1. Subcortical Neuroanatomy
Russell M. Bauer, Ph.D.
University of Florida
January 23, 2006

2. We will cover… Limbic System
Subcortical circuits involving basal ganglia
Thalamocortical circuitry relevant to cognition

3. Limbic System

4. Cingulate gyrus
Amygdala
Fornix
Septum
Mammillary body
Olfactory bulb

5. Two Limbic Circuits PRPH Lateral Medial (Papez) Anterior Thalamus
Dorsomedial Thalamus
Mamillothalamic Tract
Mammilary Bodies
Cingulate Gyrus
Orbitofrontal
Amygdalofugal pathways
Fornix
Uncus
Hippocampus
Amygdala
PRPH
Lateral
Medial (Papez)
Bauer, Grande, & Valenstein, 2003

8. Thalamus

9. “Thalamus” means “inner chamber” or “bedroom” in Greek
“Thalamus” means “inner chamber” or “bedroom” in Greek. Nearly all pathways that project to the cortex do so via synaptic relays in the thalamus. It is tempting to think of the thalamus as a “relay station”, but it also participates significantly in higher cortical function, as we will see. Thalamus is part of the diencephalon (anything ending in “…thalamus”, which includes the hypothalamus, the epithalmus (consisting of habenula, parts of pretectum, and pineal).
Medial nuclear group, lateral nuclear group, anterior nuclear group, internal medullary lamina, midline nuclei, and nucleus reticularis (thalamic reticular nucleus). ANOTHER WAY OF DIVIDING THALAMIC NUCLEI:
Relay Nuclei: Send and receive from cortex. For example, VPL, VPM participate in somatosensory function from spinal cord and cranial nerves. Visual is LGN, auditory is MGN. Motor pathways leaving the cerebellum and basal ganglia have specific thalamic relays in VL enroute to motor, premotor, and supplementary motor cortex. Limbic pathways served by anterior nuclear group. Pulvinar has widespread connections to large regions of parietal, temporal, and occipital association cortices. Diffuse relays of limbic inputs and other inputs involved in cognitive function, occur in the mediodorsal nucleus as well as midline and intralaminar thalamic nuclei. Intralaminar nuclei lie within the IML; they receive inputs from numerous pathways and project to the cortex (sometimes classified as “nonspecific”); main inputs and outputs are from basal ganglia. Two functional regions of intralaminar nuclie: caudal (including centromedian; mainly involved in basal ganglia circuitry) and rostral (basal ganglia and ascending RAS; important in alterness. The reticular nucleus is a thin sheet around the thalamus, just medial to the internal capsule. It does not project to the cortex (the only thalamic nucleus that has this claim to fame). It receives its input from thalamic nuclei and cortex, and then projects almost purely back to the thalamus. It is populated by inhibitory GABAergic neurons. It is involved in regulating thalamic activity.

10. Blumenfeld, 2002

11. Blumenfeld, 2002

12. Blumenfeld, 2002

13. Basal Ganglia

14. Blumenfeld, 2002
Lateral view

15. ventral striatum
Blumenfeld, 2002
Anterolateral view

16. Basal Ganglia Caudate + Putamen = Striatum
Putamen + Globus Pallidus = Lenticular nucleus
Subthalamic Nucleus
Substantia Nigra
Nucleus accumbens and ventral pallidum also considered part of BG

17. Integrated Subcortical Circuitry

19. General Organization of Frontal cortical-striatal-pallidal-thalamic-cortical loops

20. Blumenfeld, 2002

21. Blumenfeld, 2002

23. This slide illustrates the basic architecture of circuits through the basal ganglia as a way of understanding movement disorders. If you also understand that the same basic principles apply to cortical-subcortical relationships more generally, this provides a framework for understanding cognitive impairments in frontal lobe syndromes.
Two predominant pathways from input to output nuclei through the basal ganglia. The DIRECT PATHWAY (left hand side of right panel) travles from the striatum directly to the internal segment of the GP or the Sni pars reticulata. The net effect of cortical excitation through the direct pathway will be excitation of the thalamus (cortex excites striatum, such excitation provides increased inhibition of the Gpi/SNr, inhibiting its GABAergic inhibition of the thalamus). The INDIRECT PATHWAY goes first to the external segment of the GP and then to the subthalamic nucleus, finally reaching the internal segment of the GP and the Sni pars reticulata. The net effect of cortical excitation of the indirect pathway is inhibition of the thalamus (cortex excites striatum; this increased excitation increased striatal inhibition of the Gpe, which results in inhibited inhibition (e.g., excitation) of the STN. More STN excitation results in excitation of the internal segment of the GP/SNr, resulting in increased inhibition of the thalamus. Deep brain stimulation treatments of PD seek to take the STN off line, resulting in net inhibition of thalamocortical portions of the circuit.
Dopamine excites striatal neurons in the direct pathway, but inhibits striatal neurons in the indirect pathway (see side portions of upper portion of diagram around striatum). Therefore, loss of dopamine will result in net inhibition of the thalamus (in the direct pathway, it fails to excite striatum, resulting in less inhibition of Gpi/SNr, and therefore increased thalamic inhibition; in the indirect patheway, its loss results in less inhibition of the striatum, which results in an increased inhibitory effect on Gpe, which results in reduced inbhibition of STN, increased excitation of Gpi/SNR, and increased inhibition of the thalamus, a double whammy). This is one of the bases of Parkinson’s Disease.
In Huntington’s disease, the striatal neurons in the Caudate and Putamen degenerate; enkalphalin-containing striatal neurons of the indirect patheway are most severely affected. This causes removal of inhibition from the external segment of the GP, allowing it to inhibit the STN. Such inhibition results in decreased STN activation of Gpi/SNr, and therefore more excitation of thalamus, potentially resulting in a hyperkinetic movement disorder. In more advanced stages, both direct and indirect pathways become involved, resulting in a mixed HD/PD picture.
Blumenfeld, 2002

24. Dorsolateral (Prefrontal) Loop
Critical for executive function
Damage produces
Inflexibility
Planning
Problem-solving
Goal-directed behavior
Dorsolateral Critical for executive function Damage produces: Inflexibility Planning Problem-solving Goal-directed behavior

25. Orbitofrontal (Limbic) Loop
Involved in social and emotional functioning
Damage produces:
Disinhibition
Hyperactivity
Emotional lability
Aggressiveness
Reduce self-awareness

26. Phineas Gage
( , accident in 1848)

27. Phineas Gage’s lesion reconstructed
(H. Damasio and R. Frank, 1992)

28. Medial Frontal/Cingulate Loop
Important in behavioral activation
Damage results in
Akinetic mutism
Abulia
Impairments in spontaneous initiation of behavior

29. (Burruss, et. al., Radiology, 2000)

30. Motor Activation/Preparation
Heilman, Watson, & Valenstein, 2003

32. Selective Engagement
(Nadeau & Crosson, 1997)