Motor system Flashcards
Movement systems and sensory information
- We talk about movement systems and sensory perception seperatly but they are not seperate - they are constantly interacting with each other.
- You use sensory information to initiate movement.
- As you are making the movement, you are getting continuous sensory feedback. You are getting somatic sensory feedback and all that feedback is helping to guide the movements in action while they are happening.
- Most movements you don’t need to think about it (except for complex movements).
- Your visual system is actually taking in all of this informaton and constructing a coherent world out of it. Movement system is incredibly complicated too. Our capacity for movement is really quite amazing.
How does a movement start
- Movement starts with an internal representation (the goal of the intended movement) and translates it into the appropriate motor commands to achieve the goal.
- Movement control in a sense is the opposite in how sensory systems work. Your sensory system starts with little bits of information scattered over the entire sensory space and then assemble it together into more complex things (hierarchy going up).
- Movement system are the opposite. When you make a movement, you do not start by thinking. All you do is think this is what I want to do and then it happens.
- The point is that the person is able to right the sentence with his hand, feets, mouth…
- Movement starts with an abstract goal, it starts with what you want to do, how you want to move. And somehow that through a series of steps get translated into the details of specifically which muscles need to contract and the timing of those muscle contractions. How do we go from an abstract goal down to the specific comands to specific muscles and the timing of those movement comands.
Organization of motor systems
The motor system has both hierarchical and parallel organization.
* Image summarizes the fundamental hierarchy of the core movement system.
* Has 3 levels of hierarchical levels: cerebral cortex (motor region of cerebral cortex), brainstem (complex stereotyped movements - a way station on way to spinal cord), spinal cord (final output for movements of your limbs and movements of your body, it has built in circuitry that sort of pre programs certain kinds of stereotyped movements).
* There’s also a hierarchy within the motor regions of the cortex itself. There are regions in the cortex that are more involved in abstract goals.
* This core pathway is often reffered to as the pyramidal tract
How is the core pathway modulated?
- The core pathway is modulated/regulated by two other brain regions/systems:
1. the cerebellum: involved in motor coordination, and also motor timing and motor learning (the more you practice something, the better you get at it).
2. the basal ganglia: set of nuclei underneath the cerebral cortex which are also involved in motor learning and selection and amplification of movements in the appropriate ways. - These two systems are working in parallel with this core system to enable you to engage in complex voluntary movements.
Central Sulcus
- Central sulcus forms the boundary for the frontal lobe.
- The frontal lobe is involved in action.
- It is functionally organized along a rostralcaudal gradient (it has a hierarchical organization): most anterior part (the front) is invovled in the abstract aspect of action and the more middle parts are involved in translating our abstract goals into more specific movement plans (abstract goals into more specific movement plans = directly involved in movements). The most caudal/posterior is involved in the actual execution of the movements.
- The abstract aspects of action (e.g., “I’m going to make a sandwich.”) are rostral, whereas the specific action required to achieve the abstract goal (e.g., the movements involved in slicing bread) are caudal.
BA of the motor system
- Notice how much of the frontal lobe is not actually directly invovwled in movement. It is involved in action, planning and setting goals but not actually involved in directly controlling movement.
- Motor cortex comprises area 4 (primary motor cortex, M1) and area 6 (lateral premotor cortex, supplemental motor area (SMA) and preSMA)
Primary motor cortex (BA 4) = region that is the most directly involved in controlling movements.
lateral premotor cortex (BA 6) = involved more in the planning of movements and what we call sensory motor integration.
supplementary motor area and pre-supplementary motor area: SMA is mostly on the medial surface. Involved in 3 different aspects of controlling movement.
What do the different regions of motor cortex do?
- Primary motor cortex (most involved in controlling movement), premotor cortex and supplemental motor area mediate different aspects of movement.
- Lesions of primary motor cortex result in contralateral paralysis and increased muscle tone (spasticity). Movements requiring dexterity are especially affected.
- Premotor cortex is involved in using sensory information to guide movement.
- Lateral premotor cortex is especially important for translating vision into movement.
- SMA - involved in complex movement sequences (ie: playing the piano) and internally generated movements.
- In contrast, lesions to premotor cortex or SMA affect the organization and control of movements. (e.g., alien limb syndrome for SMA lesions; loss of ability to use sensory information to reach for objects for premotor lesions).
Primary motor cortex
Primary motor cortex is most directly connected to movement.
Where is the motor map found?
- Early work by Wilder Penfield and others showed that primary motor cortex contained a map of the body musculature that paralleled the somatotopic map in primary somatic sensory cortex (lines up perfectly with map of primary somatic sensory cortex).
- There are extensive connections between these two maps. It makes sense that they are close to each other so that they can talk very efficiently.
- The map implies that primary somatic sensory cortex is sort of a final output pathway.
Neurons in primary motor cortex
- Neurons in primary motor cortex fire before and during voluntary movements of contralateral muscles.
- Just like the sensory system, everything crosses over. Meaning the primary motor cortex on the left side of your brain is controling the right side of your body and vice versa.
1) These neurons fire only for that specific movement, so they’re specific to that movement. So, neurons in the primary motor cortex only fire when you are moving and the individual neurons only fire in response to specific movements.
2) The neuron begings to fire APs just before the movement begins and continues to fire during the movement and then stoprs firing when the movement is over.
Premotor and supplemental motor areas
The premotor and supplemental motor areas organize the motor programs for complex voluntary movements.
Lateral premotor cortex
- Reciprocal connections between the parietal lobe and premotor cortex mediate sensory-motor transformations, the computations that enable sensory information to guide interactions with objects in the environment.
- Parietal lobe is a higher cortical area where visual and somatic sensory information are being combined together, and then these neurons project and feed forward to the lateral premotor cortex. These neurons are conveying information about vision and somatic sensation to premotor cortex. So, the parietal regions combined with the lateral premotor regions work together in this phenomenon called sensory motor transformation.
- Sensory motor transformation: transforming a sensory input into the appropriate movement commands that enable you to interact with objects in the environment.
Parietal Premotor Network
A network comprising the parietal lobe, dorsal premotor cortex and primary motor cortex is involved in directing arm movements toward objects.
