Neuroscience Test 2, Motor System Overview, Cerebellum, Movement Disorders, and Basal Ganglia

Card Set Information

Neuroscience Test 2, Motor System Overview, Cerebellum, Movement Disorders, and Basal Ganglia
2013-04-04 17:53:52
Neuroscience nMedical School nCarver College Medicine

Flashcards over the above lectures for the second neuroscience test
Show Answers:

  1. The basic motor control unit (αγ neurons)
    • α motor neurons innervate extrafusal muscle fibers
    • γ motor neurons innervate intrafusal (Golgi tendon organ) muscle fibers in order to maintain the same level of tension in order to appropriately report muscle length
  2. Organization of ventral horn of spinal cord
    • Dorsal groups: Innervate flexors
    • Ventral groups: Innervate extensors
    • Medial groups: Axial muscles
    • Lateral groups: Limbs; the lateral dorsal groups innervate the most distal muscles
    • Spinal reticular zone: Central pattern generators, which are important for coordinating walking, running, skipping, etc through a central core of interneurons
  3. In the medulla and pons, what are the homologous formations to the spinal reticular zone?
    • The medulla and pons have their own reticular formations, which regulate stereotypic movements of the head (swallowing, chewing, breathing) and to allow for rapid eyemovements (saccades) through the paramedian pontine reticular formation (PPRF)
    • These interneurons also interact with bulbar motorneurons
  4. The function of the five main descending motor systems
    • Corticospinal: Strong influence on contralateral flexor muscles
    • Reticulospinal: Medial facilitates excitation of axial and proximal limb extensors bilaterally, also helps rhythmic respiration by accessory respiratory muscles; lateral inhibits axial and proximal limb extensors
    • Vestibulospinal: Lateral excites axial and proximal limb extensors ipsilaterally; medial excites extensor muscles for head and neck contralaterally; both are to maintain upright, level position/posture
    • Rubrospinal: Facilitates neck and upper limb flexors
    • Tectospinal: Turns head in response to visual stimuli
  5. Corticospinal and corticobulbar system
    • Origin: Cerebral motor cortex (M1), premotor cortex, somatosensory cortex (S1), and adjacent parietal cortex
    • Descent: Most synapse with interneurons in the contralateral spinal cord after decussating in the pyramids
    • Effects: Strongest influence on flexor muscle groups; about 20% of corticospinal neurons end on alpha motorneurons in the cervical enlargement; intrinsic hand muscle motorneurons are carried in the dorsal part of the ventral horn at C7-T1 and are directly innervated by the corticospinal fibers
    • Corticobulbar fibers: Similar to corticospinal fibers
    • Uncrossed anterior corticospinal pathway: Mediates voluntary control over posture
  6. Homunculus of the cerebral motor cortex (M1)
    • 40% dedicated to the hand, jaw, and lower face muscles
  7. Rubrospinal pathway
    • Thought to be of limited significance in humans
    • Facilitates upper limb and neck flexors
  8. Reticulospinal pathway
    • Important for maintaining posture and modulating muscle tone; also relates to viseromotor activity and pain modulation
    • Receives input from cortico-reticular fibers and fastigial nucleus of the deep cerebellar nuclei
    • Medial reticulospinal pathway: Originates from pontine tegmentum; runs in the anterior fasciculus; ends bilaterally on interneurons in the ventral horn but not on alpha motorneurons; facilitate excitation of axial and proximal limb extensors; also activate compound limb movements and stereotypic limb movements; a subcomponent of this pathway is influenced by respiratory centers of the pons and medulla and sends axons to the phrenic nucleus and motor nuclei of accessory respiratory muscles
    • Lateral reticulospinal pathway: Originates from central and ventral medulla; runs with the lateral corticospinal funiculus; inhibit excitation of axial and proximal limb extensors
    • In addition, the descending monoamine pathways from the locus ceruleus (noradrenaline) and pontine and midbrain raphe (serotonin) may be an important command system for complex stereotypic movements
  9. Tectospinal pathway
    • Arises from middle and deep layers of the superior colliculus and innervates the contralateral ventral horn of the cervical spinal levels
    • Excites contralateral motor neurons and inhibits ipsilateral motor neurons of the neck
    • Stimulation of the superior colliculus on one side causes the head to turn to the opposite side
  10. Vestibulospinal pathways
    • Lateral vestibulospinal pathway: Originates in the lateral vestibular nucleus and descends ipsilaterally through the whole length of the cord; ends in the medial part of the ventral horn on interneurons; excites axial and proximal limb extensors
    • Medial vestibulospinal tract: Originates from the medial vestibular nucleus and is mostly crossed; extends to midthoracic level ending in the medial ventral horn at levels C3-T1; facilitates extensor muscles for head and neck movements leading to an upright, level position for the head
  11. Decerebrate rigidity
    • The lateral vestibulospinal pathway remains intact (extensors of axial and proximal limb muscles) but damages the corticospinal fibers, causing no antagonism to the LVST
  12. Decorticate rigidity
    • Caused by damage to the cortex, excluding the motor cortex
    • Lower limbs and back are extended but arms and neck are flexed
    • Disinhibited rubrospinal fibers cause upper limb flexion (supposedly) since the red nucleus is intact
  13. Parts of the frontal lobe important for planning and preparation of motor control
    • Premotor and supplementary motor areas: Most of frontal lobe is premotor; Broca's area is premotor for language
    • Premotor cortex: Planning in response to external cues (also mirroring movements); also for 'ownership' of body parts (sense of agency)
    • Supplementary motor cortex: Important in internally generating movements
    • These cortices have huge influences on the primary motor cortex; in fact, they can actually replace the function if the primary motor cortex is lesioned!
