M3 L3 Flashcards
What is the basal ganglia role in the CNS? composed of what neurons
a muscle movement regulatory component of the central nervous system
- GABAergic neurons (inhibitory)
2 core missions of basal ganglia:
- operational learning
- action selection
What is operational learning (basal ganglia)
constantly leaning about moving muscles
What is action selection (basal ganglia)
sees many possibilities of different movements but only selects one
What is grouping in the basal ganglia?
multiple movement but to you it seems like 1 movement
- like u open the door it seems like 1 movement but its made up of 2 movements
Explain basal ganglia general circuitry
Possibilites come from cortex, the basal ganglia (casting director) sees the auditions and sends movements to the thalamus who sends output to the cortex and the superior colliculus for visual reflexes
what is the Skeletal Motor Loop
circuit involving the basal ganglia that helps control and refine body movements (except for eye movements).
what does the VLo do (Ventral Lateral Nucleus of the Thalamus) do?
Relays information between the basal ganglia and motor cortex.
What does it mean when the basal ganglia focuses activity?
the basal ganglia selects and enhances the motor signals needed for a specific movement while inhibiting competing or unnecessary movements.
- The cerebral cortex sends many movement-related signals.
The basal ganglia acts as a filter, amplifying the correct movement signal and suppressing others.
Explain the flow of motor control processing:
- How does everything get started?
* what are the 2 places info gets sent to?
1️⃣ Prefrontal Cortex (Planning & Decision-Making)
- Decides what movement to perform
- Sends input to Area 6 (PMA & SMA) for motor planning
AND also to basal ganglia
Explain the flow of motor control processing:
- What happens at the basal ganglia once it recieves input from the cortex?
2️⃣ Basal Ganglia Processes Movement Plan
BG filters, selects, and refines movement by inhibiting unnecessary actions.
Sends this refined signal to the Thalamus (VLo).
3️⃣ Thalamus (VLo) Sends Output to Area 6
The Thalamus (VLo) relays the “approved” movement back to Area 6 (PMA & SMA).
Explain the flow of motor control processing:
- What happens in area 6 once it receives input from the prefrontal cortex and basal ganglia? (step 1/2)
3️⃣ Area 6 (Motor Planning - PMA & SMA)
- PMA (Premotor Area): Plans movements based on external cues
- SMA (Supplementary Motor Area): Plans internally driven movements
- Sends instructions to Area 4 (Primary Motor Cortex - M1)
Explain the flow of motor control processing:
- What happens in area 4 once it receives input from area 6? (step 3)
* via which tract?
executes the movement by sending the planning signals (received fro area 6) commands to the spinal cord via the corticospinal tract
Explain the flow of motor control processing:
- What happens once the signals sent from area 4 down the corticospinal tract (step 4) reach their destination?
The signals will activate the lateral or ventromedial pathway (or sometimes both)
- Lateral Pathway:
Activated for voluntary, fine motor control of limbs & distal muscles (e.g., reaching, grabbing). - Ventromedial Pathway
Activated for postural control & balance using proximal & axial muscles (e.g., standing, walking).
How does area 4 know to activate the appropriate motor pathway (Lateral for voluntary movement, Ventromedial for stability)?
Inside the basal ganglia, it will receive input from the prefrontal cortex and decide to use either the direct pathway or indirect pathway based on the striatum (if it inhibits GPi or GPe).
2️⃣ Direct Pathway (Go!) → Excites M1 → Promotes voluntary movement via Lateral Pathway
3️⃣ Indirect Pathway (Stop!) → Inhibits M1 → Helps stabilize posture, working with Ventromedial Pathway
How does the direct pathway get turned on? brief
Cortex excites D1-receptor MSNs (Medium Spiny Neurons) in the Striatum.
These neurons inhibit GPi → GPi stops inhibiting the Thalamus → Movement happens.
How does the indirect pathway get turned on? brief
Cortex excites D2-receptor MSNs in the Striatum.