* Research where monkeys see a cue and then need to reach forward and grab something.
* This research has identified two subnetworks in the parietal premotor network: one of the networks is a more dorsal network, it goes from the parietal lobe to a dorsal region of the premotor cortex and then from the premotor cortex it foes back to the arm region of the primary motor cortex (that is the final output region). This region is invovled in the animal using its arm to reach out. Arrows are two way because there is two way communication between these two regions
Within the parietal lobe, there are neurons that are integrating vision and somatic sensation.
- When we record APs from this region, we discover that there are neurons in this region of the parietal lobe that will respond to both visual input and to somatic sensory input. But the visual input and somatic sensory input are aligned with each other.
- Many neurons in the parietal lobe respond to both tactile and visual stimuli with receptive fields that are spatially in register. It is a visual somatic sensory neuron (it is integrating the two together).
- These neurons are thought to be involved construction of a peripersonal spatial map used to guide goal-directed movements.
- This is what you need to do if you are going to use vision and somatic sensation to enable you to guide movements.
Premotor neurons
- monkey fixates a central spot, cue appears telling him where to reach, can only move once the yellow light turns green. So, there is a delay where the monkey knows what it is supposed to do.
- The recording from the premotor neuorns shows that neurons start to fire as soon as the monkey sees where his arm is supposed to go. Fires a burst of AP when the monkey sees the cue. Then another burst of AP when it reaches out to touch the spot.
- Premotor neurons fire both during movements and during an imposed delay prior to the movement, suggesting they are involved in the planning and preparation to move.
But maybe this neuron in the monkey’s brain is just a visual neuron?
- If the monkey is given the same cue, but preceded by an instruction not to move, the neurons do not fire during the delay. So, when the moneky knows it does not have to move or plan a movement, the neuron does not fire AP.
- This result shows that they are not sensory neurons. They are connecting the sensory input to the appropriate action.
Neurons in premotor cortex vs neurons in primary motor cortex
- The premotor neuron on the left is active in preparation for and during the execution of an arm movement toward a target, regardless of which arm is used.
- In contrast, the neuron in primary motor cortex is active only during the execution phase and only for the contralateral arm.
- Some premotor neurons will actually fire for the same movement by either arm.
The more ventral pathway
A network comprising the parietal lobe, ventral premotor cortex and primary motor cortex is involved in shaping the hand to grasp objects.
Pathway from a slightly different region in the parietal lobe to a more ventral region of the premotor cortex and then to the hand region of the primary motor cortex.
* When you are reaching for something, you start to shape your hand in a way that is appropriate to interact with the object.
* Parietal premotor network is calculating what the object looks like and the various ways your hand can interact with the object and choses the appropriate way to interact with the object.
Different neurons like different shapes
- Many ventral premotor neurons respond to preferred shapes.
- This neuron prefers a ring and responds strongly both when the stimulus is presented and when the monkey reaches for the object. It responds much less strongly to a sphere.
- The response of a monkey vPMC neuron when different shaped objects become visible (red) and when the monkey reaches for the objects (green).
Mirror neurons
- Mirror neurons were first discovered in premotor cortex.
- Mirror neurons respond when the monkey reaches for an object and when he watches the experimenter reach for the object. They do not respond to the object alone or to non-goal directed movements of the experimenter’s arm.
- Mirror neurons are a subset of neurons in the premotor cortex that fire when someone else is executing the movement - not only when it itself does the movement. This demonstrates that the monkey understands other’s goals and intentions:
- Then moneky is watching the experimenter do that movement and this activates the same motor areas in the monkey as if it was doing the action.
- These neurons in the monkey will not fire it it is not a purposeful goal-directed movement.
Role of SMA
- The SMA has been proposed to be involved in internally generated (i.e “free-willed”) movements, especially learned complex movement sequences and linking together these complex movement sequences. Seems to be involved in activating the movement
- In support of this hypothesis, lesions to SMA and pre-SMA can cause paradoxical effects on volitional movement, including alien limb syndrome (limbs acting on their own - they do purposeful things but the person has no conscious control over it), or, conversely, loss of spontaneous movement (cannot do anything for a long period of time - won’t talk or move).
- SMA is not actually connected to any kind of movement.
How does a neuron identify where a sound is coming from?
SMA and imagined movements
- SMA is active during complex learned movement sequences even when they are just imagined.
- experiment: subjects are asked to do very simple hand motion with their fingers.
- When you imagine yourself making that complex movement sequence, the SMA is the area activated.
SMA neurons respond to…
- SMA neurons respond to selective components of learned movements sequences.
- This monkey SMA neuron is active prior to the turning motion in a sequence of movements, but only when the turn is followed by a pull and not a push movement.
What is this neuron firing for?
This SMA neuron is active prior to the third movement in the sequence, regardless of what the movement
One hypothesis for the SMA involvement…
One hypothesis of the SMA is that it is involved in internally generated (“free-willed”) behavior.
- involved in freewill movement!
Readiness potential
- The readiness potential (Berietschaftspotential) is an EEG signal that is recorded from the medial frontal lobes (~ SMA) of humans, starting around 1 second before voluntary movements.
- People discovered that if they did EEG recordings from the cortex; when people make voluntary movements before the movement actually beging (typically about one second before the movement begins), electrical activity actually builds up in the supplementary motor areas, it reaches a peak and then the movement is executed and then the electrical activity drops back down again.
- Suggests that the activity in the supplementary motor area is the intention to move. That ‘feeling’ of the intention to move is building up in the supplementary motor area until it reaches a threshold and then the movement is actually executed.
Work by Wilder Penfield
Early work by Wilder Penfield and others showed that primary motor cortex contained a map of the body musculature that paralleled the somatotopic map in primary somatic sensory cortex. There are extensive connections between these two cortical regions. This somatotopy suggests that the primary motor cortex is the final common pathway for motor output from the cortex …
- higher order areas are activating the proper regions (this is an oversimplification of what the primary cortex is doing).
- We think that it is all just feeding into the primary motor cortex and then all the different muscles are just being activated directly through this map in the primary motor cortex.
- We think this because most of the output that goes down to the spinal cord does not come from the primary motor cortex.
