diff --git a/2016-11-14-lecture15.md b/2016-11-14-lecture15.md index d2104a2..1286e63 100644 --- a/2016-11-14-lecture15.md +++ b/2016-11-14-lecture15.md @@ -1,157 +1,172 @@ +## Upper motor neuron control + +* Axons from the upper motor neurons descend to influence the local circuits in the brainstem and spinal cord that organize movements +* Upper motor pathways include several brainstem centers and a number of cortical areas in the frontal lobe +* Brainstem centers are especially important for postural control +* Motor and premotor cortex are responsible for the planning and precise control of complex sequences of voluntary movements + +Note: + +Upper + +lower motor neurons +: are the neurons that make synapses with muscle fibers +: located in ventral horn of the spinal cord gray matter and cranial nerve nuclei of the brainstem + +-- + ## Overall organization of neural structures that control movement -Lower motor +
Neuroscience 5e Fig. 16.1
-system - -State of muscle - -contraction/relaxation - -Execute - -movement - -Output - -system - -Upper motor - -system - -Gating - -Motor - -learning - -2016-03-01 09:46:39 - -
Note: +Today we will begin our examination of the pathways in the nervous system that modulate and give rise to volitional control of our skeletal muscles. +-- ---- +## Midterm 2 -## Upper motor control - -* Axons from the upper motor neurons descend to influence the local circuits in the brainstem and spinal cord that organize movements. -* Upper motor pathways include several brainstem centers and a number of cortical areas in the frontal lobe. -* Brainstem centers are especially important for postural control. -* Motor and premotor cortex are responsible for the planning and precise control of complex sequences of voluntary movements. - -Note: +Original stats: +```r +mean 74 +median 74 +std 10.5 +max 97 +min 45 +``` +**Everyone got 7 extra points on top of their written scores due to a couple unclarities in part 3,4** --- ## Arrangement of motor neurons and local circuit interneurons within the spinal cord +
+
+ * Medial ventral horn: motor neuron pools that innervate axial muscles and proximal limb muscles -* Lateral ventral horn: motor neurons that innervate distal limb muscles. -* Local circuit interneurons lie in the intermediate zone of the spinal cord grey matter. +* Lateral ventral horn: motor neurons that innervate distal limb muscles +* Local circuit interneurons lie in the intermediate zone of the spinal cord grey matter -Neuroscience 5e Fig. 16.3 +
- - -
+
Somatotopic organization of lower motor neurons
Neuroscience 5e Fig. 16.3
Note: - - ---- - -## Overview of descending motor control - -
- -Note: - -somatotopic organization of the ventral horn in the cervical enlargement. Locations of descending projections from the motor cortex in the lateral white matter and from the brainstem in the anterior-medial white matter are shown. - - - ---- +-- ## Arrangement of motor neurons and local circuit interneurons within the spinal cord -* Medial intermediate zone local circuit neurons project to medial ventral horn motor neurons. -* Medial local circuit neurons have axons that may project to targets along the entire length of the cord, and also cross the midline to innervate contralateral side. -* Lateral regions of the intermediate zone contain local neurons that synapse with motor neurons in the lateral ventral horn. -* Lateral circuit neurons project over a smaller area and do not cross the midline. -* Allows distal regions to act independently of each other. +
+
-
+* Medial intermediate zone local circuit neurons project to medial ventral horn motor neurons +* Medial local circuit neurons have axons that may project to targets along the entire length of the cord, and also cross the midline to innervate contralateral side +* Lateral regions of the intermediate zone contain local neurons that synapse with motor neurons in the lateral ventral horn +* Lateral circuit neurons project over a smaller area and do not cross the midline +* Allows distal regions to act independently of each other + +
+ +
Neuroscience 5e Fig. 16.4
Note: - --- ## Overview of descending motor control -Neuroscience 5e Fig. 17.1 - - - -
+
Somatotopic organization of descending upper motor neuron projections
Neuroscience 5e Fig. 17.1
Note: -med ventral horn has lower motor neurosn for posteure balance and orienting movements of head and neck during shits of visual gaze. receipve descending input from the pathways orginating mainly in the brainstem, course through the anterior medial white matter of the spional cord and terminate bilaterally. - - - -lateral ventral horn contains lower motor neurons that mediate skilled voluntary movements of the distal extremities. Receive descending projection from the contralateral motor cortex via lateral division of the corticospinal tract. - - - - +**Somatotopic organization** of the ventral horn in the **cervical enlargement**. Locations of descending projections from the motor cortex in the lateral white matter and from the brainstem in the anterior-medial white matter are shown. --- -## Medial brainstem pathways modulate theaction of motor neurons in the ventromedial area +## Pathways for descending motor control -* Vestibular nuclei: -* Receive information from inner ear -* Project to medial regions of spinal gray matter. -* Controls axial muscles and proximal limbs. -* Called the vestibulospinal tract. +
Upper motor neurons, light red. Lower motor neurons, dark red
Neuroscience 5e Fig. 17.1
-
Note: -info from semicircular canals in inner ear. balance. feedback postural control +Medial ventral horn has lower motor neurosn for posteure balance and orienting movements of head and neck during shits of visual gaze. Receive descending input from the pathways orginating mainly in the brainstem, course through the anterior medial white matter of the spional cord and terminate bilaterally. + +Lateral ventral horn contains lower motor neurons that mediate skilled voluntary movements of the distal extremities. Receive descending projection from the contralateral motor cortex via lateral division of the corticospinal tract. + +*First lets discuss the upper motor neurons of the brainstem* --- -## Medial brainstem pathways modulate theaction of motor neurons in the ventromedial area +## Medial brainstem pathways modulate the action of motor neurons in the ventromedial area -* Reticular formation: -* Receives input from higher motor cortex. -* Complex network of circuits located in the core of the brainstem-from midbrain to medulla. -* Important for posture. -* Called the reticulospinal tract. +
