Abstract
Resting-state functional magnetic resonance imaging (rs-fMRI) measures spontaneous fluctuations in blood oxygenation level-dependent (BOLD) signal in the absence of external stimuli. It has become a powerful tool for mapping large-scale brain networks in humans and animal models. Several rs-fMRI studies have been conducted in anesthetized and awake adult rats, reporting consistent patterns of brain activity at the systems level. However, the evolution to adult patterns of resting-state activity has not yet been evaluated and quantified in the developing rat brain. In this study, we hypothesized that large-scale intrinsic networks would be easily detectable but not fully established as specific patterns of activity in lightly anesthetized 2-week-old rats (N = 11). Independent component analysis (ICA) identified 8 networks in 2-week-old-rats. These included Default mode, Sensory (Exteroceptive), Salience (Interoceptive), Basal Ganglia-Thalamic-Hippocampal, Basal Ganglia, Autonomic, Cerebellar, as well as Thalamic-Brainstem networks. Many of these networks consisted of more than one component, possibly indicative of immature, underdeveloped networks at this early time point. Except for the Autonomic network, infant rat networks showed reduced connectivity with subcortical structures in comparison to previously published adult networks. Reported slow fluctuations in the BOLD signal that correspond to functionally relevant resting-state networks in 2-week-old rats can serve as an important tool for future studies of brain development in the settings of different pharmacological applications or disease.
Highlights
Resting-state functional magnetic resonance imaging provides an important experimental approach to understanding the nature of the brain’s intrinsic functional activity in the absence of controlled stimuli or any observed behaviors (Fox et al, 2005; Raichle, 2006)
Sensory stimulus evokes neural, but not blood oxygenation level-dependent (BOLD) fMRI signal, in rats younger than PD11, while the earliest significant sensory stimulus evoked BOLD signal was observed at PD13 rat (Colonnese et al, 2008)
Such anesthesia management provided successful immobility during scanning session; only 1 out of 13 animals was excluded from the subsequent Resting-state functional magnetic resonance imaging (rs-fMRI) analysis due to motion-related imaging artifacts; see below
Summary
Resting-state functional magnetic resonance imaging (rs-fMRI) provides an important experimental approach to understanding the nature of the brain’s intrinsic functional activity in the absence of controlled stimuli or any observed behaviors (Fox et al, 2005; Raichle, 2006). Data from infant rat models demonstrated that in the absence of any stimulation, significant neuronal activity of somatosensory (Colonnese and Khazipov, 2012), as well as prefrontal (Brockmann et al, 2011) cortex matures during the first 1–2-weeks of life. Sensory stimulus evokes neural, but not BOLD fMRI signal, in rats younger than PD11, while the earliest significant sensory stimulus evoked BOLD signal was observed at PD13 rat (Colonnese et al, 2008) Such findings suggest that substantial changes in maturation of neural (Colonnese et al, 2008), neurovascular and autoregulatory (McCandlish et al, 1993; Kozberg et al, 2013) systems occur during the first 2-weeks of life in infant rat to establish the neurovascular coupling. Inhibitory and excitatory neurotransmission (Dorrn et al, 2010; Harris et al, 2011) known to have an effect on cerebral vascular perfusion
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