Hypothesis-driven structural connectivity analysis supports network over hierarchical model of brain architecture

Abstract

The brain is usually described as hierarchically organized, although an alternative network model has been proposed. To help distinguish between these two fundamentally different structure-function hypotheses, we developed an experimental circuit-tracing strategy that can be applied to any starting point in the nervous system and then systematically expanded, and applied it to a previously obscure dorsomedial corner of the nucleus accumbens identified functionally as a "hedonic hot spot." A highly topographically organized set of connections involving expected and unexpected gray matter regions was identified that prominently features regions associated with appetite, stress, and clinical depression. These connections are arranged as a longitudinal series of circuits (closed loops). Thus, the results do not support a rigidly hierarchical model of nervous system organization but instead indicate a network model of organization. In principle, the double-coinjection circuit tracing strategy can be applied systematically to the rest of the nervous system to establish the architecture of the global structural wiring diagram, and its abstraction, the connectome.brain systems | connectome | appetite | depression | stress

Orexin in Rostral Hotspot of Nucleus Accumbens Enhances Sucrose ‘Liking’ and Intake but Scopolamine in Caudal Shell Shifts ‘Liking’ Toward ‘Disgust’ and ‘Fear’

“…For example, the NAc rostrodorsal quadrant of medial shell has distinct inputs from a region in infralimbic cortex and outputs to ventral pallidum and hypothalamus that are different from other medial shell quadrants (Thompson and Swanson, 2010), resulting in a closed-circuit corticolimbicthalamocortical loop that runs parallel to loops passing through other regions of NAc shell. In addition, the rostral half of shell also has septal-like anatomical features that distinguish it from the extended amygdala-like features of caudal shell (Thompson and Swanson, 2010;Zahm et al, 2013). Neurons in rostrodorsal medial shell also have distinct morphological features, such as fewer spiny dendrites and smaller medium spiny neuronal cell bodies than other areas of NAc (Meredith et al, 2008;Zahm et al, 2013).…”

Foundational model of structural connectivity in the nervous system with a schema for wiring diagrams, connectome, and basic plan architecture

“…6B) in a myotatic reflex. This connection is interpreted at three successively higher-resolution analysis levels: macroconnectional, mesoconnectional, and microconnectional (52). For macroconnections, regions are black boxes ( Fig.…”

Disentangling pleasure from incentive salience and learning signals in brain reward circuitry

“…Food, sex, drugs, winning money, and other rewards or predictive cues all activate these pathways in humans and other animals (11,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Recent evidence indicates a surprising multiplicity of control systems within the NAc and VP, including multiple parallel and segregated loops that carry point to point signals through restricted subregions of prefrontal cortex-NAc-VP-thalamus and back again (7). Modulation by diverse neurochemicals also contributes to mediating separable hedonic and motivation functions (1,10,25,30,31).…”

“…Diverse information about rewards is funneled through pathways from the nucleus accumbens (NAc) to the ventral pallidum (VP) embedded in larger mesocorticolimbic circuitry (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Food, sex, drugs, winning money, and other rewards or predictive cues all activate these pathways in humans and other animals (11,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”