+
-
+* Vestibular nuclei + * Receive information from inner ear for body position and balance + * Project to medial regions of spinal gray matter (**vestibulospinal tract**) + * Controls axial muscles and proximal limbs to correct for postural instability (feedback control) + +
+ +
Neuroscience 5e Fig. 17.11
Note: +Info from semicircular canals in inner ear. Provides sensory information for self motion, head position, and body position relative to gravity. It is neural feedback for postural control + +There are actually both crossed and uncrossed vestibular projections. + +--- + +## Medial brainstem pathways modulate the action of motor neurons in the ventromedial area + +
+
+ +* Reticular formation + * Complex network of circuits located in the core of the brainstem-from midbrain to medulla + * Receives input from motor cortex, hypothalamus, brainstem + * Project to medial regions of spinal gray matter (**reticulospinal tract**) + * Important for feedforward postural control (anticipating instability) + +
+ +
Neuroscience 5e Fig. 17.11
+ +Note: + +Reticular formation neurons functions +: cardiovascular (regulate output of nucleus ambiguous) and respiratory control (ventrolateral medulla) +: sensory motor reflexes +: coordination of eye movements +: regulation of sleep and wakefulness +: coordination of limb and trunk movments + +* rostral portions (mesencephalic and pontine) of reticular formation modulate forebrain activity (Moruzzi and Magoun EEG Clin. Neurophys 1949) + * cholinergic neurons (superior cerebellar peduncle) and noradrenergic neurons (locus coeruleus) and serotonergic neurons (raphe nuclei) +* caudal portions involved in premotor coordination of lower somatic and visceral motor neuron pools + feedforward postural control. stabilization during ongoing movements. +*Reticulospinal tract is uncrossed (except for commisural spinal segment collaterals?)* + + --- ## Location of the reticular formation in relation to some other major landmarks -
+
Neuroscience 5e Fig. 17.12
+ +
Neuroscience 5e Box 17D
+ Note: @@ -159,69 +174,70 @@ Note: --- -## Medial brainstem pathways modulate theaction of motor neurons in the ventromedial area +## Medial brainstem pathways modulate the action of motor neurons in the ventromedial area + +
+
* Superior colliculus -* Projects to medial cell groups in the cervical cord -* Influences neck muscles (colliculospinal tract) -* But major output of superior colliculus to spinal cord mediated by reticular formation. Axial musculature control of neck and performing orienting movements of head and eye movements. + * Projects to medial cell groups in the cervical spinal cord + * Direct projections to spinal neurons (colliculospinal tract) + * Indirect projections– most collicular mediated spinal influence is relayed through reticular formation + * Axial musculature control of neck for performing orienting movements of head as well as eye movements (saccades) -
+
+ +
Neuroscience 4e Fig. 17.2
Note: -tectospinal tract. - ---- - -## The medial descending motor pathways +colliculo- or tectospinal tract. There are actually both crossed and uncrossed tectal projections. +*Also rubrospinal tract in non-human primates and other mammals. Red nucleus in midbrain tegmentum. Axons terminate in lateral ventral horn region (distal extremities control). Few if any large neurons in red nucleus in human and don't project to spinal cord. Instead project to inferior olive in human (for learning signals/error control with cerebellum)* + --- ## Feedforward processing -* Able to predict changes in posture, and generate an appropriate stabilizing response. -* Some muscles fire in anticipation of a need for postural adjustment. -* Reticulospinal tract important for this process. If it is severed in a cat, no change in compensatory muscles occur during the process. -* Stimulate motor cortex in the right place can induce paw lifting, and several limb muscles to fire. Inhibition of the reticulospinal tract will allow the paw to move but will prevent the movement of other limbs. +* Able to predict changes in posture, and generate an appropriate stabilizing response +* Some muscles fire in anticipation of a need for postural adjustment +* **Reticulospinal tract** important for this process. If it is severed in a cat, no change in compensatory muscles occur during the process +* Stimulate motor cortex in the right place can induce paw lifting, and several limb muscles to fire. Inhibition of the reticulospinal tract will allow the paw to move but will prevent the movement of other limbs Note: - --- -## Anticipatory maintenance of body posture +## Reticulospinal tract function– anticipatory maintenance of body posture -Severed reticulospinal tract will allow biceps to fire but - -will not allow the gastrocnemius to fire for posture. - -EMG= electromyography. Measure muscle APs - -Neuroscience 5e Fig. 17.13 - - - -
+
+Upon cue (audible tone) for pulling, gastrocnemius contracts before biceps. +EMG: electromyography. Measure extracellular muscle APs +
Neuroscience 5e Fig. 17.13
Note: - +Severed reticulospinal tract will allow biceps to fire but will not allow the gastrocnemius to fire for posture. --- ## Feedforward and feedback mechanisms of postural control -
+
+Feedforward activity for postural control (green) precedes limb movement (e.g. reticulospinal tract). +Feedback activity for postural control initiated by sensory inputs detecting instability (e.g. vestibulospinal tract). +
+
Neuroscience 5e Fig. 17.14
+ Note: @@ -231,7 +247,7 @@ Note: ## Primary motor cortex and premotor cortex are in the frontal lobe -
+
Neuroscience 5e Fig. 17.2
Note: @@ -242,42 +258,51 @@ Note: ## Primary motor cortex * Located in the precentral gyrus -* Receives inputs from S1, posterior parietal structures (incorporates multiple sensory modalities, used for planning). +* Receives inputs from S1, posterior parietal structures (incorporates multiple sensory modalities, used for planning) * Controls contralateral side of the body -* Topographic organization- body represented across the medial-lateral axis. More space given to areas of fine motor control. Multiple neurons can get the same muscle to fire- not located in exact same place in cortex. - -
+* Topographic organization- body represented across the medial-lateral axis. More space given to areas of fine motor control (e.g. hands) Note: - +*Multiple neurons can get the same muscle to fire- not located in exact same place in cortex* --- -## Somatotopic representation across S1 and M1 +## Primary motor cortex -[http://www.pbs.org/wgbh/aso/tryit/brain/probe.html](http://www.pbs.org/wgbh/aso/tryit/brain/probe.html) +
