Locomotion Flashcards
Which species locomote?
all
TRUE or FALSE: lower vertebrates contract muscles of the 4 limbs at the same time (co-contractors)
FALSE:
- lower vertebrates use sinusoidal body contractions for locomotion
- avian species contract muscles of the 4 limbs at the same time (co-contractors)
What are the 2 phases of locomotion?
- swing = flexion (i.e. flexor muscles are active)
- stance = extension (i.e. extensor muscles are active)
When does the beginning of the locomotion cycle occur?
when leg hits the ground (going from swing to stance)
TRUE or FALSE: locomotion is all or none
FALSE: specific pattern of muscle activation is more complex
TRUE or FALSE: locomotion is controlled by the spinal cord
TRUE
During which phase do flexors BEGIN to activate?
stance phase
What is spinalization and what was it used to demonstrate?
- cut all afferent inputs to spinal cord
- prove that theory that afferents cause locomotion is WRONG
TRUE or FALSE: activation of extensor half center will inhibit flexor half center
TRUE
What does the locomotor CPG do?
generate complex locomotor patterns
(CPG = central pattern generator)
Describe the stumbling corrector response after tripping. Is this response activated by the brain or the spinal cord?
- tripping activates the stumbling corrector response
- this response increases knee and hip FLEXION & ankle hyper-EXTENSION
- activated by the spinal cord
TRUE or FALSE: the locomotor CPG does not require assistance
FALSE: locomotor CPG requires assistance (e.g. visual and sensory info)
TRUE or FALSE: although supraspinal/sensory structures are not necessary for basic locomotor rhythm generation, they are responsible for stopping activity within the locomotor CPG and modulating its output to suit the environment
FALSE: responsible for INITIATING and modulating CPG activity
The locomotor CPG is ________________ (initiated/modulated) by descending input and ________________ (initiated/modulated) by sensory input.
- initiated by motor input
- modulated by sensory input
What is an example of descending input and sensory input affecting locomotor CPG in the SC?
- descending input = DECISION to perform locomotion (activate CPG)
- sensory input = going DOWNSTAIRS (i.e. consider the environment of locomotion)
how many cervical nerves are there? thoracic? lumbar? sacral?
- C1-C8
- T1-T12
- L1-L5
- S1-S5
How are grey and white matter arranged in the spinal cord?
grey matter on the inside (unmyelinated)
Where are 2 locations on the spinal cord that you can find more grey matter?
cervical and lumbar enlargements
In which enlargement of the spinal cord is the locomotor CPG found?
lumbar enlargement
Mammalian spinal cord has a laminar distribution. What does this mean?
neurons in different lamina have related functions
Which spinal cord lamina are associated with the dorsal horn? intermediate nucleus? ventral horn?
- dorsal horn = lamina I - V
- intermediate nucleus = lamina VI - VIII
- ventral horn = lamina IX
What kind of neurons are found in lamina I - V? Which part of the spinal cord is this?
- sensory-related interneurons
- dorsal horn
What kind of neurons are found in lamina VI - VIII? Which part of the SC is this?
- sensory and motor-related interneurons (excitatory and inhibitory)
- intermediate nucleus
What kind of neurons are found in lamina IX? Which part of the SC is this?
- motor neurons
- ventral horn
Which part of the spinal cord controls locomotion?
a) dorsal horn
b) intermediate nucleus
c) ventral horn
Which lamina control locomotion?
b) intermediate nucleus (lamina VI - VIII)
TRUE or FALSE: interneurons with variable functions are intermingled in the the intermediate and dorsal spinal cord.
FALSE: intermediate and VENTRAL spinal cord
What are the different types of cells and their subtypes that exist in the SC?
- glia (astrocytes, oligodendrocytes)
- neuron (motor neuron, interneuron (+/-))
Describe the first spinalized cat preparations and what it demonstrated. (hint: were the first studies physiological?)
- first studies were NOT PHYSIOLOGICAL (drugs and spinalization and stimulation of PNS to generate locomotion)
- after application of L-DOPA stimulation of flexor reflex afferents –> left-right alternation of hindlimbs similar to stepping (slow locomotor pattern)
- first studies showed that the locomotor CPG was found in the INTERMEDIATE NUCLEUS, as majority of the interneurons that receive input from FRA are found here
In comparison to spinalization to evoke locomotion, what was another experiment done to activate the locomotor CPG more physiologically? Describe this experiment.
