Lectures 4, 12-14 (Riccardo Storchi) Flashcards

Question

What is the term for descending tracts and what are the two main types of them? Where does the information they carry originate from?

Answer 1

Corticospinal tracts. Pyramidal and extrapyramidal tracts. Originates in the upper motor neurons in motor and premotor cortex (Brodmann Area 4, 6)

Answer 2

Lateral corticalspinal tract and the ventral corticospinal tract. They pass through the pyramids of the Medulla Oblongata.

Answer 3

Lateral decussates at the level of the pyramids, whereas the Ventral/Anterior tract does this at the level of the spinal cord.

Answer 4

Extremity muscles: voluntary contralateral movements. - Limbs, fingers. - Upper motor neurons innervate single muscles or small sets of muscles. - Therefore, responsible for fine motor control.

Answer 5

Controls voluntary contralateral movements of the axial muscles (e.g., neck, trunk muscles).

Answer 6

Johann Prus 1898 – could not stop epileptic motor activity by disturbing the pyramids. Thus, alternative descending pathways – extrapyramidal

Answer 7

Control of learned/automatic and/or involuntary movements Control of muscle tone Control posture, drive postural adjustments Control reflexes and orienting responses to sensory stimulation

Answer 8

Reticulospinal tract Rubrospinal tract Vestibulospinal tract Tectospinal tract

Answer 9

Control of posture and gross movements - locomotion, reaching. Neurons branch extensively contacting many pools of motor neurons controlling synergistic muscles. Single axons may innervate muscles on both sides.

Answer 10

Control of muscle tone, arm muscles. Originates in Red Nucleus (pink due to iron in haemoglobin/ferritin). Transmit signals from cerebellum and motor cortex.

Answer 11

Receive information from vestibulococlear cranial nerve about angular and linear head accelerations. Originate from vestibular nuclei in the pons. Medial: - Stabilises head position by innervating neck muscles. - Receives input from the medial vestibular nucleus Lateral: - Controls “antigravity” muscles – extensor muscles of the legs. - Receives information from the lateral vestibular nucleus

Answer 12

Coordinated orientation of neck, head and eyes according to visual and auditory stimuli (Note eyes control via cranial nerves III,IV,VI not via spinal cord) Originates in superior colliculus (in non-mammalian vertebrates called optic tectum). (Superior colliculus is an important centre of multisensory & sensorimotor integration– combines information to detect salient stimuli and orient the animal towards them).

Answer 13

Surgical separation of the upper part of the brain from the lower part of the brain. (transection between superior and inferior nucleus)

Answer 14

1. Decerebrated the cat and found the stretch reflex was still intact. Therefore the reflex doesn't depend on most of the brain. 2. Cut the sensory afferent reaching the dorsal horn (so a cut at dorsal root) and found the reflex was abolished. Shows that the reflex was reliant on this connection being intact.

Answer 15

There is direct sensory innveration (by 1a afferents) of the motor neurons that stimulate homonymous muscle and synergistic muscles. Step 1. 1a afferents are excited by muscle elongation so excite the motor neurons from the same and synergistic mucsles to contract. Step 2. 1a afferents excited by muscle elongation, excite 1a inhibitory interneurons which inhibit muscle contraction in antagonist muscles. This results in contraction of the agonist and relaxation of the antagonist.

Answer 16

This is a polysynaptic reflex. Step 1. Starts with sensory informaiton from the Adelta fibres (nociceptive) exciting the spinal sensory neurons (interneurons). Step 2. These interneurons then synapse two other interneurons, which are inhibitory and excitatory. Inhibitory signal inhibits the extensor muscles and the excitatory signal excites the flexor muscle. This results in a quick **withdrawal** away from the nociceptive stimulus (due to harsh unihibited flexion at the joint)

Answer 17

This is a polysynaptic reflex. Step 1. Spinal interneurons that receive the nociceptive signal on the ipsilateral side stimulate contralateral commissural neurons - one inhibitory and one excitatory. Step 2. The inhibitory neuron will inhibit the flexor muscles. The excitatory neuron will inhibit the extensor muscles. This allows us to steady our posture and ensure we have balance, as the limb on the ipsilateral side will withdraw quickly and impact our balance (literally pulling your leg out from underneath you without conscious control).

