Week 6: Basal Ganglia Structure and Function Flashcards
Does damage to the basal ganglia cause paralysis?
Damage of basal ganglia leads to inability to carryout smoothly executed skilled movements but not paralysis.
What are the principle structures of the basal ganglia?
- striatum:
dorsal: caudate nucleus and putamen
ventral: nucleus accumbens - globus pallidus
external segment (GPe)
internal segment (GPi) - substantia nigra
- subthalamus
Describe the divisions of the substantial nigra (SN).
- Pars compacta (SNpc)- pigmented dopamine neurons. Dorsal strip. pigment due to presence of neuromelanin
- Pars reticulata (SNpr)-non pigmented GABA neurons. Ventral strip.
Describe generally how the basal ganglia influences motor activity.
- influence on motor activity is indirect via conniptions with motor cortex. Ipsilateral.
- BG influences motor activity on contralateral side of the body (since motor cortex controls muscles on contralateral side).
Where does the predominant input to the BG come from? Where does it terminate?
From all parts of the cerebral cortex and terminates in the striatum. Excitatory pathway.
From striatum, goes to GP and SN
What is the output of the BG? Where does it go?
Output from GPi and SNpr neurons. Directed mainly to thalamus, ventral anterior (VA), and ventral lateral (VL) nuclei
-terminal output releases GABA and have tonic inhibitory effect on VA and VL
What are the afferents and efferents of the VA and VL nuclei of the thalamus?
- Afferents: from Basal ganglia, GPi and SNpr neurons
- thalamocortical efferents: project back to same areas of cortex where cortical input to BG originated (feedback back to the cortex)
- VA and VL use glutamate and are excitatory. Serves to increase activity of motor areas.
Describe the function of the direct pathway of the corticostriatal circuit.
Increases excitatory feedback from thalamus to cortex
Results in promotion of desired motor activities
What does the indirect pathway of the corticostriatal circuit result in?
- decreases excitatory feedback from the thalamus to cortex
- reduces cortical activation by thalamus
- reduces unwanted motor activities
Summarize the direct pathway of the corticostriatal circuit.
Striatum–>GPi/SNr–>Thalamus
- increases inhibition to GPi/SNr
- reduces inhibition to VA/VL nuclei of thalamus (disinhibition)
- facilitates cortical activation by VA/VL nuclei
- sustains wanted motor programs and desired motor activity
Summarize the indirect pathway of the corticostriatal circuit.
Striatum (inhibitory)–>GPe (inhibitory)–>STN (excitatory)–>GPi/SNr (inhibitory)–> thalamus
- increases STN stimulation of GPi/SNr
- increases inhibition of VA/VL nuclei
- reduces cortical facilitation by VA/VL (negative feedback that suppresses cortical activity)
- suppresses unwanted programs and undesired motor behavior
List the distinct areas of frontal cortex where corticostriatal circuits originate.
- Motor cortex: primary motor (M1), supplementary motor (SMA), premotor (PMA)
- Prefrontal cortex (executive/associative fxn): dorsolateral prefrontal (DLPFC), lateral orbitofrontal (LOFC)
- Oculomotor cortex (eye): frontal eye fields (FEF), supplementary frontal eye fields (SEF)
- Limbic cortex (emotion/motivation): ant. cingulate area (ACA), medial orbiofrontal cortex (MOFC)
Describe the motor circuit.
- from M1, SMA, PMA
- projects to putamen
- action selection, preparation for movement, sequencing of movements, control of movement parameters i.e. direction & velocity, involved in reinforcement learning
Describe the oculomotor circuit.
- from FEF and SEF
- projects to caudate
- involved in coordination of voluntary and saccadic eye movements
Describe the dorsolateral prefrontal circuit that originates from the prefrontal cortex.
- from DLPFC and projects to caudate
- involved in working memory, learning new info, planning ahead, temporal ordering of recent events
- can use Tower of London Test- how many moves to go from a a set of colored donuts to another sequence of colored donuts
- clinical syndromes: impaired reasoning, easily distracted, poor organization abilities
Describe the orbitofrontal circuit (OFC) that originates from the prefrontal cortex.
- From OFC and projects to caudate and nucleus accumbens
- personality, emotional stability, determining appropriate time, place, and strategy for socially elicited behaviors
- clinical syndrome: inappropriate social behavior, lack of judgement and empathy, don’t learn from mistakes
Describe the anterior cingulate circuit.
- from anterior cingulate cortex and projects to caudate and nucleus accumbens
- involved in motivated behavior
- clinical syndrome: lack of motivation and communication
What is the role of the basal ganglia in developing motor and social skills?
Integrates information from all 4 corticostriatal circuits.
- modulating synaptic strength to develop motor and cognitive behaviors.
- mediated by dopamine dependent changes in strength of striatal synapses
- important in learning to choose responses that lead to reward and not punishment
Describe the D1 family of dopamine receptors.
- D1 and D5 receptors
- postsynaptic only
- Responds to PEAK bursts of DA only
- expressed by DIRECT pathway striatal neurons
- elevate cAMP via G proteins, increases PKA signaling pathway
Describe the D2 family of dopamine receptors.
- D2, D3, D4 receptors
- can be postsynaptic and presynaptic
- responds to LOW tonic and PEAK levels of DA
- expressed by INDIRECT pathway striatal neurons
- decreases cAMP via Gi
What are normal dopamine levels in the D1 and D2 receptor systems?
- balance between D1 and D2
- tonic DA levels are low nano molar range, enough to inhibit indirect pathway but little effect on direct pathway
- results: positive feedback from thalamus to cortex bc partially removes inhibition to thalamus
How does dopamine modulate learning of a new motor skill by changing the strength of the corticostriatal synapse?
- DA neurons of the substantial nigra increase firing rate and release a burst of DA in assoc. w/ learning a new motor skill or behavior response to social situation
- as new task is learned, DA activity decreases as task transformed from goal directed behavior to reproducible habit
What does the change in dopamine activity measure?
- dopamine signal is a measure of the difference between what we expect
- rate of learning depends on estimated value of difference between the true reward and predicted reward
- represented in change in spike activity
What is the prediction error in reinforcement leaning models?
- positive prediction error: true reward>predicted value (things better than I thought)
- negative prediction error: true reward<predicted value (things worse than I thought)
- Zero prediction error: true reward=predicted
What happens when we are learning a new motor skill, and we are unexpectedly doing better than we anticipated?
- burst in DA activates D1 and direct pathway
- positive feedback to cortex and strengthens synaptic circuits
- D2 reduces activity in indirect pathway, removing inhibition on thalamus, allows direct pathway an even stronger influence
- As skill is learned, DA activity goes to 0 bc skill is learned
What is the etiology of parkinsons disease?
Two forms
- idiopathic or sporadic (unknown): most cases
- Familiar: 15% w/ family hx
- genetic linkage not absolute, more important for early onset
What is the effect of DA loss such as in Parkinson’s Disease on the corticostriatal motor loop?
- DA loss removes brake on indirect pathway–>greater inhibition of VA/VL and reduced cortical facilitation
- Over activation of indirect pathway due to decreased effect of DA on D2 receptors
What is the target of treatments of Parkinson’s Disease? What are some examples of therapies?
- all therapies try to down regulate the indirect pathway
1. L-DOPA therapy: first line treatment - stimulate D2 receptors and reduce inhibition on thalamus
2. DA agonists: focused on D2 receptors
3. Deep Brain stimulation: reduce inhibition by silencing STN and GPi output
