intact lamprey
this indicates the spinal cord is generating a fictive locomotor pattern= CPG - it is still present even without inputs to muscle or any sensory inputs
What receptors are involved in the pacemaker properties of lamprey spinal interneurones and how does it work ?
NMDA receptors and calcium-activated potassium channels
1) NMDA and calcium activated potassium channels are closed
2) glutamte actiavtes NMDA receptors causing calcium influx which releases magnesium block so more calcium enters and cell depolarises
3) intracellular calcium concntration rises and this causes calcium-activated potassium channels to open leading to potassium efflux and cell hyper polarisation and the NMDA channels close causing the magnesium block to reform
4)calcium levels fall and this causes potassium channels to close- membrane potential is reset, ready for another oscillation
How was the pacemaker properties of lamprey determined?
by using TTX to block sodium influx
How can rhythms emerge from a network?
rhythms can arise from collective behaviour of a circuit
- it is an "emergent property" formed from synaptic coupling between non-bursting neurones
- a network can act as a pacemaker to impose their own rhythm on other neurones
How can simple networks generate rhythmic activity?
they can only do this if they have a time-dependent process that can enhance and/or reduce activity within other neurones
How does the neurona network in lamprey swimmining work?
the activity of each segment is initiated by glutamatergic axons from the reticular formation and this increases activity of neurones by NMDA receptors
What are the neurones involved in lamprey swimming and how do they interact? (for rhythm generation (L+R ) and pattern generation (flexor-extensor))
excitatory interneurones act on motor neurones and inhibitory interneurones
there are inhibitory interneurones inch side of the spinal cord that can inhibit other interneurones on the opposite side to them , they cross the midline - this allows reciprocal inhibition allowing alternating activation of flexor and extensor muscles bilaterally
PROCESS REQUIRES MANY DIFFERENT NEURONES
Why have transgenic mice models been helpful in determining the neurones involved in generating locomtion?
allows identification and/or ablation of specific groups of neurones to give an insight into their function
- knock out a group of interneurones or
- record from a specific group of interneurones that express a specific transcription factor
THEN YOU OBSERVE MOTOR ACTIVITY-SEE HOW ITS CHANGED
What pacemaker neurones did they record from in rodents?
carried out recordings in the ventral roots
- recorded from EphA4 positive interneurones using a single electrode
- indication they were involved in pacemaker activity
1) interneurones demonstrated coordinated activity when NMDA/5HT is applied
2) have monosynaptic connections to motoneurones
these results indicate that they could be important in CPG
What happens when EphA4 interneurones were deleted in mice?
it produces hopping in the mice
- although this is abnormal it doesn't prove they are the main pacemaker cells
What was discovered about Hb-9 positive interneurones?
Hb-9= transcription factor
recorded from these neurones and they had analogous activity to the motor neurones in the ventral roots
they were excitatory
this evidence indicates they could be involved in the CPG
What evidence indicates that HB-9 positive interneurones are not the main pacemaker cells?
when all other inputs were removed and these interneurones were recorded from they didn't demonstrate much activity
- then they continually activated them and oscillations occurs even when they were synaptically isolated
then another group determined that they actually fire just after motor neurones in the ventral root fire, therefore although they are likely important in the netwrok, they are not driving the activity
What happened when VI interneuron population was knocked out?
this involved also knocking out renshaw cells that express En1
the rhythm is slowed but the flexor-extensor alternation is not changed
when the GIRK channels(linked to allostatin receptors) of these interneurones are activated it silences the VI interneurones and this also slows the rhythm
What is the main candidate for the interneurones involved in L-R coordination?
VO commissural interneurones
-Dbx ko deletes VO interneurones and Left and right ventral root activity loses reciprocity but flexor (IL2) and extensor (IL5) alternation is maintained
What other interneurones may also be involved in left and right coordination ?
V2A interneurones (may include some Eph4 neurones)
How do babies indicate that humans demonstrate CPGs?
when you hold a baby up erect they show rhythmic stepping movement - this suggested basic locomotor circuits are established at birth
When are basic circuits brought under control ?
they are brought under control of supra spinal systems in 1st year- from automatic stepping to walking
What is the difference between spinal transaction in human adults compared to cats?
there is little rhythmic activity in adults compared to cats and this is likely due to the dependence on upper motor neuronal pathways in humans
in humans why cant rhythmic activity be achieved?
because human locomotion is bipedal therefore we need to maintain posture (via brainstem) so it cant be achieved only at the spinal level
In humans what is critical for locomotion?
supraspinal control is critical as we get older to make our walking better -central pathways are crucial
What does motor complete spinal cord injury mean ?
it means the patient is incapable of any motor activity
What did 10 motor complete patients receive?
continuous epidural stimulation
- all 4 muscle groups co-activated and "locomotor-like" patterns with alternating activations of antagonists
What factors influence spinal pattern generators?
DESCENDING INPUTS (epidural stimulation)
- cerebral cortex- visuolomotor coordination
- serotonin, dopamine, NMDA, bicculine, strychinine and NA
- sensory inputs - proprioceptors
What can stimulation of the parapyramidal medulla do ?
it can induce locomotor activity
- serotonin is important in many different activities