Serotonergic Modulation of Nigrostriatal and Mesolimbic Dopamine and Motor/Exploratory Behaviors in the Rat

Purpose: The 5-HT2A receptor (R) is known to modulate dopamine (DA) release in the mammalian brain. Altanserin (ALT) and 2,5-dimethoxy-4-iodoamphetamine (DOI) act as 5-HT2AR antagonist and agonist, respectively. In the present study, we assessed the effects of ALT and DOI on motor and exploratory behaviors and on D2/3R binding in the rat brain with in vivo imaging methods.Methods: D2/3R binding was determined after systemic application of ALT (10 mg/kg) or DOI (0.5 mg/kg) and the respective vehicles [dimethyl sulfoxide (DMSO) and 0.9% saline (SAL)] with [123I]IBZM as a single-photon emission computed tomography (SPECT) radioligand. Anatomical information for the delineation of the target regions was obtained with dedicated small animal MRI. Immediately after 5-HT2AR antagonistic or agonistic treatment, motor/exploratory behaviors were assessed for 45 (ALT) or 30 min (DOI) in an open field. Additional rats underwent behavioral measurements after injection of DMSO or SAL.Results: ALT increased D2/3R binding in the ventral hippocampus relative to vehicle, while DOI augmented D2/3R binding in caudate putamen, frontal cortex, motor cortex, and ventral hippocampus. The 5-HT2AR agonist as well as antagonist decreased parameters of motor activity and active exploration. However, ALT, in contrast to DOI, decreased explorative head–shoulder motility and increased sitting.Conclusions: The regional increases of D2/3R binding after ALT and DOI (90 and 75 min post-challenge) may be conceived to reflect decreases of synaptic DA. The reductions of motor/exploratory activities (min 1–45 and min 1–30 after challenge with ALT and DOI, respectively) contrast the regional reductions of D2/3R binding, as they indicate elevated DA levels at the time of behavioral measurements. It may be concluded that ALT and DOI modulate DA in the individual regions of the nigrostriatal and mesolimbocortical pathways differentially and in a time-dependent fashion.

MRI Powered and Triggered Current Stimulator for Concurrent Stimulation and MRI

Bioelectric stimulation during concurrent magnetic resonance imaging (MRI) is of interest to basic and translational studies. However, existing stimulation systems often interfere with MRI, are difficult to use or scale up, have limited efficacy, or cause safety concerns. To address these issues, we present a novel device capable of supplying current stimulation synchronized with MRI while being wirelessly powered by the MRI gradient fields. Results from testing it with phantoms and live animals in a 7 Tesla small-animal MRI system suggest that the device is able to harvest up to 72 (or 18) mW power during typical echo-planar imaging (or fast low angle shot imaging) and usable for stimulating peripheral muscle or nerve to modulate the brain or the gut, with minimal effects on MRI image quality. As a compact and standalone system, the plug-and-play device is suitable for animal research and merits further development for human applications.

An Optimized Registration Workflow and Standard Geometric Space for Small Animal Brain Imaging

The reliability of scientific results critically depends on reproducible and transparent data processing. Cross-subject and cross-study comparability of imaging data in general, and magnetic resonance imaging (MRI) data in particular, is contingent on the quality of registration to a standard reference space. In small animal MRI this is not adequately provided by currently used processing workflows, which utilize high-level scripts optimized for human data, and adapt animal data to fit the scripts, rather than vice-versa. In this fully reproducible article we showcase a generic work-flow optimized for the mouse brain, alongside a standard reference space suited to harmonize data between analysis and operation. We present four separate metrics for automated quality control (QC), and a visualization method to aid operator inspection. Benchmarking this workflow against common legacy practices reveals that it performs more consistently, better preserves variance across subjects while minimizing variance across sessions, and improves both volume and smoothness conservation RMSE approximately 2-fold. We propose this open source workflow and the QC metrics as a new standard for small animal MRI registration, ensuring work-flow robustness, data comparability, and region assignment validity, all of which are indispensable prerequisites for the comparability of scientific results across experiments and centers.

Acquisition of Spatial Search Strategies and Reversal Learning in the Morris Water Maze Depend on Disparate Brain Functional Connectivity in Mice

Learning has been proposed to coincide with changes in connections between brain regions. In the present study, we used resting-state fMRI (rsfMRI) to map brain-wide functional connectivity (FC) in mice that were trained in the hidden-platform version of the Morris water maze. C57BL6 mice were investigated in a small animal MRI scanner following 2, 10, or 15 days of acquisition learning, or 5 days of reversal learning. Spatial learning coincided with progressive and changing FC between telencephalic regions that have been implemented in spatial learning (such as hippocampus, cingulate, visual, and motor cortex). Search strategy assessment demonstrated that the use of cognitively advanced spatial strategies correlated positively with extensive telencephalic connectivity, whereas non-spatial strategies correlated negatively with connectivity. FC patterns were different and more extensive after reversal learning compared with after extended acquisition learning, which could explain why reversal learning has been shown to be more sensitive to subtle functional defects.