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

F. Zoratto, G. M. Palombelli, L. A. Ruocco, E. Carboni, G. Laviola, A. G. Sadile, W. Adriani, R. Canese

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)171-178
Number of pages8
JournalBehavioural Brain Research
Volume333
DOIs
Publication statusPublished - Aug 30 2017

Keywords

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

ASJC Scopus subject areas

  • Behavioral Neuroscience

Fingerprint Dive into the research topics of 'Enhanced limbic/impaired cortical-loop connection onto the hippocampus of NHE rats: Application of resting-state functional connectivity in a preclinical ADHD model'. Together they form a unique fingerprint.

  • Cite this