Striatum= main input side of BG system

GP & SNR= major output structures

In a resting state, BG suppress mvmt by inhibiting the motor thalamus & inhibiting the pre-motor cortex...generation of mvmt results from DISINHIBITION  of the thalamus

Disinhibition: one neuron inhibits the inhibition of another neuron resulting in activation/facilitation

direct= execution of desired movement

indirect= suppression of unwanted mvmt

Normal BG function depends on a balance b/t the 2 systems-BG disorders reflect an imbalance in the 2 circuits

MSN (SP/DYN/D1)-->GPi/SNR-->VA--> PMCTX

1. Arises from the MSNs (which contain subs. P & dynorphin and express D1 dopamine receptors)

2. MSNs sned their axons to the GPi and SNR where they inhibit neurons projecting to the thalamus

3. neurons in the GPi/SNR are inhibitiory to thalamic neurons projecting to the cortex & continuiously active, suppressing movement

4. Excitation of the MSNs by cortical inputs inhibits GPi/ SNR neurons resulting in the removal of inhibition (disinhibion) of thalamic neurons, allowing for mvmt to occur

MSN (ENK; D2)-->GPe-->STN-->GPi/SNR-->VA-->PMCTX

1. arises from MSNs (contain enkephalin & express D2 dopamine receptors)

2. MSNs send their axons to the GPe where they inhibit neurons projecting to the subthalamic nucleus

3. GP3 neurons are inhibitory to STN neurons

4. Neurons in the Subthalamic Nuclues are excitatory & send their axons to the GPi & SNR

5. Excitation of the indirect pathway MSNs inhibits GPe neurons resulting in "disinhibtion" of the STN

6. Disinhibtion of the STN increases their excitation of GPi/SNR leading to increased inhibtion in the thalamus, suppressing mvmt

dopamine is the key monaaminergic transmitter modulating BG re-entrant circuit

serotonin & noradrenaline also important

Dopaminergic axon terminal end on the dendrites of the MSNs in the striatum

dopamine relase in the striatum precedes mvmt

differnt than direct/indirect pathway

runs from striatum to the SNC

beleived to be the main activator of SNC

involved in the selection of initiation of a desired mvmt...current thinking is that this is achieved by dopamine acting differently on direct & indirect pathways via their differnt dopamine receptors

Dopamine excitatory: direct

Dopamine inhibitory: indirect

MSNs possessing D1 receptors (direct pathway to GPi/SNR)

Excitation of direct MSNs inhibits GPi/SNR casuing a reduction in their inhibition of the thalamus....

LEADING TO MOVEMENT

MSNs possessing D2 receptors

D2 containing MSNs from the indirect pathway to GPi & SNR

Inhibition of these indirect MSNs reduces inhibition of GPe neurons leading to increased inhibition of the STN

Reduced excitation by STN inputs to the GPi & SNR also leads to reduced inhibition of the thalamus

1. Parkinson's

2. Huntington's chorea

3. Hemiballismus (lesion in STN)

4. Progressive supranuclear palsy

5. Tourette Syndrome

6. Dystonias

Hypokinetic= absence (akinesia) or paucity & slowness (bradykinesia) of mvmt

Parkinson's= progressive loss of dopaminergic neurons in the SNC resulting in a substantial decrease in dopamine in the striatum (primary the PUTAMEN)

1. Loss of excitation of direct pathway MSNs resulting in increased inhibition (loss of disinhibition) of the thalamus by GPi & SNR

2. Loss of inhibitino of indirect pathway MSNs resulting in increased activity in the STN & increased inhibition of the thalamus by GPi & SNR

Increased thalamic inhibition reduceds motor cortex ativity leading to akinesia

GOAL: reducing inhibition of the thalamus

1. L-DOPA (dopamine precursor) to restore striatal dopamine levels

2. Lesion of the GPi- to reduce thalamic inhibition

3. High frequency stimulation of the STN-to "jam" its excitatory input to GPi/SNR

sudden, involuntary & purposeless jerking mvmts of the head, limbs & trunk

Pathological hallmark=degeneration of MSNs in the stiratum (mostly the CAUDATE) leading to loss of inhibition in the thalamus and increased activity in the motor cortex

Enkephalin

This loss of MSNs in the indirect pathway increases inhbition of the STN by GPe

Loss of excitatory input (from STN) input to GPi/SNR reduces the inhibition of thalamus