This somatotopy suggests that the primary motor
cortex is the final common pathway for motor output from the cortex … is this true?
… but it’s more complicated. M1 is indeed most directly connected to movement; however, it contributes only around 1/3 of cortical motor output to the brainstem and spinal cord. The remainder comes largely from premotor cortex, SMA and S1.
* The outputs from the spinal cord are going to go all the way to the brainstem.
* If the model previously decribed was correct, then we would expect all the outputs that are coming out of the motor region and going down to the spinal cord to control voluntary movement, that all of these outputs would be coming from primary motor cortex and that that is the final output.
* BUT, in fact only about 1/3 of the projections that end up in the spinal cord come from the primary motor cortex. Rest of them come from the premotor cortex, SMA or primary somatic sesnory cortex.
* Somehow the control of movement is not just feeding through primary motor cortex and down to the spinal cord but all of these regions somehow are converging on the spinal cord to control voluntary movements.
Neurons in primary motor cortex have axons that project all the way down to the brainstem and spinal cord.
- Projections from motor cortex to the spinal cord form the corticospinal tract.
- Projections from motor cortex to the brainstem form the corticobulbar tract.
- There are projections that go from motor cortex to spinal cord and other projections that go from motor cortex and end in the brainstem and then there are neurons in the brainstem that project down to the spinal cord.
- So, there are two parallel pathways by whihc info gets from motor region of cerebral cortex down to the spinal cord and out to the muscles:
- one path that goes directly from motor cortex down to the spinal cord (corticospinal tract)
- projections from motor cortex that go down to brainstem and then neurons in braistem send their axons down to the spinal cord.
Anatomy of these pathways
Motor fibers pass within the internal capsule and then form the cerebral peduncles and the pyramids. Some fibers (corticobulbar) end in the brainstem. Others (corticospinal) project to the spinal cord.
* Cerebral peduncles (huge bundle of axons) are the outputs of the motor regions of cerebral cortex. The cerebral peduncles dissapear inside the pons and then emerge on the other side of the pons as a fiber tract that runs right along the midline of the ventral surface of the medulla. These fiber tracts are called the pyramids.
* Right at the point where the brainstem ends and the spinal cord begins, the pyramids dissapear. These fibers are going inside the spinal cord and cross over to the other side.
* The decasation is where the crossover takes place and this is why the right side of your brain controls the left side of you body and vice versa. They crossover and then continue down to the spinal cord to control voluntary movements. This is the cortical spinal tract
* Cerebral peduncles are really big but the pyramids arent as big. That is the case because a lot of these axons never make it out of the pons. A lot of them end up making synapses in the pons and some of those synapses are going to be on neurons that are actully going to go up to the cerebellum, which is another structrure involved in movements.
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Corticospinal tract
Motor fibers pass within the internal capsule and
then form the cerebral peduncles and the pyramids. Some fibers (corticobulbar) end in the brainstem. Others (corticospinal) project to the spinal cord.
Saggital section
Following the fibers of the corticospinal tract as they go through the brainstem. Starting with the
Midbrain: corticospinal tract
- In the cerebral peduncle (bundles of white matter), these are all axons that are outputs from the motor cortex that are heading on down toawards the spinal cord.
Pons: corticospinal tract
Now slicing right through the pons
Rostral medulla: corticospinal tract
At the junction between the pons and the medulla.
Caudal medulla: corticospinal tract
Almost at the point where you are leaving the skull and heading out towards the spinal cord.
Lesion to the pyramids
- 2 parralel pathways by which motor information gets from cerebral cortex down to the spinal cord to control voluntary movement. The direct pathway is the corticospinal tract (responsible for making your muscles contract). Other parallel pathway that goes from motor cortex to the brainstem and then from the brainstem down to the spinal cord. And one of the reasons we know this is the case is by studies where we lesioned the pyramids.
- Monkeys with lesions to the pyramids, after a period of recovery, exhibit almost normal movement, except for loss of control of individual fingers. This result indicates that there are alternate parallel pathways for control of voluntary movement.
- After recovery, their ability to move their limbs around is reasonably normal. Must be another way that motor information can get from the cerebral cortex down to the spinal cord to control the limbs. This pathway goes from the cortex to the brainstem, brainstem to spinal cord. So it it bypassing the corticospinal tract.
- However, if you cut the cerebral penuncles, the animals would be permanently paralyzed because at that point it conatains all the fibers that have left the cerebral cortex.
- But if you cut lower, the animals can still have recovery of function due to this alternative pathway.
- The one permanent defecit is that they can no longer move their fingers. Indicates that the corticospinal tract is essential for control of finger movements. Same is true for humans.
- The corticospinal projections from the primary motor cortex that go down to the spinal cord and actually interact directly with motor neurons in the spinal cord, those are crucial for you ability to have individual control of your digits.
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Brainstem and its circuitry that controls the details of movements.
The brainstem controls stereotyped movements of the head (e.g. facial expressions, chewing, gag reflex). In addition, through descending connections with the spinal cord it contributes to the control of voluntary movements of the body.
* By having movement systems hierarchichally organized, the details of the movement can be relegated to the level of the brainstem or in the spinal cord and the broader motor commands can come from the cerebral cortex. Ex: the details about actually initiating, controling those eye movements are relegated to the level of the brainstem and other kinds of rhytmic movements like chewing, facial expressions.
Part of what is going on at the level of the brainstem involved control of voluntary movements of your face.
Some corticobulbar projections control cranial nerves involved in voluntary movements in the head (e.g. facial expressions, tongue movements, jaw movements, and eye movements.)
* These voluntary movements of your eyes, jaw, facial expression, they are controlled by motor neurons that are contained in the brainstem. Messages coming down from cerebral cortex are ultimately interacting either directly and indirectly with groups of motor neurons contained in the brainstem (the somatic motor cranial nerve nuclei).
* Outputs from the cortex are projecting to brainstem and interacting with these pools of motor neurons.
Medial brainstem pathways
Medial brainstem pathways (close to the midline) innervate axial muscles that control posture and balance. These fibers travel down the ventral spinal cord white matter and terminate in ventromedial regions of the cord gray matter.
