Projectomic profiles of calbindin D28K-expressing neurons in the mediodorsal thalamic nucleus of mouse

Expression of calbindin D28K (CB) and parvalbumin (PV) distinguishes matrix and core type thalamic neurons, respectively, in primates. Whether the nice correspondence of intracellular calcium binding proteins and matrix/core neuron types translates to mouse remains unknown. Sixty reconstructed 3D mediodorsal thalamic nuclear neurons (MD^Calb1 neurons), defined by calb1, the gene encoding CB in mouse MD, were mapped onto Allen Mouse Brain Common Coordinate Framework (CCFv3). Most MD^Calb1 neurons (54/60) were isocortex-projecting ones, possessing collateral connections with caudate putamen (CP). Collectively, MD^Calb1 neuron ensemble linked 93 anatomically-defined brain structures/regions with their axons; and of these 93 axon-connected structures/regions, the single MD^Calb1 neurons had projection areas (receiving ≥ 2 axon terminals) ranging from 3 to 34 in number. Distinct projectomic profiles defined roughly 8 neuron subgroups, which differed from each other in composition of axon targets involving cortical and subcortical regions. Isocortical areas in prefrontal and sensorimotor cortices such as agranular insular cortex (AI), secondary motor cortex (MOs) and orbital cortex (ORB) etc., as well as structures of striatopallidal and olfactory systems such as CP, nucleus accumbens (ACB) and main olfactory bulb (MOB), among others, constituted the main axonal projection targets. Intriguingly, some proximal axon branches from over a dozen MD^Calb1 neurons (14/60) were seen to be spatially confined to MD, most frequently within dendritic territories of their source neurons, suggesting intra-MD innervation. For thalamocortical connectivity, most neurons (49/54, i.e., about 91%) had widespread, tangentially distributed axons terminating in layers 1-3 (L1-3) of multiple cortical areas. Thus, these neurons were of thalamic matrix type, per core-matrix-intralaminar classifying framework. Our morphometric data support the role of MD^Calb1 neurons for coordinated signal processing in networks integrating broad cortical areas, as well as subcortical structures, to fulfil emotion/cognition-related executive behaviors.