basal ganglia Flashcards
What’s special about the basal ganglia’s connections to the motor pathway?
- The basal ganglia receive no direct sensory input
- They do not directly generate a descending spinal control pathway
- They exert their modulation of motor performance by their massive interconnections with the motor cortices
- Input comes from cerebral cortex and output is directed to thalamus and from there back to cortex
Why are metabolic disturbances that mess with NT biosynthesis likely to manifest first in the basal ganglia?
- The basal ganglia are disproportionately active in NT biosynthesis
- 80% of the brains dopamine is in the basal ganglia, though they collectively are 0.5% of the total brain weight
In general, what is the major role of the basal ganglia?
• Motor program selection
What and where are the basal ganglia?
- Bilaterally paired masses of cells, gray matter, situated below the neocortex
- More or less surrounding the thalamus
What nuclei are the basal ganglia?
- 4 of them total
- Caudate + Putamen = striatum
- Globus pallidus
- Substantia nigra
- Subthalamic nucleus
What member of the basal ganglia is the prinicple output?
- To the thalamus
- Gpi
- Globus pallidus interior
Unilateral basal ganglia issues manifest how?
Contralateral motor issues.
*the basal ganglia on the left side of the brain interact with the left cerebral cortex
What is the major direct pathway in the basal ganglia?
• Input comes from the cortex
• The basal ganglia components nearest the cortex are input nuclei
○ Caudate and putamen
• From the striatum to the globus pallidus
• Information flows from the globus pallidus interna to the thalamus (VA and VL for motor portion, DM for cognitive and associattional)
• Globus pallidus interna is the major output nucleus
• The main circuit of the basal ganglia involves cortical input to the striatum, then to the globus pallidus interna, out to the thalamus and from there back to cortex
• Feedback loop to cortical function
What are the internal feedback loops in the basal ganglia?
• Those components not directly involved with cortical function (striatum, globus pallidus) are invloved mostly in internal feedback loops within the basal ganglia
• Substantia nigra receives a projection from striatum, projects back to caudate and putamen
• Back projection is made by neurons that contain and release dopamine to produce their effects
○ Pars compacta
• Cells in another protion fo the substantia nigra (pars reticulata) project to thalamus
○ Provide an additional output pathway for basal ganglia
• Subthalamic nucleus receives a projection from the external segment of the globus pallidus
• Projects back to both the external and internal segment of the globus pallidus
○ Pallidal feedback loop
What is the difference in response to a D1 and D2 receptor activation?
• Both are dopamine receptors
• Cortex projects to medium spiny neurons in the striatum
• Two populations of neurons: D1 and D2 expressing
• D1 is a Gs metabotropic receptor, which activates those neurons
• D2 is a Gi/o metabotropic receptor, inhibiting those neurons
• The D1 neurons in the striatum project directly to the Gpi
○ Direct pathway
• The D2 neurons in the striatum project to the Gpe, then to subthalamic nucleus (STN) then to Gpi
○ Indirect pathway
What is the indirect pathway thought to be doing?
- Inhibiting simultaneous competing motor programs
* The brain chooses a motor program over another one, so the other one is inhibited
What is the input and output of the Putamen?
• Putamen recieves input from the sensori-motor cortex
• Output projections are to a specific subsection of the globus pallidus
• Globus pallidus in turn projects to mostly VA thalamus (some VL)
• Thalamic nuclei project back to motor cortex
○ Mostly supplementary motor area = SMA
What is the input and output of the caudate?
• Receives input widely from frontal association cortex (frontal lobes)
• Sends information to it’s own subsection of the globus pallidus
• Globus pallidus transmits info to dorso-medial thalamus
• Dorso-medial thalamus projects to association cortex
○ Thus cognitive problems in basal ganglia disorders
The cerebellum projects to the VA thalamus. Does this system converge with the putamen circuit?
• Not really, there is separation between them
• A thalamic neuron either receives an EPSP from the dentate nucleus OR IPSP from globus pallidus
○ Never both
What is the nucleus accumbens?
- Caudal juncture between caudate and putamen is also called the nucleus accumbens
- Processes information from paleo-cortex (near olfactory cortex)
- Part of the limbic system
- Subserves emotional and drive-related aspects of behavior
In general, what is the difference in the systems between the caudate and the putamen?
• The caudate and putamen might be seen as parallel systems, receiving cortical input that is directly related to:
○ the motor system (putamen) or
○ cognitive/affective process (caudate)
• Individual neurons in putamen fire in synchrony with ongoing movements
• Localized stimulation of putamen produces discrete movements
• Few caudate neurons respond during movement, nor does stimulation produce movement
Follow the information from the VL thalamus and back.
- VL thalamus
- Supplementary motor area (cortex)
- Putamen
- Globus pallidus
- Substantia nigra
- VL thalamus
Follow the information from the DM thalamus only and back
• DM and VA thalamus together project to caudate in a different parallel pathway • DM thalamus only ○ DM thalamus ○ Cingulate anterior and medial orbito frontal cortex ○ Nucleus accumbens ○ Globus pallidus ○ Substantia nigra ○ DM thalamus
Follow the information from the VA and DM thalamus and back
• Could be one of two pathways • One ○ VA and DM thalamus ○ Dorsolateral prefrontal cortex ○ Caudate (DL) ○ Globus pallidus ○ Substantia nigra ○ VA and DM thalamus • Two ○ VA and DM thalamus ○ Lateral orbito frontal cortex ○ Caudate (VM) ○ Globus pallidus ○ Substantia nigra ○ VA and DM thalamus
What is the major principle of cellular information processing through the basal ganglia?
- DISINHIBTION
* Activation of a motor control signal is achieved by release from inhibiton, not by direct excitation
The direct pathway is mediated by disinhibtion of thalamic neurons. Explain this.
- Pallidal neurons have high frequency of resting AP (50 AP per second)
- Pallidal neurons are thus at rest inhibiting thalamic neurons, which is trying to activate a certain area of cortex
- Inhibition of pallidal neurons means there is a relative activaiton of thalamic neurons, increasing activation in that area of cortex
- Disinhibiton principle, and pallidal neurons are inhibited by activating striatal neurons (GABA)
Describe the three steps of information processing through the basal ganglia (cellular)
- Cells in layer V of cerebral cortex are output cells
- Send axons to the synapse in basal ganglia where they release glutamate to excite cells in caudate or putamen
- Cells in caudate or putamen send axons to globus pallidus where they release GABA to inhibit cells in GP
- Cells in GP send axons to thalamus where they release GABA to inhibit thalamic neurons
- THUS, GP is principle output, and thus principle output is inhibitory, preventing thalamic excitation of the cortex
What is going on in the substantia nigra?
- The striatal neurons that project to the substantia nigra produce inhibition there by release of GABA
- Substantia nigra sends dopaminergic axons back to the striatum
- DA release in striatum appears to be largely excitatory, and largely diffuse
- Think of it as essentially a “go ahead” signal for the general activity increase of the striatum
- No selection for specific neurons with SN DA release
- SN activation is not phase locked with a given motor response, but can happen before and after it
What does the subthalamic nucleus do?
• Receives an inhibitory input from external (lateral) globus pallidus and projects excitation back to the internal (medial) globus pallidus
• If you blow-out the subthalamic nucleus you disinhibit the thalamus
○ Thus showing that STN stimulates globus pallidus interna normally