* These three pathways are all involved in controlling what we call axial muscles (muscles of your body important for posture and balance).
* When you move, they allow you to make subtle adjustments in your posture to enable you to stay upright.
* Constant adjustements in balance and posture that involve control of muscles of your trunk and limbs near your trunk.
* The axons coming down from the brainstem and going down to the spinal cord, these axons are not making synapses with motor neurons in the spinal cord. The final output pathway for control of voluntary movement are motor neurons that are foind in the ventral grey matter of the spinal cord. And the motor neurons are sending their axons out to the muscles to control voluntary movement.
* These projections that are going from the brainstem are NOT making synapses with those motor neurons. They are making synapses with interneurons that are found in the brain or in the spinal cord.
* PROGRAMS FOR POSTURAL ADJUSTEMENTS ARE CONTAINED WITHIN THE GRAY MATTER OF THE SPINAL CORD.
Lateral pathway
(in addition to the medial pathway, there is a main lateral pathway called rubrospinal tract)
- The main lateral pathway is the rubrospinal tract, which originates in the red nucleus of the midbrain (begins in red nucleus found in midbrain then crossover and project down to the spinal cord).
- This pathway is parralel to the direct corticospinal projections (cortex to spinal cord), rubrospinal fibers descend in the contralateral dorsolateral column of the spinal cord and terminate in the dorsolateral gray matter (this pathway goes from motor cortex to red nucleus and then from red nucleys down to the spinal cord).
- The rubrospinal tract contributes to control of voluntary limb movements.
- This is why the monkeys were able to move around after the pyramids were severed. The medial pathways were intact so info could still get from cortex to brainstem, ranstem to spinal cord. Ability of monkey to control posture was intact even though corticospinal tract was severed and they could still move their limbs because they still have projections that go from cortex to red nucleus and red nucleus to spinal cord to control limb movement.
Evolution of these parallel pathways
- The course of evolution, as you go from rats and mice up to primates then up to apes and humans, the importance of the brainstem decensing pathways become less and less and the importance of the corticospinal pathways become more and more.
- This is because of the direct corticospinal connections in controlling movements of the fingers. Movements of fingers require the corticospinal projections. But limb movements can be controlled by this paralled pathway that goes through the red nucleus.
- Presumably, in the intact animal both the direct connections from the cortex and indirect connections that are going through the brainstem are working in parallel to control voluntary movement. But if the direct corticospinal projections are leasioned, the projections that are going through the brainstem can compensat enough that the animals can still move their limbs but not their fingers.
Spinal Cord Level
The complex circuitry of the spinal cord gray matter enables rhythmic and coordinated movements of the body.
How the cortex and these brainstem projections are controlling movement?
- Most of the projections from the cerebral cortex to the spinal cord and all the projections from the brainstem to the spinal cord are NOT making direct synapese on motor neurons.
- They are not makind direct synapese onto motor neurons in the spinal cord. Instead, they are making synapses on neurons on the spinal cord gray matter that are part of larger, more complex networks.
- Descending projections terminate on spinal cord premotor neurons or directly on ventral horn motor neurons. The direct connections may be especially important for control of individual digits.
- Details of the movement is encoded in the spinal cord (ie: automated postural adjustments).
- Motor neurons are projecting down to the circuits in the spinal cord and then the details are being worked out by these more complex circuits in the spinal cord.
Projection coming down from cerebral cortex and into spinal cord
This axon from primary motor cortex makes many divergent synaptic connections in ventral gray matter, both directly onto motor neurons (blue regions) and onto spinal cord interneurons (yellow regions).
* Axon coming from motor cortex is making a huge number of synapses in the spinal cord and most of those synapses are not on motor neurons. They are actually on interneurons in the spinal cord that in some more complex way are connected to motor neurons.
Exceptions:
- finger movements
- direct projections from hand region of motor cortex that directly synapse onto motor neurons that directly control fingers. This is consistent with the idea that you have a great deal of fine concious control over individual finger movements.
Damage to Basal Ganglia
- Damage to the basal ganglia = people can still move, their movements are not normal anymore.
Parts that comprise the basal ganglia
The basal ganglia comprise the striatum (the caudate and
putamin), the globus pallidus, the substantia nigra and the
subthalamic nucleus. Cortical inputs go to the striatum, whereas outputs from the basal ganglia emerge from the internal segment of the globus pallidus.
Coronal section of the brain that is fairly anterior (anterior to the thalamus).
Coronal section further down (still anterior to thalamus).
Coronal section - moving back more
Coronal section
Coronal section
Coronal section
Horizontal Section
Horizontal section
What are all these different nuclei doing to control movement?
- The cerebral cortex, the thalamus and the basal ganglia are forming a loop.
- Motor commands from the cerebral cortex will go down to the basal ganglia, something will happen to them in the basal ganglia and the basal ganglia are going to send their outputs to the thalamus and then thalamus will project back to the cerebral cortex.
Ventral Anterior and Ventral Lateral Nuclei
These are the two thalamic nucleis (ventral anterior and ventral lateral) that are specific relay nuclei connectecting the cerebellum and basal ganglia with motor cortex.
Basal ganglia loop
stationary
When you are stationary/not moving:
* The neurons in the Globus Pallidus internal segment are firing lots of action potential (very active when you are not moving).
* Therefore, the GPi is inhibiting the thalamus and the thalamus is NOT exciting the cortex. You are getting less activation of the cortex and you are not moving.
Basal ganglia loop
movement
You want to do a movement:
* The cortex will send excitatory projections down to the putamen which will activate/excite the neurons in the putamen.
* The neurons in the putamen are inhibitory neurons, so they inhibit the GPi. Neurons in the GPi fire less.
* GPi neurons firing less, relieves inhibition on the thalamus. Now, the thalamus can excite the cortex.
* Hence, this pathway promotes movement, and is called the direct pathway.
Indirect pathway
- Subthalamic nucleus (another part of BG). The neurons in the STN are the only neurons in this whole circuit that are excitatory.
- When these neurons fire APs, they are going to activate the GPi neurons and therefore increase the firing of these inhibatory neurons. In turn increasing inhibition on thalamus.
