Neuroanatomy L1 Central Pattern Generators and Locomotion Flashcards
Movement planning begins in the_____ cortices, then the axon leaves the primary motor cortex extends down the ______ tracts to the _____ for cranial nerves or ______ for peripheral nerves. Collaterals are sent to the ______ tracts.
motor; pyramidal; brainstem; spinal cord; extra-pyramidal
Descending fibres are located in the _____ funiculus (pyramidal pathway), and synapse on a motor neuron in the _____ horn of the grey matter in the ______. The axon then extends to the ____ to innervate the muscle.
lateral; anterior; spinal cord; periphery
Sometimes we directly exert ____ control over movement of muscles - ie. climbing on rocks or tapping your fingers to the thumb. But for highly stereotyped behaviours (ie. walking or reflexes) there are ________ that induce movements that are controlled at the level of the spinal cord.
cortical; central pattern generators
Most of the CPG are _____, and all is needed is a _______ command from the brain that excites the group of neurons. Give an example.
interneurons; descending motor
- Eg. A headless chicken with an intact brainstem was still able to walk and stand due to central pattern generators
If there is a lesion in the internal capsule you have a ____ based response due to the dominant action of the ____ tract.
flexor; rubrospinal
If there is a lesion below the red nuclei there is an _______response.
extensor
A lot of spinal cord lesions due to accidents involve a _____ displacement of the vertebra which compromises the ____ spinal cord - thus we see damage to the _____ tract - loss of voluntary motor control.
sideways; lateral; corticospinal
The spinal cord is not just a conduit, it is capable of _____ processing.
complex
Medial and ventral is the ____ limb.
Proximal limb
Lateral and dorsal is the _____ limb.
Distal limb
Flexors are more _____ and _____.
medial; posterior
Extensors are more ____ and _____.
lateral; anterior
There is somatotopic organisation in the grey matter of the spinal cord. Proximal muscles are _____ (medial/lateral), and distal muscles are _____(medial/lateral). The extensors are ____ (anterior/posterior), and flexors are ___ (anterior/posterior).
medial; lateral; anterior; posterior
There are continuous columns of _______ up and down the spinal cord - they are not broken up, it is a continuum. The motor neurons are interconnected with___neurons and ______ neurons that forms the basis for reflex arcs.
neuron cell bodies; inter; sensory
What is Rexed’s laminae?
Dividing the spinal cord in 10 zones based on cytoarchitecture (cell distribution and shape)
How was the Rexed’s laminae formed?
Described them based on how they looked under a microscope with a certain staining on of the section.
Research indicates that the central pattern generators are located in rexed lamina _____.
7
Where does sensory input pass through?
Sustantia gelatinosa (2)
How does Rexed’s laminae relate to function?
cells look different because they serve different functions
What Rexed’s lamina is intermediate grey?
Rexed’s lamina 7
What is intermediate grey (Rexed’s lamina 7) associated with?
Associated with modulator reflex arcs and central pattern generators.
Crucial area for locomotion, and may have therapeutic potential for rehabilitation. Induces purposeful movements
What Rexed’s lamina are motor neurons (anterior horn)?
Lamina 9
What horn are motor neurons found in?
Anterior horn
What horn is substantia gelantinosa found in?
Posterior horn
What horn is IML (autonomic) found in?
Lateral
What Rexed’s lamina is the marginal zone?
I
What Rexed’s lamina is the substantia gelatinosa?
II/III
What Rexed’s lamina is the nucleus proprius (spinothalamic tract)?
IV-VI
What Rexed’s lamina is the intermediate grey?
VII
What Rexed’s lamina is the propriospinal?
VIII
What Rexed’s lamina are the motorneuron pools?
IX
What is the function of spinal interneurons?
Allows us to control reflexes and modulate responses
What are the 2 types of neurotransmitters in spinal interneurons? (functional classification) Give examples.
- Inhibitory (GABA/glycine)
- Excitatory (glutamatergic)
What is the function of the inhibitory neurotransmitter?
