Module 5 - Motor Flashcards
L5.1 - Describe that movements are part of most behaviors and the only output measure of brain activity
Movement is important for behavior and includes voluntary movement (oriented), rhythmic movement, movement for equilibrium and reflexes. They’re the only output of the brain that we can see and is crucial for behavior.
L5.1 - Explain feedforward and feedback movement control
Feedforward is the direct, fast movements that don’t allow sensory information to correct the movement (example is the visibulo-occulo reflex) – not all reflexes are feedforward
Feedback is slower and more precise movements, where the movement is guided by sensory feedback (proprioception but could also be vision). Here the motor plan will be adjusted based on the sensory feedback (corrects ongoing) – example is the smooth pursuit eye movements
L5.1 - Explain that movements are regulated by cognitive, sensory and autonomic functions
As movements are the primary outcome the brain, our movements will reflect needs and desires of us: ex you might be hungry, leading to you grabbing the fridge, you might move your hand away from something hot or you might go to the bathroom because you have to pee (you can’t just do it on the floor –> cognitive process)
L5.1 - Define primary movement centers of the nervous system and their overall connectivity
M1 (motor execution), pre-motor (movement planning) are the primary ones interact with the somatosensory/posterior partial (for sensing movement feedback), basal ganglia (initiate action), cerebellum (online error correction and procedural memory) and general efferent effects (spinal cord LMN/central pattern generators -> final command).
The basal ganglia and cerebellum project to the motor cortex (M1 + premotor) through the thalamus. Efferent effectors will get efferent projections from the motor cortex to execute the movement that has been planned. Main projections happen to the local interneurons, and very few directly to motor neurons.
The motor cortex connects to other areas to support movement such as the hippocampus (memory of strategy and movement outcome (declarative)), amygdala (could trigger movement in fear to run) and hypothalamus (adjust HR to support movement)
L5.1 - Describe circuit complexity in movement centers, including basal ganglia circuitry and interneurons and motor neurons in the spinal cord
Basal ganglia is important in movement initiation and has an intricate system of multiple brain stem areas that though both a direct and indirect pathway leads to movement initiation or lack of movement due to disinhibition
Interneurons in the spinal cord enable reflexes and are important in the pattern generation necessary for swimming, walking (anything rhythmic)
Motor neurons are important in executing the actual movement
Motor circuitry is complex, as motor is one of the only outcomes of the body, and we therefore see that most of the brain takes part in modulating it. Many different cell types takes part in intricate cuitcuits
Motor activity is modulated by the monoamines as well
L5.1 - Describe methods to study and quantify the motor behavior at a high level; e.g. monitoring the movement with video during different motor tasks
- Kinematic (you look at the movement pattern in stick diagrams to get on overview of e.g. swing)
- You can look at the locomotion behavior though video recording: Gait in mice will change with speed (walk, trot, gallop, bound)
- Electromyogram (EMG) shows muscle contraction patterns
- Motor equivalence: see the effect of using one limb over another (e.g. writing with right hand vs foot)
L5.1 - To explain recordings of cellular activity in behaving animals from brain regions or muscles
- You can perform extracellular recordings from the brain to see M1 activity (force correlates to amplitude)
- Muscles is the electromyogram – you look at the firing pattern of individual muscles (force correlates to amplitude the closer you get to the cell)
- Calcium imaging is a correlated with cellular activity – Ca2+ influx is seen for active cells if animals lifts the paw, you will see a ca2+ changes are specific to the cells firing and therefore more precise than extracellular recordings
L5.1 - To describe methods to reveal connectivity anatomically (classical and viral tracing) and physiologically (recordings from neurons)
Classical tracing can be retrograde and anterograde with a tracer (not specific, we don’t know what type of neuron, we label cell bodies). To be sure we’re only tracing the cell type of interest, we can inject a virus that uses the cre-lox system, where the fluorescent protein is flanked by p-lox sequences and therefore only will be activated when cre is present (dre-driver lines).