- electrical brainstem stimulation
- site in the midbrain of cats was identified that could evoke locomotion when electrically stimulated
- site = MESENCEPHALIC LOCOMOTOR REGION (MLR)
MLR vs CPG?
- MLR = initiation of stepping in locomotion
- CPG = generation of locomotor patterns
How does increasing stimulation strength affect in vivo fictive locomotor activity?
increasing stimulation = increasing speed of locomotion
How are the MLR and CPG anatomically related?
MLR –> reticular formation –> reticulospinal tract –> locomotor CPG
Which nuclei was the MLR initially presumed to include?
- pedunculopontine nucleus (PPN)
- cuneiform nucleus (CN)
Describe the in vivo fictive locomotor preparation.
- animal is decerebrated, paralyzed, and deafferented
- electrophysiological recording made from cut muscle nerves
- electrical stimulation of MLR –> rhythmic alternation of flexor and extensor related muscle nerves on either side of animal –> this pattern is known as FICTIVE LOCOMOTION
- this preparation enabled sensory afferents to be stimulated to investigate HOW SENSORY INPUT MODULATES THE STEP CYCLE
TRUE or FALSE: in the in vivo fictive locomotor preparation, locomotion was evoked by stimulation of sensory afferents
FALSE: only neural correlates (nerve activity) of locomotion was recorded
What is fictive locomotion?
rhythmic alternation of flexor and extensor related to muscle nerves on either side of an organism (generated by stimulation of the MLR)
TRUE or FALSE: flexor and extensor nerve/motor activity is in phase
FALSE: out of phase
Describe the in vitro fictive locomotor preparation. main findings?
- isolate SC in neonatal rat –> now drugs in bath have no systemic effect and only affect locomotion (i.e. this preparation allows for pharmacological control)
- cervical enlargement innervates front limbs
- lumbar enlargement innervates hind limbs
- L2 = flexor muscle axons
- L5 = extensor muscle axons
- L2 and L5 activity OUT OF PHASE
TRUE or FALSE: the in vivo locomotor preparation allowed for good pharmacological control
FALSE: the in VITRO locomotor preparation
TRUE or FALSE: L2 innervates the front limbs, L5 innervates the hind limbs
FALSE:
- L2 = flexor motor axons
- L5 = extensor motor axons
What are 2 general techniques that have been used to study the locomotor CPG? describe these techniques.
- ELECTROPHYSIOLOGICAL STUDIES - intracellular recording from single neurons OR extracellular recordings from groups of neurons during locomotion
- ANATOMICAL TRACING STUDIES - anterograde/retrograde tracers to visualize axonal projections of neurons
TRUE or FALSE: the caudal spinal cord is more rhythmogenic than the ventral spinal cord
FALSE: ventral more rhythmogenic
How was it discovered that the ventral spinal cord plays a larger role in generating rhythm of locomotion? What does this imply about the location of the CPG?
lesion ventral SC –> impair locomotion
therefore, CPG is found ventrally
What are the 2 main problems with using electrophysiological and anatomical studies to investigate the locomotor CPG?
- NUMBER of neurons in the mammalian SC
- extent to which theses cells are INTERMINGLED
considering the 2 main problems using electrophysiological and anatomical studies to investigate locomotor CPG, why do we still use it?
these studies can give detailed info on SINGLE CELLS, but it is little help when attempting to identify STRUCTURE OF MECHANISM OF FUNCTIONS of the locomotor CPG
What is the logic behind using developmental genetics to study the CPG?
cells with similar genetic background have similar function; therefore, we can simplify the spinal cord into well defined populations of functionally homogenous cells
(i.e. bypass the issue of number and intermingled neurons)
what are the 3 developmental stages of the nervous system?
- blastulation
- gastrulation
- neurulation
blastulation
- process by which blastula is produced from fertilized ovum
- spherical layer cells of with large fluid filled space called the blastocoel
(fertilized ovum –> blastula)
gastrulation
embryo reorganized to form 3 layers: ectoderm, mesoderm, endoderm
neurulation
specialized region of ECTODERM forms the nervous system
which germ layer of the embryo does the spinal cord originate from?
ectoderm
what does the endoderm give rise to? mesoderm? ectoderm?