- Now the activity of the neurons in the STN, is held in check by the GPe which is inhibiting the STN and reducing the amount of excitation on these neurons.
- But in the putamen, there are actually 2 types of neurons (mixed together). One population of neurons contribute to the direct pathway and the other contributes to the indirect pathway.
- When the indirect pathway is activated, the neurons in the putamen start firing AP and inhibit neurons in the GPe (which are inhibitory). Inhibition in the STN is relieved, so STN neurons start to fire which increases the activity in the GPi, therefore increasing its abilty to inhibit the thalamus.
- Indirect pathway inhibits movement.
What does the basal ganglia-thalamus-cortex circuit do?
- The basal ganglia-thalamus-cortex circuit is thought to select and scale appropriate movements, while inhibiting inappropriate movements.
- The basal ganglia is important for habit learning. It is chuncking movements togther, organizing movement sequences and creating habitual movement sequences.
What is the basal ganglia doing?
1) Basal ganglia is involved in action selection. direct pathway is promoting movement and indirect pathway is inhibiting movement. The direct pathway will select correct movements and indirect pathway is going to inhibit movements that you do not want to be doing (unwanted movements).
2) Other idea: the activation of the direct pathway can be the ON signal and the activation of the indirect pathway can be the OFF signal. So you might initiate a movement by activation of the direct pathway and then stop the movements by activation of the indirect pathway.
Parkinson’s explained by the basal ganglia loop
- In Parkinson’s disease, loss of dopaminergic input from the substantia nigra results in reduced activity in the direct pathway and accentuated activity in the indirect pathway.
- Parkinson’s patients exhibit a paucity of spontaneous movement.
- Starts in the braistem (lots of spots in the brainstem).
- Loss of dopamine neurons in the substantia nigra. Once you lose more than 80% of your dopaminergic neurons then the parkinson’s system start to kick in. Not enough dopamine in the substantia because these neurons are degrading.
- Too much inhibition of movement!
Indirect and direct pathway in Parkinsons’
- In Parkinson’s disease, loss of dopaminergic input from the
substantia nigra results in reduced activity in the direct pathway and accentuated activity in the indirect pathway. Parkinson’s patients exhibit a paucity of spontaneous movement. - Proposed role of basal ganglia: scalling movements. this is why parkinson’s patients have small movements.
Explanation of Huntington’s disease by basal ganglia loop
- In Huntington’s disease, reduced activity in the indirect pathway reduces the normal inhibition on the thalamus, resulting in excessive, unwanted movements.
- Abnormal expression of a protein causes (at early stages):
- Direct pathway is intact
- Indirect pathway is not intact
- Leads to too much movement because you do not have enough inhibition of innapropriate movements.
Huntington’s Disease direct and indirect pathway
In Huntington’s disease, reduced activity in the indirect
pathway reduces the normal inhibition on the thalamus,
resulting in excessive, unwanted movements.
Mesenphalic Locomotion Region (MLR)
- Tonic output from the basal ganglia inhibits neurons in the mesencephalic locomotion region (MLR).
- Cortical motor commands for walking cause relief of this inhibition. MLR neurons activate descending medullary reticulospinal neurons which activate locomotion central pattern generators in the spinal cord.
How does the brain communicate to the spinal cord?
* Output projections of the BG to brainstem especially to the MLR (region involved in locomotion (circuitry for locomotion is in the spinal cord)).
* The BG outputs inhibits the MLR (inhibitory outpits). Active when the animal is not moving.
* MLR neurons make excitatory synapses on other neurons that are found further down in the brainstem and these excitatory neurons activate the walking program in the spinal cord.
Animal wants to walk:
- message comes down from cerebral cortex
- activate this BG pathway
- BG inhibits the output of these inhibitory neurons (neurons stop firing). Relieve inhibition on these MLR neurons.
- MLR neurons can activate the walking program in the spinal cord.
Multiple parralel loops in the BG.
- The basal ganglia comprise multiple parallel loops involved in motor control, eye movements, motivation/emotion, and cognition.
- basal ganglia is a series pf 4 seperate loops in the BG that are parallel and running. They are involved in 4 different aspects of brain function.
- Symptoms that come first are disorders of movement,
What is the surface of the cerebellum covered with?
The surface of the cerebellum is covered with folds called folia. The folia greatly increase the surface area of the cerebellar cortex.
* the folia is foleded up (flat sheet wrinkled up in 1D - it is similar size to cerebral cortex).
* Most of cerebellum is a cortex (thin seet of tissue). It is folded wrinkled and these folds all go in the same direction (across the long axis). An individual fold is called Folia.
* The medial part of body is mapped in medial part of cerebellum.
* The lateral part of body (limb) is represented on the outside (more lateral part) of cerebellum.
Folia
The surface of the cerebellum is covered with folds called folia. The folia greatly increase the surface area of the cerebellar cortex.
Stains white matter: cerebellum is cortex without white matter under it.
Functional domains of the cerebellum
Spinocerebellum:
* Input comes from spinal cord direct or indirect from brainstem.
* Gets most of its inputs direct or indirect from spinal cord.
* Main output to brainstem then spinal cord.
* has 2 subregions: intermediate hemisphere and vermis
1) Vermis = ‘worm’: central part that is involved in controlling posture and balance.
2) Intermediate hemisphere: controlling limbs
Cerebrocerebellum:
* Big in humans compared to animals.
* Interconnected with cerebral cortex
* Gets input from cerebral cortex + output goes back to cerebral cortex.
* Suggested to be involved in mental rehearsal of movements. Same role in cognitive processes.
Flocculonodular lobe:
* Oldest part of the cerebellum
* Completely consumed in human cerebellum (but big in fish)
* balance (vestibular function) + eye movement.
Cerebellar Peduncles
The cerebellum is connected to the brainstem through three large fiber tracts called cerebellar peduncles.
Inferior Cerebellar Peduncle:
* Gets inputs from spinal cord (directly and through brainstem) and vestibular nuclei.
