Motor systems Flashcards
What colour is white matter?
beige
Adult human gross brain anatomy (dont need to know but for scale)
- Human CNS- most complex system known
- 1011 neurones -100,000,000,000, 100 billion
- >1014 synapses- 100,000,000,000,000, 100 trillion
Lateral view of the cerebral cortex in human, cat and rat
nb. relative increase in human cortex that is not primarily motor or sensory cotex
Section of the brain and the homunculus
What do the following allow?
- Action potential
- Synapses
Action potentials: allow rapid signalling within one neurone.
Synapses: allow convergence and divergence of signals between different neurones
What are the layers of organisations of the cells?
Layers
Cell body layers (e.g. pyramidale)
Molecular layers- mainly neurites and synapse
Six layers in cortex
What are the cell types and their subtypes ?
Cell types
- Neurons:
Excitatory / Inhibitory
morphology / location
- Glia
astrocytes
oligodendrocytes (cns)
Schwann cells (pns)
microglia
Neuronal morphology- evolved for fast information transfer
- Where are APs transduced?
- What does the structure of myelinated axons allow?
Nervous systems scales- distances and speed
What types of voltage recordings can be taken?
Where is the energy from?
What does it drive?
- Record membrane potentials, APs, EPSPs, IPSP
- Energy from mitochondria
- Drives ion pumps
What is the cell membrane in referance to conductivity and composition?
Cell membrane is nonconductive lipid membrane bilayer
How do all ions flux?
All ion flux via protein channels- Voltage gated and neurotransmitters-gated
Differential membrane conductance sets up membrane potential
Passive (electrotonic) properties of membranes- signals fade with distance/ capacitance requires energy to change voltage
Passive membrane properties
Simple electrical model of a neuron?
Voltage clamp: determination of ionic basis of action potential
Sir John Carew Eccles, Alan Lloyd Hodgkin and Andrew Fielding Huxley 1963 Nobel Prize in Physiology or Medicine
“for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane”
Seminal Paper:
A Quantitative Description of Membrane Current and its Application to Conduction and Excitation in Nerve, J. Physiol. (I952) 117, 500-544
A. L. HODGKIN AND A. F. HUXLEY
Voltage-clamp
Whats isolated using the voltage clamp technique?
What does this ensure?
- The currents through the different sets of voltage-gated channels that are responsible for the AP can be isolated using the Voltage-Clamp technique.
- This ensures the membrane voltage is controlled at pre-set values, and the currents that flow can be measured
Whats Patch clamp?
What can it be used to resolve?
- A form of voltage clamp that allows the measurement of the properties of individual ion channels
- It can resolve the ion flow through single multimeric membrane-protein molecules of the order of 1 pico Amp - (1x10-12Amp)
What single channel properties can be measured?
- i - current
- g – conductance
- Open times
- Closed times
- Probabilities
- Voltage-Dependence
Voltage clamp
Saltatory AP transmission in myelinated axons
nb. V-gated sodium channels at Nodes of Ranvier produce AP inward current
At the neuromuscular junction, what determines which muscle is stimulated?
Modality is coded by WHICH axon is activated
WHICH AXON determines which muscle (or another effector) is stimulated
Summary of lecture 11
- CNS functions are localised (eg. motor/sensory)
- Within these areas there is Topological mapping
- Nervous system has had to evolve fast long-distance communication - evolutionary pressure
- Action Potentials in myelinated axons provide fast long-distance signalling from CNS to peripheral muscles
- Modality coded by which axon / Intensity by number APs
Overall organisation of neural structures involved in the control of movement
Tell me about muscle when its relaxed
Without stimulus, muscle is relaxed - high membrane conductance (at rest theres many ion channels open that let chloride though) and negative membrane potential (-70 to -90mV)
What are muscles stimulated to contract by?
Cholinergic (ACh) neuronal inputs at neuro muscualr junctions (nmj)
Is there a direct inhibition of muscle?
No direct inhibition of muscle- inhibition of motor neurons in spinal cord (glycinergic drive)
What is skeletal muscle force controlled by?