These neurons inhibit GPe → GPe stops inhibiting STN → STN excites GPi → GPi strongly inhibits the Thalamus → No movement.
do the ventromedial pathway and lateral pathway ever get turned on together? give ex
Example: Reaching for an object while standing
Lateral pathway moves your arm to grab the object.
Ventromedial pathway keeps your posture stable so you don’t fall over.
What is the basal ganglia made up of?
The striatum (caudate and putamen)
globus pallidus
substantia nigra
what is the target of cortical input to the basal ganglia
the striatum
What are the medium spiny neurons?
The cerebral cortex sends motor-related signals to the striatum. The striatum contains medium spiny neurons (MSNs), which process this input and relay signals to other parts of the basal ganglia.
Why do medium spiny neurons require a larger threshold to fire?
They have a low resting membrane potential so they need a bigger stimulation to fire
Where do medium spiny neurons receive input from?
from the cerebral cortex
How do medium spiny neurons help regulate movement?
by inhibiting other neurons in the basal ganglia circuit using GABA which is an inhibitory NT
Where does the caudate send information to?
The substantial nigra pars reticulate (SNr) and GPI
Where does the Putamen send info to?
both GPI and GPE
What are the 3 medium spiny neuron inputs?
- Cortical pyramidal neurons
- Dopaminergic (DA) neurons - which receive inout from SNr
- Local circuit neurons
What are local circuit neurons
* do they respond fast?
* where synapse?
interneurons found in the spinal cord and brain, responsible for modulating and coordinating movement by connecting different neurons within a local area.
- yes because they are close to the cell body so they’re fast and have more influence
- on cell body not dendrite
What do dopaminergic neurons do?
modulates synapses - specifically pyramidal neurons
why do Medium Spiny Neurons (MSNs) have very little spontaneous activity
because of their inward rectifier K⁺ (potassium) channels, which help maintain them in a hyperpolarized (inhibited) state at rest.
Inward rectifier K⁺ channels allow potassium to flow into the neuron at resting membrane potentials, keeping the neuron more negative inside and making it less likely to fire.
These channels close when the neuron becomes depolarized, allowing MSNs to become active only when they receive strong excitatory input (e.g., from the cortex).
Where does the caudate receive input from
– Receives cortical projections from multimodal association area and from frontal lobe eye movement area
– Neurons in the caudate fire prior to eye movement
Where does the putamen receive input from?
Receives inputs from the primary and secondary somatic sensory cortices in the parietal lobe, the visual cortices in the occipital and temporal lobe, the premotor and motor cortices from the frontal lobe, and the auditory association area from the temporal lobes
- In the putamen, neurons fire action potentials in anticipation of limb and trunk movement
Role of red nucleus in lateral pathway?
relay information from the cerebellum to the spinal cord via the rubrospinal tract, which influences motor neuron activity and muscle tone, particularly in flexor muscles
What are some projections from the basal ganglia?
- Caudate
- Putamen
- sub thalamic nucelus
- GPe
- GPi
Why is the striatum (caudate and putamen) not spontaneous?
because they rely on excitatory input from the cortex and thalamus to fire action potentials.
The striatum primarily receives excitatory (glutamatergic) input from the cortex. Without this input, the neurons in the caudate and putamen remain relatively silent.
Is the Caudate and Putamen Inhibitory? What do they inhibit?
* what do their MSNs release
Yes, the caudate and putamen are inhibitory because their MSNs release GABA, which is an inhibitory neurotransmitter.
When activated, they inhibit their target structures in the basal ganglia, mainly the globus pallidus internus (GPi) and substantia nigra pars reticulata (SNr).
What are the spontaneously active parts of the Basal Ganglia?
- Globus Pallidus Internus (GPi)
- Substantia Nigra Pars Reticulata (SNr)
- Globus Pallidus Externus (GPe)
- Subthalamic Nucleus (STN)
What does the STN do?