* It is the closest to the spinal cord (most posterior)
* Gets proprioceptive and somatosensory inputs
Middle Cerebellar Peduncle:
* Inputs from cerebral cortex, by way of pontine nuclei (input is coming from cerebral cortex but is going through pons)
Superior Cerebellar Peduncle:
* Most anterior
* Outputs to brainstem (brainstem nuclei) and thalamus (then from thalamus to cerebral cortex)
Anatomy of cerebral peduncles
What is going on in the cerebellum at the basic level
- The cerebellum comprises a cortex and deep nuclei.
- Inputs to the cerebellum project to both the cortex and the deep nuclei. Inputs are coming from the motor cortex and spinal cord and they are carrying motor and sensory information (excitatory inputs).
- Outputs from the cortex project to the deep nuclei, which, in turn, form the outputs of the cerebellum. This means that the outputs of the cerebellum are actually not coming directly from the cortex but in fact from nuclei deep down inside the cerebellum.
- The deep nuclei (the output neurons) are getting 2 sources of input about sensory and motor function. One is direct input and then another is processed input that is coming out of the cerebellar cortex.
- the outputs from the cortex are inhibitory
The 3 deep cerebellar nuclei
There are three deep cerebellar nuclei, called fastigial, interposed and dentate.
Fastigial nuclei: (most medial deep nuclei)
* receives outputs coming from vermis
* outputs of the fastigial nuclei are going to project to medial descending pathways that are found in braistem that are involved in controlling posture + balance.
Interposed nuclei:(2 of them)
* Intermediate hemispheres are projecting to the Interposed nuclei.
* Neurons in the interposed nuclei, some of their outputs are going to the cortex and some are going down to influence the output of the lateral pathway (red nucleus/rubrospinal tract pathway) involved in controlling limb movements.
Dentate nucleus:
* Outputs from the lateral hemispheres from the cerebrocerebellum are projecting to the dentate nucleus.
* Outputs from dentate nucleus are going back up to thalamus then to the cortex.
Layers of the cerebellar cortex
The cerebellar cortex consists of five cell types, arranged in three layers: the molecular layer, the Purkinje cell layer and the granule cell layer.
Molecular layer: outer layer
* lots of dendrites and synapses
* very few neurons (cell bodies)
* a synaptic layer. Most of the molecular layer is made-up of synapses on the purkinje cell dendrites.
Purkinje cell layer:
* In between the molecular layer and granule cell layer, there is one single layer of purkinje cells (very large) forming a monolayer.
* Dendrites of the purkinje cells are extending up into molecular layer.
Granule cell layer:
* Full of tiny granule cells, make up most of the neurons in the cerebellum
* half the neurons in your brain are granule cells (small and densily packed).
How are the 5 cell types of neurons arranged in the cerebellar cortex?
- The five cell types of neurons in the cerebellar cortex are arranged in a highly ordered, repeating architecture.
- The folds are comprised of rows of purkinge cells. They are lined up in rows down the entire lenght of the folia.
- purkinje cells are the output of the cerebellar cortex.
How many granule cells are there in the cerebellum?
The human cerebellum contains ~ 100 billion granule cells. Purkinje cells form a monolayer above the granule cells.
Purkinje cell dendrites are 2 dimensional. Explain this
- Lined up one after the other along the lenght of the folia.
- They have a flattened orientation of their dendrites.
Synaptic organization of the basic cerebellar circuit module
- The circuitry of the system can actually determine the kinds of computations it is carrying out.
- Consists of a relatively small number of neurons that are interconnected in a very specific way and they are all sort of doing the same thing.
- There are 5 types of neurons in the cerrebellum: granule cells, purkinje cells.
- There are 3 inhibitory interneurons: local neurons that are influencing the local circuit: golgi cells, stellate cells and basket cells.
- Remember: Purkinje neurons are inhibitory but they are actually projection neurons (start in cortex and project down to deep nuclei).
Granule cells in this circuit and input to granule cells in this circuit.
- Remember: there are a huge number of granule cells in the cerebellar cortex, and there are a huge amount of inputs coming in through the inferior and middle cerebellar peduncles. These axons are excitatory and making excitatory synapses in the deep nuclei.
- Mossy fibers make excitatory connections with granule cells and with neurons in the deep cerebellar nuclei.
- most of the axons coming into the cerebellum cortex are mossy fibers.
- each mossy fiber is only making synapses with a few granule cells (1-1 connectivity). By the standards of the nervous system, that is very little divergence of information coming in.
- There are a whole lot of mossy fibers because there are a huge number of granule cells and all of those granule cells have mossy fiber excitatory synapses on them now.
- Granule cell axons form parallel fibers in the molecular layer, which make excitatory synapses on Purkinje cells.
- These branches extend maybe half a centimeter along the length of the purkinje neurons.
- The branch parts that are going through the molecular layer and through the dendrites of the purkinje neurons are called the parallel fibers. - There are a lot of granule cells which means there must be a lot of parallel fibers. And this is true. There are a ton of parallel fibers.
Number of parallel fibers in the molecular layer
- Parallel fibers are densely packed in the molecular layer.
- A single parallel fiber spans around 5 mm and synapses with hundreds of Purkinje cells.
- A single Purkinje cell receives excitatory input from hundreds of thousands of parallel fibers.
- The whole molecular layer is mainly comprised of the dendrites of purkinje neurons and parallel fibers.
- Purkinje cells have incredibly branching dendrites meaning each purkinje cell is getting excitatory input from anywhere from a few hundred thousands (100000) up to perhaps a million parallel fiber synapses.
- Cerebellar cortex is a really good example of divergence and convergence:
- huge amount of divergence because each parallel fiber is making synapses with a bunch of purkinje neurons that are lined up in a row.
- Each purkinje neuron is receiving input from a vast number of granule cells and parallel fibers.
Bundles of parallel fibers
- Bundles of parallel fibers that run through a row of purkinje cells, called beams, run transversely and excite the dendrites of Purkinje cells and basket cells.
- when the groups of parallel fibers are activated, they are going to be sending action potentials through this row of Purkinje neurons and exciting them.
- The basket cells inhibit the Purkinje cells flanking the parallel fiber beam.
- Turns out that along these rows there is a topographic map of the body and it goes from the outside in.
- The medial part represents the outside of your limbs
- The lateral parts of these beams represent the medial part of your body.