- endoderm = gut, liver, lungs
- mesoderm = muscles, connective tissue, vascular system
- ectoderm = skin, CNS, PNS
The developing neural tube secretes signalling molecules in a gradient manner. What does this imply about differentiation of cells?
position in the neural tube determines cell fate (i.e. what function the cell will take on after differentiation)
TRUE or FALSE: ventral cells respond to bone morphogenic protein (BMP) and dorsal cells respond to sonic hedgehog (Shh)
FALSE:
- dorsal cells respond to BMP
- ventral cells respond to Shh
Where is BMP released from? Shh?
- BMP released from neural crest cells/roof plate
- Shh released from notochord/floor plate
How does BMP regulate gene expression? Shh? (Hint: consider proteins that are involved)
- BMP phosphorylates SMAD proteins which translocate to nucleus
- Shh bind to patched protein, activate smoothened protein, activate Gli TFs
TRUE or FALSE: dorsal cells in the embryonic spinal cord are important for locomotion and CPG
FALSE: VENTRAL cells important for locomotion and CPG
neuronal cell populations resulting from dorsal cell differentiation? ventral cell?
- 6 dorsal interneuronal cell populations (dl1-dl6)
- 5 ventral cell populations (V0-V3, i.e. 4 interneurons; VMN i.e. 1 motor neuron)
Like the BMPs, Shh directs different cell fates at _____________________________.
different concentration thresholds
how many interneurons develop from the ventral cells?
4
TRUE or FALSE: interneuronal populations in the developing spinal cord undergo migration which causes intermingling
TRUE
How can we identify cell types in the SC after they have migrated?
immunohistochemistry using antibodies raised against specific TFs at early time points
When are TFs expressed?
only from E10-E13
How can using transgenic mice that express reporter genes be used to follow internuronal populations from birth to maturity? What is this technique called?
these mice allow:
- immunohistochemical and ANATOMICAL techniques to characterize these cell populations (rather than single neurons)
- ELECTROPHYSIOLOGICAL techniques to determine whether specific populations are part of the locomotor CPG and their role in the production of locomotor behaviour
(immunohistochemistry)
Which interneuron population contains the CPG?
V0 INs
which TF is expressed in all V0 interneurons from E10.5-E12?
Dbx1
what kind of transgenic mice can be used to visualize V0 interneurons postnatally?
Dbx1 LacZ mice
In which lamina of the spinal cord are V0 cells located?
lamina VIII
What kind of transynaptic tracer was applied to hindlimb muscles of Dbx1 LacZ mice to provide evidence that V0 cells make contact onto contralateral motor neurons?
retrograde
TRUE or FALSE: V0 cells are rhythmically active during locomotion in phase with contralateral motor neuron bursting
FALSE: V0 out of phase with contralateral motor neuron
TRUE or FALSE: V0 cells only play a role in initiating locomotion.
FALSE: play a role in coordination of left-right alternation during walking
note: NOT flexor extensor alternation on same leg (i.e. V0 cells inhibit LEFT FLEXOR activation when RIGHT FLEXOR is activated)
What mediates alternation of flexor-extensor on one side? alternation of left and right activation?
- flexor-extensor alternation = MLR
- left-right alternation = V0 cells
How does loss of V0 INs affect locomotion?
left right alternation deficits (i.e. co-bursting of left and right sides)
In which lamina of the spinal cord are motor neurons found?
lamina IX
TRUE or FALSE: VMN are an essential component of the locomotor CPG circuitry
FALSE: V0 INs
Describe how optogenetics works?
- insert light sensitive channel (CHANNELRHODOPSIN) into cell population of interest
- channel will be inactive unless exposed to certain wavelength of light
- when appropriate light source is on channel, the channel will be activated and neuron will depolarize
What approach was used to determine the functional relevance of the Cnf and PPN in the MLR?
optogenetic approach
Describe how optogenetics was used to determine the function of Cnf and PPN in the MLR.
- channelrhodopsin inserted into EXCITATORY NEURONS throughout CNS
- light target to either CnF or PPN, selectively activating excitatory neurons in ONE of these 2 regions
- activation of both regions control SLOW ALTERNATING LOCOMOTION
- ONLY GlutNs in CnF necessary for high-speed synchronous locomotion
which nucleus in the MLR regulates high-speed synchronous locomotion (i.e. galloping)
CnF
CnF function vs PPN function
- CnF: escape-related locomotor behaviour (FAST)
- PPN: exploratory locomotor behaviour (SLOW)
TRUE or FALSE: when CnF is activated, the mouse is more curious
FALSE: when PPN is activated –> curious