topographic representation in motor cortex
Neuroscience 5e Fig. 17.5
-
- -
Note: +Somatotopic representation across S1 and M1 + + +Wilder Penfield 1940s + +Link not working (shockwave director needed) +[http://www.pbs.org/wgbh/aso/tryit/brain/probe.html](http://www.pbs.org/wgbh/aso/tryit/brain/probe.html) --- ## Motor cortex +
+
+ * Located in the frontal lobe * Several adjacent and interconnected areas * Primary motor cortex located in the precentral gyrus * Gets input from sensory cortex, basal ganglion and cerebellum * Has 6 layers, layer V is the output layer (pyramidal cells, including the large Betz cells consisting of about 5% of projection to spinal cord and concerned with fine distal movements) -* Primary pathway- the corticospinal tract. Axons cross in the caudal medulla, and innervate in lateral ventral horns +* Primary pathway- the corticospinal tract. Axons cross in the caudal medulla, and innervate in lateral ventral horns + +
+ +
Neuroscience 5e Fig. 17.3
-
Note: @@ -287,179 +312,143 @@ Note: ## Pathways from the motor cortex to the spinal cord -Indirect pathway: postural +
+
-adjustments, especially for +* Corticospinal tract (direct pathway) + * Direct pathway: fine motor control (e.g. fingers) +* Corticobulbar tract (indirect pathway. "bulbar" refers to brainstem nuclei) + * Indirect pathway: postural adjustments, especially for axial and proximal muscles. Facial movements -axial and proximal muscles. +
- - -Corticospinal tract - -(direct pathway) - - - -Corticobulbar tract (indirect pathway. “bulbar” == brainstem nuclei) - -Neuroscience 5e Fig. 17.5 - - - -
+
Corticobulbar pathway
Neuroscience 5e Fig. 17.5
Note: - - - - 90% of corticaospinal axons at caudal end of medulla cross (decussate, lateral corticospinal tract). 10% remain ipsilaterally (ventral corticospinal tract). - - most corticobulbar inputs (except lower face and tongue) terminate bilaterally. - - maps: muscle, movement sequences, intention? --- ## The corticospinal and corticobulbar tracts -Neuroscience 5e Fig. 17.4 - - - -
+
Neuroscience 5e Fig. 17.4
Note: -Corticobulbar is blue, corticospinal in red. Note that corticospinal cross the midline in the caudal medulla. Corticobulbar is for facial muscles. +Corticobulbar is yellow, corticospinal in red. Note that most corticospinal axons cross the midline in the caudal medulla. Corticobulbar is for facial muscles. + +internal capsue to cerebral peduncle at base of midbrain to scatter among pontine fibers and basal pontine gray matter then coalesce at ventral surface medulla to form medullary pyramids + +*corticobulbar axons terminate primaryly on local circuit neurons rather than brainstem motor neurons* + +*For animals with little silled movements of distal limbs/paws corticospinal projections mostly directed to the dorsal horn of spinal cord to modulate proprioceptive and mechanosensory inputs relevant to body movements. Projection to the ventral horn from corticospinal tract largest for animals with skilled fractionated movements of hands and forepaws.* --- ## Facial pathway -* The primary pathway to facial muscles is the corticobulbar pathway. -* Projection from motor cortex to motor nuclei in brainstem that control facial muscles. -* Some of these projections are bilateral and some only contralateral. -* Important for diagnosis where motor damage occurs after a stroke. +* The primary pathway to facial muscles is within the corticobulbar pathway +* Projection from motor cortex to motor nuclei in brainstem that control facial muscles +* Some of these projections are bilateral and some only contralateral +* Important for diagnosis where motor damage occurs after a stroke Note: - +anterior cingulate gyrus, region important for emotional processing +sparing in of superior facial muscles in B compared to C. Because of ACC has --- ## Patterns of facial weakness and their importance for localizing neurological injury -Neuroscience 5e Box 17A +
Neuroscience 5e Box 17A
- -
- Note: - --- -## Motor fields +## Motor maps -* A stimulation of a neuron in the primary motor cortex will get multiple muscles to fire, and will inhibit other muscles. -* Stimulating any of multiple upper neurons can get the same muscle to fire. -* The “receptive field” of a upper motor neuron has to do with organized movements rather than specific muscle groups. -* Upper motor neurons therefore act upon more than one motor pool. +* A stimulation of a neuron in the primary motor cortex will get multiple muscles to fire, and will inhibit other muscles +* Stimulating any of multiple upper neurons can get the same muscle to fire +* The "receptive field" of a upper motor neuron has to do with organized movements rather than specific muscle groups +* Upper motor neurons therefore act upon more than one motor pool Note: - +Maps of musculature or maps of movements? --- ## What do motor maps represent? -
+
microstimulation of awake, behaving monkeys
Neuroscience 5e Box 17B. Graziano et al., J. Neurophysiol 2005
Note: Topographic distribution of microstimulation sites that evoke behavorially relevant movements in a macaque monkey. - - Shaded region in map of stimulation sites indicates cortex folded into the anterior bank of the central sulcus. +More complex maps (not just connected to id. motor pools) in cortex than appreciated by Penfield stimulation studies (Penfield and Boldrey *Brain* 1937). Woolsey 1958. Lemon TINS 1988 +Movement encoding also applies to frontal eye fields for eye movements --- ## Activity of single upper motor neurons is correlated with muscle movements -Neuroscience 5e Fig. 17.6 - - -
- -
+
Neuroscience 5e Fig. 17.6
+
Neuroscience 5e Fig. 17.6. Porter and Lemon, 1993
Note: left illustrates spike triggered averaging method for correlating muscle activity with the discharges of single upper motor neurons. - - -right shows the response of a thumb muscle by a fixed latency to the single spike discharge of a pyramidal tract neuron. This can be used to determine all muscles influenced by a given motor neuron. - - - - - - - - +right shows the response of a thumb muscle by a fixed latency to the single spike discharge of a pyramidal tract neuron. This can be used to determine all muscles influenced by a given motor neuron. --- ## Purposeful movements resulting from prolonged microstimulation of the primary motor cortex -
+
Stimulation of limb movements. Blue crosses are start positions. Reds dots are final positions.
