Lecture 14 - basal ganglia Flashcards
Basal ganglia
- Old system
- Important in motor control and behaviour
- Influence through thalamus
- Exerts influence on limbic systems
- Helps promote most appropriate choice and inhibit less appropriate
Structure and location
- Sits at top of spinal cord and brain stem
- Beneath cerebral cortex
- In center of head
- Collection of nuclei:
- ->Striatum (caudate, putamen, nucleus accumbens)
- ->Globus pallidus
- ->Subthalamic nucleus
- ->Substantia nigra
Basal ganglia loop with cortex:
-Start with cells in cortex = they have projections within different nuclei through the basal ganglia = output to thalamus and back up to cortex = generally into same area they received input from
Direct and indirect pathways
- Simplest circuit = direct pathway = goes from the striatum to the globus pallidus and then will output back up to the cortex
- Indirect pathway = doesn’t project straight down to globus pallidus (GPi = internal part of Globus pallidus) = GPe (external part of globus pallidus) then goes to STN and then GPi and back to thalamus and then whole thing outputs back up to cortex
- Both pathways provide us with balance of excitation vs inhibition
- Striatum gets input from cortex
- Substantia nigra = delivers dopamine into striatum = also connects onto different dopamine receptors that balance the two pathways = dopamine can be excitatory or inhibitory = in basal ganglia direct pathway receptors are excitatory and indirect pathway receptors are inhibitory
Neuronal loss in substantia nigra pars compacta (Sac): Parkisons
- With someone with Parkisons substantia nigra degrades = wouldn’t see normal black strip in brain dissection as most of cells will have died = insufficient dopamine being pumped into circuits in basal ganglia = consequences of behaviour
- Degeneration of dopamine neruons in substantia nigra
- Neurological/psychiatric disease caused by alteration in single neurochemical = dopamine
- Disordered signals sent to SMA: motor disorder
- Also influences limbic system: motivation and emotional disturbance
Weak direct pathway –> akinesia
- Low levels of dopamine would lead to slow and reduced movements
- Cell death of SNC reduced dompaine in striatum = not exciting D1 receptors = not driving direct pathway = not promoting movements = at the same time cell death in substantia nigra wont be inhibiting D2 receptors = have overactive indirect pathway = over suppressing actions
- This leads to akinesia = loss of movement
- Bradykinisea = slow movement
Direct pathway normal condition
-Motor cortex wants to perform task
Direct:
-Connected to striatum
-If it was to be promoted would activate direct pathway more
-Striatum inhibits GPi
-GPi inhibits thalamus
-If inhibiting something that’s inhibitory = its releasing inhibition and allowing thalamus to drive cortex = called disinhibition
Indirect
-For indirect pathway increasing inhibition onto GPe = decreases inhibition into STN = STN drives GPi = inhibitory suppresses the movement
-Have two double negatives = direct pathway will promote movement if appropriate and indirect will suppress movements that’s aren’t appropriate
Symptoms of Parkinson’s disease
3 cardinal symptoms:
- Absence/slowness of movement
- Stiffness or rigidity
- Tremor at red
Other symptoms:
- Gait and postural disturbances
- Depression
- Speech and swallowing problems
- Mental confusion
- Sleep disturbances
- Loss of sense of smell
Treatments for Parkinsons disease
Levodopa = L-DOPA: precursor for dopamine
- Dopamine cant cross blood-brain barrier so cant be administered directly but can give something that’s transformed into dopamine in brain
- Floods system with dopamine and elevates baseline levels across striatum and other brain regions
Neuro-surgery to rebalance connections between striatum and SMA:
- Thalamotomy
- Pallidotomy
- Deep brain stimulation = electric pulses overcome what cells in certain part of brain are doing = disrupt activity and prevent from transmitting info
Transplants:
- Bone marrow derived stem cells
- Embryonic stem cells
- Adult brain cells
Strong direct/weak indirect pathway –> hyperkinesia
-If have too much dopamine will overdrive direct pathway and underdrive indirect pathway (cant make movement)
-Alters excitation inhibition pathway
-You are over inhibiting Gpi and under inhibiting thalamus = too much output
-Under inhibiting GPE and over inhibiting STN
-Loss of striatal neurons of STN:
o Huntington’s
o Hemiballism
o Tourette’s
Huntington’s disease
-Genetic disease
-Onset after 40 years
-Degeneration of striatal neurons:
o Mutant Huntingtin protein
o Mitochondrial dysfunction
o Striatal energy demands (atypically high) not met
o Death via calcium ions overload
-Abnormal movements, chorea
-Mood disorders, cognitive problems
Multiple cortical-basal ganglia loops
Oculomotor system:
- When want to voluntarily make eye movements have same situation
- Have multiple motor plans and want to select most appropriate = comes through basal ganglia and down to superior colliculus
Executive and associative functions
-People with Parkinson’s respond differently to reward
Basal ganglia and eye movement
-•Basal ganglia acts as filter to add contextual info onto reflex control of eye movements – generalised inhibitory of the superior colliculus except for target of interest
Function of basal ganglia in context of surroundings
- Acts as filter/selector with broad cortical input and motor output
- Inputs: sensory-motor, limbic and cognitive
- Outputs: excitatory and inhibitory modulation of thalamus, modulation of cortical state
- Selection of appropriate behaviors
- Self-initiation of behaviors
Different learning systems
- Basal ganglia is selecting most rewarding actions
- Cortex = learning relationships
- Cerebellum = learning through error corrections
Reinforcement learning:
- Basal tanaglia selecting actions that maximise chance of future reward
- Punishment not error
- Reinforcement signal doesn’t directly provide information about how to improve performance
Instrumental/operant:
- Skinners box
- Initial exploratory behaviour
- Reinforcement to repeat action: exploit behaviour
- Balance exploration – exploitation
Rewards
- Natural reinforcers
- Rewards stimulate release of dopamine (DA)
- Substance of abuse increase DA release in nucleus accumbens (NAcc, ventrial striatum)
- Animals will work to self-adminster DA into NAcc
- Animals will work to self stimulate DA
