Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision-making

Abstract

The focus of this literature review is on the three interacting brain areas that participate in decision-making: basal ganglia, ventral motor thalamic nuclei, and medial prefrontal cortex, with an emphasis on the participation of the ventromedial and ventral anterior motor thalamic nuclei in prefrontal cortical function. Apart from a defining input from the mediodorsal thalamus, the prefrontal cortex receives inputs from ventral motor thalamic nuclei that combine to mediate typical prefrontal functions such as associative learning, action selection, and decision-making. Motor, somatosensory and medial prefrontal cortices are mainly contacted in layer 1 by the ventral motor thalamic nuclei and in layer 3 by thalamocortical input from mediodorsal thalamus. We will review anatomical, electrophysiological, and behavioral evidence for the proposed participation of ventral motor thalamic nuclei and medial prefrontal cortex in rat and mouse motor decision-making.

Keywords: action selection; basal ganglia; cognitive functions; rodents.

Figure 1

Cartoon of the rodent brain illustrating the prefrontal cortex (shaded light pink), and its sensory and motor inputs from mediodorsal (layer 2/3, red) and ventral motor thalamic nuclei (layer 1, blue) that mediate associative learning, action selection, and decision‐making in rats and mice. a‐ prefrontal cortex, b‐ motor cortical areas, c‐somatosensory cortical areas.

Figure 2

Innervation of cortex by ventromedial (VM) and ventral anterior nuclei (VA) of the ventral motor thalamic nuclei or basal ganglia zone (BZ) as defined by (Nakamura et al., 2014). Afferents of VM (blue) mainly terminate in cortical layer 1, with some ramifications in layers 3 and 5, 6. Afferents of VA innervate cortical layers 1 and 5. Afferents of ventral motor thalamic nuclei to superior cortical layers have been demonstrated to drive cortical pyramidal neurons and may drive layer 1 inhibitory interneurons that can, in turn, induce feedforward inhibition in lower level pyramidal neurons. Here, we propose that VA and VM afferents to layer 1 of the medial prefrontal cortex can provide an important modulation on corticostriatal, corticocortical, and corticofugal pyramidal neurons.

Figure 3

Immunohistochemistry of cortical projections from the ventromedial motor thalamic nucleus (VM) to cortex. (A) Section at the level of the injection site in ventral motor thalamus (GAD67 immunostaining), magnified on the right‐hand side insert. (B) Frontal section of the brain to illustrate the presence of VM axon terminals in the medial prefrontal cortex (expressing GFP). Axon terminal in layer 1 decrease in magnitude from a marked anterior cingulate projection (top insert) to a noticeable prelimbic and a less prominent infralimbic projection (lower insert). Projections to the orbitofrontal cortex have not been reported from VM, see text. Method: Briefly, an anesthetized Sprague‐Dawley rat received a stereotaxic unilateral injection of 90 nL of AAV5‐CAG‐ArchT‐GFP (UNC Vector Core) in VM (interaural AP +7.0 mm, ML +1.2 mm and DV −6.56 mm from Bregma). After a survival time of three weeks, the rat was sacrificed with an overdose of anesthetic and perfused with 4% paraformaldehyde. Tissue slices (60 μm) were counterstained for GAD67 (red). Cell nuclei were stained with with 4′,6‐Diamidino‐2‐Phenylindole, dihydrochloride DAPI (blue). Expression of VM axon terminals labeled by AAV5‐CAG‐ArchT‐GFP (green) can be observed in the prefrontal cortex and infected cells in VM (the GABA rich‐area in thalamus).