With the cell recordings (electrophysiology), you get a functional output in addition to just the anatomical information that we get with tracing and you can see if the synapse is inhibitory/excitatory
L5.1 - To describe genetic methods to trace circuits (viral tracing) and to activate and inactivate motor circuits (optogenetic and chemogenetic)
Viral tracing with an AAV is infecting some cells with a cre-depended and lox-p flanked fluorescent protein. Other method includes AAVs with a fluorescent protein that is depended on its promotor for expression (and that promotor is cell-specific)
We can also deliver opsins to specific cell types with our cre-loxP AAV insert light sensitive channels into our neuro-syptype of choice that will depolarize (channelrhodopsin) or hyperpolarize (Halorphodopsin) in response to its appropriate wavelength.
Cre-lox and AAVs can also deliver DREADDs (chemoreceptors/designer receptors) to the cells of interest, where a later injected ligand will activate that receptor.
L5.2 (Cortical control) - To describe the somatotopic organization of primary motor cortex
The organization of the primary motor cortex relies on topographic organization, which means that areas close to each other in the body will be located close to each other in the cortex.
L5.2 (Cortical control) - To explain the role of primary motor cortex in movement planning and execution
The M1 is important in motor execution – has major projections to the corticospinal tract
Premotor is mainly for planning but interacts with the primary motor cortex
Premotor cortex thinks and plans the conscious movement. Supplementary motor area will plan and rehearse the movement and then the primary motor cortex carries out the actual action.
L5.2 (Cortical control) - To define direct corticomotoneuronal projections versus indirect corticospinal projections via spinal interneurons
The direct corticospinal tract goes directly from the tract to the alpha motor neurons, whereas the indirect signals through spinal interneurons first. The indirect is slower but enables better control of the movement. It seems that finger/hand movement is mediated more by the direct corticospinal tract, whereas the proximal muscles are controlled more by the indirect one.
L5.2 (Cortical control) - To explain how movements are coded in activity of populations of corticospinal neurons
Neurons are directionally tuned in M1, and that the frequency of firing will depend on the tuning and the movement –> you will have max firing rate for a certain neuron if you move in the exact direction that neuron is tuned to. Other neurons tuned close to this one might have lower frequency
L5.2 (Cortical control) - To describe readiness potential in relation to voluntary movements
The readiness potential is building in the frontal cortex that is preparation for motor movement
if you put electrodes on the brain, you can see the motion building in terms activity - lots of premotor activity up to the 800-1000 ms before the motor action – helps in movement planning and preparation –> will make the premotor more excitable
it’s believed to form the intention to move
From Kandel:
recordings of slow cortical potentials at the surface of the skull during the execution of self-paced movements show that the initial potential arises in the frontal cortex as much as 0.8 to 1.0 second before the onset of movement. This signal, named the readiness potential, has its peak in the cortex centered in SMC. Because it occurs well before movement, the readiness potential has been widely interpreted as evidence that neural activity in this region is involved in forming the intention to move, not just in executing movement
SMC is part of the SMA
L5.2 (Cortical control) - To describe brain areas and networks involved in initiation of voluntary movement
The primary cortex is important in movement execution
Premotor is in planning movement
The SMA is in mental imaging of movement and knowing certain sequence (using internal images to process it) (bilateral movement too)
The parietal cortex important in conscious intent/urge to perform an action (as it’s for attention) – also for the information necessary to act based on objects (where pathway)
The basal ganglia is important for movement initiation
The cerebellum plays a role in movement correction
External relies on learning and attention where the internal is more previously known. When the internal loop is achieved, having attention on a task is no longer needed.
L5.2 (Cortical control) - To describe role of supplementary motor cortex in sequence learning
The SMA becomes important once learning has been achieved and we can rely on declarative knowledge to recall the sequence. Prior to this we rely on the premotor.
L5.2 (Cortical control) - To describe the coding of hand movements in activity of neurons in parietal and premotor cortex
In the parietal cortex, there are neurons that are part of the dorsal stream (where pathway) that will fire in respond to reaching (“reach neurons”) and their activity helps guide the hand towards the object. They are specific to the location of the object we’re reaching for and the movement needed to grasp it.
The premotor cortex holds “grasping” neurons, which plan and execute grasping. They help determine how to hold the object.
These two areas play together in manipulating objects.
L5.2 (Cortical control) - To describe the role of mirror neurons
The mirror neuron system is found in multiple areas in the brain (PMA, SMA, S1, inferior parietal). They fire when others move and when we imitation – might enable learning by imitation and understanding others movement.
