9/20 Basal Ganglia - Glendinning Flashcards Preview

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Flashcards in 9/20 Basal Ganglia - Glendinning Deck (40)

what are the basal ganglia?

tightly woven group of nuclei in cerebrum, diencephalon, midbrain


  1. caudate nucleus
  2. putamen
  3. globus pallidus
    • external segment
    • internal segment
  4. subthalamic nucleus
  5. substantia nigra


functions of basal ganglia

regulate frontal lobe, motor, limbic fx


*involved in several neurodegen, neuropsych disorders

  • motor disorders: movement disorders or extrapyramidal disorders
  • disorders of "habit"/neuropsych disorders: addiction, OCD, tics


basal ganglia loop fx

help facilitate motor cortical areas

  1. initiating movement
  2. sequencing movement
  3. automaticity

bc they play a role in gating proper initiation of movement, lesions to this area lead to incr/decr movement


overview: basal ganglia regulation of motor areas

basal ganglia...

  • inputs: premotor cortex, primary motor cortex
  • output: VA (ventral ant) and VL (ventral lat) thalamus → projects back up to cortical areas

DO NOT get sensory feedback

  • BG are not sensory structures (as opposed to cerebellum, which gets a lot of sensory input)


basal ganglia anatomy


  • caudate: head/body/tail, wraps around lateral wall of lateral ventricle
  • putamen: lateral to caudate nucleus
  • C/P are referred to as a unit bc they come from same embryological tissue, perform the same fx. would be same structure except that they are bisected by internal capsule

globus pallidus: medial to putamen

  • comprised of internal and external segments


*together, putamen + globus pallidus = lentiform nucleus


basal ganglia structures outside cerebrum

1. subthalamic nucleus (diencephalon)

2. substantia nigra (mesencephalong)

  • pars compacta neurons: deep, contain dopamine, which modulates BG fx
  • pars reticulata neurons: more superficial


dopamine modulates basal ganglia


3 pathways

  • associated fx
  • associated diseases

1. mesostriatal (nigrostriatal) pathway

  • fx: movement control
  • Parkinson's Disease

2. mesolimbic pathway

  • fx: reward pathway
  • schizophrenia
  • depression

3. mesocortical pathway

  • fx: working memory
  • schizophrenia (negative signs)


2 "connected" units within basal ganglia

even though separated somewhat in space, 

  • caudate and putamen
  • globus pallidus and substantia reticulata of substantia nigra

receive same inputs, perform same fx in response to those inputs


general flow of info through basal ganglia loops


normal excitation in basal ganglia loops

normal inhibition in basal ganglia loops

cortex → caudate/putamen  → VA/VL complex of thalamus → cortex

  • cortex then influences motor output


under normal circumstances,

  • thalamus is providing excitatory (Glu) stim → cortex
  • cortex is providing excitatory (Glu) stim → motor pathways
  • globus pallidus (GPi & SN reticulata) is providing tonic inhibition (GABA) stim → VA/VL thalamus 


excitation and disinhibition

GPi&SN_reticulata are inhibiting the thalamus, reducing level of excitatory signal to cortex/motor pathways



stimulate the GPi&SN_ret → increase inhibition → decrease movement

INHIBIT the GPi&SN_ret → decrease inhibition → increase movement

  • state known as disinhibition


excitation/inhibition of GPi


players & roles

subthalamic nucleusexcites GPi → inhibition of cortex/movement

  • lesions produce EXTRA movement (contralat hemiballismus)

striatum: inhibits GPi → excitation of cortex/movement (disinhibition)



basal ganglia "direct" pathway

facilitates movement via disinhibition


cortex sends excitatory signal to striatum → potentiates inhibitory signal to GPi → disinhibition of thalamus leads to increased movement


basal ganglia "indirect" pathway

inhibits movement


cortex sends excitatory signal to striatum →

striatum sends INHIBITORY signal to GPe →

GPe reduces its inhibitory signal to subthalamus →

  • GPe is typically inhibiting subthalamic
  • inhibition of GPe means LESS INHIBITION of subthalamic means MORE EXCITATION of GPi

