Thalamus-prefrontal cortex parallel loops

A recent paper by Zikepoulos and Barbas (citation below) traces the detailed anatomy of connections between the prefrontal cortex and the ventral anterior thalamus. Here is the abstract:

Pathways linking the thalamus and cortex mediate our daily shifts from states of attention to quiet rest, or sleep, yet little is known about their architecture in high-order neural systems associated with cognition, emotion and action. We provide novel evidence for neurochemical and synaptic specificity of two complementary circuits linking one such system, the prefrontal cortex with the ventral anterior thalamic nucleus in primates. One circuit originated from the neurochemical group of parvalbumin-positive thalamic neurons and projected focally through large terminals to the middle cortical layers, resembling ‘drivers’ in sensory pathways. Parvalbumin thalamic neurons, in turn, were innervated by small ‘modulatory’ type cortical terminals, forming asymmetric (presumed excitatory) synapses at thalamic sites enriched with the specialized metabotropic glutamate receptors. A second circuit had a complementary organization: it originated from the neurochemical group of calbindin-positive thalamic neurons and terminated through small ‘modulatory’ terminals over long distances in the superficial prefrontal layers. Calbindin thalamic neurons, in turn, were innervated by prefrontal axons through small and large terminals that formed asymmetric synapses preferentially at sites with ionotropic glutamate receptors, consistent with a driving pathway. The largely parallel thalamo-cortical pathways terminated among distinct and laminar-specific neurochemical classes of inhibitory neurons that differ markedly in inhibitory control. The balance of activation of these parallel circuits that link a high-order association cortex with the thalamus may allow shifts to different states of consciousness, in processes that are disrupted in psychiatric diseases.

It is interesting that these loops are similar to sensory loops, but connect to an area of the cortex that is not primarily sensory. The prefrontal cortex is active in executive functions: thought, planning, emotional control, working memory, goals, decisions, patterns of activity, levels of awareness. The thalamus is guiding/driving these cortical functions and they, in turn, are guiding/driving the ventral thalamus. Of course, both these areas are also connected to other centers – these loops are not isolated. The prefrontal cortex is strongly connected to other parts of the cortex and the ventral thalamus is strongly connected to the basal ganglia. The authors point out how important these paired loops are in understand a number of diseases including schizophrenia.

Here is the paper’s illustration of the loops and an explanation of the diagram:





Figure 11. Schematic diagram summarizing the features of reciprocal driving and modulatory pathways linking the prefrontal cortex with the ventral anterior nucleus. The thickness of the lines, connecting thalamus and cortex, indicates the strength of the projection. The size of the dot indicates the size of the terminals. Solid lines (d1 and d2) represent driving projections, and dotted lines (m1 and m2) represent modulatory projections. Green represents PV+ labeling and red CB+ labeling. There were two parallel reciprocal circuits between the prefrontal cortex and ventral anterior nucleus. One originated mostly from PV+ thalamic projection neurons (green, bottom panels), and terminated focally as large boutons in the middle-deep layers (IIIb–VI, center blue panels) of the prefrontal cortex (d1). In turn, presumed layer VI neurons projected (m1) and terminated as numerous small boutons that formed synapses mainly with PV+ thalamic projection neurons (green, bottom panels), enriched with metabotropic receptors (mGluR1a, purple). The other circuit originated from CB+ thalamic neurons and sent widespread projections (m2) mainly to the superficial layers (I–IIIa) of the prefrontal cortex (grey), and terminated mostly as small terminals traversing the borders of neighboring regions and in association with the apical dendrites of neighboring layer V neurons. In turn, a prefrontal pathway (d2) established synapses through many small and fewer large boutons mainly on CB+ thalamic projection neurons (red) with ionotropic receptors (NR1, white). The PV+ thalamo-cortical pathway (d1) terminated mostly in the middle-deep layers, which were also rich with PV+ local inhibitory neurons (green spheres). In contrast, the CB+ thalamo-cortical pathway (m2) terminated in the superficial layers, which were rich in CB+ local inhibitory neurons (red spheres).

Work like this will get us closer to understanding consciousness.

Zikipoulos B, & Barbas H (2007). Parallel Driving and Modulatory Pathways Link the Prefrontal Corex and Thalamus PLoS ONE, 2 (9) DOI: 10.1371/journal.pone.0000848

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