7 - the basal ganglia Flashcards
what makes up the striatum?
putamen and caudate nucleus
what does the lentiform nucleus consist of?
putamen and globus pallidus
what separates the lentiform nucleus from the caudate and thalamus?
internal capsule
what can basal ganglia dysfunction cause?
movement disorders
- hypokinetic — too little movement eg. Parkinson’s
- hyperkinetic — too much movement, often abnormal involuntary movements
what is the input region of the basal ganglia?
striatum
what are the output regions of the basal ganglia?
globus pallidus internal and SNr
what is the main inhibitory neurotransmitter?
GABA
what are the main neurones in the striatum? describe them
medium spiny neurones — have a number of dendritic spines — vastly increases SA of neurones (lots of spines) allowing very fine tuning of signal in those neurones
= projection neurones
what neurotransmitter do medium spiny neurones use?
GABA +/- neuropeptides
what are the other type of neurone in the striatum?
interneurons
- modulate transmission withi the neural networks of the striatum
- there are GABAergic interneurons and cholinergic (large aspiny neurones)
what input does the striatum have?
- glutamatergic cortciostriatal pathway = input from all regions of cerebral cortex
- dopaminergic nigrostriatal pathway = from SNc
what pathway is damaged in parkinson’s?
nigrostriatal pathway
the interaction between what controls the level of activity within the striatum?
dopamine and glutamate
what kind of input is striatal input?
excitatory
what does the input from the whole cerebral cortex excite?
medium spiny neurons
DA regulates the activity of what?
medium spiny neuroens
where is DA produced?
SNc
what type of output is the output from medium spiny neurones?
inhibitory
glutamate from corticostrial neurone acts on what receptors?
ionotropic AMPAR and NMDAR receptors and metatrobic receptors mGluR on tip of spine of MSN
what interact to modulate synaptic strength?
dopamine and glutamate
what is key to long term potentiation?
dopamine — without dopamine the long-term enhancement of synaptic strength doesnt happen
dopamine alters level of activity in the neuron
what neuropeptide is in the direct pathway?
dynorphin substance P
what neuropeptide is used in the indirect pathway?
enkephalin
what receptors are used in the 2 pathways?
direct = D1
indirect = D2
the output of the basal ganglia is overall what?
inhibitory
how does D1 receptor enhance neuronal activity?
G protein coupled with GaS — activates adenylyl cyclase to convert ATP —> cAMP which allows the phosphorylation/activation of intracellular substances
how does the D2 receptor decrease neuronal activity?
coupled with Gi/o which inhibits adenylyl cyclase
direct vs indirect pathway functions
D1 = facilitation of desired movements
D2 = suppression of unwanted movements
how is dopamine released in resting conditions?
tonic dopamine release — low synaptic levels and extra synaptic levels — preferential D2R activation indirect pathway neuroens higher excitability at rest — action inhibiton “no-go” long term depression
indirect pathway overactive at rest
how is dopamine released in active movement?
phasic dopamine release — preferential D1R activation — motor initiation, enhances motor learning via long-term potentiation
what is the hyper direct pathway?
- from cortex to STN
- additional role in inhibitory control (enhance fine tuning of inhibition)
describe the dorso lateral to ventromedial in terms of function in the basal ganglia?
dorslolateal = more motor
ventromedial = more limbic
there are parallel loops in the basal ganglia subserving different functions such as what?
eye movements, limbic
what happens in parkinson’s to the 2 pathways?
- degeneration of SNc — loss of dopamine
- reduced D1 activation — reduced excitation
- reduced D2 activation — less (-) stimulation
there is the relative overactivity of what in parkinson’s? what is the result?
indirect pathway — reduced voluntary movement (bradykinesia), rigidity
why is there impaired motor learning in parkinson’s?
loss of long term potentiation as dopamine and glutamate don’t interact to facilitate motor learning
what is the subthalamus like in parkinson’s?
over active — lesion of STN alleviates experimental parkinsonism
what are cognitive disturbances in PD linked to?
- linked to changes in DA handling in basal ganglia loops
what is later dementia in PD related to?
cortical spread of Lewy body pathology
what impulsive behaviour are there in PD?
pathological gambling, hyper sexuality, compulsive eating
what is impulsive behaviour in PD linked to?
more severe dopaminergic deficit in ventral (limbic) striatal area
what is depression and anxiety in PD linked to?
monoamine cell loss in brainstem
what may improve depression in PD?
dopamine agonists
what are 2 choreiform disorders?
Huntingtons disease and levodopa-induced dyskinesia
what is chorea?
- rapid, multi focal irregular movements
- flitting between various muscle groups and body parts
- motor impersistence
pathophysiology of chorea
- imbalance between direct and indirect pathways
- relative overactivity of direct pathway — excessive movement
- underactivity of indirect pathway — no suppression of unwanted movements
pathophysiology of Huntingtons disease
- selective loss of D2 receptor-bearing indirect pathway neurones —> involuntary movements
- later loss of direct pathway neurons —> hypokinetic movement disorders
in Huntington’s disease there is loss of neuroens in what layers of the cortex?
layers V and VI
striatal pathology in Huntington’s disease
degeneration in caudate and indirect pathway D2 receptor-bearing medium spiny neurones
what neuropsychiatric disturbances are there in Huntington’s disease?
- anxiety, depression
- impulsivity, apathy
what is a potential treatment to Huntington’s disease?
cell transplantation — replace MSNs
what is enkephalin like in huntington’s disease?
rapidly reduced
describe tourette syndrome
- tic disorder
- usually onset age <20
- rapid, repetitive, stereotyped movements or vocalisations
- frequent comorbid neuropsychiatric illness
pathophysiology of tourette syndrome
- loss of cholinergic and GABAergic striatal interneurones — reduced basal ganglia inhibition
- increased striatal dopamine D2 receptor binding in patients with TS
how a tic disorders treated?
- anti dopaminergic therapy
- alpha receptor agonists - clonidine, helpful for ADHD symptoms too
- deep brain stimulation (GPm/thalamic DBS may help in some cases)
what is hemiballismus?
Hemiballismus is a hyperkinetic involuntary movement disorder characterized by intermittent, sudden, violent, involuntary, flinging, or ballistic high amplitude movements involving the ipsilateral arm and leg caused by dysfunction in the central nervous system of the contralateral side
thrashing movement contralaterally. caused by a subthalamic stroke