subthalamic nucleus sends large excitatory signal to GPi →

GPi sends large inhibitory signal to thalamus 

→ inhibits movement


graphic summary of direct and indirect pathways


striatal dopamine receptors

dopamine receptors are located on medium spiny neurons

  • dendritic spines receive cortical inputs
  • base of spines receive dopaminergic inputs


medium spiny neurons project to 

  • globus pallidus
  • substantia nigra pars reticulata


dopamine receptors


families and characteristics

metabotropic receptors


D1 receptor family : EXCITATORY

  • incr cAMP
  • incr PIP2 hydrolysis
    • Ca mobilization
    • PKC activation

D2 receptor family : INHIBITORY

  • decr cAMP
  • incr K current
  • decr voltage-gated Ca current


role of dopamine in pathways

nigrostriatal dopamine facilitates "direct" pathway via D1 receptors (excitatory)

SNpc releases dopamine → hits DA1 receptor on striatum, excitation occurs

  • potentiates inhibitory signal to GPi → increases disinhibition → increases movement!


nigrostriatal dopamine inhibits "indirect" pathway via D2 receptors (inhibitory)

SNpc releases dopamine → hits DA2 receptor on striatum, inhibition occurs

  • inhibits inhibitory signal to GPe → potentiates inhibitory signal to subthalamus → dampens excitatory signal to GPi → dampened inhibitory signal from GPi → increased movement!


SUMMARY: dopamine is excitatory to direct pathway, inhibitory to indirect pathway → FACILITATES MOVEMENT in both cases!


role of Ach interneurons in striatum


pharma link

20% of striatal neurons contain ACh

  • preferentially excite INDIRECT PATHWAY → increase inhibition → decrease movement


implication: anticholinergics can have tx benefit in PD


general classification of movement disorders


3 types


  • too little movement
  • "negative sx"


  • too much movement
  • "positive sx"


  • abnormal movement
  • often drug induced by tx for psych/PD/etc

*all contralateral to lesion!


negative sx

akinesia: no movement (can't initiate)

bradykinesia: slow movements

decreased postural adjustments

hypokinesia: decr amplitude of movement

rigidity: "waxy", "lead pipe", "cogwheeling"


all best characterized by PD


positive sx

occur at rest


hemiballismus: spontaneous, invol movements

  • usually due to lacunar infarcts in subthalamic nucleus

chorea: almost cont rapid movements of face, tongue, limbs

  • most common: Huntington's disease

athetosis: slow, writing movements (hands, fingers)

  • can't maintain fixed position
  • often kids with cerebral hypoxia affecting BG



  • slower, twisting postures triggered by voluntary movements
  • role of BG is unclear: could be disorder of synaptic plasticity in BG
  • botulinum tox, electrical stim of GP has shown some benefit


most common: writer's cramp

most cases familial


hyperkinetic sx

tics: sudden, brief action preceded by an urge to perform it

  • Tourette's Syndrome is characterized by persistent motor and vocal tics

Restless Leg Syndrome (RLS): discomfort and urgent desire to move legs

  • usually during sleep, usually relieved by movement
  • familial pattern
  • might be related to DA neurotrans!
    • PET scans show decr D2 receptors


tardive dyskinesia

most commonlly in schizophrenia from antipsychotic or antiemetic drugs

  • prolonged use of DA antagonists → receptor hypersensitivity
  • can persist after discont of drugs
  • less of an issue with new anti-psychs

can cause any dyskinesia or combo




why do tremors happen?

cerebellum, thalamus, BG all have regular, oscillating rhythms

  • disruption in rhythm leads to tremor


Parkinson's (3-5 Hz at rest)

  • hands and arms common; can also include legs and mouth
  • begins unilaterally

essential tremor (5-8 Hz)

  • hands, arms, face, legs, trunk
  • usually bilat (cerebellar origin)


4 parallel basal ganglia pathways

general loop: cortex → striatum → pallidum → thalamus → back to cortex


1. motor → abnormal movement

2. oculomotor → abnormal eye movements

3. cognition (prefrontal) → poss relationship to psychosis and impaired exec fx

4. emotions (limbic) → addictive/impulsive behaviors


Huntington's Chorea


what is it


psych manifestations


autosomal dominant neuroderen disorder with cell loss in caudate and putamen, also frontal/temporal cortex

