9/20 Basal Ganglia (Mandel) Flashcards
Be able to identify the individual structures in the basal ganglia
Caudate, putamen, globus pallidus (GPi and GPe) substantia nigra, pars reticulata (non pigmented), pars compacta (pigmented DA neurons), subthalamic nucleus, associated thalamic nuclei for indirect pathway.
Be able to describe the functions of the basal ganglia
Planning (direction, force, velocity, acceleration), preparing for action, inhibit unwanted movements, stopping. Voluntary movement (unclear), motor planning, initiation of movement, procedural learning, habit formation. No direct connection with spinal cord. Input from cortex. Output to cortex via thalamus which will transmit signals to spinal cord. Output to other motor nuclei via SNpr to superior colliculus and pendunculopontine n. motor pathway is debatable. BG and cerebellum may talk to each other. With lesions—starting and stopping are difficult. BG is usually engaged before movement.
Be able list the cell types of striatum and their relative abundance
Caudate and putamen=striatum. 95% medium spiny neurons. These are in the middle of the bell curve as far as size. GABAergic projection neurons, multiple branches and long axons. Major interneurons: Ach, NPY, parvalbumin. Colaterals from corticospinal glutamate synapse on spines of MSN, DA sits on neck of spine and modulates input from cortex. There are very few DA neurons, each synapse on 10-30,000 MSN, huge terminal and overlapping fields.
Be able to define compartmentalization of the striatum, where each part receives input
Caudate—recieves input from frontal eye fields and multimodal association cortices. Putamen—recieves input from primary and secondary motor and somatosensory cortices as well as visual and auditory association areas.
Be able to recognize the functional loops of the basal ganglia (body, oculomotor, prefrontal, and limbic)
- Body movement loop: Cortical input=motor, premotor, somatosensory cortex to striatum (putamen) to pallidum (lateral gp, internal) to thalamus (ventral lateral and ventral anterior nuclei)
- Oculomotor loop: Posterior parietal, prefrontal cortex to caudate (body) to GP internal, SN pars reticulata to mediodorsal and ventral anterior n.
- Prefrontal loop: Dorsolateral prefrontal cortex to anterior caudate to GP internal, SN pars reticulata to mediodorsal and ventral anterior nuclei.
- Limbic loop: Amygdala, hpc, orbitofrontal, anterior cingulate, temporal cortex to Ventral striatum to ventral pallidum to mediodorsal nucleus.
Pathways and connections of the basal ganglia (from lab): corticostriatal, nigrostriatal, striatonirgral, pallidopallidal, pallidothalamic, telamocortical
- Corticostriatal: cortex (no occipital) to corona radiata to putamen and caudate. Ipsi
- Nigrostriatal: SN pars compacta and reticulata to internal capsule to Compacta—caudate and putamen, retuculata—SC, VL, PPN. Ipsi
- Striatonigral: Caudate and putamen to direct/posterior limb IC to GPe/GPi/SNr. Ipsi
- Pallidopallidal: Gpe to direct to GPi. Ipsi.
- Pallidothalamic: GPi to Pallidothalamic projection to VL of thalamus. Ipsi.
- Talamocortial: VL of thalamus to posterior ICmotor/premotor cortex. Ipsi
Be able to define the functional 3 loops (pathways) within the motor BG: direct, indirect, hyper direct
Direct, indirect, hyperdirect. Dopamine inhibits the indirect pathway and stimulates the direct pathway, yielding a net bias that allows purposeful movement. The direct pathway is mediated by D1 and signals from cortex to putamen to GPi to thalamus to cortex, while the indirect pathway signals from putamen to GPe to STN to GPi to thalamus to cortex. DA from substantia infra acts on D2 receptors in the putamen to inhibit the indirect pathway which inhibits movement. Both direct and indirect pathway neurons in the putamen receive inputs from the nigrostriatal dopaminergic system and from cortical glutamatergic systems, process these inputs in the context of local cholinergic influences (ACh), and transmit a GABAergic output (not shown). Degeneration of dopaminergic neurons in the substantia nigra results in under stimulation of the direct (movement-enabling) pathway and under inhibition of the indirect (movement-inhibiting) pathway. The net result is a paucity of movement. Hyperdirect pathway—cortex to stn GPi-cortex. Newly identified large projection.
Be able to define disinhibition
The act of inhibiting inhibitory neurons so the net result is more firing. Example: Striatum neurons are getting glutamate from cortex. Fires and slows down GP. When GP is slowed down, VA/VL is disinhibited and fires more.
Be able to define the neurotransmitter systems and match them to their BG structures (corticostriatal, striatum, GPi, GPe, SNpr, subthalamic, nigrostriatal, MSNs)
Corticostriatal projections are glutamatergic (excitatory). Projections from caudate, putamen, GPi, GPe, and SNpr are GABAergic (inhibitory), subthalamic nucleus projections to GPi are glutamatergic, nigrostriatal projections are dopaminergic (excitatory or inhibitory depending on cell type). On striatal MSNs of direct pathway, DA is excitatory (D1) cAMP formation. MSNs of indirect DA inhibitory (D2) negatively coupled cAMP.
Be able to define the relationship of DA receptor subtypes to direct and indirect pathway
The direct pathway is mediated by D1 and signals from cortex to putamen to GPi to thalamus to cortex, while the indirect pathway signals from putamen to GPe to STN to GPi to thalamus to cortex. DA from substantia infra acts on D2 receptors in the putamen to inhibit the indirect pathway which inhibits movement. Both direct and indirect pathway neurons in the putamen receive inputs from the nigrostriatal dopaminergic system and from cortical glutamatergic systems, process these inputs in the context of local cholinergic influences (ACh), and transmit a GABAergic output (not shown).
• Describe the two types of input into the basal ganglia (da, cortical)
• Colaterals from corticospinal glutamate synapse on spines of MSN, DA sits on neck of spine and modulates input from cortex. There are very few DA neurons, each synapse on 10-30,000 MSN, huge terminal and overlapping fields.