The STN is spontaneously active but excitatory (glutamatergic), meaning it continuously stimulates the GPi/SNr, reinforcing their inhibition of movement.
What does the GPe do to the STN?
The GPe is also spontaneously active and inhibits the subthalamic nucleus (STN) as part of the indirect pathway.
What do the Gpi and SNr
Both GPi and SNr are GABAergic (inhibitory) and fire continuously at rest, meaning they are always sending inhibitory signals to their targets (e.g., the thalamus and superior colliculus).
This constant inhibition prevents unwanted movements.
What are the Tonically Inhibited Parts of the Basal Ganglia?
Thalamus (VA/VL nuclei) → Motor Cortex
* The thalamus is constantly inhibited by the GPi/SNr, which prevents it from exciting the motor cortex and triggering movements.
Superior Colliculus (SC) → Eye Movements
* The superior colliculus is tonically inhibited by the SNr to prevent unwanted saccadic eye movements.
If the GP is active, what gets inhibited and what is this called?
The thalamic is inhibited and no info can get to the cortex
* tonic inhibition
- GP is inhibitory - if the striatum is inactive and doesn’t block her - then she attacks thalamus - no info sent
What happens to GPi if the striatum is active?
if striatum is active then she inhibits Gpis powers which means the thalamus is free to communicate
What happens to the Snr when the striatum is active? Inactive?
When striatum active - Snr itself is inhibited and cannot block superior colliculus - eye movement occurs (if u need to quickly look to see a car coming)
When striatum inactive - Snr is active and inhibits the superior colliculus - no eye movement (ur reading a book and ned to lock in)
How Is the Globus Pallidus Tonically Active?
because their neurons fire continuously at rest, even when no movement is happening.
so when the striatum is inactive, the GP will fire and do her thing
What are the Three Major Pathways of Basal Ganglia
- Direct pathway
- Indirect pathway
- Hyperdirect pathway
what is the direct pathway?
The direct pathway in the basal ganglia facilitates movement by reducing inhibition on the thalamus, allowing it to excite the motor cortex.
* EXCITATORY
What happens when the direct pathway is inactive?
When the direct pathway is inactive, the motor cortex receives less excitation from the thalamus.
if the direct pathway is inactive, this means the cerebral cortex is not strongly sending signals to the striatum, which means that the striatum is not active and doing its thing (needs to be stimulated to speak), which means that the Gpi is free to do her thing and inhibit the thalamus, which means no thalamus and cortex communication.
* overall inhibitory if inactive
What happens when the direct pathway is active?
When the direct pathway is active, the overall effect is excitatory, leading to movement.
if the direct pathway is active, this means the cerebral cortex is sending signals/stimulation to the striatum which means the striatum is active and able to do her thing and inhibit the Gpi which means the Gpi is blocked off and can’t inhibit the thalamus, so the thalamus speaks to the cortex to produce movement.
* overall excitatory
How does the striatum inhibit the Gpi?
through medium spiny neurons (MSNs), which are the main output neurons of the striatum.
How it works:
1) The cerebral cortex sends excitatory glutamatergic signals to the striatum. This activates medium spiny neurons (MSNs) in the striatum.
2) Medium spiny neurons (MSNs) in the striatum become active and release GABA (inhibitory neurotransmitter).
3) GABA inhibits the GPi, reducing its activity.
whats the indirect pathway?
The indirect pathway of the basal ganglia is the movement-suppressing pathway. It works opposite to the direct pathway by increasing inhibition of the thalamus, making movement less likely to occur.
- overall inhibitory
What happens if the indirect pathway is inactive?
If the indirect pathway is inactive, this means it is not suppressing movement, so movement is more likely to occur.