Answer 18

They can be used to control reflexes and muscles in a very efficient way: - Renshaw cells produce recurrent inhibition of activated muscles through motor neuron collaterals. - They also inhibit 1a inhibitory interneurons, thus indirectly exciting antagonist muscles. Descending pathways can control these above stated "double action" via a single projection onto Renshaw Cells = efficient for descending control

Answer 19

It can be repurposed due to current behavioural state - behavioural state performed at that moment.

Answer 20

The experiment has two conditions under which it stimulates 1b afferents. AT REST: - 1b inhibitory interneurons are more active - stimulation induces non-reciprocal inhibition of muscle (inhibiting muscle) WALKING: - Excitatory interneurons are more active. - stimulation induces excitation of muscle during walking. SUMMARY: The activity of 1b inhibitory interneurons and excitatory interneurons is controlled by descending pathways according to behavioural state.

Answer 21

The perception of joint and body movement as well as position of the body, or body segments, in space.

Answer 22

The perception of external/environmental stimuli acting on the body (e.g., touch, vision, sound, smell).

Answer 23

The existence of PIEZO1 and PIEZO2 mechanosensitive ion channels. They open upon the delivery of a mechanical force on a cell membrane. Specifically, Piezo2 is highly expressed in proprioceptive peripheral endings (both muscle spindles and golgi tendon organs).

Answer 24

They used conditional KO mice in which PIEZO2 was not expressed in dorsal root ganglion proprioceptive neurons. These animals could perform basic locomotion but express impaired limb coordination. (Because there was little to no mechanotransduction to provide feedback about where their limbs are in space).

Answer 25

Extrafusal and Intrafusal.

Answer 26

Fibres that provide force to the muscle and are stimulated by alpha motor neurons.

Answer 27

Fibres that lay in parallel to EF fibres, do not provide force, and are stimulated by gamma motor neurons.

Answer 28

They are spindle-like structures that are made up of IF fibres. Central muscle spindle regions are non-contractile and contain sensory endings. Contractile regions of IF fibres used to adjust length and are important to modulate sensory signalling.

Answer 29

Dynamic Nuclear Bag Fibre Static Nuclear Bag Fibre Nuclear Chain Fibre

Answer 30

Dynamic Nuclear Bag Fibre: - Dynamic gamma MN's - 1a afferents Static Nuclear Bag Fibre: - Static gamma MN's - 1a afferents - II afferents Nuclear Chain Fibre: - Static gamma MN's - 1a afferents - II afferents

Answer 31

Ia afferents: sense velocity and length (change) - Innervates all 3 IF's II afferents: sense length - **Doesn't** innervate Dynamic nuclear bag fibres

Answer 32

IN and EF fibres are positioned in parallel. When the muscle is stretched it elicits a firing rate in the dorsal root ganglion interneurons that are associated with sensory endings. The firing rate is related to the amount of stretch. HIGH FIRING RATE = STRETCHED

Answer 33

They are arranged in series with the muscle and their sensory endings are 1b afferents, which are intertwined with collagen fibres. When the muscle fibres contract, collagen fibres compress the axons which generates 1b signalling.

Answer 34

They encode the force in the muscle. Their firing rate increases as a function of the force applied to their endings. (The higher the force of the contracting muscles, the higher their firing rate)

Answer 35

They are proprioceptors found in the joints. There are 4 types: - Type 1: ruffini endings. - Type 2: paciniform endings. ^^Both of these respond to deformation of joint capsule or ligaments - Type 3 and Type 4 Both these respond to noxious mechanical stimuli.

Answer 36

Muscle spindle-primary Myelinated, large, diameter: 12-20um, conductance velocity: 72-120m/s Muscle length and dynamic change in length

Answer 37

Golgi tendon organ Myelinated, large, diameter: 12-20um, conductance velocity: 72-120m/s Muscle contraction/tension.

Answer 38

Muscle spindle secondary, Joint capsule mechanoreceptor. Myelinated, medium, diameter: 6-12um, conductance velocity: 36-72m/s Muscle stretch and joint angle/deep pressure

Answer 39

Ration between output from and (sensory) input to a given system.

Answer 40

If you apply weight to a muscle then the muscle spindle length increases, therefore increasing the Ia fibres firing rate. However, stimulation of EF fibres alone causes EF fibres to contract but not the IF fibres. This INHIBITS feedback and therefore we don't have control of muscle length - GAIN DROPS TO 0 So, not only do we need muscle control from alpha and gamma neurons, we also need gamma neurons to control the length of muscles spindles - to maintain sensory feedback GAIN.