Neuroscience 5e Fig. 17.7. Graziano et al, 2005
Note: -Coordinated movements of hand and mouth after stimulation near the middle of the precentral gyrus towards head (like for eating). +*stimualtion that more roughly corresponds to volitional movemetns (hundreds of ms to sec), Graziano 2005.* With these stimus, movements are sequentiall distrubted across mutliple joints and purposeful. -Coordinated movements of hand towards belly as if inspecting an object. Notice clustering of centralized trajectories after many trials instead of just random movements. +Coordinated movements of hand and mouth after stimulation near the middle of the precentral gyrus towards head (**like for eating**). + +Coordinated movements of hand towards belly as if **inspecting an object**. Notice clustering of centralized trajectories after many trials instead of just random movements. + +Blue crosses are start positions, curved black lines are final positions are reds dots. --- ## Directional tuning of an upper motor neuron in the primary motor cortex -Monkey trained to move joystick in response to light - -
+
Monkey trained to move joystick in response to light
Neuroscience 5e Fig. 17.8
Note: - --- ## Directional tuning of an upper motor neuron in the primary motor cortex -Activity of a single neuron recorded in motor cortex +
+
Activity of a single neuron recorded in motor cortex +is dependent on the direction of the future movement +
Neuroscience 5e Fig. 17.8
-is dependent on the direction of the future movement. - -Neuroscience 5e Fig. 17.8 - - - -
Note: @@ -469,80 +458,89 @@ Notice that the neuron is broadly tuned, even with this colored shading. ## Directional tuning of an upper motor neuron in the primary motor cortex +
+
+ * Individual neurons are tuned too broadly to accurately predict direction of movement -* By comparing populations of neurons, one can calculate a direction. -* Can use the activity of motor cortex to control robots. +* By comparing populations of neurons, one can calculate a direction +* Can use the activity of motor cortex to control robots -[https://www.youtube.com/watch?v=7kctOHnrvuM](https://www.youtube.com/watch?v=7kctOHnrvuM) +
-Neuroscience 5e Fig. 17.8 +
Directional, broad range tuning +of cortical motor neurons +
Neuroscience 5e Fig. 17.8
- - -
- -
+
+
+Population vector (red) for a population of simultaneously +recorded upper motor neurons (black lines indicate each id. neuron's spike rate) +
+
Neuroscience 5e Fig. 17.8, Georgeopoulos et al., 1986
Note: Summing response from a bunch of neurons shows that the direction is better encoded from an ensemble or population of neurons— so that different movement directions/sequences are represented by overlapping and distributed populations of neurons giving rise a series of neuronal population vectors rep all the different directions. ---- +-- -## Section of pyramidal tracts in monkeys produces loss of independent digit control +## Controlling a robotic arm using motor cortex activity patterns in real time -Intact (normal) - -After section of - -corticospinal fibers - -
+
Monkey brain machine interface
Note: -corticalspinal, lateral dorsal input for control of distal/fine movements of the fingers. + --- ## Primary motor cortex and the premotor area in human +
Neuroscience 5e Fig. 17.2
+ Note: - +lateral premotor and supplementary motor areas are involved in selecting and organizing purposeful movements of the limbs and face. --- ## Primary motor cortex and the premotor area in macaque monkey -
+
Neuroscience 5e Fig. 17.9
+ Note: Divisions of the motor cortex in the macaque monkey brain. - - lateral premotor and supplementary motor areas are involved in selecting and organizing purposeful movements of the limbs and face. - - the frontal eye fields organize voluntary gaze shifts. The cingulate motor areas are involved in expression of emotional somatic behavior. - - - - --- ## The premotor cortex +
+
+ * Lies adjacent (rostral) to the primary motor cortex * Makes extensive reciprocal connections with the primary motor cortex -* Projects directly to spinal cord (30% of axons in the corticospinal tract). -* Lateral premotor cortex- has neurons that are tuned to a particular direction of movement (like primary motor cortex) but differs in that they fire earlier than neurons in the primary motor cortex. This is especially important in conditional motor tasks, that pair a movement with a visual cue. -* During the pairing of a visual cue with a motor task, the neurons will fire before any initiation of the task. This is used for intentions. -* Lesions in monkey prevent vision conditioned tasks, although vision is fine and the task can be done in other ways. +* Projects directly to spinal cord (30% of axons in the corticospinal tract) +* Lateral premotor cortex- has neurons that are tuned to a particular direction of movement (like primary motor cortex) but differs in that they fire earlier than neurons in the primary motor cortex. This is especially important in conditional motor tasks, that pair a movement with a visual cue +* During the pairing of a visual cue with a motor task, the neurons will fire before any initiation of the task. This is used for intentions +* Lesions in monkey prevent vision conditioned tasks, although vision is fine and the task can be done in other ways + +
Note: @@ -552,89 +550,71 @@ thes neurons encode intention to perform a movement rather than just the movemen ## Mirror motor neuron activity in a ventral-anterior sector of the lateral premotor cortex -[https://www.youtube.com/watch?v=RuK2Y8JojN8](https://www.youtube.com/watch?v=RuK2Y8JojN8) - -
+
Monkey mirror neuron for hand reaching is active while observing a human hand reach
Neuroscience 5e Fig. 17.10. Rizzolatti et al., 1996
Note: Indeed a nice way to understand this is by examining portions of the lateral premotor cortex that contain so called mirror neurons that have been focus of a bit of attention over recent years. - - peristimulus response histograms - - passive observation of human hand interacting with (placing food on) tray and also during motor monkey’s own movement to retrieve food - - based on Giacomo Rizzolatti et al, 1996 +[https://www.youtube.com/watch?v=RuK2Y8JojN8](https://www.youtube.com/watch?v=RuK2Y8JojN8) +Found in two cortical areas-- the posterior part of the inferior frontal cortex and the anterior part of the inferior parietal lobule [Rizzolatti:2004](http://www.ncbi.nlm.nih.gov/pubmed/15217330) --- ## Mirror motor neuron activity in a ventral-anterior sector of the lateral premotor cortex -
+
Mirror neuron for hand reaching not active while observing pliers reaching