Suppresses the activity of the neuron it synapses on.
What is the function of the excitatory neurotransmitter?
Increases the activation of the neurons it synapses on.
What are the 3 projections of spinal interneurons?
- Intrasegmental
- Intersegmental
- Commissural
What is the intrasegmental projection of spinal interneurons?
Within one spinal cord segment - ie. simple reflex arcs (sensory neuron - interneuron - motor neuron).
Stays within a segment
What is the intersegmental projection (include propriospinal) of spinal interneurons?
Interneurons connecting different spinal segments. Allows different segments to communicate (ie. the propriospinal interneurons relay information from the lumbar segments to motor neurons in the cervical spinal segments to drive the stereotypical behaviour of an arm swing while walking - this is unconscious).
Different segments (across different levels)- for proprioception
What is the commissure projection of spinal interneurons?
Connects the left and right sides of the spinal cord (ie. reflex arc triggered by a painful stimulus - flexor response on the side of the stimulus and extensor response on the opposite side - communication through commissural interneurons).
Crosses midline
Spinal interneurons make up the majority of _____ matter cells.
grey
The more interneurons, the ____ (more /less) complex our adaptations and processing in response to stimuli can be.
more
What are 2 things that connections within our spinal cord contribute to? What is this called?
- reflexes
- coordination of movements
central pattern generator (CPG)
What is a central pattern generator?
EXAM QUESTION
A flexible network of interneurons that can produce purposeful movement
The central pattern generators aren’t ___ neurons, they are _____ that affect the ____ neurons in the ____ horn.
motor; interneurons; lower motor; ventral
_____ spinal cord - could be the location of the central pattern generator for locomotion.
Lumbar
The _____ (respiration, chewing , eye movements) are pattern generators.
brainstem
______ involves a pattern generator - moving between active and non-active cycles.
Sleep
The nervous system is composed of functional units (ie. blocks of nerve cells) that need the brain to provide _____, and _____ feedback to ____ the output.
input; sensory; modulate
The loop from thalamus to motor cortex are for more ______ patterns.
sterotypical
Mesencephalic locomotor region (mammals) - the equivalent in humans is the penducullarpontine nucleus - provides input to the ______ pathways.
extra-pyramidal
The pathway from locomotion CPG network to cerebellum is for ________ and _____.
learning; adjustment
What is the pathway from motor cortex to locomotor CPG network for?
Direct input on motor neurons - involved with goal directed and more complex behaviours. For learned behaviors, we don’t need this direct, attentive execution. Can used inherent stereotypical behaviours.
There is some direction communication between corticospinal and motor neurons but only _____ movements
specific direct
What can the reticulospinal and vestibulospinal tract do?
Can modulate the activity of the spinal reflexes through the descending pathways from the brain.
Input in the extensor overstretching - the interneurons activate the muscle to contract and take stretch off, and inhibit the _____muscle.
antagonist
- eg. excitatory of flexors inhibition of extensors
Neurotransmitters (in the frameworkof locomotor control) are ____, _____ and ____.
serotonin; acetycholine; glutamin
What is a simple CGP of reciprocal inhibition?
Eg. excitation of extensor and collateral (inhibits) flexor
During gait, the amount of reciprocal inhibition is modulated by ____ (upper/lower) motor neurons
upper
During gait, it is the same process as a simple CPG with reciprocal inhibition. How?
extension (of one leg) and flexor/pull (of other leg) = vice versa
Without _____ (ascending/descending) control from the brain, it is not a smooth pattern of normal gait. Need to slowly release inhibition and cause excitation for smooth movement.
descending
Motor neurons are always ____ (excitatory/inhibitory)
excitatory
What are models for reciprocal innervation?