Answer 41

Muscle spindles signal both muscle length (static response) and changes in muscle length (dynamic response). Static gamma fibres increase the gain of static response. - Their firing rate is a relatively flat line as it signals the current length of muscles (current length will always be constant) Dynamic gamma fibres increase the gain of dynamic response. - Their firing rate is graded because they show that the stretch of the muscle is changing. Differential modulation of both these fibre types changes sensory feedback by altering the balance between static and dynamic responses.

Answer 42

Static gamma fibres: - Preferentially active during static postures or slow movements. Dynamic gamma fibres: - Active during fast or unpredictable or complex movements requiring fast corrections

Answer 43

METHODS: - Monkey trained to use a joystick to move a cursor on a screen in response to a visual cue. - At the same time, an interneuron from the spinal cord was recorded from. - It received sensory feedback from either muscle (proprioception) or cutaneous afferents (tactile) - Each would be stimulated when the monkey was resting or was engaged with the joystick. RESULTS: - IF they stimulated the tactile feedback during rest, there was a strong response, therefore strong gain. - IF the monkey was moving the joystick, this stimulation of tactile was reduced massively (therefore reduced gain). - However, the proprioceptive feedback had much more gain because it now needed feedback from the muscles that it was using.

Answer 44

So that the CNS can amplify the more relevant feedback and suppress the less relevant one depending on the situation.

Answer 45

METHODS: - Developed mutant mice in which the proprioceptive feedback from the dorsal root ganglion was abolished (Erg3 mutant mice). - Used a gate analysis and electromyographic recordings from the flexor and extensor muscles to compare the mice. RESULTS: SIMPLE WALK: - Mutant mice's pattern was partially compromised - still able to walk and had alternation between extensor and flexor muscles. - WT mouse was fine. COMPLEX LADDER WALK: - The mouse would either slip of fall through the ladder rungs and had irregular contractions of the flexor and extensor muscles. CONCLUSION: - Proprioception is more important in complex movements as it requires fine motor control.

Answer 46

Chain of Reflexes vs Central Model (CPGs)

Answer 47

* Rhythmic pattern arise through series of reflexes * One reflex after another generates the motor pattern * Know we have sensory afferents from tactile receptors in our feet, and have proprioception in our muscles → such tactile and proprioceptive sensory reafference is necessary for rhythmic movements

Answer 48

* Rhythm is centrally generated not mediated by sensory reafference * I.e not provided by the interaction between the central and periphery nervous system * Sensory reafference is therefore not necessary → however sensory reafference is important to adjust motor patterns to external conditions

Answer 49

In the chain of reflexes model, sensory reafference is necessary for the generation of rhytmic movements due to the sequential generation of rhytmic movements. However for the central model, though important, sensory reafference is not necessary for rhytmic movement generation as the rhythmn is centrally generated

Answer 50

* Graham Brown observed rhythmic movements in cats with removed cerebral hemispheres (decerebrate cats), showing that these movements can occur independently of higher brain centers. This suggested the presence of CPGs in the spinal cord, capable of generating rhytmic motor patterns w/o direct brain input

Answer 51

Brown's study provided early evidence supporting the idea that spinal cord mechanisms can control rhythmic movements, contributing to our understanding of CPGs.

Answer 52

Fictive motor patterns are rhythmic firing patterns generated by nervous tissue in the spinal cord ex-vivo, resembling those observed in-vivo. | (ex-vivo = outside the living body, in-vivo = inside the living body)

Answer 53

Further demonstration & thus further evidence of CPGs

Answer 54

Sequential patterns of muscle activation in the stomatogastric ganglion region via recording electroneurography traces This was seen both in-vivo and ex-vivo | (ex-vivo = outside the living body, in-vivo = inside the living body)

Answer 55

CGPs Located in * Brainstem (e.g respiratory CPGs, chewing CPG, swallowing CPG) * Spinal cord (defecation CPG, ejaculation CPG, locomotion CPGs)

Answer 56

very few/none have been recorded in humans, thus the locations of CGPs in humans are estimations based off of recordings on animal models

Answer 57

1. The circuitry - the connectivity among cells in the network (synapses and gap junctions) 2. The circuit elements - the intrinsic dynamics of individual cells within the network The rhythm is an emergent property of these interactions

