Pathways for emotions and memory II. Afferent input to the anterior thalamic nuclei from PF, temporal, hypothalamic areas and the BG in the rhesus ...

The anterior thalamic nuclei are a key link in pathways associated with emotions and memory. In the preceding study we found that one of the anterior nuclei, the anterior medial (AM), had particularly robust connections with specific medial prefrontal and orbitofrontal cortices and moderate connections with frontal polar cortices. The goal of this study was to use a direct approach to determine the sources of projections to the AM nucleus from all prefrontal cortices, as well as from temporal structures and the hypothalamic mammillary body, known for their role in distinct aspects of memory and emotion. We addressed this issue with targeted injections of retrograde fluorescent tracers in the AM nucleus to determine its sources of input. Projection neurons directed to the AM nucleus were found in the deep layers of most prefrontal cortices (layers V and VI), and were most densely distributed in medial areas 24, 32 and 25, orbitofrontal areas 13 and 25, and lateral areas 10 and 46. Most projection neurons were found in layer VI, though in medial prefrontal cortices and dorsal area 9 about a third were found in layer V, a significantly higher proportion than in lateral and orbitofrontal cortices. In the temporal lobe, projection neurons originated mostly from the hippocampal formation (ammonic field CA3 and subicular complex), and the amygdala (basolateral, lateral, and basomedial nuclei). In the hypothalamus, a significant number of neurons in the ipsilateral medial mammillary body projected to the AM nucleus, some of which were positive for calbindin (CB) or parvalbumin (PV), markers expressed, respectively, in “diffuse” and “specific” pathways in the thalamus [Adv. Neurol. 77 (1998a) 49]. As recipient of diverse signals, the AM nucleus is in a key position to link pathways associated with emotions, and may be an important interface for systems associated with retrieval of information from long-term memory in the process of solving problems within working memory. Finally, the internal segment of the globus pallidus (GPi) issued projections to AM, suggesting direct linkage with executive systems through the basal ganglia. The diverse connections of the AM nucleus may help explain the varied deficits in memory and emotions seen in neurodegenerative and psychiatric diseases affecting the anterior thalamic nuclei.



Fig. 12. Summary of the connections of the anterior medial nucleus with prefrontal and temporal structures, the hypothalamic mammillary body and the internal segment of the globus pallidus. The bi-directional arrows for connections of prefrontal cortices with AM summarize findings obtained from this and the preceding study, and are shown on the lateral (top, left), medial (top, right) and basal surfaces (bottom) of the cerebral hemisphere. The projections from temporal cortex, the amygdala, the hippocampus, the hypothalamic mammillary body, and the basal ganglia to AM are according to the findings from this study. Density variations of prefrontal projections to AM are depicted in pseudocolor denoting dense (red) to light (blue) projections, as reconstructed from serial coronal sections (this paper). cal outputs of the AM nucleus, the cingulate cortex (Gaffan and Harrison, 1989; Gaffan, 1993, 2002; Parker and Gaffan, 1997a,b; Gaffan et al., 2001). In humans, infarction of the AM nucleus dramatically impaired episodic and recognition memory resulting in anterograde amnesia (Parkin et al., 1994; Ghika-Schmid and Bogousslavsky, 2000; Nolan et al.,

Pathways for emotions and memory II. Afferent input to the anterior thalamic nuclei from prefrontal, temporal, hypothalamic areas and the basal ganglia in the rhesus monkey.
D. Xiao b, H. Barbas.
Thalamus & Related Systems 2 (2002) 33–48.

http://www.bu.edu/neural/Final/Publications/2002/Thalamus%20&%20Related%20Systems,%20Volume%202,%20Issue%201,%20December%202002,%20Pages%2033-48.PDF

