Lec 33 Basal Ganglia Flashcards
What are main functions of basal ganglia?
- refine motor plan
- regulate action selection
- facilitate habit learning
- reward seeking
What comprises the striatum?
dorsal = caudate nucleus and putamen caudate = medial; putamen = lateral ventral = nucleus accumbens septi [NAS]
What separates caudate and putamen?
anterior limb of internal capsule
What are the major components of the basal ganglia system?
neo-striatum [dorsal and ventral] pallidum [external, internal, ventral] substantia nigra [compacta, reticulata] ventral tegmental area [VTA] subthalamic nuclei
What comprises the lenticular nucleus?
putamen and globus pallidus
What are the striatal cell bridges?
cells that cross the internal capsule to link the caudate to the putamen
What 2 structs does the posterior limb of internal capsule separate?
thalamus [medial]
lenticular nucleus [lateral]
What are medium spiny neurons [MSNs]? function?
striatal projection neurons
- cell bodies medium, dendrites have spines
- receive major input to BG system and are major output cells of striatum
- GABAergic
What are two types of medium spiny neurons?
- those that co-localize substance P and have D1-like DA receptors = stimulate cAMP –> mediate post-synaptic excitation
- those that co-localize enkephalin and have D2-like DA receptors = inhibit cAMP and post-synaptic activity
Where do MSNs project?
from striatum to globus pallidus and substantia nigra
What is nucleus accumbens septi?
major structure of ventral striatum
Where do major inputs to BG system arise from?
cerebral cortex = but especially frontal lobe! thalamus midbrain raphe nuclei locus coeruleus
For each of the 5 major inputs of BG system, which type of NT?
- cerebral cortex
- thalamus
- midbrain
- raphe nuclei
- locus coeruleus
- cerebral cortex == glutamate
- thalamus == glutamate
- midbrain == DA
- raphe nuclei == 5HT
- locus coeruleus = NE
What is globus pallidus?
lateral to internal capsule and medial to putamen
3 parts: external, internal, ventral
dorsal pallidum = external + internal
What structures make up the dorsal pallidum?
external and internal globus pallidus together = dorsal pallidum
Where is ventral pallidum located?
ventral to anterior commissure?
What type of output cells of GP?
all GABAergic = inhibitor
What is the subthalamic nucleus [STN]? type of output?
rostral/lateral to substantia nigra
output = glutamatergic [excitatory]
What is substantia nigra pars compacta?
GABAergic
often considered part of GPi
mainly same projections
source of DA neurons to striatum MSNs
What is unique projection of substantia nigra pars compacta?
superior colliculus = coordination eye, head, neck movement
Where do VTA DA neurons go?
to ventral striatum and limbic structures and frontal lobes
What are VTA DA neuron dysfunction associated with?
schizophrenia
psychoses
drug addiction
Which thalamic nuclei give input directly to striatum?
- ventral group [VA/VM; VL with Vop and Vim
- intralaminar nuclei [CM]
- medial dorsal nucleus [MD]
What is function of medial part of VPM?
taste VP-MMMMMM
Sensory-motor areas of cortex send input to which parts of striatum?
putamen
limbic-related input from cortex goes to which part of striatum?
ventromedial part
Where do GABA/substance P MSNs from striatum project?
to GPi and SNr
Where do GABA/enkephalin MSNs from striatum project?
to GPe
What is the basic cortex-striatal circuit?
cortex –> BG –> internal processing –> thalamus –> back to cortex
What happens to SN pars compacta and VTA in parkinsons?
pars compacta DA neurons degenerate
VTA does not
Where does ventral striatum receive inputs from? where does it project to?
input:
cortex
also: amygdala, hippocampal formation, most of 5HT input to striatum
output:
ventral pallidum
What is path of ventral striatum input/output?
cortex/amygdala/hippocampus/5HT –> ventral striatum –> ventral pallidum –> STN –> thalamus
What is the “nigrostriatal pathway”? importance?
DA projection from substantia nigra pars compacta to striatum
circuit of motor functions
- degenerates in parkinsons disease
Where do dopaminergic projects from VTA go? function?
to ventral striatum
circuit of emotions/motivation = mesolimbic reward path
Where does GPe primarily project?
to subthalamic nucleus
What is function of STN? inputs/outputs?
- receives GABAergic input from GPe and ventral pallidum
- receives glutamate input from cerebral cortex
- receives DA from SNpc
- projects glutamate to pallidum and substantia nigra
- target for deep brain stimulation
What are the instrinsic processing structures of basal ganglia?