  14. How the basal ganglia are important for motor or procedural learning
    • The striatum component of the basal ganglia receives input from the corticospinal system and learns/stores these motor actions
    • The striatum can then inhibit the globus pallidus internus/substantia nigra, thereby disinhibiting the actions of the ventral anterior thalamic nucleus, allowing it to exert effects upon the cortex
    • However, the striatum also initiates an indirect pathway which supports inhibition of the thalamus
    • The frontal lobe affects dopamine release in the basal ganglia; dopamine release is associated with initiation and selection of movements
  15. Parkinson's disease
    • Occurs in 200/100,000 people in late 50s to early 60s
    • Cause: Loss of dopaminergic neurons in the substantia nigra results in lack of disinhibition of the thalamus (loss of direct pathway); also includes loss of cholinergic neurons in cortex (cognitive) and brainstem (postural loss) and loss of serotogenergic neurons in the brainstem (affective); environmental and genetic factors
    • Clinical signs: Resting tremor, bradykinesia (slowness of movement), absence of automatic movements, loss of postural/blinking/swallowing reflexes; loss of willed motor activity
    • May include rigidity and drecreased olfaction, constipation, depression, and fatigue
    • Treatment: A precursor of dopamine, L-DOPA is administered with a peripheral DOPA decarboxylase inhibitor to allow L-DOPA to cross the BBB
    • New therapies: Fetal mesencephalic tissue transplantation, deep brain stimulation of subthalamic nucleus (to prevent its effects by jamming it), lesion of globus pallidus internus, new drugs, gene therapy (introducing GAD into subthalamic nucleus, trophic factors into substantia nigra, or dopa decarboxylase into striatum)
  16. Huntington's disease
    • Cause: Autosomal dominant loss of enkephalin/GABA striatal neurons that inhibit the globus pallidus externus (loss of indirect pathway), causing excessive disinhibition of the ventral anterior thalamus and uncontrollable movement (chorea)
    • Clinical signs: Onset after child-bearing years, generalized chorea, and dementia
  17. Chorea
    • Rapid non-stereotypic movement that flows from one body part to another
    • Ballism: Chorea affecting the proximal extremities with large amplitude
    • Pathology: Usually is a lesion in the subthalamic nucleus
    • Huntington's disease includes chorea
  18. Dystonia
    • Twisting as if around an axis and slow, sutstained abnormal movements of trunk and extremities or cranial musculature
    • A variatey of lesions in the CNS/PNS result in dystonia, but the most common site is the putamen (often caused by medications)
  19. Idiopathic torsion dystonia
    • Cause: Autosomal dominant mutation of the DYT1 gene on chromosome 9; penetrance is not 100%; no clear structural abnormality in the CNS
    • Clinical features: Begins in childhood, lower extremities affected at first, and generalization occuring ultimately
    • Treatment: New strategies include pallidal stimulation or RNA interference to silence the affected gene; botulism toxin is a local treatment
  20. Movement disorders caused by the use of dopamine-blocking agents
    • Cause: No clear CNS abnormality rather than the result of aberrations of dopamine receptor function
    • Clinical signs: Tardive dyskinesia (involuntary, repetitive body movements, especially of tongue or mouth) and akathisia (desire to keep moving)
  21. How the cerebellum is important for 'hitting the target' with regards to motor control
    • The pontine nuclei are the largest source of input to the cerebellum, and they get their input by the vast numbers of corticopontine projections from almost every cortical area
    • The cerebellum also gets continuous feedback about body and limb position from the spinocerebellar tracts and the vestibular system
    • The cerebellum then exerts its major influence on the motor cortex via the deep cerebellar nuclei and the ventrolateral thalamic nucleus
    • The cerebellum can be considered to provide an 'error signal,' and cerebellar deficits involve degradation of fine movements and postural difficulties
  22. Development and size of the cerebellum
    • Originates from the rhombic lip from CNS (rhombencephalon), between 3 weeks gestation and 20 months post-natal life
    • Granule cells migrate in the transverse plane of the rhombic lip and migrate medially deep to the Purkinje cells
    • Becomes 1/10th the weight of the cerebrum and 40% of the surface area of the cerebral cortex if unfolded
  23. Gross topography of the cerebellum
    • Anterior, posterior, and flocculonodular lobes in the sagital plane
    • Vermis, paravermis, and hemispheres in the transverse plane
    • ???