Neuroscience 5e Fig. 17.10. Rizzolatti et al., 1996
Note: does not respond when pliers are used to interact with food. - - - --- ## Mirror motor neuron activity in a ventral-anterior sector of the lateral premotor cortex -
+
Mirror neuron for hand reaching active even when not observing self reaching
Neuroscience 5e Fig. 17.10. Rizzolatti et al., 1996
Note: Also fires when the behavior is executed behind a visual barrier. - - Suggests that parts of the premotor cortex play a role in encoding the actions of others. - - Studies of this mirror neuron system is an active area of neurosci research and some hypotheses anticipate that this connections in the mirror neuron system could be disrupted in neurodevelopmental disorders such as autism or schizophrenia— but it is still important to note that these are active investigations and hypotheses still be tested. - - - - http://nautil.us/blog/mirror-neurons-are-essential-but-not-in-the-way-you-think - --- ## Premotor cortex – two-hand coordination * The monkey has learned the task: push the object through the hole and catch it with the other hand -* With damage to premotor cortex, cannot coordinate two hands to do the task +* With damage to premotor cortex cannot coordinate two hands to do the task -
+
Note: - +image src unknown --- ## Medial premotor cortex -* Mediates the selection of movements. -* Specified by internal rather than external cues. -* Important for selecting movements based on memory, not in response to cues. -* Cells will fire when just thinking about an event. +* Mediates the selection of movements +* Specified by internal rather than external cues +* Important for selecting movements based on memory, not in response to cues +* Cells will fire when just thinking about an event Note: @@ -642,84 +622,30 @@ Note: --- -## Planning movement sequence without moving activates supplemental motor area (medial premotor area) +## Planning a movement sequence without moving activates supplemental motor area (medial premotor area) -Mental rehearsal of finger sequence +
-Motor cortex - -Sensory cortex - -Repeated simple finger flexion - -Repeating sequence finger-thumb apposition - -Supplementary - -motor area - -
Note: First neuroimaging data ---- - -## Activation of motor areas depend different on behavioral context - - - - - -Primary motor cortex - -Lateral premotor area - -Medial motor area - -1st key touch - -1st key touch - -1st key touch - -Visual - -Cue - -Learned - - Sequence - -
- -Note: - - +image src unknown --- ## Effects of damage to the cerebral cortex +
+
+ * By investigating patients with various types of brain damage we can see how the various components of motor performance may be affected. Examples: -* Lesions to primary motor cortex (e.g. from a stroke) result in loss of voluntary movements on the contralateral (opposite) side of the body. -* Apraxia is the specific loss of the ability to plan and correctly perform co-ordinated motor skills, mainly as a result of damage to the supplementary motor area. Speech disorders result from damage to motor cortex. -* Patients can move muscles, and walk on command but can no longer link gestures to a coherent act, or to recognize the appropriate use of an object even though they can recognize what an object is. + * Lesions to primary motor cortex (e.g. from a stroke) result in loss of voluntary movements on the contralateral (opposite) side of the body + * Apraxia is the specific loss of the ability to plan and correctly perform co-ordinated motor skills, mainly as a result of damage to the supplementary motor area. Speech disorders result from damage to motor cortex + * Patients can move muscles, and walk on command but can no longer link gestures to a coherent act, or to recognize the appropriate use of an object even though they can recognize what an object is -Note: - - - ---- - -## Damage to cortex: alien limb syndrome - -* A disorder in which person feels unable to control movements of a body part, believes that the limb is alien, or believes that the body part has its own personality -* It is typically associated with lesions in the supplementary motor area or those affecting blood flow to the anterior regions of the corpus callosum and the anterior cingulate -* Man who simultaneously tried to strangle and save his wife from himself. - -[https://www.youtube.com/watch?v=dIBBDuQrd-I](https://www.youtube.com/watch?v=dIBBDuQrd-I) +
Note: @@ -729,51 +655,48 @@ Note: ## The Babinski sign +
Neuroscience 5e Fig. 17.16
+ +Note: + [https://www.youtube.com/watch?v=ZFu7bdbnZx8](https://www.youtube.com/watch?v=ZFu7bdbnZx8) [https://www.youtube.com/watch?v=oI_ONptx2Ns](https://www.youtube.com/watch?v=oI_ONptx2Ns) -Neuroscience 5e Fig. 17.16 - - - -
- -Note: - -normal response on left. Following damage to descending corticospinal pathways stroking sole give abnormal fanning of toes. - - - -Also common in infants during maturation of the descending corticospinal pathways - - - - - -spinal shock and decr activity deprived of input from motor cortex and brainstem - - - -after several days recovery begins (not fully understood) and includes +* Normal response on left. Following damage to descending corticospinal pathways stroking sole give abnormal fanning of toes. +* Also common in infants during maturation of the descending corticospinal pathways. +* Spinal shock and decreased activity deprived of input from motor cortex and brainstem (period of hyptonia after upper neuron injury). +* But after several days recovery begins (not fully understood) and includes -babinski sign --spasticity (decerebrate rigidity). Cause by removal of suprresive infl by cortex on postural centre of vesitbulaer nuclei and reticular formation.. Rep abnormal incr in the gain of th spinal corste strech reflesxes. +-spasticity (decerebrate rigidity). Cause by removal of supressive influence by cortex on postural centers of vestibular nuclei and reticular formation. Represents abnormal increase in the gain of the spinal cord stretch reflexes. -loss of ability of fine movements. +muscle tone +: level of activity in alpha motor neurons +: damage to alpha motor neurons or sensory afferents to alpha motor neurons results in hypotonia +: damage to descending pathways that terminate in spinal cord usually result in hypertonia +spasticity +: decreased resistance to passive movement following damage/disruption to higher centers (e.g. seizure) +: sudden collapse in resistance to stretch +: incr resistance due to hyperactivity of stretch response +: sudden collapse may be because of activation of Golgi tendon organs +clonus +: rhythmic contractions (3-7 Hz) +: due to alternate stretching and unloading of muscle spindles in spastic muscle - - +But changes in muscle tone and spasticity are different than then tremors at rest seen in Parkinson's. --- -## Signs of motor neuron lesions +## Signs of upper and lower motor neuron lesions + +
