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

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 att...

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Published in:	Behavioural brain research Vol. 333; pp. 171 - 178
Main Authors:	Zoratto, F., Palombelli, G.M., Ruocco, L.A., Carboni, E., Laviola, G., Sadile, A.G., Adriani, W., Canese, R.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 30-08-2017
Subjects:	ADHD Amygdala Animals Attention Deficit Disorder with Hyperactivity - pathology BOLD Brain Mapping Cerebral Cortex - diagnostic imaging Cerebral Cortex - physiopathology Disease Models, Animal Dopamine Dorsal striatum Electroencephalography Hippocampus Hippocampus - diagnostic imaging Hippocampus - physiopathology Image Processing, Computer-Assisted Limbic/Cortical loop Magnetic Resonance Imaging Male Neural Pathways - diagnostic imaging Neural Pathways - physiopathology NHE rats Nucleus accumbens OFC Oxygen - blood PFC Rats Rats, Inbred Strains Rats, Sprague-Dawley Rest Resting state fMRI Nucleus accumbens ADHD NHE rats Dopamine Amygdala Limbic/Cortical loop Resting state fMRI BOLD PFC OFC Hippocampus Dorsal striatum
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0166-4328 1872-7549
DOI:	10.1016/j.bbr.2017.06.026