CPG is made up of ___ neurons.
interneurons
How are flexors and extensions affected by reciprocal innervation. 4 steps
- Input activates the stereotyped output (in CPG)
- In CPG, collaterals branches of an interneuron
- CPG inhibits the extensor motor neuron, so that it doesn’t release it’s excitatory neurotransmitter while simultaneously excitates the flexor motor neuron
- Thus, flexor muscles are activated by the interneurons while the same interneuron inhibits the extensors
Based on a mammalian CPG from animal studies, simulation of the spinal cord can result in complex patterns of ______ in rootlets
‘muscle activity’
What happens in the experiment of the mammalian CPG animal study of rats?
- Rat pups that have just been born - discet out the spinal cord and put it in a petri dish.
- Record output from the nerve roots, by injecting excitatory neurotransmitters (seratonin or glutamatergic).
What is lL3?
Left L3, mostly flexor biased.
What is rL3?
Right L3 root is also flexor biased, but activates alternately with the right side.
What is rL5?
Right L5, extensor biased - when the left flexor activates, the right extensor activates.
What happens in the the experiment of a mamillian CPG animal study of cats?
- Complete transection (lesion) of the spinal cord, and the animal is paralysed.
- Stimulate the pereonal region for three weeks, and give them treadmill training (given rehab)
What was the impact on the cats who were given treadmill training in the animal study? How was this achieved?
Began displaying stepping like patterns, even without connections from the brain.
- If the treadmill goes forward, the animal walks forward, if the treadmill goes backward, the animal walks backward, and if you put the on an angle, the animals steps sideways.
This is achieved by sensory information that is processed at the spinal cord level only (no descending modulation).
Why can babies not walk? What do they have instead?
babies don’t have descending motor neurons yet
- Touch ground= extensor effect eg. Babinski reflex
What is different when studying cats vs humans? 2 differences .
- Amplitudes of muscle contraction signal is not as large in human patients with spinal cord lesions.
- Timing is slightly different as well (due to foot drag)
Noting the rhythmic activation of flexors and extensors during treadmill induced ‘walking’, which 2 muscles come on at the same time?
- Sartorius
- Tibialis anterior
Thus, what is the impact of treadmill “walking” in SCI patients (humans)?
Because we are bipedal, we need a lot more descending modulation to maintain balance when walking (compared to cats).
Networks in the spinal cord are capable of producing stepping-like movements, thus people with complete paralysis of the lower limb are able to walk when they are supported by a harness, with loading on the ankles and the treadmill going.
If cats can under certain circumstances, why then can people with similar spinal cord injuries not walk? What specifically do they need?
more descending control needed (postural adjustments for upright walking)
10% weight loading is the minimum sensory feedback for spinal cord,
What is driving the CPG? Is it sensory input?
People thought that sensory input from the leg moving on the treadmill was processed by the spinal cord, and initiating the CPG to produce a stepping pattern.
This is NOT true.
Sensory input is important for the CPG to adjust its output - ie. sideways, backwards or forwards stepping - but it doesn’t initiate the output.
In the experiment, cats with lesion separatinng cerebrum from the brain stem and with the limbs deafferented (supported by sling). What did that mean?
walking can be induced by simulating locomotor areas in the brain stem
Muscle activity ____ (is/ is not) dependent on sensory input into the spinal cord
is not
What is then the role of sensory input in motor function?
Sensory feedback is important for the CPR to adjust its output, and for adaptation of movement.
In the experiment, If a cat with complete SCI is prevented from moving during induced walking, muscle activity ______. Why?
persists
There is no sensory feedback to alter the pattern, and change mid-swing to stance again, so the muscle just keeps contracting.
Thus, why is sensory feedback important?
Sensory feedback is needed to change from ‘swing’ to ‘stance’ and back
The CPR is a flexible network of interneurons that can create a purposeful movement, that doesn’t need _____ feedback to ____ movement (we can induce limb movement in the absence of sensory movement). Rather, what is the sensory feedback important for? 2 features.
EXAM QUESTION
sensory; produce
- to change from swing to stance in the normal step cycle
- to adapt or adjust the output (ie. sideways or backwards stepping, or responding/adapting to a object).
Adaptation of the CPG to environmental stimulus- response reversal: What happens when touch the dorsal surface of the paw during swing phase? Why?