- rate of stimulation of motor units
- Number of motor units stimulated
- Properties of motor units stimulated
Where are alpha-motor neurones (aka lowe motor neurons) located?
What do they direct?
What do they occur in?
- Located in ventral horn of spinal cord
- Direct innervation of muscle
- Occur in “pools” driving different muscles
How are alpha motor neurons organised?
Topographically organised
- Grey matter gives the butterfly shape
- Interneurones projects are within a given structure
Motor neuron pools in vental horn
- Transverse sections of spinal cord showing motor pools expressing single transcription factors (in red). Motor pools are defined by retrograde labeling of motor neurons (in green) after tracer injections into individual muscles in chick forelimb. Image: Jeremy
- Transverse sections of chick spinal cord stained with antibodies against transcription factors expressed in motor neurons. Motor neuron occupy the ventral-lateral region of the spinal cord. Image: Jeremy Dasen, HHMI at Columbia University.
How many alpha-motor neurons are each muscle fibre stimulated by?
Each muscle fibre ONLY innervated by ONE α–motor neurone
How many fibres can one alpha-motor neuron innervate?
one alpha-motor neuron can innervate many muscle fibres
How many muscle fibres can one motor neuron innervate?
- ONE α–motor neurone PLUS all its muscle fibres
- Muscle fibre is only innervated by only one motor unit
- Motor units can go to several fibres, but each fibre is only innervated by one motor unit
- Motor neuron can innervate many muscle fibres
Transmission and neuro muscular junction- nmj/ qunatal release ACh
Control of muscle force: stimulation rate from alpha-motor neurones and muscle response
Describe what is seen in the graphs
- Force of muscle contraction increases with stimulation rate
- Single motor nerve stimuli produce individual twitches that completely relax between stimuli
- Rapidly repeated stimuli lead to increased force as muscle does not fully relax between stimuli leading to smooth sustained contraction – temporal summation
Control of muscle force: type of motor unit recruited- types differ in force and fatigability
Motor units differ in their responses and myosin heavy chain subtypes,
tell me about
- type1
- type2A
- type2X
Motor units differ in their reponses and myosin heavy chain subtypes:
type1– slow twitch/oxidative /high myoglobin / darker red
type2A– intermediate
type2X- fast twitch /glycolytic/low myoglobin / pale
Control of muscle force: size prinicple in motor unit recruitment
Contorl of muscle force: progressive recruitment of motor units
Recruitment of parallel motor units in hand to produce increasing force – cf. spatial summation
Answer: 4
Summary- all direct control of muscle activity from alpha-motor neurons
- Without stimulus, muscle is relaxed- high membrane conductance and negative membrane potential (-70 to -90mV)
- Muscles stimulated to contract by cholinergic nicotinic (ACh) neuronal inputs at neuro-muscular junction (nmj) / end plate
- No direct inhibition of muscle – inhibition of motor neurones in spinal cord (glycinergic)
- Skeletal muscle force controlled by:
- rate of stimulation of motor units
- number of motor units stimulated
- properties of motor units stimulated
What do spinal reflexes involve?
Involve motor neurons and local circuit neurons
Spinal reflexes involve motor neurons and local circuit neurons.
What do the motor neurons provide?
What do the local circuits provide?
What causes the spinal reflex activity?
- Spinal Reflexes involve Motor Neurones & Local Circuit Neurones
- Motor Neurons provide the direct control of muscle action
- “Hard Wired” Local Circuits in the Spinal Cord create the reflex circuit that determines simple responses
- Sensory Inputs to the same level of the Spinal Cord can induce stereotypical SPINAL REFLEX activity
Knee-jerk (myotatic) relfex
answer= 2
Tell me about extrafusal and intrafusal sensory feedback
alpha (α) motor neurone axon from cell bodies in Ventral Horn to EXTRAFUSAL muscle fibres
gamma (γ) motor neurone to INTRAFUSAL muscle fibres controls region of sensitivity
What do sensory afferents send signals to?
The spinal cord (cell bodies in the dorsal root ganglia)
What are intrafusal muscle fibres?
