Neuroscience weeks 6-10

• In 2015, lifetime risk of being diagnosed with Parkinson's disease was 2.7%
• James Parkinson published first detailed description of Parkinson's disease


  1817
• People are born with a certain amount of dopamine cells
• Idiopathic Parkinson's disease


  Most Parkinson's disease has no known cause
• Genetic Parkinson's disease


  1. 15% of cases
• Other causes of Parkinson's disease


  • Vascular Parkinson's disease (damage to dopaminergic pathways following stroke)
  • Other neurodegenerative diseases
  • Neuroleptic drugs
• Symptoms of Parkinson's disease


  • Tremor
  • Rigidity
  • Bradykinesia
  • Postural instability
  • Gait disorder
  • Dysarthria
  • Mask face
  • Micrographia
• Loss of black pigment in Substantia nigra when cells die off is a key feature of Parkinson's disease
• Other neurological disorders


  • Addiction
  • Bruxism
  • Cerebral palsy
  • Foreign accent syndrome
  • Huntington's
  • OCD
  • Parkinson's
  • Tourette's
  • Stuttering
  • ADHD
• Motor behaviour


  Determined by balance of direct and indirect pathways in the basal ganglia
• Hypokinetic disorders


  Insufficient direct pathway output, excess indirect pathway output
• Hyperkinetic disorders


  Excess direct pathway output, insufficient indirect pathway output
• Parkinson's disease is a common neurodegenerative disorder, more common in the elderly
• Medium spiny neurons (MSNs)


  Receive excitatory input from cortex on dendritic spines, dopaminergic projections from substantia nigra synapse on dendritic shafts, facilitating direct pathway D1 MSNs and inhibiting indirect pathway D2 MSNs
• Loss of dopamine cells


  Causes akinesia (lack of movement) and bradykinesia (slow movement) in Parkinson's disease
• Direct pathway


  Cortex > Striatum > Globus Pallidus > Thalamus > Cortex
• Indirect pathway


  Cortex > Striatum > Globus Pallidus external > Subthalamic Nucleus > Globus Pallidus internal > Thalamus > Cortex
• D1 MSNs


  Excited by dopamine, part of direct pathway
• D2 MSNs


  Inhibited by dopamine, part of indirect pathway
• Substantia Nigra


  Provides massive dopaminergic input onto MSNs in striatum, excites D1 receptors, inhibits D2 receptors
• Direct pathway activation


  Increases cortical activity by releasing thalamus from inhibition, pro-movement
• Indirect pathway activation


  Decreases cortical activity due to increased inhibition on thalamus, anti-movement
• Disinhibition of direct pathway


  Occurs when cortical inhibition of striatum is released
• Direct pathway


  1. Runs directly through BG

  2. Quick, short

  3. Originates from D1 MSN in putamen
• Indirect pathway


  1. Takes detour via Subthalamic nucleus

  2. Originates from D2 MSN in putamen
• Direct pathway


  Increases cortical activity by releasing thalamus from inhibition
• Indirect pathway


  Decreases cortical activity due to increased inhibition on thalamus
• Disinhibition happens when tonic inhibition is 'released' by inhibitory input in the direct pathway when GPi's inhibited by input from Striatum
• Substantia Nigra


  2 parts: Pars Compacta (SNC) supplies dopamine, Pars Reticulata (SNR) is structurally and functionally like GPi
• Cortical input to the BG: Whole of cortex (not just primary motor + auditory cortex) projects to BG via monosynaptic excitatory connections
• Neuronal circuit


  1. Cortical output neurons send collaterals to BG

  2. Synapse onto medium spiny neurons in the striatum

  3. These project out of striatum to GPi or SNR

  4. Then to cortex
• Medium Spiny Neuron (MSN)


  • Makes up 95% of the cells in striatum
  • 12 types depending on dopamine receptor they express: D1 or D2 type
• Lexical decision procedure


  • Measures how quickly people classify stimuli as words or non-words
  • Analysis based on reaction times (error rate) for various conditions
• Common effect: Words that are more frequent in the lexicon are recognised faster
• Basal Ganglia


  • Interconnected subcortical nuclei that form series of segregated parallel loops with cerebral cortex
  • Individual basal ganglia loops are associated with different cortical areas and process signals separately for skeletomotor, oculomotor, associative and limbic systems
• Thalamus Pallidum Stratum Cattral


  • Input
• Cortical targets


  • Dorsolateral
  • Bocon pe prefrontal
  • Cortex
• Cortical targets


  1. Anterior caudate

  2. Globus pallidus Internal

  3. Substantia nigra, pars reticulata

  4. Mediodorsal + ventral

  5. Antenor nucle
• Parkinson's disease


  STN (subthalamic nucleus) is overactive, if STN activity is decreased then balance can be achieved again
• Cortical targets


  • Amygdala, hippocampus
  • Choral anterior cingulate
  • Temporal
  • Cortex