week 8: basal ganglia

week 8: basal ganglia

1. cerebellum - error based learning, reducing error to make the circuit more accurate

   • old system - predates the neocortex. important connections to brainstem. influences motor and prefrontal areas via thalamus. influences the limbic system

2. basal ganglia - selecting which actions we want to make. collection of different structures. chose the movement which is the most rewarding. consists of several seperate nuclei - striatum (caudate, putamen, nucleus, accumbens), globus pallidus, subthalamic nucelues, substantia nigra

   • highly connected in middle of brain - helps us decide which reward we want for the future
   • direct and indirect pathway: direct = excitation, indirect = inhibition.
     • direct = CORTEX > STRIATIM > GPi > THALAMUS (feedback to cortex)
       • indirect = CORTEX > GPe > STN > GPi > THALAMUS (feedback to cortex)

3. motor programmes will inhibit onto the striatum + GPi = double disinhibition. This will drive up the command, end up excitation.

   • The indirect pathway = net inhibitory. Direct = will help us produce an action

4. SNc = substantia nigra pars compacta >> THE ROLE OF DOPAMINE. Different types of dopamine will react differently in the pathway

   • Thalamus = the gatekeeper to the cortex.
     • Indirect = double disinhibtion which will drive the GPi and inhibit the thalamus, therefore will be supressed.
   • D1- excitatory D2 - inhibitory

5. SNc - neuronal loss = losing dopamine in the circuit. No longer pushing dopamine into the striatum - PARKINSONS DISEASE.

   • Low levels of dopamine will lead to reduced movement. A weak direct pathway = Akinesia. Loss of projection up to the striatum. D1 excitatory lost = loss of drive in the direct pathway, lower D2 = not inhibting the indirect pathway
     • lower overall dopamine, reduced movement, failure to intiate. the choices coming from the cortex are not reaching a threshold to fulfill the movement
       • no drive in the direct + not reducing the influence of indirect = reduced drive (lower accelerating, higher braking)

6. Parkinsons three cardinal symptoms = absence or slowness of movement - AKINESIA = absence/ BRADYKINESIA = slow. stiffness or rigidity. tremor at rest

   • other major symptoms = gait (small steps, stooped posture) depression, speech, and swallowing problems, sleep distrubances, loss of sense of smell
     • treatment = Levodopa/L-Dopa = a precursor for dopamine. prompts the brain to synthesise more dopamine and flood the circuit to try and correct it.
       • Transplants - bone marrow derived from stem cells, embryonic stem cells, adult brain cells
         • deep brain stimulation - electrically stimulate the subthalamic nuclei to reduce the inhibitory effect. this regulates the overall circuit- can switch the stimulator on/off. most prominent effect on the tremor - steady stream of electricity to the brain
       • long term L-dopa tilts the balance of direct/indirect back towards direct. Hyperkinesia = too much drive, leads to excessive and involuntary movements
         • the more dopamine you take = changes the plasticity of the system. on/off cycle of being too rigid or unwanted movements. Becomes worse the longer you take the medication for- Levodopa induced dyskensia

7. Huntington's disease - genetic disease. degeneration of the striatum, too much drive of direct + not enough indirect

   • results in complex, involuntary movements. choreic movements/abnormal. dance like/sequenced as the basal ganglia is involved in the sequencing of choosing the most appropriate actions. degeneration of striatal neurons.

8. multiple cortical-based ganglia loops. motor = cortex/putamen/Snr/GPi(motor)- thalamus

   • Oculomotor - cortex - caudate nucleus - SNr/GPi (oculomotor) - thalamus
     • Executive/associate - cortex - caudate nucleus - SNr/GPi (associative) - thalamus
       • function = acts as a filter/ selector with broad cortical input and motor output. inputs = sensory-motor, limbic and cognitive. outputs = excitatory and inhibitory modulation of the thalamus, modulation of the cortical state
         • selection of appropriate behaviours. self-initiation of behaviours. if we make use of basal ganglia we can refine the multiple potential actions and chose the most appropriate
           • balancing between selection and inhibition, Mink 1996 - the indirect pathway provides a level of inhibtion and the direct is chosen for the programme of movement you want to execute.

9. basal ganglia and eye movement: the BG acts as a filter to add contextual information onto the reflex and control of eye movements, influences a low level circuit. reflex control of the eye> BG can give voluntary control

   • allows us to block out/ supress movements we dont want to make and we can chose to make a saccadic movement
     • basal ganglia = reinforcement learning. learns the association between rewards and punishment. instrumental conditioning/ operant
       • we perform an action, we either get a reward or not. if we do not, we update out actions. rewards = water/food/sex (natural reinforcers). dopamine. animals will work hard to self-stimulate dopamine.
         • secondary reinforcers = humans + money, dopamine neurons in the VTA respond to primary reinforcing stimuli. after training VTA cells become more responsive to conditioned secondary reinforcers. no longer responsive to primary. the timing of dopamine has changes to the beginning to help you get the expected reward

10. neural basis of reward = reward causes the release of dopamine, animal presses lever for intra-cortical electical stimualtion (ICSS) of dopamine neurons, more reliable ICSS sites include DA fibres.

    • mesolimbic - ventral tegmental area VTA >> NAcc.
      • mesocortical - VTA >> frontal cortex
        • Nigrostriatal - SNc >> striatum
    • ICSS causes dopamine release in NAcc (nucleus accumbens)/ striatum/ cortex. potentiates the glutamate transmission in the cortex. leads to strengthening of the cortical inputs to striatum. LTP of synapses. Reinforces behaviour over long term - can lead to habit forming

11. reward and punishment in parkinsons = parkinsons patients = less sensitive to reward when not on medication, more sensitive to punishment. When on medication = hypersensitive to reward and less sensitive to punsihment

    • motivation and sensitivity to reward - on dopamine = hyper-pupil dilation, without dopamine = flatter response and less sensitive to reward. not that they are physically unable to make the movements but unmotivated

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