  24. Functions of the lobes
    • Flocculonodular (archicerebellum): Has vestibulo-cerebellar input about body equilibrium and eye movements; oldest zone
    • Vermis and paravermis (paleocerebellum): Has spino-cerebellar input about muscle tone and execution of trunk and limb movements; newer zone
    • Lateral hemispheres (neocerebellum): Has cerebrocerebellar inputs about planning, initiation, and timing of movements; newest zones
  25. Functions of anatomical lobes of the cerebellum
    • Flocculonodular lobe: Balance and eye movement
    • Anterior lobe: Mainly involved in motor control
    • Posterior lobe: Motor and non-motor functions
    • Paleocerebellum: Equilibrium and posture; autonomic responses and limbic functions (emotion, sexuality, affectively important memory)
    • Neocerebellum: Coordination of muscles; cognitive functions (planning, memory, language, learning)
  26. Somatotopic organization of the cerebellum
    • Trunk in midline, extremeties laterally placed, and face near primary fissure in posterior lobe
    • Every body part represented more than once
  27. A lesion in what general area of the cerebellum will result in extremity ataxia?
    • Paravermis lesions will yield extremity ataxia, or a staggered walk due to uncoordinated limbs
    • Midline lesions yield truncal ataxia
  28. Deep cerebellar nuclei names, input, and output
    • All signals leaving the cerebellum originate here
    • They are excited by mossy fibers that arise from contralateral pontine nuclei, spinocerebellar tract, and vestibular nuclei; these cells contact about 20 granule cells each
    • Climbing fibers also excite the deep cerebellar nuclei; these fibers run from the contralateral inferior olive (these cells also excite a single Purkinje cell)
    • They are inhibited by Purkinje cells, and integrate these inputs to fire accordingly
  29. Layers of the cerebellar cortex
    • Molecular: Has processes of granule cells and Purkinje cells; contains stellate and basket inhibitory interneurons
    • Purkinje: Contains Purkinje cells, which have very large somas, tree-shaped dendritic arbors in one plane, and are the only cells that send projections out of the cerebellar cortex
    • Granule: Contains the cell bodies of granule cells (the most numerous neuron in the brain) that have T-shaped axons that go into the superficial molecular layer and form many synapses with Purkinje cell dendrites, and Golgi cells, that are inhibitory neurons much larger than granule cells
  30. Cerebellar input tracts from spinal cord
    • Dorsal spinocerebellar tract: Originates in the secondary neurons of the ipsilateral ventral horn; carries unconscious proprioceptive information from legs and trunk; enters via inferior cerebellar peduncle
    • Cuneocerebellar tract: Originates in the accessory cuneate nucleus; carries unconscious proprioceptive information from arms and head (analogous to dorsal nucleus of Clarke); enters via inferior cerebellar peduncle
    • Ventral spinocerebellar tract: A double-cross system whose function is unclear; enters via superior cereellar peduncle
  31. Cerebellar input tracts from vestibular system, cerebral cortex, and hypothalamus
    • Vestibular system: Originates in the vestibular nuclei and from the end organs; carries information about the head's location and acceleration; enters via the juxtarestiform body, which is adjacent to the inferior cerebellar peduncle
    • Cerebral cortex: Via pontine nuclei and inferior olive
    • Hypothalamus: Complex reciprocal connections
  32. Cerebellar output tracts
    • A small set of Purkine cells project to the vestibular nuclei via inferior cerebellar peduncle (remember, the large majority of purkinje cells only go to the deep cerebellar nuclei)