Cortical Structure Predicts the Pattern of Corticocortical Connections

Cortical areas are linked through pathways which originate and terminate in specific layers. The factors underlying which layers are involved in specific connections are not well understood. Here we tested whether cortical structure can predict the pattern as well as the relative distribution of projection neurons and axonal terminals in cortical layers, studied with retrograde and anterograde tracers. We used the prefrontal cortices in the rhesus monkey as a model system because their laminar organization varies systematically, ranging from areas that have only three identifiable layers, to those that have six layers. We rated each prefrontal area based on the number and definition of its cortical layers (level 1, lowest; level 5, highest). The structural model accurately predicted the laminar pattern of connections in ~80% of the cases. Thus, projection neurons from a higher-level cortex originated mostly in the upper layers and their axons terminated predominantly in the deep layers (4–6) of a lower-level cortex. Conversely, most projection neurons from a lower-level area originated in the deep layers and their axons terminated predominantly in the upper layers (1–3) of a higher-level area. In addition, the structural model accurately predicted that the proportion of projection neurons or axonal terminals in the upper to the deep layers would vary as a function of the number of levels between the connected cortices. The power of this structural model lies in its potential to predict patterns of connections in the human cortex, where invasive procedures are precluded.



Figure 11. Summary of the pattern of connections predicted by the structural model. (A) Connections between cortices with large differences in laminar definition show a readily distinguishable pattern. (Top) Projection neurons originate predominantly in the deep layers of cortices with low laminar definition and their axons terminate predominantly in the upper layers of cortices with high laminar definition. (Bottom) The opposite pattern is seen for the reciprocal connections. (B) A less extreme version of the above pattern is predicted in the interconnections of cortices with moderate differences in laminar definition. (Top) Most neurons (though fewer than in A) originate in the deep layers of the cortex with comparatively lower laminar definition, and their axons terminate primarily in the upper layers of the cortex with comparatively higher laminar definition. (Bottom) The opposite pattern is predicted for the reciprocal connections.

Cortical Structure Predicts the Pattern of Corticocortical Connections.
H. Barbas and N. Rempel-Clower.
Cerebral Cortex Oct/Nov 1997;7:635–646; 1047–3211/97/

http://www.bu.edu/neural/Final/Publications/1997/Cereb%20Cortex.%201997%20Oct-Nov.%207(7)635-46.pdf

Circuits through prefrontal cortex, basal ganglia, and ventral anterior nucleus map pathways beyond motor control

The ventral anterior (VA) nucleus of the thalamus is connected with prefrontal and premotor cortices and with the basal ganglia. Although classically associated with motor functions, recent evidence implicates the basal ganglia in cognition and emotion as well. Here, we used two complementary approaches to investigate whether the VA is a key link for pathways underlying cognitive and emotional processes through prefrontal cortices and the basal ganglia. After application of bidirectional tracers in functionally distinct lateral, medial, and orbitofrontal cortices, we found that projection neurons were embedded in much larger patches of axonal terminations found in the magnocellular part of VA (VAmc), and in the principal part of VA. Connections from medial prefrontal cortices occupied the dorsomedial and ventromedial VA, and orbitofrontal connections were found in ventrolateral VAmc. Moreover, about half of all projection neurons in orbitofrontal areas directed to the VA or VAmc were positive for calbindin but not parvalbumin, even though comparable populations of neurons were positive for each marker in the VA.We then applied tracers in VA and investigated simultaneously projections from all prefrontal areas, the internal segment of the globus pallidus (GPi), the substantia nigra reticulata (SNr), and the thalamic reticular nucleus. Projection neurons were most densely distributed in anterior cingulate areas 24 and 32, and dorsolateral areas 9 and 8, innervating the same VA sites that received projections from a large part of GPi and dorsal SNr. Nearly as many projection neurons originated from cortical layer V as from layer VI. There is evidence that cortical layer VI neurons innervate thalamic neurons that project focally to the middle cortical layers, whereas layer V neurons synapse with thalamic neurons projecting widely to cortical layer I. Projections from layer V to the VA may facilitate cortical recruitment for executive functions within a cognitive context through lateral prefrontal areas, and autonomic responses within an emotional context through anterior cingulate areas.

Circuits through prefrontal cortex, basal ganglia, and ventral anterior nucleus map pathways beyond motor control.
Danqing Xiao, Helen Barbas.
Thalamus & Related Systems 2 (2004) 325–343.

http://www.bu.edu/neural/Final/Publications/2004/Thalamus%20&%20Related%20Systems,%20Volume%202,%20Issue%204,%20July%202004,%20Pages%20325-343.pdf