Intrafusal muscle fibers are skeletal muscle fibers that serve as specialized sensory organs (proprioceptors) that detect the amount and rate of change in length of a muscle. They constitute the muscle spindle and are innervated by both sensory (afferent) and motor (efferent) fibers.
What are extrafusal muscle fibres?
Extrafusal muscle fibers are the skeletal standard muscle fibers that are innervated by alpha motor neurons and generate tension by contracting, thereby allowing for skeletal movement. They make up the large mass of skeletal muscle tissue and are attached to bone by fibrous tissue extensions (tendons).
Ia afferents from bag fibres AP output is sensitive to what?
Rate of change of length (phasic)
II afferents that come from chain fibres, are sensitive to what?
length
gamma efferents (motor) control what?
Sensitivity via stim of intrafusal fibres
Muscle spindle-sensory feedback- AP coding
Cell activity during stretch reflex
Intracelluarly recorded response underlying the myotatic reflex
summary from lecture 13
- Local circuits produce RAPID BUT Stereotyped reflexes (for monosynaptic ~30ms)
- Sensory information INPUT via Dorsal Root Ganglia
- OUTPUT from motor neurones in Ventral Horn
- Sensory information INPUT and Motor OUTPUT via α-motor neurones at same spinal cord level
- Myelinated axons (~80-120 m/sec) allow rapid reflex responses
Why is the myotatic/ stretch reflex the fastest reflex?
It involves only one synapse and fully myelinated sensory and motor fibres
What can spinal reflexes involve?
Spinal Reflexes can involve more elaborate circuitry with Multiple Interneurons giving more complex motor outputs
What can spinal circuits involve?
Spinal circuits involve motor neurons and local circuit neurons
Descending control from CNS
Knee-jerk myotatic reflex
Negative feedback regulation of muscle tension- Clasp knife reflex
This is known as the Golgi tendon reflex
- inhibitory effect from muscle tension stimulating golgi tendon organs of the muscle and is self-induced
- the reflex arc is a negative feedback mechanism preventing too much tension on the muscle and tendon
- When the tension is extreme, the inhibition can overcome the excitatory effects on the muscles alpha motoneurons causing the muscle to suddenly relax
- This reflex is also called the inverve myotatic reflex, as its the inverse of the stretch reflex
Crossed extensor reflex has basics of pattern generation
- Sensory input…
- Circuitry…
- Motor output…
What type of refexes do local circuits produce?
Local circuits produce RAPID BUT Stereotyped reflexes (for monosynaptic ~30ms)
What is sensory information input via?
Dorsal root ganglia
Can the interneurons in the circuitry within the spinal cord produce complex reflex (stereotypes patterns)?
yes
What is the output from motor neurons via?
Ventral horn
Spinal reflex summary
- Local circuits produce RAPID BUT Stereotyped reflexes (for monosynaptic ~30ms)
- Sensory information INPUT via Dorsal Root Ganglia
- Circuitry within spinal cord – interneurons- can produce complex reflex (stereotyped) patterns
- OUTPUT from motor neurones in Ventral Horn
What can spinal reflexes involve?
Spinal Reflexes can involve more elaborate circuitry with multiple interneurons giving more complex motor outputs
What does the spinal cord circuitry contain?
Spinal cord circuitry contains CENTRAL PATTERN GENERATORS that underlie basic patterns of locomotion
Locomotion in leeches…
Central pattern generator: spinal circuits underlie locomotion (e.g. in Lamprey)
Locomotion
- Locomotion is a complex motor act that, to a large degree, is controlled by neuronal circuits in the spinal cord. Using a systems neuroscience approach in several model systems of non-limbed and limbed animals, important advances have been made in revealing the functional organization of the spinal locomotor networks
- The key circuit elements in the spinal locomotor networks are the rhythm-generating circuits and the pattern-generating circuits, which include circuits that control bilateral muscle activity, and circuits that control flexor–extensor muscles in limbed animals.
- Locomotor networks, whether they control swimming or over-ground locomotion, are built around modules of rhythm- and pattern-generating modules.