Answer 58

We do not have a definitive answer, but we do have several proposed models | (will be elaborated on in other flash cards)

Answer 59

Distinct CPGs are associated w/ individual limbs (as we know single limbs can generate rhythmic patterns)

Answer 60

Limb coordination (e.g alternation in walking) arises from connectivity among the CPGs of individual limbs Left-right coordination achieved by commissural interneurons crossing the spinal cord midline | commisural interneuron = cell w/ axonal projection that crosses midline

Answer 61

* By long propriospinal descending neurons (LPDNs) * LPDNs connect cervial and upper thoracic segments w/ lumbar spine segments

Answer 62

Half centre model, multilevel model, multiple interacting CPG model

Answer 63

* Features both excitatory and inhibitory interneurons * The activation of an excitatory interneuron (for flex) ecites an inhibitory interneuron which inhibits the other excitatory interneuron (for extension) * Rhythm is generated by reciprocal inhibition & rhythm provides alternate excitation of extensor and flexor motor neurons * Downstream interneuron provide reciprocal inhibition of motor neurons

Answer 64

the half centre CGP model is simple but does not account for many experimental observation * Does not explain the complexity of both natural and fictive motor patterns - There are other muscles that have activation patterns that does not follow strict extensor-flexor alternation * Does not explain the effects of sensory reafference on phase and/or duration of locomotor patterns - Changes in relative duration of flexor and extensor activation phase does not always cause an effect on the overall cycle duration

Answer 65

* There is an intermediate level between the rhythm generator level (RG) and motorneurons called the Pattern formation level (PF) * while the RG provides the rhythm, the PF adjusts the specific pattern activations (e.g by interacting with Ia and Renshaw interneuron cells) * In this, the pattern formation level can adjust/control the phases of extensor and flexor activation indepndently according to sensory reafference, without affecting cycle duration * The rhythm generator level connects to multiple pattern formation levels, allowing it to achieve complex sequential muscle activations that we see in animals

Answer 66

* Within each limb there are separate CPGs for each set of synergistic muscles. * Interactions among CPGs generate complex patterns of muscle activation * still debated whether the multilevel or multiple CPG model apply to locomotion.

Answer 67

* Refers to cells that can generate a rhythm w/o needing stimulation * also referred to as a pacemaker property due to myogenic rhythm generation

Answer 68

* Refers to cells that have bistable properties * These cells can be turned on w/ a positive current and will start firing and keep firing until they are turned off w/ a negative current * these cells can be used by health centres to generate flexor or extensor muscle contraction

Answer 69

We think a large fraction of interneurons in the spinal cord are inhibitory, so when they communicate, a useful response would be to express this rebound in electrical activity when the inhibition is released

Answer 70

An idea proposed originally by Graham brown in the half centre model, under the name of 'fatigue' (EXTRA CONTEXT: Two half-centre CPGs - one for each side. When active, they inhibit the other side, allowing for the alternation. Spike frequency adaptation is the slow decrease in firing rate due to adaptation. As a result, the inhibition from to the other side decreases. When this decreases, the other side increases and inhibits the originally firing side. This repeats again and again to create alternating patterns of movement) | (this is all the info he tells us)

Answer 71

Stance - the foot is in contact w/ the floor Swing- there is no contact, the leg is swinging

Answer 72

Walking at a higher speed

Answer 73

* Proprioception * Sensory reafferrence also controls transition at the level of the spinal cord

Answer 74

They are able to adjust their locomotor pattern according to the different speeds on a treadmill

Answer 75

Extensor (anti-gravity) muscles

Answer 76

Flexor muscles

Answer 77

* Swing is initiated when the leg is extended * in spinalized cats extending the hip (but not knee or ankle) initiates flexor burst * This effect is elicited by muscle spindles in hip flexors | (Spinalised = surgical severing of spinal cord)

Answer 78

* swing is initiated when the leg is unloaded * in decrebrated cats,loading of ankle extensors inhibits flexor burst * this effect is mediated by 1b afferents

Answer 79

The brainstem

Answer 80

It is a loosely defined region within the brainstem which was discovered using electrostimulation.