Neuroscience 5e Table 17.1
-
Note: @@ -781,26 +704,24 @@ Note: --- -## Principles +## Summary + +
+
* Motor -* Output to muscles via ventral root -* Two main pathways: -* 1. Ventromedial system for balance, posture and controlling head & eye movements. Important for muscles of legs & trunk needed for walking. -* 2. Dorsolateral system for controlling movements of upper limbs & extremities such as fingers and toes as well as movement of facial muscles. -* - + * Output to muscles via ventral root + * Two main pathways: + 1. **Ventromedial system for balance, posture** and controlling head & eye movements. Important for muscles of legs & trunk needed for walking + 2. **Dorsolateral system for controlling movements of upper limbs** & extremities such as fingers and toes as well as movement of facial muscles * Sensory -* Input to primary somatosensory area via dorsal root -* Two main pathways: -* 1. Dorsal spinothalamic tract for proprioception (body awareness and position in space) and haptic feedback (sensation of fine touch and pressure)– crosses in medulla -* 2. Ventral spinothalamic tract for nocioceptive information– crosses over in spinal cord + * Input to primary somatosensory area via dorsal root + * Two main pathways: + 1. **Dorsal spinothalamic tract for proprioception** (body awareness and position in space) and haptic feedback (sensation of fine touch and pressure)– crosses in medulla + 2. **Ventral spinothalamic tract for nocioceptive** information– crosses over in spinal cord + +
Note: - - --- - ---- - diff --git a/2016-11-18-lecture16.md b/2016-11-18-lecture16.md new file mode 100644 index 0000000..80daeec --- /dev/null +++ b/2016-11-18-lecture16.md @@ -0,0 +1,869 @@ +## What does the basal ganglia do? + +* Modulate the initiation, termination, amplitude, and selection of movement +* Initiation and selection +* Learning +* Response-outcome associations +* Stimulus-response associations +* Used in dopamine circuits + +Note: + +[http://www.youtube.com/watch?v=Td4QGHNJ8Q0](http://www.youtube.com/watch?v=Td4QGHNJ8Q0) + +-- + +## Overall organization of neural structures that control movement + +
Neuroscience 5e Fig. 16.1
+ + +Note: + +Today we will begin our examination of the pathways in the nervous system that modulate and give rise to volitional control of our skeletal muscles. + +--- + +## Basal ganglia and the control of movement + +* Anatomy +* Basal Ganglia components +* Anatomical connectivity +* Function– modulation through disinhibition +* Neuromodulators– dopamine +* Diseases of the basal ganglia +* Other disinhibition loops + +Note: + +We will discuss… + +--- + +## Modulation of movement by the basal ganglia + +* Basal ganglia do not project directly to the spinal cord, instead they influence movements by regulating the activity of upper motor neurons +* The basal ganglia are a large set of nuclei that lie deep within the cerebral hemispheres +* Three main nuclei– caudate, putamen, and the globus pallidus +* Together with the substantia nigra and the subthalamic nucleus make a loop that links most areas of the cortex with upper motor neurons +* These neurons are required for the normal course of voluntary movements. Supervise motor movements + +Note: + + + +--- + +## Corpus striatum + +* Corpus striatum (striped body)– contains two main nuclei, the caudate and putamen. These two areas are the input zone of the basal ganglia +* Most all areas of the cortex project here. Prominent innervation from the associational cortical areas of the frontal and parietal lobes. Collectively called the corticostriatal pathway. The receiving neurons are called medium spiny neurons. Large dendritic trees, integrate information form a variety of structures + +Note: + + + +--- + +## Most cortical areas project to striatum + +* Most cortical areas (except A1 and V1) project to the corpus striatum + +Neuroscience 2001e + +
+ +Note: + + + +--- + +## Anatomical location of the basal ganglia + +Neuroscience 2001e + +
+ +
+ +
+ +Note: + + +--- + +## Anatomical location of the basal ganglia + +Neuroscience 5e Fig. 18.1 + +Note: + + + +--- + +## Anatomy of the basal ganglia:caudate and putamen + +Neuroscience 5e Fig. 18.1 + +
+ +
+ +Note: + +Striatum: caudate and putamen + +Make up what type of nuclei? (input) + +Globus Pallidus interna and substantia nigra pars reticulata + +Make up what type of nuclei? (output) + +Globus pallidus externa, STN, and substantia nigra pars compacta + +make up what nuclei? (intermediate) + +--- + +## Striatum: medium spiny neurons + +* Medium spiny neurons (MSNs) located in caudate and putamen +* ~90% of neurons in striatum; primary projection neurons +* GABAergic; inhibitory +* Very little spontaneous activity; dependent on excitatory input for discharge +* Large dendritic trees +* Inputs from cortical, thalamic, and brainstem structures + +
+ +
+ +
+ +Note: + +[lower spine image: http://en.wikipedia.org/wiki/Image:Spines.jpg](http://en.wikipedia.org/wiki/Image:Spines.jpg) + +--- + +## Medium spiny neuron in the corpus striatum + +
+ +
+ +
+ +Note: + + + +--- + +## Cortical inputs to the caudate and putamen + +* Caudate receives cortical projections primarily from multimodal association cortices and motor areas from frontal lobe that control eye movements +* Putamen receives input from the primary and secondary somatic sensory cortex and extrastriate visual cortex in occipital and temporal lobes, premotor and motor cortex, and auditory association areas in temporal lobe +* These inputs are excitatory, glutamatergic synapses +* Each spiny neuron can get synapses from lots of different cortical neurons. Each cortical neuron synapses onto a few MSNs + +Note: + + +--- + +## Organization of inputs to basal ganglia + +Neuroscience 5e Fig. 18.2 + + + +