  • progressive → leads to akinetic/rigid form of disease


major sx:

  • chorea
  • dementia

psych manifestations

  • anxiety
  • mood changes
  • OCDs
  • impulsiveness
  • cognitive impairment
  • memory loss

tx: drugs that decrease dopamine


which pathway is affected in Huntington's?

cells in INDIRECT pathway affected

  • caudate and putamen die, which means...

inhibitory signal to GPe is dampened

→ inhibitory signal from GPe to subthalamus is amplified

→ excitatory signal from subthal to GPi is dampened

→ inhibitory signal from GPi to thalamus is dampened

→ movement is increased!


Parkinson Disease



risks/decr risk

neurodegen disease

progressive and chronic


risk factors

  • family history
  • older age
  • exposure to pesticides
  • migraine

risk diminishers

  • coffee
  • cig smoking


PD cardinal symptoms

begin unilaterally

1. bradykinesia: slowed movement

2. resting tremor: "pill rolling"

3. rigidity: lead pipe (through range of motion) OR cogwheeling (w reg jerking)

4. postural instability


other PD motor symptoms


  • masked facies (hypomimia)
  • Parkinson's gait: festinating
  • loss of automaticity (can't do two things at once, ex. stand, shake hands)
  • stooped posture
  • difficulty moving


lots of signs incl personality changes, psych sx


dx for Parkinson's disease

1. look at symptoms and history

  • bradykinesia + one other sx
    • resting tremor (pill rolling)
    • rigidity: lead pipe
  • postural instability is a later syndrome

2. rule out other causes

  • repeated stroke, multiple head injury, encephalitis, neuroleptic tx, exposure to toxins (Mn, CO, MPTP), cerebral tumor, hydroceph

3. look for supportive evidence

  • responsiveness to Levodopa
  • unilateral onset
  • other typical motor/non-motor signs


neuropatho of PD

death of cells in substantia nigra

  • degree of cell death correlated to severity of sx

neurons that do exist in substantia nigra have abnormal aggregations of proteins: Lewy bodies


Lewy bodies

spherical masses within cell body of PD substantia nigra cells containing abnormal aggregations of proteins

  • primarily alpha-synuclein: cytosol protein in many regions of brain, normal involved in vesicular transport


treatments for PD


what are they? problems?


  • dopamine agonists: L-DOPA (dopamine precursor, crosses bbb)
  • MAO inhibitors
  • anti-cholinergics

*problem with dopamine: "honeymoon period" at first, then on/off phenomena (dyskinesia, patho gambling - risk taking)


surgical lesions

  • thalamus: for young pt with unilat tremor, no rigidity/bradykinesia
  • globus pallidus (GPi): for tremor, rigidity


deep-brain stim

  • globus pallidus internus
  • subthalamic nucleus
  • thalamus


deep brain stimulation



theoretical goals


GPi or subthalamic nucleus



1. normalizes outputs

2. blocks APs


serious risks/adv effects as well: headache/pain, infection (10%), death


neuroprotective tx

lots of compounds for various reasons (pramipexole, CoQ10, creatine, green tea polyphenol, inosine, isradipine, cogane)


exercise is both neuroprotective and neurorestorative (after lesions)



"Parkinsonism Plus" syndromes

diseases that share characteristics of PD

characterized by:

  • lack of resting tremor
  • symmetrical sx
  • early postural instability
  • lack of response to dopamine

PD clinical diagnosis accuracy is approx 80%


progressive supranuclear palso

most common form of atypical Parkinsonism


  • neurodegenerative, affects multiple regions of rostral midbrain
    • red nucleus
    • superior colliculus
    • subthalamic nucleus
    • globus palliduson


sx begin after 50, progress more rapidly than PD


  • imbalance/falling/trunk rigidity
    • compare to PD: limb rigidity
  • swallowing changes
  • decr range of vertical eye movement (often first sign)
  • dementia

tx: SOME relief from dopaminergic tx


secondary Parkinsonism

caused by: stroke, tumor, infection, exposure to toxins (CO, Mn), drug exposure


ex. MPTP → frozen addicts 

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