general loop structure
Cortex 2 BG 2 Thalamus 2 Cortex
Motor Loop
putamen of BG(step 2)
ventral caudate (C) and n. accumbens(step 2)
Orbitofrontal loop
nucleus accumbens (A) [and other BG nuclei](step 2)
Limbic loop:
caudate (C) [and other BG](step 2)
Oculomotor loop and Dorsolateral prefrontal Loop:
cortical neurons project to the ----- where glutamate is released.
cortical neurons project to the striatum where glutamate is released.
------ neurons in the substantia nigra, ------- project to the striatum
Dopaminergic neurons in the substantia nigra, pars compacta (SNc) project to the striatum
----- projections provide an important pathway for the modulation of the ----- and ------ pathways
nigrostriatal projections provide an important pathway for the modulation of the direct and indirect pathways
Di +
Direct pathway: facilitates motor (or cognitive) programs
D2, –
Indirect pathway: inhibits the execution of competing motor programs
Direct pathway by D1 +
GPi/ SNr
Indirect pathway
D2-
-->GPe
excited by dopamine and project to Gpi
(direct pathway)
Striatal neurons with D1 receptors are excited by
Striatal neurons with D1 receptors are excited by dopamine
(direct pathway)
Striatal neurons with D2 receptors are inhibited
Striatal neurons with D2 receptors are inhibited by dopamine
(indirect pathway)
project to Gpe
Striatal neurons with D2 receptors
dopaminergic projections
lost in Parkinson’s disease.
Increased Activity of the Direct Pathway Occurs in the Presence of
Direct Pathway
Glutamate and Dopamine
inc GABA in GPi/ SNr from striatum
decreased GABA release in the thalamus
Direct path
low GABA put in from (GPi/SNr) ; more Glu excreted from
thalamus
more glu neurons from thalamus
more glu neurons from motor cortex(CC)
Direct pathway
1.Dopamine released from SN leads to ----- of GABAergic neurons projecting from striatum to GPe.
Direct path
1.Dopamine released from SN leads to inhibition of GABAergic neurons projecting from striatum to GPe.
STN in direct pathwya
inc GABA
decrease firing of glutamatergic neurons projecting from STN to Gpi/ SNr
caused from 3. Increased GABA levels in STN
(Direct pathway)
decreased GABA release into thalamus
b/c of Reduced excitation of GPi /SNr-GABAergic neurons
tf in the direct path
STN has inc firing of glutamatergic neurons projecting from STN to Gpi/ SNr
STN has decrease firing of glutamatergic neurons projecting from STN to Gpi/ SNr
tf dopaminergic neurons only relased from
Snc
leff; more ;less
direct path
GABAergic neurons projecting from striatum to GPe.;
GPe neurons are disinhibited, leading to increased GABA levels in STN
Increased GABA levels in STN causes decrease firing of glutamatergic neurons projecting from STN to Gpi/ SNr
Glutamate released from corticostriatal fibers leads to --------activity of----- neurons projecting from striatum to GPe
indirect path
Glutamate released from corticostriatal fibers leads to increased activity of GABAergic neurons projecting from striatum to GPe
inhibition of GPe neurons
indirect path
occurs from Activation of GABAergic projections from striatum to GPe
disinhibition of glutamatergic neurons projecting from STN to Gpi/ SNr
indirect pathway
from Inhibition of GPe neurons
Gpi/SNr - GABAergic neurons excited
in indirect pathway3
inc GABA release in indirect pathway from
Striatum
and (GPi/SNr)
inhibited glutamatergic projections in indirect path
Thalamus (VA,VL)
and motor cortex
Increased Activity of the Indirect Pathway
presense Glutamate (absence of dopamine)
degeneration of dopaminergic neurons in SNc
Parkinson’s Disease
Dopamine inhibits
GABAergic neurons projecting from striatum to GPe
Dopamine excites
GABAergic neurons projecting from striatum to GPi
lesion of the subthalamic nucleus
resulting hyperkinesia
less Glu from STN and less GABA from GBI
hyperkinesia
more GABA from striatum and GPI/SNR
indirect pathway and hyperkinesia
Degeneration of neurons in caudate and putamen
(indirect pathway)
Huntington’s Disease/ Huntington’s Chorea
excess movement
GABA D2 not stimulated much
Huntington’s Chorea