- subthalamic nucleus [STN]
- SNpc
- VTA
- GPe
What separates the ventral striatum from the olfactory tubercle?
anterior commissure
What are the cell types that exist in striatum?
projection neurons = medium spiny neurons
2 kinds –> substance P [excitatory] and enkephalin localizing [inhibitory]; both GABA
interneurons = aspiny
- mostly GABAergic
Where does dorsal striatum project to?
globus pallidus [ext and in]
substantia nigra [reticulata and compacta]
Where does ventral striatum project to?
ventral pallidum
ventral tegmental area [VTA]
What is best way to localize GPe and Gpi on picture?
start at putamen = wide part of funnel
then travel medial; next structure = external; after that all other segments are part of internal
What are the 3 output structures of basal ganglia? their NT?
globus pallidus
substantia nigra pars reticulata
ventral pallidum
all GABAergic = inhibitor
What is function of each of the 3 BG outputs?
SNpr output = motor control of eye, head, neck
GPi output = motor control of rest of body
Ventral pallidum = limbic
Where do major outputs from BG system project?
Thalamus [VLa, VA, VM, MD, ILN]
Epithelamaus/midbrain/pons
- superior colliculus; pontine tegmentum
Via what routes do GPi/SNr output axons travel?
mainly = pyramidal motor system = lateral, fine motor control
- ansal lenticularis = loops around internal capsule
- lenticular fasciculus = goes through internal capsule
the 2 fiber bundles join together rostral to red nucleus to form fiber bundle called “thalamic fasiculus”
also = extrapyramidal = medial, postural control
- some GPi/SNr output goes to prontine + medullary reticular formation to influence reticulospinal tract
- SNpr projects to superior colliculus and influences tectospinal tract
Where do fibers in thalamic fasiculus come from?
- BG output via ansa lenticularis and lenticular fasciculus
- fibers from dentate nucleus of cerebellum
How does basal ganglia coordinate higher level behavioral planning
receives info from 5 parallel functional loops of cortical info that process different types of info
- relay info back to thalamus and send to modulate motor planning and execution
- info also looped back from thalamus to basal ganglia for further refinement
What type of NT in striatal, pallidal, and SNpr projections?
GABA = inhibitors
What type of NT in input [cortex, thalamic] to BG system?
excitatory = glutamate
What is direct pathway in BG system?
cerebral cortex –> excitatory MSNs with GABA/substanceP/D1 DA receptors –> inhibit GPi –> thus thalamus is disinhibited –> cortical excitation
DA activates this path by acting on D1 receptors
What is indirect pathway in BG system?
cerebral cortex glutamate –> inhibitor MSNs with GABA/enkephalin/D2 Da receptors –> inhibit GPe –> disinhibit STN –> increases glutamatergic excitation GPi –> thalamic inhibition –> decreased cortical excitation to suppress movement
DA inhibits this path by acting on D2 receptors
How does the STN coordinate activity of the direct/indirect BG paths?
“center-surround” system
= direct path promotes desired motor programs
= indirect suppresses all alternative plans one might pursue
How does dopamine affect balance of direct/indirect paths?
dopamine excites direct path and inhibits indirect path thus net excitatory effect on thalamus
How does parkinson’s disease affect BG paths?
parkinsons = loss of dopamine in nigrostriatal path so less DA input to direct/indirect paths
–> less excitement of direct + less inhibition of indirect –> net inhibition of thalamus
What is the hyperdirect path? function?
function = fast inhibitory surround
cortex –> excites MSNs in striatum –> project to GPe and SNpc –> as SNpc synalse on DA projection neurons and INHIBIT them
What are major symptoms of PD?
- tremor
- rigidity
- bradykinesia
what is pathology of PD along direct and indirect paths?
due to degeneration of substantia nigra pars compacta DA neurons
- -> loss of DAergic D1 –> disinhibition GPi –> excess inhibition thalamus
- -> loss of DAergic D2 inhibition –> overactivity GABA/Enk –> inhibition GPe –> disinhibition STN-GPi –> excess inhibition thalamus
What is pathology of huntingtons along direct and indirect path?
atrophy of dorsal striatum = loss of striatal MSNs
direct: decreased activity of GABA/subP neurons –> less disinhibition of thalamus
indirect: decreased activity of GAPA/Enk neurons –> less inhibition of thalamus
indirect is more affected than direct –> so balance swings toward more direct path = too much movement/excitation
What are main symptoms of huntingtons?
initial fidgetiness, restlessness
abrupt jerky abnormal movements