- if the indirect pathway is inactive, then the cerebral cortex is not stimulating the striatum. if the striatum isn’t stimulated, it doesn’t do its job to inhibit the Gpe. This means Gpe uses her power to inhibit STN and Gpi. If STN is inhibited, it can’t turn on Gpi. SO Gpi and STN are out which means the thalamus is free to speak with the cortex
- overall excitatory
What happens if the indirect pathway is active?
if the indirect pathway is active, this means that the cerebral cortex is stimulating the striatum which means it is actived and inhibiting the GPe. If the GPe is blocked off, then no one is inhibiting the STN which means the STN can then activate GPi. so now GPi can do her thing and block off the thalamus so not communication with thalamus. * Overall inhibitory
Why doesn’t the direct pathway have the STN?
In the direct pathway, we’re trying to reduce GPi activity so the thalamus can be free. We don’t need extra reinforcement—just turning off GPi is enough.
But in the indirect pathway, we want to maximize GPi activity so it fully suppresses movement. That’s why the STN is necessary—it gives GPi the extra push to do its job properly.
what is the hyperdirct pathway
The hyperdirect pathway is another route in the basal ganglia that acts as a fast brake on movement.
What happens when the Hyperdirect pathway is active?
When it is active, the cerebral cortex sends excitatory signals (glutamate) to the STN which means the STN is activated and then excites the GPi and then the GPi does her thing and sends GABA to turn off the thalamus. no communication w cortex no movement
- inhibitory
What happens when the Hyperdirect pathway is inactive?
when inactive, the cerebral cortex does not send signals to the STN. So the STN is never able to stimulate/excite the GPi which means the thalamus gets to communicate with the cortex.
- excitatory
Why is the hyperdirect pathway fast?
it is myelinated
How can the direct and indirect pathway work together?
direct: Facilitates movement by reducing inhibition of the thalamus
indirect: Suppresses unwanted movement by increasing inhibition of the thalamus
The Role of the Substantia Nigra?
- Cells of the SN form dopaminergic synapses
- SNc sends dopaminergic projections to the medium spiny neurons and acts on D1 and D2 receptors in the striatum (putamen & caudate) to modulate movement:
How does dopamine Modulate the Basal Ganglia?
- where are D1 and D2 receptors located?
Dopamine modulates the basal ganglia by adjusting the strength of the direct and indirect pathways through its action on D1 and D2 receptors in the striatum.
D1 and D2 Receptors are found on the medium spiny neurons (MSNs) in the striatum.
How do D1 receptors work?
D1 receptors increase the direct pathway when dopamine binds to D1 receptors, which are excitatory (Gs-coupled). This will increase cAMP which makes the medium spiny neurons in the striatum more active. This means the striatum (the MSNs really) will inhibit GPi more using GABA which means GPi can’t inhibit the thalamus. Thalamus speaks
- they are excitatory and result in more movement
How do D2 receptors work?
Dopamine binds to D2 receptors in the indirect pathway, which are inhibitory (Gi-coupled). This decreases cAMP, which reduces the striatum’s (MSNs put less GABA onto GPe) inhibition of GPe which means it uses it powers to inhibit the STN. If STN is inhibited, it can’t activate GPi and so GPi doesn’t inhibit the thalamus. Thalamus speaks
More cAMP = More ?
Less cAMP = Less ?
More cAMP = More excitability
* D1 neurons fire more, inhibiting GPi, allowing movement).
Less cAMP = Less excitability
* D2 neurons fire less, meaning they don’t strongly inhibit GPe, allowing GPe to suppress STN, reducing movement inhibition
What type of receptor are Dopamine receptors?
G protein coupled (metabotropic)
Whats hypokinesia?
* ex
Hypokinesia = Too little movement
Caused by: Overactive indirect pathway or underactive direct pathway (maybe too much inhibition of thalamus)
Ex: Parkinson’s disease (slow movements, rigidity, bradykinesia)
Whats hyperkinesia?
* Ex?
Hyperkinesia = Too much movement
Caused by: Overactive direct pathway or underactive indirect pathway (not enough thalamus inhibition)
Ex: Huntington’s disease, Tourette’s, dyskinesias (excess involuntary movement)
