NS219: Basal Ganglia Anatomy

NS219: Basal Ganglia Anatomy

Human basal ganglia anatomy

Analagous rodent basal ganglia nuclei

Basal ganglia circuits: the classical model of direct and indirect pathways + Glutamate + - GABA -

Gross anatomy of the striatum: gateway to the basal ganglia rodent Dorsomedial striatum: -enriched in PLTS interneurons -Increased calbinden immunoreactivity Striatal subregions: Dorsomedial (caudate) Dorsolateral (putamen) Ventral (nucleus accumbens) Dorsolateral striatum: -enriched in FS interneurons -increased CB1 immunoreactivity

Gross anatomy of the striatum: patch and matrix compartments Patch/Striosome: -substance P -mu-opioid receptor Matrix: -ChAT and AChE -somatostatin

Microanatomy of the striatum: cell types Projection neurons: MSN: medium spiny neuron (GABA) striatonigral projecting direct pathway striatopallidal projecting indirect pathway Interneurons: FS: fast-spiking interneuron (GABA) LTS: low-threshold spiking interneuron (GABA) LA: large aspiny neuron (ACh) 30 um Striatal afferents: (Intralaminar nuclei) (glutamate) (Layer II/III, V) (glutamate) Substantia nigra (dopamine)

Microanatomy of the striatum: striatal microcircuits Feedforward inhibition (mediated by fast-spiking interneurons) Lateral feedback inhibition (mediated by MSN collaterals)

External Globus Pallidus (): interneuron of the basal ganglia neurons have long dendrites (up to 1.5 mm) receive highly convergent striatal GABAergic inputs (70-80%) collateral inhibitory inputs (10-20%) excitatory inputs from (10%) 2 major cell types: PV+ neurons send axons to ENK+ neurons send axons to striatum and SNr form basket-like perisomatic GABAergic synapses

Microanatomy of the Subthalamic Nucleus () Subthalamic nucleus (): the only glutamatergic basal ganglia nucleus receives inhibitory inputs from the ( classical circuit) receives excitatory inputs from the sends axons to basal ganglia output nuclei (SNr, GPi/EP)

Microanatomy of basal ganglia output nuclei (SNr, GPi/EP) Substantia Nigra pars reticulata (SNr) intermingled DA neurons/dendrites from neighboring major excitatory inputs from, major inhibitory inputs from striatum (direct pathway MSNs) and project to thalamus Globus Pallidus pars interna (GPi)/Entopeduncular Nucleus (EP) major excitatory inputs from, major inhibitory inputs from striatum (direct pathway MSNs) and project to thalamus

The simplified classical model of basal ganglia circuit function Information encoded as firing rate Basal ganglia circuit is linear and unidirectional exerts opposing effects on direct and indirect pathway MSNs

Basal ganglia motor circuit: direct pathway Glutamate + GABA Direct pathway MSNs express: D1, M4 receptors, Sub. P, dynorphin

Basal ganglia motor circuit: direct pathway Glutamate + GABA

Basal ganglia motor circuit: direct pathway Glutamate + GABA

Basal ganglia motor circuit: direct pathway Glutamate + GABA

Basal ganglia motor circuit: direct pathway Glutamate + GABA

Basal ganglia motor circuit: indirect pathway Glutamate GABA - Indirect pathway MSNs express: D2 receptors, enkephalin

Basal ganglia motor circuit: indirect pathway Glutamate GABA -

Basal ganglia motor circuit: indirect pathway Glutamate GABA -

Basal ganglia motor circuit: indirect pathway Glutamate GABA -

Basal ganglia motor circuit: indirect pathway Glutamate GABA -

Basal ganglia motor circuit: indirect pathway Glutamate GABA -

Basal ganglia motor circuit: indirect pathway Glutamate GABA -

Summary of the classical model of basal ganglia circuit function Activation of the direct pathway facilitates/selects/initiates proper movements Activation of the indirect pathway inhibits/terminates unwanted movements normally inhibits the indirect pathway and potentiates the direct pathway

Anatomical revisions to the classical model + -

Functional revisions to the classical model Thalamic lesions do not cause bradykinesia lesions do not cause dyskinesia Patterns of activity may be more important than rate in regulating thalamocortical motor circuits