The mirror neurons are assumed to play a role in mental rehearsal and optimization of movement control based on visual observation of the performance of other individuals. Human imaging studies have shown activation of a larger part of the sensory and motor areas during movement observation, and this has led to the description of a so-called ‘mirror neuron system’. The human observations have led to the suggestion that the mirror neuron system may be involved in understanding the behavior of other people as well as empathy.
L5.3 (Motor neurons/reflexes) - To explain functional organization of spinal motoneurons
Spinal motor neurons are distributed in organized columns down the spinal cord in the ventral horns. Those innervating more distal musculature are in the more lateral columns and those innervating the axial muscles are in the more medial columns.
They are organized along the spinal cord with different levels of muscles innervated by motor neurons at different segments. Here, I introduce the concept of the myotome. This refers to the group of muscles innervated by a single spinal nerve root.
We have different types of motor neurons – alpha innervate the muscles and gamma the muscle spindles
L5.3 (Motor neurons/reflexes) - To describe the concept of motor units and how they differ
The motor unit refers to a single motor neuron and the muscle fibers that it innervates.
A single motor neuron can innervate many muscles fibers, but each muscle fiber is innervated by only one motor neuron.
Motor units come in different types depending on the excitability properties of the motor neurons and number/ type of muscles fibers they innervate. There are 3 classes of motor units:
Slow: These are smaller motor units that fire, conduction action potentials and contact muscles fibers slower. They have small numbers of red oxidative fatigue resistant muscle fibers.
Fast Fatigue Resistant (FR): These are intermediate units that fire faster and have more muscles fibers which are partly oxidative and partly glycolytic and are fairly fatigue resistant.
Fast Fatigable (FF): These are the largest motor units that fire fast, conduct action potentials fast and contact muscles fibers the fastest. They have large numbers of white glycolytic muscle fibers that produce a lot of force but fatigue easily
It is called a motor unit as it acts as a unit: when a motor neurons fires an action potential it will cause a contraction in all of the muscle fibers in the motor unit.
L5.3 (Motor neurons/reflexes) - To explain how excitation of the motoneuron results in muscle contraction
This process is called excitation-contraction coupling. Then the action potential arrives at the neuromuscular junction, acetylcholine is released which depolarizes the muscle fiber. This is called an endplate potential. This is a little different from a normal EPSP in that it always reaches threshold and so this will always cause an action potential in the muscle fibers. This travels into the muscle fibers via structures call t-tubules. Here, it activates receptors that activate other receptors that ultimately lead to calcium release from the calcium stores in muscles (the sarcoplasmic reticulum). This allows the filaments in muscles (actin and myosin) to make cross-bridges and contract.
L5.3 (Motor neurons/reflexes) - To explain the main mechanisms used to control force: Summation and recruitment
Recruitment: Here we can recruit more or less motor neurons. When we want to increase
force, we recruit in a specific order: Slow, FR then FF
Summation: A single action potential in the muscle will cause a single twitch in the muscle. If
we fire our motor neuron repetitively we can get multiple muscle twitches. If we then increase
the firing frequency, the twitches will come closer together and eventually “summate” as the
next will start before the last has had a time to relax. At lower firing frequencies this give an
unfused tetanized as the force can drop a little between. At higher firing frequencies we can get
a fully fused tetanic contraction that is of a much bigger amplitude than a single twitch
We use these two mechanisms together. We recruit slow units, increase their firing frequency
then recruit our FR units, increase the firing frequency of these and finally, when we need a lot
of force, recruit the FF units and increase the firing frequency of these. But these will fatigue and we will be left with our slow and FT units
L5.3 (Motor neurons/reflexes) - To describe how proprioceptive information is conveyed to the spinal cord
Proprioception is our internal sense of body position, including information on the length of muscles, the angle of our joints and the force being exerted by our muscles. In this lecture we focus on the receptors (proprioceptors) to detect changes in muscle length and force:
Muscle spindles: These consist of the intrafusal muscle fibres that lay in parallel to the normal (extrafusal) muscle fibers you have learnt about that are doing the contraction. As they lay in parallel then a sudden stretch of the muscle will be detected by the muscle spindle.
Muscle spindles therefore detect changes in muscle length. There are different type of spindles
Nuclear Chain fibers: signal information about the static length of the muscle.
