Geometric and functional architecture of visceral sensory microcircuitry

Abstract

Is microcircuit wiring designed deterministically or probabilistically? Does geometric architecture predict functional dynamics of a given neuronal microcircuit? These questions were addressed in the visceral sensory microcircuit of the caudal nucleus of the tractus solitarius (NTS), which is generally thought to be homogeneous rather than laminar in cytoarchitecture. Using in situ hybridization histochemistry and whole-cell patch clamp recordings followed by neuronal reconstruction with biocytin filling, anatomical and functional organization of NTS microcircuitry was quantified to determine associative relationships. Morphologic and chemical features of NTS neurons displayed different patterns of process arborization and sub-nuclear localization according to neuronal types: smaller cells featured presynaptic local axons and GABAergic cells were aggregated specifically within the ventral NTS. The results suggested both a laminar organization and a spatial heterogeneity of NTS microcircuit connectivity. Geometric analysis of pre- and postsynaptic axodendritic arbor overlap of reconstructed neurons (according to parent somal distance) confirmed a heterogeneity of microcircuit connectivity that could underlie differential functional dynamics along the dorsoventral axis. Functional dynamics in terms of spontaneous and evoked postsynaptic current patterns behaved in a strongly location-specific manner according to the geometric dimension, suggesting a spatial laminar segregation of neuronal populations: a dorsal group of high excitation and a ventral group of balanced excitation and inhibition. Recurrent polysynaptic activity was also noted in a subpopulation of the ventral group. Such geometric and functional laminar organization seems to provide the NTS microcircuit with both reverberation capability and a differentiated projection system for appropriate computation of visceral sensory information.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-010-0294-5) contains supplementary material, which is available to authorized users.

Differential Ascending Projections From the Male Rat Caudal Nucleus of the Tractus Solitarius: An Interface Between Local Microcircuits and Global Macrocircuits

“…The population of neurons composing the cNTS at the level of the AP is by no means homogeneous with respect to cellular architecture, chemical neuroanatomy, or microcircuit connectivity (Whitehead, 1988 ; Kawai and Senba, 1996 , 1999 ; Negishi and Kawai, 2011 ). We have systematically investigated the cytoarchitecture of the cNTS by analyzing correlative features of morphology and electrophysiology (Kawai and Senba, 1996 , 1999 ; Okada et al, 2006 , 2008 ; Yoshioka et al, 2006 ; Negishi and Kawai, 2011 ).…”

“…The population of neurons composing the cNTS at the level of the AP is by no means homogeneous with respect to cellular architecture, chemical neuroanatomy, or microcircuit connectivity (Whitehead, 1988 ; Kawai and Senba, 1996 , 1999 ; Negishi and Kawai, 2011 ). We have systematically investigated the cytoarchitecture of the cNTS by analyzing correlative features of morphology and electrophysiology (Kawai and Senba, 1996 , 1999 ; Okada et al, 2006 , 2008 ; Yoshioka et al, 2006 ; Negishi and Kawai, 2011 ). When the cNTS is divided into the dorsal and ventral subregions, a conspicuous contrast in several features between these subregions is apparent: (1) neuron composition according to soma size—homogeneous small neurons (mean soma area, ~105 μm 2 ) vs. heterogeneous small-to-larger neurons; (2) chemical neuroanatomy—neuropeptides (neurotensin, cholecystokinin), adrenaline (C2d), calbindin vs. noradrenaline/dopamine (A2) and GABA (Kawai et al, 1988 ; Herbert and Saper, 1990 ; Riche et al, 1990 ; Yoshioka et al, 2006 ; Okada et al, 2008 ); (3) afferent axon origins—peripheral (the glossopharyngeal and vagus) vs. central (the hypothalamus, amygdala and insular cortex; Kalia and Sullivan, 1982 ; van der Kooy et al, 1984 ; Housley et al, 1987 ; Jasmin et al, 1997 ; Chan et al, 2000 ; Geerling et al, 2010 ); and (4) efferent neuron targets—the PB vs. multiple brain areas, including the PB.…”

“…The population of cNTS cells is heterogeneous with respect to morphological features such as soma size, shape, subnuclear location and axo-dendritic arborization (Yoshioka et al, 2006 ; Negishi and Kawai, 2011 ). The relationship between cell morphology and projection sites in cNTS efferent systems has not yet been studied using neural tract tracers, except for studies describing the topographical subnuclear arrangement of NTS-PB pathways (Herbert et al, 1990 ).…”

“…A quantitative correlation is evident not only between each morphological feature but also between morphological and functional parameters. For example, the soma size of cNTS neurons is an excellent marker for other morphological and functional features: (1) small cells (soma <150 μm 2 ) have mostly local axon collaterals and are divided into excitatory (glutamatergic) and inhibitory (GABAergic) neurons, of which the former are more concentrated in the dorsal region of the cNTS possessing an extranuclear projection axon in addition to intranuclear local collaterals; and (2) larger cells (soma >150 μm 2 ), which lack local axon collaterals, receive robust inhibitory synaptic inputs and are concentrated specifically in the ventral subregion (Kawai and Senba, 1996 , 1999 ; Okada et al, 2006 , 2008 ; Yoshioka et al, 2006 ; Negishi and Kawai, 2011 ). The purpose of the present study was to assess differences in projection targets or pathways of projection axons.…”

Effects of high-fat diet and gastric bypass on neurons in the caudal solitary nucleus

“…Bailey and colleagues showed that a hyperpolarizing prepulse, which deinactivates I A , suppressed the ST-evoked response of cNST neurons that expressed this current (Bailey, Hermes et al 2007). Thus, under a HFD where TOC is elevated, vagal afferent inputs such as satiety signals could be suppressed, particularly if they interacted with inhibitory signals from local interneurons (Chan and Sawchenko 1998; Negishi and Kawai 2011) or descending inputs (Pickel, van Bockstaele et al 1995; Saha, Batten et al 2000). Indeed, several studies have shown that vagally-mediated satiety-inducing manipulations, including infusions of CCK, 5-HT (Covasa, Grahn et al 2000; Nefti, Chaumontet et al 2009), and macronutrients (Nefti, Chaumontet et al 2009) induce less Fos-like immunoreactivity in the cNST of rodents fed a HFD, suggestive of reduced neuronal excitability.…”