Answer 81

Mesencephalic Locomotor Region: METHODS: - Used Cats - Electrically stimulated it at constant frequencies. - Observed the elicited behaviour. RESULTS: - Low intensity stimulation elicited walking. - High intensity stimulation elicited running. It has been found in fish, birds and other legged animals such as mice.

Answer 82

MLR firing rates determine initiation and speed of locomotion. Optogenetic stimulation of glutamatergic neurons at 10hz doesn't evoke locomotion, whereas 20hz does. SO the frequency of stimulation is important. However, there is a large degree of heterogeneity among individual neurons in this region (some neurons negatively correlate with locomotion - slide 7 lecture 14)

Answer 83

It is composed of two main anatomical regions: - PPN (the pedunculopontine nucleus) - CnF (the cuneiform nucleus) Both PPN and CnF express excitatory glutamatergic and inhibitory GABAergic neurons. PPN also expresses cholinergic neurons.

Answer 84

Glutamatergic: - Initiate and drive locomotion. GABAergic: - Terminate locomotion. Cholinergic: - Modulate locomotion. - (they also have ascending pathways back to the brain so their involvement is a bit more complex)

Answer 85

Optogenetic stimulation of glutamatergic neurons. CnF: - Evokes the full range of speed, from slow (walking) to fast locomotion (running, galloping, bounding). - Firing rate of glutamatergic neurons are linearly related to speed. PPN: - ONLY evokes slow locomotion. - Firing rate of glutamatergic neurons have more complex relationship with speed.

Answer 86

Rearing (neurons project to spinal cord) Grooming and handling (neurons project to basal ganglia)

Answer 87

Body extension. To effectively move, we need to be in the correct posture. Therefore, understanding the role of these neurons in posture is key to understanding how locomotion works. (optogenetic inhibition occurs, the extension is reduced massively to flexion - video on slide 13 lecture 14).

Answer 88

PPN neurons receive a wider range of synaptic inputs from other brain regions. CnF more specific inputs from colliculi and periaqueductal grey - regions associated with orienting and defensive movements.

Answer 89

The Medullary Reticular Formation (MRF)

Answer 90

Medullary Reticular Formation

Answer 91

Sufficient to evoke fast locomotion via glutamatergic neurons. Receives projections from limited set of regions including the Colliculi and the Periaqueductal Grey - areas mediating defensive behaviours. Plays a dominant role in fast locomotion, escape.

Answer 92

Only evokes slow locomotion via glutamatergic neurons. Different sub-classes of glutamatergic neurons encode a wider variety of behaviours including rearing, locomotion, grooming and handling. Receives a wider range of projections from cortex, basal ganglia and other brainstem nuclei. Plays a dominant role in slow pace exploratory behaviours

Answer 93

They can walk but balance and muscle tone are impaired. Their weight needs to be sustained.

Answer 94

Patients with vestibular disorders suffer from: - Postural instability - Reduced ability to respond to unexpected perturbations - Increased variability of locomotor pattern (especially at low velocity). Therefore it must play a role in all of these to some degree.

Answer 95

The Lateral Vestibular Nucleus.

Answer 96

Neurons from the LVN project to the spinal cord via the lateral vestibulospinal tract. Involved in the control of posture: - LVN controls the tone of extensor muscles (antigravity). "Decerebrated Rigidity": - Decerebrated cats expressed extended and stiff limbs, this was reduced after lesioning of the LVN> LVN neurons fire more during locomotion then at rest, with highest firing during extensor muscle contraction.

Answer 97

METHODS: - Got mice to walk along a balance beam and then perturbated the beam to test balance - Tested this in control animals and animals with lesion/ablation of LVN. RESULTS: CONTROL mice: - Can walk across easily with balance maintained. - They track with tailbase it is mainly in line with where they walk. - When perturbations occur: - Fast EMG response to perturbation in extensor muscle (~20ms latency) - Slower EMG co-activation of flexors and extensors (~50ms) LVN lesion mice: - Abolishes EMG fast and slow response. - Increases postural instability. - Even without perturbations, their tale tracking was off.

Answer 98

Vestibular reflexes (e.g., LVN excitation of extensor muscles) oppose movements to maintain stable balance. This ensures that motion vestibular reflexes are transiently downregulated during inititation and termination of locomotion.

Lectures 4, 12-14 (Riccardo Storchi) Flashcards

Spinal interneurons & spinal reflexes, Proprioception, Rhythmic movements (122 cards)