Static Nuclear Bag fibers: also signal information about the static length of a muscle.
These use group Ia and II afferent axons to take the information to the spinal cord
Dynamic Nuclear Bag fibers: primarily signal information about the rate of change of muscle length (i.e. a dynamic movement). These use Ia afferent axons to take the information to the spinal cord
Alpha gamma co-activation.
But what happens when we contract our muscles?Surely the spindles which lie in parallel will go slack and so be unresponsive. But this does not happen as, when the alpha motor neurones are activated (innervating the extrafusal muscle fibers), the gamma motor neurones are also recruited and these co-contract the intrafusal fibers to maintain their sensitivity.
Golgi tendon organs: This is receptor that lies between the muscle and the tendon. We build up force by the muscle contracting and pulling on the tendon. This stretches the GTO which causes it’s collagen fibers to compress the endings of Ib afferents causing them to depolarize and send action potentials to the spinal cord. GTOs, thus signal changes in muscle force
L5.3 (Motor neurons/reflexes) - To describe three simple sets of spinal reflexes (stretch reflex, golgi tendon reflex and flexor reflex)
A) The Stretch Reflex
Here, a sudden of the muscle will stretch the muscle spindles activating the Ia afferents.
These will travel into the spinal cord where they will make both monosynaptic and polysynaptic excitatory connections with motor neurones innervating the same (or synergistic) muscles. This will recruit more motor neurones to contract the muscles to counteract the stretch. It is also called the myotatic or monosynaptic reflex
B) The Golgi Tendon Reflex
Here, a large force exerted by the muscles will strongly activate the Ib afferents which will send the signal to the spinal cord. Here, it will go through inhibitory (Ib) interneurones which will hyperpolarize the motor neurones innervating the same muscle to cause a relaxation. However, when we walk, this reflex is reversed so that we do not fall over.
C) The Flexor reflex
This reflex is activated by a painful stimuli to a limb. This activates the Aδ pain fibers which go into the spinal cord and make polysynaptic connections with interneurones which will excite motor neurones innervating flexor muscles and inhibit motor neurones innervating extensor muscles on the ipsilateral side to produce a flexion movement away from the painful stimuli. For the lower limbs, this signal also has to go the contralateral side of the spinal cord to do the opposite (inhibit flexors and excite extensors) so that we do not fall over. This is called the Crossed-Extensor Reflex.
L5.3 (Motor neurons/reflexes) - To define and describe reciprocal inhibition
flexor and extensor motor neurons —> if i stretch muscle, we have an activation of the flexor, but an inhibition of the opposite flexor (basic reflex mechanism to inhibit the antagonist)
L5.4 (CPGs) - To describe how muscles and legs are coordinated during locomotion and at different speeds
Central pattern generators are used to either have synchronized or alternating movement (interlimb) – alternating is often seen in lower speed and synchronized at higher speeds.
Each step also has a phase (intralimb), which are the stance and swing phases
L5.4 (CPGs) - To describe the overall organization of locomotor networks in the central nervous system
CPGs (central pattern generators) can be found in the brain stem or in the spinal cord (spinal cord for movement). In the spinal cord, they’re found bilaterally from lower thoracic to L6, ventromedial in the ventral horn, ventral commissure allows the communication cross-sides, multiple burst generators. These networks can function without brain input, but can be triggered to start by inputs from the CNF or PPN nucleus in the midbrain and can be stopped by V2a neurons in the brainstem as well.
The CNF (for speed) and PPN (for slow movement) will project to the relay station in the midbrain before sending a start signal to the central pattern generators. Here the CPGs are divided into the rhythm and pattern generators. Often the rhythm generator is the excitatory interneurons. The pattern generators often include the commissural interneurons, which will do a contralateral inhibition, and the interneurons, which modulate the system internally. The pattern generators will modulate where the rhythm generators will excite.
L5.4 (CPGs) - To define a central pattern generator (CPG)
A CPG consist of a rhythm pattern generator, which will produce excitatory signals to the motor neurons. The pattern generators will receive excitatory inputs (efferent and afferent), and will from there modulate the signal ipsi- and contralaterally. They’re placed in the spinal cord and brain stem depending on what their function is. They excist in all vertebras.