Increased lift
Sensory feedback registers an object there - the spinal cord thinks it needs to clear an object - thus the paw lifts higher.
Adaptation of the CPG to environmental stimulus- response reversal: What happens when touch the dorsal surface of the paw during stance phase? Why?
Increased extension
Because the spinal cord wants to ensure stability when in stance.
How is rhythm generated?
We have a hybrid combination of model 1 and 2 in the CPG.
What is model 1 of the GPG, relating to rhythm being generated?
Pacemaker cell triggers rhythmic activity of non-pacemaker cells
Pacemaker cells are connected to various other cells nearby - the cells are turned on and off based on the pacemaker cell.
What is model 2 of the GPG, relating to rhythm being generated? What does that mean?
Rhythmic activity results from reciprocally coupled non-pacemaker cells
All of the cells are reciprocally connected. When one cell becomes active in the network, then all the cells become active.
What is the layered model for a locomotor CPG?
In a layered model for a locomotor CPG, when stimulating the spinal cord externally (ie. like transcranial electrical stimulation), at the lumbar region, leg movements are ____ (even though the person is trying hard not to). This doesn’t occur in any other region of the spinal cord, so can’t be simple activation of ______pathways.
induced; descending motor
What are the 3 layers of the locomotor CPG (lumbar spine)?
EXAM QUESTION
- Rhythm generation layer
- Pattern formation layer
- Motor output later
What occurs at the rhythm generation layer of a layered model of a locomotor CPG?
Left and right interneurons are reciprocally inhibiting each other - ie. when one is active, the other is inactive.
What occurs at the pattern formation layer of a layered model of a locomotor CPG?
Flexor and extensor pools are reciprocally inhibiting each other - ie. wen one is active, the other is inactive.
What occurs at the motor output layer of a layered model of a locomotor CPG?
These cells are driving the output.
Which layer is the top layer?
Rhythm generation layer. (highest execution layer)
Activation of V2a will activate the ____, and inhibit the opposite ____ via ______.
EXAM QUESTION
MN; MN; V0
What happens at initiation of locomotion?
The initiation of the CPG stepping motion begins with the reciprocal model.
At the start all gap junctions of the cells closed, and are only connected reciprocally via axons. The motor drive that comes down from the mesencephalic locomotor region. Calcium on the outside, potassium on the inside of the cell. Gap junction is closed
What happens at initiation of locomotion?
As the motor drive increases (calcium flows from outside to inside the cell), the gap junctions begin to open, and now some of the cells become one big functional unit pulsating on and off to stimulate stepping pattern for walking. All of the cells contribute when running.
Gap junction starts to open up (to work as one unit)
Locomotor CPG is activated, modulated (adaptive control of goal-directed locomotion) and silenced by ______ structures
supraspinal
The _______ region (brainstem) controls the intensity of locomotion: progressively increasing simulation intensity => faster locomotor rhythm
mesencephalic locomotor
Mesencephalic (mesencephalon: midbrain!) locomotor region influences the CPG mainly via the _______ and the _____ tract: => MAIN ____ (EXCITATORY/INHIBITORY) DRIVE!!
reticular formation; reticulospinal; excitatory
When locomotion is initiated, Ca2+ outside ____ (increases/decreases) while K+ ______ (increases/decreases); this provides _____ (positive/negative) feedback for I’NaP’ and gap junctions => pacemaker activities are induced.
decreases; increases; positive
Faster locomotion, more cells start to act like _____ and increase bursting frequency
pacemakers
What are 3 reasons why the current theory is that Hb9 interneurons can function as pacemaker cells?
- they can synchronise their firing (electric coupling)
- they can switch from spiking to bursting
- they project to motorneurons
Firing patterns change based upon ionic composition of ________
extracellular fluid (CSF)
LOCOMOTOR NETWORK IS A HYBRID PACEMAKER WHERE PACEMAKER NEURONS ARE THE SEEDS FOR ______.
RHYTHM GENERATION
