Basal Nuclei Flashcards
Describe the components of the basal nuclei:
Basal nuclei is a collection of nuclei embedded within the gray matter deep to the white matter of the cerebral cortex
Caudate nucleus - inhibitory output
Putamen - inhibitory output
Striatum - formed by the putamen and the caudate nucleus, overall output is inhibitory
Globus pallidus interna - inhibitory output
Globus pallidus externa - part of the indirect pathway, modulating movement, receives cortical inputs and processes motor planning
Subthalamic nucleus:
- receives afferents from both the cortex and other basal nuclei structures
- output is excitatory through glutaminergic neurons to the globus pallidus and substantia nigra
- plays a central role in basal nuclei connectivity and defines the nuclei’s rhythm
Substantia nigra:
- located in the rostral midbrain within the cerebral peduncle
- contains dopaminergic neurones which project to striatum
- excitatory D1 receptors
- inhibitory D2 receptors
Describe the direct pathway:
Facilitates movement and releases the thalamus from its tonic inhibition leading to more excitation of the cortex and in turn more cortical output
Pathway:
- cortex excites the striatum
- output from the striatum is inhibitory
- excitation of this causes an increase in inhibitory signals to the globus pallidus interna via the release of GABA
- GABA-ergic (inhibitory) signals from the striatum inhibits the globus pallidus interna (GPi)
- output from the globus pallidus interna is inhibitory so within the circuit at this point there is inhibition of the
inhibition (disinhibition) - this results in less inhibitory signals to the thalamus from the GPi
- the thalamus is released from inhibition resulting in more excitatory signals from the thalamus to the cortex.
Describe the indirect pathway:
Inhibits movement and it increases the inhibition going to the thalamus from the basal nuclei leading to less excitation of the cortex and in turn less cortical output
Pathway:
- glutamatergic excitatory input from cortex to putamen
- excitation of GABAergic inhibitory connections from putamen to globus pallidus externa (output from GPe is excitatory)
- less inhibition of GABAergic connections from GPe to subthalamic nucleus - more activity in STN
- results more excitation of the GPi
- GPi is inhibitory so excitation by the subthalamic nucleus causes more inhibitory signals to leave the GPi on route
to the thalamus - Therefore this results in less excitatory signals from the thalamus to the cortex
Describe the input to the basal nuclei and what they encode for:
Input to the basal nuclei is to the striatum and is from the cortex and subcortical areas
Putamen - receives afferent projections from the primary motor area, secondary motor area and the primary somatosensory area
Caudate nucleus - receives afferent projections from cortical association areas, frontal eye fields and limbic system
Input to the striatum enables the basal nuclei to integrate information from different cortical and subcortical regions
Basal nuclei encode for:
- Decision to move
* Direction of movement
* Amplitude of the movement
* Motor expression of emotions
What happens to the basal nuclei during Parkinson’s disease ?
Degeneration of dopaminergic neurones in the substantia nigra pars compacta (SNc) causes less dopamine to reach striatum
Effect on direct pathway:
- less excitation from SNc (substantia nigra pars compact) neurones to putamen
- less inhibition of Globus pallidus internus
- more tonic inhibition of ventral lateral thalamus
- GPi is more active → more inhibition of the thalamus
- Thalamus → less excitation to motor cortex
Effect on indirect pathway:
- less dopamine released on inhibitory D2 receptors so they’re less active
- more inhibition from striatum to GPe
- less inhibition from GPe to sub thalamic nucleus (STN)
- More excitation from STN to
GPi and substantia nigra pars reticula - More inhibition from GPi and
SNR to VL of thalamus - Increase excitation in indirect pathway
Loss of dopamine → Direct pathway underactive (less movement facilitation) & Indirect pathway overactive (excessive movement suppression)
Bradykinesia (slow movement) – Due to reduced cortical excitation from thalamic inhibition.
Rigidity – Increased muscle tone due to excessive GPi/SNr output suppressing movement.
Resting Tremor – Due to abnormal thalamocortical oscillations and compensatory hyperactivity in motor circuits.
Postural Instability – Impaired postural reflexes due to dysfunction in basal nuclei interactions with brainstem motor centers
Describe the output to the basal nuclei:
The output from the basal nuclei is from the globus pallidus interna to the thalamus and is via GABA-ergic neurons therefore
it is inhibitory
- Output nulcei of basal ganglia are Globus pallidus interna and Substantia nigra pars reticulata
- GPi and SNr project to ventral lateral and ventral anterior nuclei of thalamus which then communicates with the motor cortex
- output is tonic
- the GPi/SNr are always inhibiting the thalamus and brainstem
- To initiate movement, this inhibition must be reduced (called disinhibition)
What happens to the basal nuclei during Huntington’s disease ?
Early stage: affects indirect pathway
- degeneration of GABAergic neurons in the striatum → Reduced inhibition of GPe
- GPe becomes overactive, leading to excessive inhibition of STN
- STN cannot excite GPi/SNr, leading to reduced inhibition of the thalamus
- Thalamus becomes overactive, sending excessive excitatory signals to the motor cortex, causing hyperkinesia (involuntary movements)
Late stage:
- as neurodegeneration progresses, the direct pathway neurons also degenerate
- leads to increased GPi/SNr activity, causing excessive thalamic inhibition
Describe the role of the reciprocal connections of the substantia nigra and the subthalamic nucleus in the direct pathway:
The subthalamic nucleus provides tonic stimulation of the substantial nigra (influencing it) and there are reciprocal projections between both structures
Dopaminergic neurons project to the striatum where via D1 receptors excite inhibitory neurons which project to the GPi
Leads to decreased inhibition of the thalamus via the GPi
Substantia nigra enhances excitatory input from the cortex
Describe the role of the reciprocal connections of the substantia nigra and the subthalamic nucleus in the indirect pathway:
During the indirect pathway the striatum is influenced by projections from the substantia nigra
Dopaminergic neurons project
to the striatum where (via D2 receptors) inhibit excitatory cholinergic interneurons in the striatum
These interneurons in turn
project to inhibitory neurons going from the striatum to the GPe
The substantia counteracts the excitatory input from the cortex to the striatum
- The STN excites both the GPi and SNr.
- This increases their inhibitory output to the thalamus → suppresses movement
- The SNr sends inhibitory GABAergic projections back to the STN
- This acts as a negative feedback loop, limiting how much excitation the STN can provide to GPi/SNr