L5.4 (CPGs) - To describe the overall organization of the CPG for locomotion in a legged animal: rhythm-generation, flexor- extensor coordination and left-right coordination
Rhythm generation: excitatory neurons that rely on glutamate - generates a rhythm that is finetuning the limbs
Rhythm generation utilizes glutamatergic neurons. It is responsible for coordination/fine patterning within limbs. Patterning network also happens in the spinal cord. Excitatory neurons set the pace for the pattern generator. If you inhibit the vGLUT cells you will not have a pattern generator.
Left right coordination: The disinhibition allows for alternating movements and excitation in single synapses for synchrony (bounding) -> ventral V0 is used for high speed, dorsal V0 for low speed
For flexor-extensor we have much of the same system as left right, where there is a complex network of excitatory and inhibitory cells. Once one rhythm generators gets activated, the other circuit will be inhibited
L5.5 (Basal Ganglia) - To describe the organization of the motor part of the basal ganglia with the direct and indirect pathways
Indirect pathway suppress movement and direct to increase movement
L5.5 (Basal Ganglia) - To describe the organization of medium spiny neurons in the striatum and their inputs
MSNs are placed in the striatum and either have D1 receptors (excitatory) for the direct pathway or D2 receptor for the inhibitory indirect pathway (both projections promote movement) – Thereby there are different MSNs for the individual pathways. Inputs come from the cortex or thalamus, and interneurons will provide collateral inhibition.
L5.5 (Basal Ganglia) - To describe important inputs and outputs of the basal ganglia
Important input is the cerebral cortex and the SNpC. Important outputs is to the motor areas in the brain stem and the thalamus. You will find that there is much more precise inputs to the direct pathway, than the indirect one. For the direct pathway, we see collateral inhibition (lateral inhibition) to ensure that we only initiate movement in the place we’re interested in (output nucleus is still the GPi or SNpR for all).
L5.5 (Basal Ganglia) - To describe the cause and symptoms with Parkinson’s Disease, in terms of activity in the indirect and direct pathways
Symp: rigidity, postural instability, lack of movement, tremor
Cause: degeneration of SN DA neurons –> you have less DA input, which will decrease movement by making the direct pathway weaker and the indirect stronger
D1 normally excite the direct pathways and D2 inhibit the indirect –> decreased in PD
L5.5 (Basal Ganglia) - To describe the cause and symptoms with Huntington’s Disease
Cause: CAG repeats (autosomal disorder) – symp is hyperkinetics
You have death of indirect MSNs in the striatum direct pathway gets more power and indirect less
Spinal cord injury - To describe the pathology of spasticity after spinal cord injury, the main neural mechanisms and treatments
Spasticity is Velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks (phasic stretch reflex) resulting from hyperexcitability the spinal cord circuitries –> due to lack of brain input and the LMN being driven by sensory input – develops over time where motor neurons become hyperactive
Clinical features: increased excitation and reduced inhibition), higher motor neuron activity (alpha and Gamma), higher afferent inputs, changes in the muscle properties (enable plateau potential, which are prolonged potentials in response to no or low input)
We see partial plateau potentials in spasticity, which is supported by inward current (Na+ and C2+).
General treatment approaches are to decrease excitability, through blocking ca2+ channels (Nimodipine – has to be early and prolonged), blocking ca2+ release, blocking the neuromuscular junction, cutting the DRG or increasing GABA.
