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Behav Brain Res. 2017 Aug 30;333:171-178. doi: 10.1016/j.bbr.2017.06.026. Epub 2017 Jun 26.

Enhanced limbic/impaired cortical-loop connection onto the hippocampus of NHE rats: Application of resting-state functional connectivity in a preclinical ADHD model.

Author information

1
Cell Biology and Neurosciences Dept., Istituto Superiore di Sanità, Rome, Italy.
2
University of Campania "Luigi Vanvitelli", Naples, Italy.
3
Department of Biological Sciences, University of Cagliari, Cagliari, Italy.
4
Cell Biology and Neurosciences Dept., Istituto Superiore di Sanità, Rome, Italy. Electronic address: walter.adriani@iss.it.
5
Cell Biology and Neurosciences Dept., Istituto Superiore di Sanità, Rome, Italy; Present address: Preclinical MRI Unit, Core Facilities, Istituto Superiore di Sanità, Rome, Italy.

Abstract

Due to a hyperfunctioning mesocorticolimbic system, Naples-High-Excitability (NHE) rats have been proposed to model for the meso-cortical variant of attention deficit/hyperactivity disorder (ADHD). Compared to Naples Random-Bred (NRB) controls, NHE rats show hyperactivity, impaired non-selective attention (Aspide et al., 1998), and impaired selective spatial attention (Ruocco et al., 2009a, 2014). Alteration in limbic functions has been proposed; however, resulting unbalance among forebrain areas has not been assessed yet. By resting-state functional Magnetic-Resonance Imaging (fMRI) in vivo, we investigated the connectivity of neuronal networks belonging to limbic vs. cortical loops in NHE and NRB rats (n=10 each). Notably, resting-state fMRI was applied using a multi-slice sagittal, gradient-echo sequence. Voxel-wise connectivity maps at rest, based on temporal correlation among fMRI time-series, were computed by seeding the hippocampus (Hip), nucleus accumbens (NAcc), dorsal striatum (dStr), amygdala (Amy) and dorsal/medial prefrontal cortex (PFC), both hemispheres. To summarize patterns of altered connection, clearly directional connectivity was evident within the cortical loop: bilaterally and specularly, from orbital and dorsal PFCs through dStr and hence towards Hip. Such network communication was reduced in NHE rats (also, with less mesencephalic/pontine innervation). Conversely, enhanced network activity emerged within the limbic loop of NHE rats: from left PFC, both through the NAcc and directly, to the Hip (all of which received greater ventral tegmental innervation, likely dopamine). Together with tuned-down cortical loop, this potentiated limbic loop may serve a major role in controlling ADHD-like behavioral symptoms in NHE rats.

KEYWORDS:

ADHD; Amygdala; BOLD; Dopamine; Dorsal striatum; Hippocampus; Limbic/Cortical loop; NHE rats; Nucleus accumbens; OFC; PFC; Resting state fMRI

PMID:
28655564
DOI:
10.1016/j.bbr.2017.06.026
[Indexed for MEDLINE]

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