1. The Basal Ganglia Maryann Martone, Ph. D. NEU257 2/22/2011

2. What are the basal ganglia? Depends on whom you’re talking to: –Anatomical: Non-cortical nuclei in the forebrain Caudate nucleus, putamen, nucleus accumbens, amygdala, globus pallidus –Functional: Richly interconnected set of nuclei in the forebrain and midbrain

3. System View Dorsal Striatum –Caudate nucleus –Putamen Ventral Striatum –Nucleus Accumbens –Olfactory Tubercle Globus Pallidus –Internal segment –External segment –Ventral pallidum Subthalamic nucleus Substantia nigra –Pars compacta –Pars reticulata Pedunculopontine nucleus** Other Terms: Archistriatum Paleostriatum Neostriatum Striatum

4. Where are the basal ganglia?

5. Caudate Nucleus C shaped structure (“tail”) Lateral wall of lateral ventricle Head, body and tail

6. claustrum Septum pellucidum Insular cortex Corpus callosum Caudate nucleus Putamen Nucleus accumbens Internal capsule External capsule Extreme capsule

7. Caudate nucleus Putamen Globus pallidus external Globus pallidus internal Ventral pallidum Anterior commissure Substantia innominata Internal capsule Lentiform nucleus**

8. Head, body, tail of caudate anterior and temporal horn of lateral ventricle Globus pallidus internal and external Internal capsule, anterior and posterior limbs

9. Caudate nucleus (body and tail) Putamen Globus pallidus Subthalamic nucleus Substantia nigra Pars compacta Pars reticulata

10. Subthalamic nucleus Substantia nigra Globus pallidus external Globus pallidus internal

11. Subthalamic nucleus Substantia nigra Ventral tegmental area

12. Rodent Brain

13. Globus pallidus and entopeduncular nucleus vs. Globus pallidus (external) and Globus pallidus (internal)

14. “Chemical Neuroanatomy” was very important in increasing our understanding of basal ganglia structures From Zhou et al., Nature Neuroscience, 4, 1224 - 1229 (2001) Use of different histochemical and immunocytochemical stains revealed more extensive striatal structures than previously thought Also caused revised views of basal ganglia structures in non- mammals and pointed to considerable homologies between birds, mammals and reptiles

15. Functions of the basal ganglia Extrapyramidal motor system Motor planning, sequencing and learning Activity of striatal neurons is not sufficiently explained by the stimuli presented or the movements performed, but depends on certain behavioral situations, certain conditions or particularly types of trials -sensory stimuli but only when the elicit movements -instruction cues (go-no go) -memory related cues -reward (especially ventral striatum) -self-initiated moves Basal ganglia distinguished from cerebellum by connections with limbic system

16. Diseases of the Basal Ganglia Huntington’s disease Chorea Psychiatric disturbances Dementia Parkinson’s: Akinesia Bradykinesia Resting tremor Rigidity

17. Cytoarchitecture Main neurotransmitter in basal ganglia is GABA 95% of neurons in neostriatum are medium spiny neurons (rodent) –Contain GABA –Principal neurons: project to globus pallidus and SNpr –Subpopulations are distinguished by peptides, neurotransmitter receptors and connections –Receive bulk of afferent input Several populations of interneurons –aspiny –ACh, GABA/parvalbumin, GABA/calretinin; GABA/NPY/NADPH/Somatost atin From Groves, Brain Res. 286: 109, 1983

18. The Neostriatal Mosaic Neostriatum divided into two compartments: patch (striosome) and matrix First described by Ann Graybiel in 1978 using AChE stain Not visible in Nissl stains (“hidden chemoarchitecture”) Define input/output architecture of neostriatum From Holt et al., 1997, JCN

19. Connections Afferents (striatum): –Cerebral cortex (entire cortex) –Thalamus (intralaminar and midline nuclei) –Amygdala (basolateral nucleus) –Raphe, substantia nigra pars compacta, VTA Efferents (Gpi, VP, SNpr) –Ventral tier nuclei of thalamus –Superior colliculus –Lateral habenular nucleus

20. All regions of cerebral cortex project to the basal ganglia, but output of basal ganglia is directed towards the frontal lobe, particularly pre-motor and supplementary motor cortex

21. Basic Circuit of Basal Ganglia Neostriatum Gpi/SNpr Cerebral Cortex VA/VL thalamus + + Gpe Subth + Connections of afferents and within basal ganglia are largely non-reciprocal

22. Some numbers (rat) 2.8 million neurons in caudoputamen 46,000 neurons in Gpe 3200 neurons in Gpi 26,000 neurons in SNpr –Oorschot (1996) –Significant convergence of input from striatum to target nuclei

23. Disinhibition From Chevalier and Deniau, TINS 13:277, 1990

24. Direct vs indirect pathways From Graybiel, A. Neural Networks, Am J Psychiatry 158:21, January 2001 Different populations of spiny neurons Enkephalin vs substance P D1 vs D2 receptors

25. Facilitation vs inhibition of movement Akinetic disorders: overactivity in the indirect pathway Dopamine increases activity in the direct pathway and decreases activity in the indirect pathway Loss of dopamine decreases activity in the direct pathway and increase activity in the indirect pathway Increased activity in the indirect pathway = increased activity in the direct pathway = increased inhibition on thalamus Hyperkinetic disorder: overactivity in the direct pathway Projections to the Gpe degenerate early in HD = removal of inhibition = increased activity of indirect pathway Increased activity of indirect pathway = increased inhibition of subthalamic nucleus = decreased excitatory drive on direct pathway = decreased inhibition on thalamus Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders.Trends Neurosci. 1989 Oct;12(10):366-75.

26. Hypokinetic Inhibit Releas e Hyperkinetic

27. Functional subdivisions Sensorimotor –Putamen + globus pallidus/SNpr –SNpc Association –Caudate nucleus + globus pallidus/SNpr –SNpc Limbic –Nucleus accumbens + ventral pallidum –VTA From Parent, TINS 13: 254, 1990

28. Neostriatal Mosaic and Input/Output Organization Most inputs to the neostriatum terminate in a patchy fashion (“matrisomes”) Input from a given cortical region terminates over an extended anterior-posterior extent Functionally related cortical areas project to the same patches Output neurons to a given efferent subregion are also arranged in patches Neurons in patches project to both Gpi/SNpr and GPe

29. From Graybiel et al., The basal ganglia and adaptive motor control, Science, 265: 1826, 1994 Cortex Neostriatum Gpi/SNpr “divergent-reconvergent processing”

30. Direct and Indirect Pathways