BMS11004 WEEK 11 - THURSDAY Flashcards
basal ganglia, cerebellum, Parkinsons, Huntingtons, genes
give location of motor cortex
telencephalon
location of basal ganglia, and its subcomponents
forebrain
cuadate, putamen, globus pallidus, subthalamic nucleus
give location of lateral nucleus of thalamus
diencephalon
give location for substantia nigra
midbrain
give key components in initiation of movement
motor cortex (telencephalon)
basal ganglia (forebrain)
ventral lateral nucleus of thalamus (diencephalon)
substantia nigra (midbrain)
what is motor loop
motor cortex connecting to basal ganglia, feedbacks to premotor area via ventrolateral complex of thalamus (VLo) = indirect and direct pathway
what does VLo stand fo
ventrolateral complex of Thalamus
detail direct pathway for basal ganglia and motor loop in movement initiation
doesnt initiate cortical input, globus pallidus inhibits VLo
inputs from cortex converge on striatum, which inhibits GPi activity and releases VLo to active area 6 which then initiates movement
why is the direct pathway of basal ganglia for movement initiation set up as convergence of cortical input on striatum? what does this allow
integrating cortical input to trigger response allows rapidity of response, with “engine running” and inhibition of inhibition releasing “brake”
give an overview of role of indirect pathway of basal ganglia for initiating movement
module direct pathway, involves substantia nigra which acts via striatum to maintain balance between inhibiting/activating VLo
and GP external segment
detail indirect pathway for basal ganglia initiating movement
SN excitatory input stimulates VLo (by activating GPi inhibition via direct, and GPe inhibiting GPi in indirect which stops it inhibiting VLo)
GPe is inhibited by caudate putamen = VLo inhibitied
SN inhibition decreases GPe inhibition from caudate putamen
this allows GPi inhibition, so activates VLo
so SN balances VLo activation
in the whole GPi, GPe, VLo pathway, where does substantia nigra get info from
decision-making, emotive centres involved in risk/reward judgements
what does degeneration in GPi, GPe, VLo circuit cause
Parkinsons’/Huntington’s
what does GPe inhibition from caudate putamen cause
VLo inhibition
what does VLo activation from SN result from
direct= inhibit GPi
indirect= GPe inhibit GPi, which stops it inhibiting VLo
when GPi is inhibited, what does this allo
activates VLo
outline incidence of Pakinsons (family, sporadic)
10-15% genetic mutation
sporadic for 85-90%
define hypokinesia
paucity/insufficiency of movement
define bradykinesia
very slow movements
define akinesia
no movement
give symptoms of Parkinsons
hypok/brady/akinesia
ridigity, resting tremor (4-5Hz)
shuffling gait, bad balance, flexed posture
mask-like expression
mood disorder
lost smell sense
where are dopaminergic neurons lost in Parkinsons
Substantia Nigra
what is degeneration of dopaminergic neurons marked by?
presence of Lewy bodies- intracellular protein aggregate
how long does L-DOPA work as a treatment
5 years
how does L-DOPA work, and why not
boosts capacity of remaining dopaminergic neuron, but eventially not enough left
give side effects of L-DOPA
increased motor response fluctuation and drug related dyskinesias (erratic movements)
what does reduced dopaminergic input from substantia nigra to striatum cause for direct/indirect pathways (Parkinsons)
increased activity of indirect pathway
decreased activity of direct pathway
Parkinsons- reduced dopamine input from substantia nigra to striatum causes less/more inhibition of GPi, and what does this cause?
less inhibition of GPi = increase inhibitory activites meaning less activity in VLo and less motor cortex activation (causing hypokinesis)
what is a pallidotomy
removing GPi for parkinsons
this prevents VLo activity decreasing, causing less motor cortex activation
how does DBS treat Parkinson
inhibit GPi hyperactivity
what is commonness of huntingtons
3-7 per 100,000
give symptoms for early Huntingtons
hyperkinesia (overactivity)
dyskinesia/chorea (involuntary jerking, twitches)= erratic, discoord movements
give symptoms of late Huntingtons
akinesia, dystonia (muscle spasms)
dementia
personality disorder, psychosis
what causes Huntingtons
autosomal dominant gene mutations
in early huntingtons neuronal degeneration of indirect pathway, how does this cause hyperkinesis and chorea (including GPi, GPe and VLo)
initially in indirect pathway in striatum, reduced inputs to GPe so increased GPi inhibition, disinhibits VLo = inappropriate movement initiations
in later huntingtons neuronal degeneration of direct pathway, how does this cause akinesis (including GPi, GPe and VLo)
in striatal direct pathway GPe degenerate so releases Gpi and overinhibits VLo
compare occurance for PD, HD
PD idiopathic, sporadic, common and 10% inherited
HD rarely sporadic, rare, inherited
compare gene mutations in PD, HD
PD multiple gene mutations with either low and common or high and rare penetrance
HD only HTT mutation
explain how genetic mutations in HD, PD work
PD encodes proteins for protein degredation, mitochondiral function
HD, HTT protein unclear, perhaps in intracellular transport, protein aggregation
explain how basal ganglia act as funnel
collects info from prefrontal and motor cortex, decides what info to act on
connect cerebellum with motor learning
modulates upper motor neurons, no direct connections to spinal cord
needed for learning execution of planned, voluntary, multi-joint movements
how does muscle memories form
strengthen existing neural pathways
cerebellum form loop with motor cortex using spinal cord, vestibular system
project back to motor cortex via thalamus and detects, corrects differences between intended/actual movements
what does lesions to cerebellum cause
cerebellar ataxia- poorly integrated movement
dysynergia- lose ability to touch nose, coordinate multiple muscles and joints in sequence