Targeted neurotechnology restores
summary of lecture 14
Spinal circuits and Central Pattern Generators underlie basic patterns of locomotion driving Lower Motor Neurones
Central control of movement- upper motor neurons controlling lower circuits
What is the descending control of patterns of locomotion?
Brain stem centres
Basal Ganglia
Cortex
What do the brain stem centres do when it comes to locomotion?
Multiple sub-cortical systems produce the postural control and coordinated patterns of locomotor activity
How is the basal ganglia and cerebellum involved in locomotion?
BASAL GANGLIA and CEREBELLUM dynamically modulate Cortical and Brain Stem centre activity
How is the cortex involved in locomotion?
limited direct effect on lower motor neurone activity for axial and proximal muscle activity but control ‘intentional’ activity & fine control of distal muscles (eg. fingers)
What does the human basal ganglia control?
The initiation of movement
What does the basal ganglia target when it comes to movement?
Ventral Anterior and Ventral Lateral THALAMIC nuclei (VA/VL complex) are the targets of the BASAL GANGLIA
What does the human basal ganglia relay?
The modulatory effects of the basal ganglia to neurons in the cortex
Human basal ganglia
Substantia nigra
Tell me about how the following are involved in specific patterns of movement:
- Thalamus
- Substantia Nigra
- Cortex
- Striatal GABAergic
- Globus Pallidus
Tell me about the basal ganglia and parkinsons disease…
- What does reduced excitatory drive from the thalamus lead to?
- What does GPchronically inhibit?
- What does the loss of striatal GABAergic output prevent?
- With parkinsons what does the loss of DA neurons of substantia nigra lead to?
Tell me some treatments to parkinsons and what they help with?
- L-DOPA
- Pallidotomy
- Deep brain stimulation
Huntington’s disease is due to a loss of what?
Loss of GABAergic medium spiny N. of striatum
What does Huntington’s reduce?
Inhibition of globus pallidus (external segment)
What does Huntington’s prevent?
What does this then reduce and allow?
Prevents switching-off of Globus Pallidus (external seg) so chronic inhibition of subthalamic nuc.
REDUCES subthalamic excitation of GP internal segment - less inhibition of Thalamus
ALLOWS increased Thalamic excitation of Cortex
What is there a problem with, with Huntington’s?
Problems with STOPPING movements (chorea/hyperkinetic)
What role does the cerebellum have?
Integration of sensory feedback into coordinated motor activity
What does the cerebellum…
- Regulate?
- Planning and modulation?
- Maintainence of?
Action as comparator of intentional to actual movement and generation of correction signals into brain stem motor centres
What are the inputs to the cerebellum?
- Intentional actions from Cortex
- Actual actions from periphery
What are the functions to the cerebellum?
Compare intention to actual movement and generate correction signals
What are outputs to the cerebellum?
Correction signals into brain stem motor centres
Cerebellum
Outputs from the cerebellum
Neurons and micro-circuits of the cerebellum?
regarding inputs and outputs
Topographic map of movement in motor cortex
Where do primary motor cortex axons terminate among?
PRIMARY MOTOR CORTEX axons terminate among pools of local circuit neurones in the Ventral Horn of the spinal cord.
Corticospinal tract: lateral and vental
- lateral tract
- ventral tract
Influence of signal cortical upper motor neurons on muscle activity- lateral tracts for fine control
A brain-spine interface alleviating gair deficits after spinal cord injury in primates
Summary of lecture 15
Summary: overall organisation of neural structures involved in control of movement
- Cortical neurones have limited direct effect on lower motor neurone activity (most in primates) but control ‘intentional’ activity via brain stem
- Multiple sub-cortical systems produce the postural control and co-ordinated patterns of locomotor activity via Brain Stem centres
- Brain Stem centre activity is dynamically modulated by the Basal Ganglia and Cerebellum
- Basal Ganglia control INITIATION of movement
- Cerebellum INTEGRATES sensory information with INTENTIONAL and sends correctional information to Brain Stem and motor cortex