+ +Note: + + + +--- + +## More inputs to MSNs + +* MSNs also get non-cortical input. From interneurons within striatum, from thalamic neurons, and from brainstem dopaminergic nuclei +* Dopaminergic inputs come from the substantia nigra pars compacta +* Interneurons and thalamic neurons synapse near the dendritic shaft (inhibitory) while dopaminergic neurons synapse onto the distal dendrite +* MSNs need lots of simultaneous inputs in order to go above threshold. Therefore they are usually silent +* Neurons tend to fire in anticipation of a movement. Putamen for body movements, caudate for eye-movements + +Note: + + + +--- + +## Projections from MSNs + +* MSNs of caudate and putamen give rise to inhibitory GABAergic projections that terminate in a pair of nuclei within the basal ganglia called the globus pallidus (external and internal segments) and a region of the substantia nigra called the pars reticulata which in turn contain the major output neurons of the basal ganglia +* On average more than 100 MSNs converge onto each neuron in the globus pallidus +* Globus pallidus (GP) internal neurons then convey information back to the cortex via the thalamus (ventral lateral and ventral anterior nuclei) to make a loop + +Note: + + + +--- + +## MSNs send projections to the globus pallidus and pars reticulata + +Neuroscience 5e Fig. 18.3 + + + +
+ +Note: + + + +--- + +## The direct pathway + +* Substantia nigra (SN) pars reticulata neurons project to upper motor neurons in the Superior colliculus that command eye movements without going to the thalamus +* Globus pallidus (GP) and pars reticulata neurons are GABAergic. Unlike MSNs they have high levels of spontaneous activity that normally are used to prevent unwanted movementsThus the output from the basal ganglia is normally inhibitory +* When MSNs fire (in anticipation of movement) this inhibits the inhibition (disinhibition) and allows upper motor neurons to send commands to local circuit and lower motor neurons that initiate movement +* Called the direct pathway + +Note: + + + +--- + +## Direct pathway of outputs from the basal ganglia + +Neuroscience 5e Fig. 18.4 + + + +
+ +Note: + + + +--- + +## Example of a disinhibitory circuit… + +Neuroscience 5e Fig. 18.5 + + + +
+ +Note: + + + +--- + +## Disinhibitory interaction in basal ganglia regulates downstream activity in downstream motor centers + +[http://www.youtube.com/watch?v=P6uTlnyNaTs](http://www.youtube.com/watch?v=P6uTlnyNaTs) + +Neuroscience 5e Fig. 18.6 + + + +
+ +Note: + + + +--- + +## Direct excitatory pathway via disinhibition + +* Turns up motor activity + + + + + + + + + +
+ +Note: + +Overall excitatory by disinhibiting the upper motor neurons in the cortex (promotes movement) + +--- + +## Direct and indirect pathways through the basal ganglia + +Dopamine excites the direct and inhibits the indirect pathway + + + +Neuroscience 5e Fig. 18.7 + + + +
+ +Note: + + + +--- + +## Indirect pathway circuits + +* Provides a second route of influence via a loop back to the direct pathway. +* MSN project also to the globus pallidus external nuclei which then project to the subthalamic nucleus of the ventral thalamus. +* Subthalamic nucleus projects to globus pallidus internal which then projects out of basal ganglia to the VA/VL complex of the thalamus. +* Subthalamic projections are excitatory which increases the inhibition of Globus pallidus. Opposite of the direct pathway. Acts as a brake to prevent too much disinhibition of upper motor neurons. +* Turns down motor activity. + +Note: + + + +--- + +## Indirect pathway + + + + + + + + + + + + + +
+ +Note: + +Overall inhibitory. Serves to modulate the disinihibitory actions of the direct pathway + +--- + +## Center–surround functional organization of the direct and indirect pathways + +Neuroscience 5e Fig. 18.\8 + + + +
+ +Note: + +think center-surround receptive fields for luminance contrast in retinal ganglion cells mediated by synaptic interactions between photoreceptors, bipolar cells, and horizontal cells in the outer plexiform layer. + + + + + + + +-difference of Gaussians is a feature enhancement algorithm + +-mexican hat distribution (shaped like a sombrero) + +-multidimensional generalization of this wavelet is called the Laplacian of Gaussian function + +-frequently used as a blob detector + +[-automatic scale selection in computer vision applications; see Laplacian of Gaussian https://en.wikipedia.org/wiki/Mexican_hat_wavelet](https://en.wikipedia.org/wiki/Mexican_hat_wavelet) + + + +Attentional field has a Mexican hat distribution + +http://www.sciencedirect.com/science/article/pii/S0042698904005735 + + + +--- + +## Hemiballismus: violent involuntary movements of the limbs + +* Defects in the subthalamic nucleus of the contralateral side of the movements + + + + + + + + + + + + + + + + + +Note: + + + +--- + +## Dopaminergic neurons modulate direct and indirect pathways + +* Medium spiny neurons in striatum project to the substantia nigra pars compacta, which in turn projects back to sets of medium spiny neurons. +* Both spiny neurons that project to internal and external globus pallidus receive these inputs. +* Those that project to internal globus pallidus have type D1 receptors (coupled to a Gαs, excitatory) and those that project to external globus pallidus use type D2 receptors (Gαi, inhibitory). +* Dopamine excites the direct and inhibits the indirect pathway + +Note: + + + +--- + +## Effector pathways associated with G-protein-coupled receptors + +specificity at the level of the α subunit + +Like D1 receptors + +Neuroscience 2001 + + + +D2 receptors + +
+ +Note: + + + +--- + +## Dopamine used by the direct pathway to excite medium spiny neurons + + + + + + + + + +SN + +pars + +compacta + +dopamine (+) + +
+ +
+ +Note: + +Overall excitatory by disinhibiting the upper motor neurons in the cortex (promotes movement) + + + +Predominantly D1-receptors + +--- + +## Dopamine in the indirect pathway used to inhibit medium spiny neurons + + + + + + + + + + + + + +SN + +pars + +compacta + +dopamine (-) + +
+ +Note: + +Overall inhibitory. Serves to modulate the disinihibitory actions of the direct pathway + + + + + +Predominantly D2-Receptors + +--- + +## Synaptic input to and output from striatal medium spiny neurons + +## + + + + + + + + + +Smith and Bolam, 1990 + + + +
+ +Note: + + + +--- + +## Disinhibition in direct and indirect pathways through the basal ganglia + +Neuroscience 5e Fig. 18.7 + + + +
+ +Note: + + + +--- + +## Disinhibition in direct and indirect pathway through the basal ganglia + +Dopamine excites the direct and inhibits the indirect pathway + + + +Neuroscience 5e Fig. 18.7 + + + +Note: + + + +--- + +## Motor behavior is determined by the balance between direct/indirect striatal outputs + +* Hypokinetic disorders (decreased movement) +* insufficient direct pathway output +* excess indirect pathway output +* Hyperkinetic disorders (excess movement) +* excess direct pathway output +* insufficient indirect pathway output + +Note: + + + +--- + +## Parkinson’s disease + +* Pathophysiology is the loss of nigrostriatal dopaminergic projections + +SNc + + + +Striatum + +Michael J. Fox + +Muhammad Ali + +Pope John Paul II + +Janet Reno + +Katherine Hepburn + +