    • The deep cerebellar nuclei also project to the vestibular nuclei via the inferior cerebellar peduncle
    • The deep cerebellar nuclei project via the superior cerebellar peduncle to the brainstem, red nucleus (from dentate nucleus), and the ventrolateral and ventroanterior nuclei of the thalamus (from interposed nuclei and dentate nucleus)
  33. Types of neurons found in the cerebellum
    • Purkinje cells: Inhibitory, project to deep cerebellar nuclei (and a few to the vestibular nuclei)
    • Granule cells: Excitatory interneurons
    • Golgi, basket, and stellate: Inhibitory interneurons
  34. Functions of the cerebellum
    • Motor
    • Error detection and correction of cortically-originating movement
    • Motor learning by increasing firing of Purkinje cells during learning of a new motor task
    • Initiation of movement by the firing of deep cerebellar nuclei simultaneously with pyramidal cortical neurons prior to movement
    • Prediction of the sensory consequences of movement (ex cannot tickle self)
    • Non-Motor Functions
    • Autonomic (respiration, intestinal motility, bladder tone, etc)
    • Behavior (mood)
    • Cognition and memory
  35. Blood supply of cerebellum
    • Superior cerebellar artery: Anterior lobe
    • Posterior inferior cerebellar artery: Posterior lobe
    • Anterior inferior cerebellar artery: Ventral part of anterior and posterior lobes and the entire flocculonodular lobe
  36. Cerebellar lesions
    • All syndromes cause ipsilateral signs!
    • Midline cerebellum syndrome (aka archicerebellar syndrome): Trunk ataxia, wide gait, and nystagmus; can be caused by medulloblastoma on vermis
    • Cerebellum hemisphere syndrome (including paravermis): Limb ataxia, dysmetria (inability to estimate range of movement), dyssynergia (uneven and jerky movement), adiadochokinesia (inability to perform rapid successive movements), volitional tremor (tremor begins with conscious movement), muscular hypotonia, dysarthria (slurred speech), rhythmic nystagmus
  37. Developmental defects of the cerebellum
    • Dandy Walker malformation: Agenesis of vermis, cyst in the fourth ventricle, hydrocephalus
    • Chiari malformation: Cerebellum vermis herniates through foramen magnum; asymptomatic or can include hydrocephalus
    • Autism: Reduced connectivity to anterior cerebellum may underlie delayed acquisition of gestures important for communication and socialization
  38. General functions of the basal ganglia
    • Produce internally-generated movements
    • Learning and retention of complex motor tasks (procedural or habit learning)
  39. What are the basal ganglia?
    • Five areas of grey matter in the inferior and medial telencephalon:
    • Caudate nucleus
    • Putamen
    • Globus pallidus
    • Nucleus accumbens
    • Olfactory tubercle
    • *The substantia nigra (in the mesencephalon) and the subthalamic nucleus are critical for the basal ganglia circuitry
  40. Contents of the striatum
    • When saying "striatum," we are often referring to the dorsal striatum, which is composed of the caudate and putamen
    • The ventral striatum consists of the nucleus accumbens, olfactory tubercle, and ventral parts of the caudate and putamen
    • The corpus striatum refers to the grouping of the caudate, putamen, and globus pallidus
  41. Purpose of the (dorsal) striatum
    • Receives most of the inputs to the basal ganglia from the cerebral cortex (corticostriate projections) and amygdala
    • To caudate: The frontal lobe and eye field areas go to the head, the parietal lobe areas go to the body, and the occipital and temporal lobes areas go to the tail
    • To putamen: Somatosensory and motor cortices
    • Exception: The premotor cortex also sends axons directly to the subthalamic nucleus
