The network architecture of rat intrinsic interbrain (diencephalic) macroconnections

The endbrain and interbrain form 2 great vertebrate forebrain divisions, and the interbrain is subdivided into the hypothalamus ventrally and thalamus dorsally. General organizing principles of intrainterbrain axonal circuitry were examined here at the level of gray matter regions using network analysis tools in a mammal with the most complete available dataset-before examining interbrain input-output relationships with other nervous system parts. The dataset was curated expertly from the neuroanatomical literature using experimental axonal pathway-tracing methods, and evidence from 74,242 connection reports indicates the existence of 10,836 macroconnections of the possible 49,062 macroconnections between the 222 gray matter regions forming the right and left halves of the interbrain. Two identical sets of 6 putative hubs were identified in the intrainterbrain network and form a continuous tissue mass in a part of the right and left medial hypothalamus associated functionally with physiological mechanisms controlling bodily functions. The intrainterbrain network shows only weak evidence of small-world attributes, rich club organization is absent, and multiresolution consensus cluster analysis indicates a solution with only 3 top-level subsystems or modules. In contrast, a previous analysis employing the same methodology to the significantly denser 244-node intraendbrain network revealed 2 identical sets of 13 hubs, small-world and rich club attributes, and 4 top-level subsystems. These differences in intrinsic network architecture across subdivisions suggest that intrinsic connections shape regional functional specialization to a varying extent, in part driven by differences in density and centrality, with extrinsic input-output connectivity playing a greater role in subdivisions that are sparser and less centralized.