+ +
+ +
+ +
+ +
+ +
+ +Note: + + + +--- + +## Parkinson’s disease + +* Due to the degeneration of dopaminergic neurons of the substantia nigra pars compacta. +* Leads to tremors, slowness of movements, rigidity of extremities and neck, minimal facial expressions. +* Slowly progressing disease. +* Some success in slowing the progression comes from the use of Levadopa (L-DOPA)– gets converted to dopamine and gets to dopamine receptors in basal ganglia. + +
+ +Note: + +[from https://en.wikipedia.org/wiki/Substantia_nigra](https://en.wikipedia.org/wiki/Substantia_nigra) + +>Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. + +--- + +## Summary explanation of hypokinetic and hyperkinetic disorders + +
+ +Note: + + + +--- + +## What causes dopaminergic neurons to die? + +* Most cases are late-adult onset without a clear inheritance pattern. +* Small fraction are familial. +* α− Synuclein a synaptic protein that when mutated can lead to aggregation and cause the formation of Lewy bodies. Autosomal dominant mutations. +* Aggregates may spread from neuron to neuron. +* Two other autosomal recessive mutations Pink1 and Parkin block mitochondria function in dopaminergic neurons-conserved from fly to humans. + +Note: + + + +[from https://en.wikipedia.org/wiki/Parkinson%27s_disease](https://en.wikipedia.org/wiki/Parkinson%27s_disease) + +-mostly idiopathic, having no known cause + +>These genes code for alpha-synuclein (SNCA), parkin (PRKN), leucine-rich repeat kinase 2 (LRRK2 or dardarin), PTEN-induced putative kinase 1 (PINK1), DJ-1 and ATP13A2.[7][37] In most cases, people with these mutations will develop PD. + + + + + +Models: mptp, insecticide rotenone, herbicide paraquat and the fungicide maneb. + + + +>proportion in a population at a given time is about 0.3% in industrialized countries. PD is more common in the elderly and rates rises from 1% in those over 60 years of age to 4% of the population over 80 + + + +alzheimers: + +[http://www.alz.org/facts/](http://www.alz.org/facts/) + +2/3 women + +6.4% dementia over 60 & 4.4% with AD over 60 + + + +--- + +## Parkinson’s like pathology in mouse after injection of α-synuclein protein aggregates into striatum + +
+ +Note: + +(A) Serial coronal brain maps of a wild-type mouse 180 days after injection of preformed α-synuclein fibrils (PFF) into the dorsal striatum revealed the development of α-synuclein pathology across the brain. Cells with α-synuclein aggregates are shown in red; the injection site is marked by a light red circle in the 2nd map from left. (B) A high-magnification image of the substantia nigra, showing two dopamine neurons with aggregated α-synuclein in Lewy body-like inclusions (arrows). Dopamine neurons are visualized in green by immunostaining against tyrosine hydroxylase, a marker for dopamine neurons. α-Synuclein is visualized in red using an antibody that preferentially stains aggregated α-synuclein. (C) Substantia nigra pars compacta (SNc) cells that exhibited α-synuclein pathology were located primarily on the ispilateral side of the injection. Injecting phosphate-buffered saline (PBS) into wild-type (wt) or injecting PFF into α-synuclein knockout (Snca−/−) mice did not cause α-synuclein pathology. + +--- + +## Genes linked to Parkinson’s disease regulate mitochondria function + +
+ +Note: + + + +--- + +## Treatments for Parkinson’s + +* Dopamine can’t cross the blood brain barrier but L-dopa can. Stops working after a few years. +* Deep brain stimulation– bypass the circuit by inhibiting the the STN output. +* Cell replacement therapy– implant dopamine making neurons into the striatum. + +[http://www.youtube.com/watch?v=mO3C6iTpSGo](http://www.youtube.com/watch?v=mO3C6iTpSGo) + +[http://www.laskerfoundation.org/awards/2014_c_description.htm](http://www.laskerfoundation.org/awards/2014_c_description.htm) + +[https://www.youtube.com/watch?v=JAz-prw_W2A](https://www.youtube.com/watch?v=JAz-prw_W2A) + +
+ +Note: + +[from: http://www.ncbi.nlm.nih.gov/books/NBK28180/](http://www.ncbi.nlm.nih.gov/books/NBK28180/) + +>Neutral l-amino acids have various rates of movement into the brain [13,14]. Phenylalanine, leucine, tyrosine, isoleucine, valine, tryptophan, methionine, histidine and l-dihydroxy- phenylalanine (l-DOPA) may enter as rapidly as glucose. These essential amino acids cannot be synthesized by the brain and, therefore, must be supplied from protein breakdown and diet (see Chap. 33) + + + + + +L-DOPA is transported across the blood brain barrier by LAT-1 (L or Large amino acid transporter). Dopamine is too polar to be lipid soluble and has no specific transporter + + + +non-polar: symmetric distribution of charge. + + + + + +--- + +## Huntington’s disease + +One of the most common inherited neurological disease. + +Progressive deterioration of the caudate and putamen that project to the GP external, the head of the indirect pathway. + +Leads to a movement disorder consisting of rapid jerky motions with no clear purpose. + +
+ +Note: + + + +--- + +## Huntington’s Disease + + + + + + + + + + + + + + + + + + + + + +Note: + + + +--- + +## Summary explanation of hypokinetic and hyperkinetic disorders + +
+ +Note: + + + +--- + +## Huntington’s disease + +* Dominantly inherited– strikes around midlife. +* Patients develop depression, mood swings, and abnormal movements (striatum). +* Caused by alterations in a single gene that encodes the huntingtin protein. +* Huntingtin protein has an expansion of a CAG trinucleotide repeat, resulting in an extended polyglutamine (poly Q) repeat. Leads to aggregation of proteins and cell death. + +Note: + + + +--- + +## The huntingtin protein has expanded glutamine repeats in the diseased state + +
+ +Note: + + + +--- + +## Non-motor loops of the basal ganglia + +* Basal ganglia are also involved in loops that modulate non-motor behaviors. +* Maybe work the same way to suppress outputs. +* A limbic loop that may regulate emotional behavior and motivation. +* Tourette’s may be a problem with limbic loop (no longer have inhibitions about language?) +* Drugs of abuse affect dopamine release. +* Schizophrenia, may be due to aberrant activity in multiple loops resulting in hallucinations etc. + +Note: + + + +--- + +## Types of corticostriatal loops + +[http://www.youtube.com/watch?v=jYRa-fpNonY](http://www.youtube.com/watch?v=jYRa-fpNonY) + +Neuroscience 5e Box 18D + + + +
+ +Note: + +Tourettes may be a disruption to non-motor corticostriatal loops. + +--- + +--- +