- One idea is that this is a way of linking together parts of the body to ensure the timing of movements is coordinated appropriately.
- Basic idea = rows and rows of parallel fibers activating rows and rows of purkinje neurons.
Mossy fiber activity
- Mossy fiber activity produces a steady stream of simple spikes in Purkinje cells, at rates of up to several hundred simple spikes per second.
- The frequency of simple spikes is strongly modulated by
sensory stimuli and voluntary movements. - If you look at one of those synapses between a parallel fiber and a purkinje neuron’s dendrite, when the synapse is active, its going to make an EPSP.
- There is a huge number of synapses, so if many of these EPSPs happen at the same time, they will add together as the electrical signal spreads through the dendrites and this will cause the Purkinje neuron to reach the AP threshold and fire and AP.
- In a typical purkinje neuron, even if the animal is not firing at all it can be firing action potentials at up to 100APs/second.
- When the animal moves, all of a sudden there is all this sensory information that comes into the cerebellum and a specific rows of purkinje neurons will start firing much faster (up to 200AP/sec). This tells us that the sensory info coming in is changing the firing rate and the firing pattern/timing of these purkinje cells. Firing rate and firing timing/pattern is conveying information that is going down to the deep nuclei and that info is modulated - when the animal moves, the frequency of the AP changes.
- These APs are called simple spikes.
- This is the main output of the Purkinje cells and modulation of that input is affecting the neurons in the deep nuclei.
Second input to the cerebellar cortex and to the Purkinje neurons.
- Each Purkinje cell receives powerful excitatory input from a single climbing fiber.
- Each climbing fiber innervates 5 – 10 Purkinje cells. Climbing fiber tends to make synapse with a few purkinje cells that are lined up.
- Climbing fibers originate in the inferior olive. They send collateral projections to the deep nuclei.
- Relationship of climbing fibers to the purkinje cells is in every way the opposite of the parallel fibers.
- Every time a climbing fiber is going to fire an AP the purkinje cell will result in firing an AP too.
Climbing fibers
- Red = purkinje neuron (dendrites
- green = climbing fibers
- These are called climbing fibers because they go up to the purkinje cells and they wrap around and around the purkinje cell. Especially around the proximal dendrites, the parts of the dendrites near the cell body.
- Synapses that are far away from the cell body will generally have less effect than synapses near cell body of purkinje cells (initial segment).
- A single climbing fiber is making a whole bunch of synapses on the proximal dendrites of the purkinje cells. This results in a very powerful excitation. So when a climbing fiber fires an AP it always triggers an AP in the purkinje cell.
Climbing fibers fire very infrequenctly.
- Climbing fibers are firing APs at a rate of 1-2 APs/second at a fairly regular rhythm. Firing APs at a very slow rhythm (parralel fibers at a much faster rhythm).
- Every time the climbing fiber fires an AP, the purkinje cell fires an AP. But, the AP is completely different, it does not look like the simple spikes.
- Climbing fibers generate complex spikes in Purkinje cells comprising a large, prolonged depolarization caused by voltage-gated calcium channels (when this calcium channel opens it stays open for a long time) and smaller sodium spikes. Complex spikes occur at steady, low frequencies, suggesting they are involved in detection of specific events.
- remember, calcium is some form of biochemical signal, when the concentration of calcium goes up in a cell, it is typically signalling that some kind of new biochemistry is going to be activated inside the cell. Seems to be the case for purkinje cell - long calcium spikes are playing some role in the function of the purkinje cell.
- Fast spiked riding on top of it are probably just classic APs.
- These complex spikes are coming infrequently but arriving at specific times that relate to specific sensory events.
- When specific sensory events happen in the envrionment then information is going to be conveyed through the climbing fibers to the purkinje cells. This means that the information the climbing fibers are carrying is not being carried by their frequency (their frequency hardly changes at all) but the exact timing of when those spikes happen. The timing of the complex spikes is what matters.
- It is the modulation of the frequency of the APs that matters in the context of the simple spikes.
Circuit with parallel fibers and climbing fibers
Purkinje cells make inhibitory GABAergic synapses on neurons in the deep nuclei. Excitatory drive on deep nuclear neurons comes from the mossy fiber and climbing fiber collaterals. The neurons of the deep nuclei make excitatory connections with neurons in the brainstem and thalamus as well as inhibitory projections to the inferior olive.
The 3 inhibitory interneurons
- All 3 inhibitory interneurons make synapses with the parallel fibers. So they will all be excited by parallel fibers. So they excite the purkinje cells but also the golgi cells, stellate cells and basket cells.
- Golgi cell: Found in the granule layer but their axons extend up into the molecular layer and they are excited by purkinje cells. Golgi cells inhibit the granule cells which means that when granule cells are active, they are going to excite purkinje cells but also going to excite golgi cells, which will feeback and inhibit the granule cells.
- When excitatory neurons are activated, they might activate other neurons but they also activate inhibitory neurons to feeback and inhibit the excitatory neurons. It is a feedback control of excitation.
- The golgi cells are feedback inhibition on the granule cells.
- The stellate cells are found in the molecular layer, these cells make synapses on the dendrites of the purkinje cells. This means that when the granule cells are activated they are going to depolarize the purkinje cell but also activate the stellate cells which will inhibite the purkinje cells. This is a feedback inhibition on the purkinje cells. The purkinje’s cell firing is going to be controlled by the fact that there is this additional inhibtion coming from the stellate cells.
- Basket cells are also found in the molecular layer. The axons of the basket cells are heading off in two directions. They are also activated by the parallel fibers and they inhibit the purkinje cells in a particular way.
- The basket cells have axons that go over to different rows of purkinje cells
Flocculonodular lobe
- The vestibulocerebellum comprises the flocculonodular lobe.
- It receives inputs from the semicircular canals, the otolith organs, the visual system and somatic sensory input from the head and neck.
- It is involved in balance and eye movements.
Spinocerebellum
- The spinocerebellum receives its input from the spinal cord and sends its output to the brainstem.
- This region is involved in controlling balance and posture (vermis).
- The spinocerebellum consists of the vermis and the intermediate hemispheres.