  42. What is the lentiform nucleus?
    Meaning "seed-like," this nucleus is composed of the putamen and globus pallidus
  43. Differences in the neuronal makeup of the striatum
    There are virtually no differences between the caudate and the putamen, but they are largely separated from each other by the internal capsule
  44. Medium-sized spiny neurons
    • Found in the striatum, these neurons make up about 95% of the neurons present with interneurons making up the rest
    • They send their axons out of the striatum and inhibit the next cell with GABA
    • There are many dendritic spines (which are plastic) thought to be the substrate for information storage
    • Dynorphin and substance P: These neurons contain these peptides and have D1 dopamine receptors, which are excited by dopamine
    • Enkephalin: These neurons contain the peptide enkephalin and D2 receptors, which cause inhibition of firing
  45. Globus pallidus
    • Has two components, internus and externus
    • Neurons are large with few spines and are inhibitory to their targets through GABA
    • Though these cells receive many inhibitory inputs, they are constantly active and fire at a high frequency
    • Is the main output structure of the basal ganglia with the substantia nigra pars reticulata
  46. Subthalamic nucleus
    • Included in the diencephalon and is separated from the basal ganglia by the cerebral peduncle
    • Excites the basal ganglia with glutamate
  47. Substantia nigra
    • Pars reticulata: Structurally similar to the globus pallidus; also release GABA and are constantly active
    • Pars reticulata and globus pallidus internus are the main output structures of the basal ganglia
    • Pars compacta: Lies deep to the pars reticulata and provides dopaminergic innervation of the striatum (nigrostriatal pathway) to both MSNs and interneurons; also innervates globus pallidus and subthalamic nucleus (by a much lesser extent)
  48. Inputs to the basal ganglia
    • Corticostriate: Excitatory glutamate pathway ending on the dendritic spines of the MSNs; these project to different parts of the striatum based on where they arise
    • Also to striatum: Inputs from amygdala, thalamus, substantia nigra pars compacta (dopamine), locus ceruleus (noradrenaline), and dorsal raphe (serotonin)
  49. Thalamic outputs from the basal ganglia
    • Ventral anterior: Innervated by globus pallidus internus on the lateral part (connect the premotor and supplementary motor areas) and substantia nigra pars reticulata on the medial part (connect the frontal eye fields)
    • Mediodorsal nucleus: Connects the prefrontal cortex for complex cognitive control and is innervated by the substantia nigra pars reticulata
    • Posterior intralaminar nuclei: The centromedian-parafascicular complex receives input from the globus pallidus internus and the substantia nigra pars reticulata in order to innervate the premotor and supplementary motor areas AND the motor cortex
  50. Other important outputs from the basal ganglia
    • Superior colliculus: The substantia nigra pars reticulata sends axons to control saccadic eye movements (involves an oculomotor re-entrant loop)
    • Midbrain tegmentum: The mesencephalic locomotor region connects the basal ganglia and the reticulospinal pathways in order for learned, complex movements to be combined with stereotypic movements
  51. The "input" and the "output" sides of the basal ganglia (really general)
    • Input: Striata
    • Output: Globus pallidus internus and the substantia nigra pars reticulata
  52. Direct internal basal ganglia circuit
    • Function: Allow movement by disinhibiting the thalamus
    • MSNs involved: The dynorphin- and substance P-containing neurons which have D1 receptors that are excited by dopamine
    • Presence of dopamine excites the MSNs which release GABA on the GPi/SNR, causing them to be inhibited
    • When GPi/SNR are active, they are releasing GABA on the thalamus, inhibiting it
    • Since this pathway inhibits the GPi/SNR, the thalamus (and our desired movements) is active when this pathway is
  53. Indirect internal basal ganglia circuit
    • Function: Be active in the normal state, preventing movement from occurring
    • MSNs involved: Enkephalin-containing neurons that have D2 receptors, causing them to be inhibited by dopamine
    • When MSNs are not receiving dopamine, they are active, releasing GABA on the GPe
    • When active, the GPe cause inhibition of the subthalamic nucleus
    • The MSN activity causes inhibition of the GPe and activation of the subthalamic nucleus
    • The subthalamic nucleus excites the GPi, causing inhibition of the thalamus
    • Therefore, this pathway causes excitation of the GPi/SNR and inhibition of the thalamus (and our desired motor activity)
  54. Dopamine release
    • Occurs from the substantia nigra pars compacta (SNC)
    • This seems to be activated by the striosomal pathway from the striatum to the SNC
    • Dopamine is excitatory to D1 receptors (causes movement by exciting the direct pathway)
    • Dopamine is inhibitory to D2 receptors (also causes movement by inhibiting the indirect pathway)
    • It is believed that each complex motor movement has its own loops, so dopamine must be released on the correct ones