Treatment options: blocking l-type ca2+ channels (Nimodipine) might be a treatment for injury (will prevent parts of the inward current) treatment has to be early and prolonged
L5.6 Cerebellum - To describe the organization and subdivisions of the cerebellum
Cerebrocerebellum: Motor planning and coordination
Spinocerebellum: Control of ongoing body and limb movements
Vestibulocerebellum: Posture , balance, eye movements
L5.6 Cerebellum - The describe the functional organization of the inputs to the cerebellum
The Cerebrocerebellum is important in motor planning and organization, so it therefore gets input from the association cortex (parietal)
The Spinocerebellum controls ongoing body movements (Has somatotopic organization) and is therefore gets input from the somatosensory cortex and other sensory inputs (parietal)
The Vestibulocerebellum is for balance, eye movements and posture and therefore gets information from the vestibular nucleus and visual information and somatosensory feedback
- Pontine nuclei: cortical input
- Inferior olive: movement error/correction
- Cuneate & Clarke: proprioceptive input
Descending (from cortex)
- Motor cortex: Movement commands
- Premotor cortex: Planning/selecting movement
- Relayed via pontine and red nuclei
Ascending input (sensory information)
- Proprioceptive information
- Vestibular information
L5.6 Cerebellum - To describe the functional organization of major outputs from the cerebellum to cortical motor systems
Picture on the left describes the projections to the cortex, on the right to the spinal cord
L5.6 Cerebellum - To describe neurons and internal circuits of the cerebellum
Purkinje Cell
Only output of cerebellum
GABAergic inhibition
1.000.000 synapses
Spines modifiable by LTD
Climbing fiber can modulate the response much stronger
Climbing fibers project to Purkinje cells directly (from inferior olive)
Mossy fibers comes from pontine nuclei (and other brainstem nuclei and spinal cord) and project to the granule cells (glomerulus synapse) –> these form parallel fibers that can project to the purkinje cells
Interneurons:
- Golgi: in granule cell layer (synapse with the mossy fibers)
- Basket and stellate in molecular layer to purkinje cells
L5.6 Cerebellum - To explain the role of the cerebellum in motor learning and regulation of equilibrium
The cerebellum is important in procedural learning (we learn how to make the most effective movements –> creates a stored program for these skills) and in creating the forward internal model
The cerebellum helps adjust then equilibrium is disturbed in 2 ways:
1. It adjusts the tone of different limbs in response to vestibular changes
2. It helps coordinate eye movements with head movements during accelerations
L5.7 Sensory motor integration - To explain spinal-cerebellar sensory integration (dorsal and ventral spinocerebellar tracts)
The cerebellum gets an afferent copy of sensory information (dorsal ventral spinocerebellar tract) and an efferent copy for the motor plan (ventral spinocerebellar tract) so they can be compared and errors can be estimated.
L5.7 Sensory motor integration - To describe visuomotor integration in cortex
Posterior parietal cortex (PPC) is involved in planning changes in movements and helps determine where you are in space. It utilizes visual input to modify movement –> you plan your movement according to your position of your body and your surroundings –> your visual input helps guide the calculations by the PPC (PPC helps in this process – it’s stored in PPC)
L5.7 Sensory motor integration - To mention the role of the superior colliculus for orienting behavior
The SC is the visuomotor integrating center and can modulate behavior based on sensory inputs from the retina, visual cortex, somatosensory
The upper layers receive the input, the deeper layer creates motor output (lower in picture) seen as a 6-layer structure
It’s used in orienting, but also approaching/orienting (e.g. food), avoidance (Fear), escape, and freezing behavior.
Signals from above project to the medial SC part (avoidance/ threat, uses uncrossed pathway)
Signal from below goes to the lateral part for orientation (approaching/orientation, uses the crossed pathway)
L5.10 ALS - To describe the pathophysiology of ALS, including genetic causes of familial and sporadic ALS
Pathology
Motor neurons degenerate and lose contact to muscles in the PNS of our body – problems happen at the NMJ. Corticospinal neurons (upper) degenerate at a later stage leads to progressive paralysis. The MNs in the eyes (ocular) are spared in the disease (seems to have intrinsic things stopping the issue) – we use eye tracking to communicate
Multiple cell types are affected – progression has inflammation
ALS targets the fast fatigable ones first – slow ones most resistible
Excitotoxicity is the main reason for motor neuron degeneration
Genetics: 10% familial, 90% sporadic
Genes associated:
- SOD1 - regulating copper and zinc levels.
- TARDBP - splicing of RNA
- FUS - processing of RNA.
L5.10 ALS - To describe symptoms of ALS and the cells that are primarily involved in the disease
Primary cells: Upper and lower motor neurons degenerating. Glial cells might also play a role in disease progression.
Symptoms:
Patients may experience difficulties doing daily tasks like buttoning a shirt. The have issues walking, often leading to tripping. They will also experience weakness in the legs and feet, as well as cramping and twitching in the arms, shoulders, and facial muscles. They can also experience speech impairment, problems swallowing, as well as cognitive and behavioral changes.