- It receives massive somatic sensory input (mainly proprioceptive) as well as efference copy of motor commands, through mossy fibers, coming either directly from the spinal cord or from the cord by way of the brainstem reticular formation.
Vermis
- The vermis projects to the fastigial nucleus, which in turn projects to the vestibular nuclei and the reticular formation. These projections are mainly
involved in posture. - Not only important for posture, but important for voluntary movements because anytime you make a movement there has to be all kind of complex adjustements for postures for you to be able to maintain your balance (postural adjustements).
- It has to do with being able to maintain posture and balance while you are carrying out voluntary movements.
Intermediate Hemispheres
- The Intermediate hemispheres project through the interposed nuclei to primary motor cortex (via the ventral lateral thalamic nucleus) and to the magnocellular red nucleus, which sends descending projections involved in control of limb movements.
- Outputs go down to brainstem then brainstem goes down to spinal cord
Outputs that go back up to cerebral cortex.
- Intermediate hemispheres also send outputs that go back up to the cerebral cortex.
- Specific set of thalamic nucleis that are involved in movement –> ventral anterior and ventral lateral nucleus –> relay movement information from the basal ganglia and cerebellum up to the cerebral cortex.
- It is the ventral lateral nucleus that is relaying information from cerebellum up to cerebral cortex.
- The interposed nuclei also project to the ventral lateral thalamic nucleus which in turn projects to motor cortex.
Cerebrocerebellum
- Cerebrocerebellum is getting all of its inputs from the cerebral cortex and sending all of its outputs to the cerebral cortex (specifically the frontal lobes).
- The cerebrocerebellum is getting a huge amount of input from the primary motor cortex, premotor and supplementary motor areas. All the motor regions in the frontal lobes are sending inputs to the cerebrocerebellum.
- Also getting inputs from the prefrontal cortex that is involved in more cognitive and executive control processes. This implies that the cerebellum is involved in those functions as well. Must be playing some higher order function in terms of motor control, probably involved in movement planning.
- Cerebrocerebellum might be involved in visualization of movements, like when an athlete is visualizing what they are going to do. Also involved in timing of movements, anything related to timing and dimensions (ie: which of the two tones lasted the longest).
- The lateral hemispheres form the cerebrocerebellum.
- This region gets all its input from the cerebral cortex and sends its output through the dentate nucleus to the frontal lobes and to the parvocellular red nucleus.
- The cerebrocerebellum is much larger in humans than in other primates. It is thought to be involved in the planning, programming and timing of complex, precisely coordinated movement sequences.
- Abnormalities in cerebrocerebellum in patients that have schizophrenia and in people with autism. This region is involved in cognition.
feedforward experiment with monkeys
Cerebellum is using feedforward control to make movements more coordinated and the timing of the different muscles more appropriate.
Cerebellum Model
- We start out with some sensory input, start out knowing where your body is and what the starting point of the movement is. When you make the movement, this generates sensory feedback. You are getting sensory feedback that is telling you about the movement. A copy of that sensory feedback is also going to the cerebellum.
- Cerebellum is getting feedback about what the consequences of the movement are as well. Think of this sensory feedback as whether or not the movement was carried out successfully. You use sensory feedback to figure out if you have done what you wanted to do properly.
- The cerebellum is getting information about the motor command (what you were trying to do) and it is also getting information on how close you were to succeeding in what you did (this is coming back through the sensory systems). Getting a copy of “what i intended to do and this is what i did”.
The cerebellum is using the efference copy of the motor command that is being fed into it and the cerebellum is using this feedforward system. The cerebellar cortex has an internal model of your body plan and so the cerrebellum can take a copy of this motor command and run a simulation. The cerrebelum predicts what should happen based on this motor command. This information can be relayed back to the motor system to tell the motor system: “if you run this motor program this is the outcome that will happen”. Cerebellar circuitry creates an internal model of your body and the various ways in which your body and the movements of your body are controlled.
Sensory content part:
* Cerrebellum is receiving sensory feedback. This means it can make a prediction about what is going to happen and it can compare the prediction to what actually happened.
* Is there a discrepancy between what I planned and what happened (error signal).
* Cerebellum is getting a copy of the feedback and what it can do is it can compare what is expected to happen based on its internal model and what actually happened based on the feedback, the discrepency between these two generates an error signal. Cerebellum uses this error signal to update the model. If the movement wasn’t what it was planned that means there is something wrong with the internal model and it will use that signal to update the model and improve it.
* Cerebellum is involved in motor learning. As you are learning a new skill, it is progressively updating its model of what that set of motor commands in that context is going to lead to. It can improve the internal model and as a result the feedforward anticipatory control of the movement gets better and better with time.
Where does the error signal come from?
- The error signal is coming from the climbing fibers.
- One idea is that the error signal is relayed to the cerebellar cortex by climbing fibers.
- Even though the climbing fiber spikes are happening infrequently, they happen at the key times that signal error in the movement (discrepency).
- A single AP in a climbing fiber will always generate an AP in the purkinje cell. Purkinje cell AP is this very long lasting depolarization called a complex spike. Those complex spikes are signifying errors in the movement.
What is altered in the physiology of purkinje cells making them fire simple spikes.
- Synapses in which simple and complex spikes occur concurrently have reduced efficacy.
- This form of synaptic plasticity is called long-term depression. It is thought to be involved in motor learning.
- the parallel fiber purkinge cell synapses that happen to be active when the complex spike comes along, those synapses get weaker.
- Specifically, the synapses that get weaker are the synapses that happen during the complex spike. The timing of the complex spikes can cause certain connections between the parralele fibers and the purkinje cells to drop out (become weak and have little influence).
- LTD enables the climbing fibers to sculpt out the firing pattern of the simple spikes.
Hypothesis of what the complex spikes do?
- One hypothesis is that complex spikes, through long term depression, eliminate simple spikes that create movement errors, sculpting out an increasingly accurate forward model.
- Initially, when you first do something, a new skill, initially you need to think about everuthing you are doing and what this is telling you is that initiallu there is lots of conscious control taking place in the cerebral cortex but with time and practice, you no longer need to think about it (if you think about it more you will actually do worse) –> this is because the internal model is getting better and can do this effortlessly.
