Thalamic Relay Nuclei of the Basal Ganglia Form Both Reciprocal and Nonreciprocal Cortical Connections, Linking Multiple Frontal Cortical Areas

Abstract

Thalamic relay nuclei transmit basal ganglia output to the frontal cortex, forming the last link in corticobasal ganglia circuitry. The thalamus regulates cortical activity through differential laminar connections, providing not only feedback, but also initiating "feedforward" loops, via nonreciprocal projections, that influence higher cortical areas. This study examines the organization of thalamic connections with cortex from basal ganglia relay nuclei, including ventral anterior (VA), ventral lateral (VL), and mediodorsal (MD) nuclei, in the Macaque monkey. Anterograde and bidirectional tracer injections ([3H]-amino acids, dextran conjugates of Fluorescein, Lucifer Yellow or FluoroRuby, or wheat germ agglutinin) into discrete VA/VL, MD, and frontal cortical sites demonstrate specific thalamocortical connections. VL projections target caudal motor areas (primary, supplementary, and caudal premotor areas), whereas VA projections target more rostral premotor areas (including cingulate and presupplementary motor areas) and MD projects to dorsolateral and orbital prefrontal cortices. Thalamocortical projections innervate cortical layers I and III, and to a lesser extent, layer V. In motor areas layer I projections are more extensive than those to layer III (and V). The complex laminar organization of projections from specific thalamic sites suggests differential regulation of cortical function. Injections of bidirectional tracers into thalamic and frontal cortical sites also show that in comparison to thalamocortical projections, corticothalamic projections to VA-VL and MD are more widespread. These findings demonstrate both reciprocal and nonreciprocal components to the thalamo-cortico-thalamic relay. Together, these experiments indicate a dual role for VA-VL and MD nuclei: (1) to relay basal ganglia output within specific cortical circuits and (2) to mediate information flow between cortical circuits.