Cerebellum and Basal Ganglia Flashcards
What brain structure carries the major outputs from the cerebellum?
Superior cerebellar peduncle
What structures carry the major inputs to the cerebellum?
Middle and inferior cerebellar peduncles
What is the connectivity of the flocculo-nodular lobe (archicerebellum)
aka: vestibulocerebellum. inputs from vestibular organs, outputs to vestibular nucleus in the brainstem
What is the connectivity of the vermal and paravermal corticies (paleocerebellum)?
aka: spinocerebellum. inputs from spinal afferents. Outputs to motor control nuclei (eg: red nucleus)
What is the connectivity of the corticocerebellum (neocerebellum)?
Located on the lateral aspects of cerebellum, these regions are interconnected with the CEREBRAL corticies
The vermal zone extends outputs through which nucleus?
fastigial nucleus –> control of axial musculature, posture and balance, integration of head and eye movement
The paravermal zone extends outputs through which nuclei?
interposed nuclei –> fine-tuned movement of limbs
What is the functional role of the flocculo-nodular lobe?
axial control and vestibular reflex (balance and eye movement)
What is the functional role of the neocerebellum?
projections via dentate nucleus –> higher-level coordination of movement
What is the output connectivity of the medial (vermis and vestibulocerebellum) regions of the deep cerebellar nuclei?
Vermis –> fastigial nucleus –> bilateral vestibular nucleus and pontine reticular formation –> lateral vestibulospinal tract and pontine reticulospinal tract (equilibrium and posture)
Vestibulocerebellum –> vestibular nucleus of the BRAIN
What is the output connectivity of the lateral (paravermis and neocerebellum) regions of the cerebellar deep nuclei?
Paravermis –> interposed nuclei –> contralateral red nucleus –> motor output through rubrospinal tract (lateral descending system)
Neocerebellum –> dentate nucleus –> contralateral VL thalamus –> M1 and pre-motor cortex
Where in the cerebellum do vestibular inputs go?
flocculo-nodular lobe (vestibulocerebellum)
Where in the cerebellum do spinal inputs go?
vermal and paravermal portions
What is the primary afferent input in the neocerebellum?
There is none! Contralateral cortex crosses and synapses in pontine nuclei –> lateral cerebellum
From what side do deficits arise upon cerebellar damage?
ipsilateral! (sensory/descending cerebellar inputs are uncrossed; corticocerebellar tracts decussate, therefore right cerebellum = right side of body = left cortex)
How does a large cerebellar lesion present?
ipsilateral loss of coordination, with spared sensation and muscle strength
What is the mnemonic for symptoms of cerebellar lesions?
HANDS Tremor! Hypotonia Ataxia (3D's: dysdiadochokinesia, decomposition of movement, dysmetria) Nystagmus Dysarthria Stance and gait problems Tremor
What is dysdiadochokinesia?
impairment of rapid, alternating movements
What is dysmetria?
inability to bring a limb to required/desired point in space (past-pointing)
Describe the cellular constituents of the uppermost layer of cerebellar cortex
parallel fibers, dendrites of Purkinje cells, Stellate cells, and basket cells
Describe the cellular constituents of the middle layer of cerebellar cortex
bodies of Purkinje cells
Describe the cellular constituents of the lowest layer of cerebellar cortex
Granule cells (processes extend superficially to become parallel fibers of top layer)
How does information flow through cerebellar cortex?
Climbing fibers and mossy fibers
What is the connectivity of climbing fibers?
Input from CONTRALATERAL inferior olivary nucleus. Output to Purkinje cells
What is the connectivity of mossy fibers?
Receives all input not carried by climbing fibers (mostly vestibular afferents and pontine nuclear cells). Output: granule cells –> parallel fibers –> purkinje cell excitation
What are the only cells in cerebellar cortex that do NOT make inhibitory connections with target neurons?
granule cells
What is the function of basket and stellate cells?
inhibition of Purkinje cells –> disinhibition of deep cerebellar neurons –> increased firing rate of deep cerebellar neurons
What is the function of golgi cells?
feedback inhibition of granule cells
Describe the climbing fiber activity when presented with intense, novel motor movement
climbing fibers activate purkinje cells –> numerous complex spikes in Purkinje activity
Describe the climbing fiber activity as the movement is learned
complex spikes from purkinje cells stop; replaced by simple spikes from mossy fibers, which fire at lower frequency
What structure senses discrepancies between planned and actual motor performance?
inferior olive
What is the significance of long term depression in the cerebellum
Occurs after climbing fiber activation when learning a new motor movement. Leads to decreased sensitivity to mossy fiber input (lower frequency of simple stroke)
Describe the cascade leading to LTD
Climbing fiber activation –> VSCC activation on Purkinje fibers –> Ca influx –> LTD
How are parallel fibers involved in motor learning?
Release glutamate –> AMPA binding (depolarization of Purkinje cells); metabotropic receptor binding (PKC activation)
Nearly all non-traumatic, metabolic disruption of motor control involves:
basal ganglia dysfunction
80% of the brain’s dopamine levels reside in:
the basal ganglia
what is the result of a unilateral basal ganglia deficit?
contralateral functional deficit
What is the major input source for basal ganglia
cerebral cortex
What is the major output source of the basal ganglia?
globus pallidus
From the globus pallidus, where does information about motor function travel?
VA and VL of the thalamus
From globus pallidus, where does cognitive and associational travel through?
DM thalamus
Are the basal ganglia inhibitory or excitatory?
Inhibitory
What are characteristic features of Parkinson’s disease?
Increased tone (simultaneous activation of flexors/extensors), bradykinesia, resting tremor
What is the probable cause of Parkinson’s disease?
Loss of dopamine neurons in substantia nigra –> reduced disinhibition on thalamus (bradykinesia), tremor
What is the treatment of Parkinson’s disease?
levodopa –> maximal dopamine output of remaining dopaminergic neurons –> diminuation of symptoms
Carbidopa blocks degradation of levodopa
What is hemiballismus?
Unilateral flailing movements of arms/legs
How would stroke in the subthalamic nucleus cause hemiballismus?
Stroke in PCA –> unilateral subthalamic nucleus damage –> reduced inhibitory outflow of globus pallidus –> disinhibited thalamus –> hemiballismus
What is the indication for use of deep brain stimulation in patients with Parkinson’s disease?
patients who still benefit from meds, but have debilitating on/off episodes
What is the mechanism of action of DBS in Parkinson’s disease?
DBS –> hyperpolarization of subthalamic nucleus or globus pallidus interna –> regained inhibition of globus pallidus –> disinhibition of thalamus –> attenuated bradykinesia, decreased tone
What is the genetic cause of Huntington’s disease?
autosomal dominant mutation of chromosome 4 –> increased CAG repeats
What is the average age of onset of Huntington’s disease?
Age 30-50
What would be considered early onset Huntington’s disease?
Before age 20
What basal ganglia areas are involved in Huntington’s disease
Striatum. Contains cholinergic and GABAergic neurons. Glutamate exicitotoxicity leads to cell death. Loss of striatal action on globus pallidus externa (indirect pathway) leads to Huntington’s chorea
Relationship between globus pallidus and subthalamic nucleus
Subthalamic nucleus: inhibitory input from GP; excitatory output to GP
Dopamine effect on striatum
excitation. Decrease DA –> decreased inhibition of GP –> increased inhibition of thalamus –> parkinson’s symptoms
Describe the indirect pathway of movement
motor cortex –> glutamate release to striatum –> GABA to globus pallidus externa –> disinhibition of subthalamic nucleus –> glutamate to globus pallidus interna –> GABA to thalamus –> inhibition of thalamic excitation to motor cortex –> decreased muscle movement
What is the result of indirect pathway dysfunction?
dyskinesias (eg: tardive dyskinesia, Huntington’s disease)
Describe the direct pathway of movement
motor cortex –> glutamate to striatum –> GABA to globus pallidus interna and substantia nigra pars reticulata –> disinhibition of thalamus –> glutamate to motor cortex –> increased movement
What is the result of dysfunction of direct pathway of movement?
decreased movement (eg: parkinson’s)
