Live imaging of neuronal connections by magnetic resonance: Robust transport in the hippocampal–septal memory circuit in a mouse model of Down syndrome

Abstract

Connections from hippocampus to septal nuclei have been implicated in memory loss and the cognitive impairment in Down syndrome (DS). We trace these connections in living mice by Mn 2+ enhanced 3D MRI and compare normal with a trisomic mouse model of DS, Ts65Dn. After injection of 4 nl of 200 mM Mn 2+ into the right hippocampus, Mn 2+ enhanced circuitry was imaged at 0.5, 6, and 24 hr in each of 13 different mice by high resolution MRI to detect dynamic changes in signal over time. The pattern of Mn 2+ enhanced signal in vivo correlated with the histologic pattern in fixed brains of co-injected 3kD rhodamine-dextranamine, a classic tracer. Statistical parametric mapping comparing intensity changes between different time points revealed that the dynamics of Mn 2+ transport in this pathway were surprisingly more robust in DS mice than in littermate controls, with statistically significant intensity changes in DS appearing at earlier time points along expected pathways. This supports reciprocal alterations of transport in the hippocampal-forebrain circuit as being implicated in DS and argues against a general failure of transport. This is the first examination of in vivo transport dynamics in this pathway and the first report of elevated transport in DS.

Manganese-Enhanced Magnetic Resonance Imaging

“…Moreover, several studies addressed the transport of manganese into the striatum, amygdala (111,112,188), and hippocampus (189). In birds, the song control circuit could be visualized by Mn 2+ injection into the high vocal center (HVL) (115).…”

Songs My Mother Taught Me: Gene‐Environment Interactions, Brain Development and the Auditory System: Thoughts on Non‐Kin Rejection

“…Recently my lab has probed whether connectivity is greater or less in mental retardation such as found in Down syndrome, a trisomy of chromosome 21 (Bearer, Zhang & Jacobs, 2007). We discovered that connections within the memory circuit from hippocampus to forebrain were more robust in Down syndrome than in normals, a paradoxical finding.…”

Automated Computational Processing of 3‐D MR Images of Mouse Brain for Phenotyping of Living Animals

“…This is especially useful when imaging living animals because imaging time must be short (Pautler, 2004; Pautler and Koretsky, 2002; Pautler et al, 2003; Pautler et al, 1998; Silva and Bock, 2008; Silva et al, 2004). MEMRI has been used to observe functional circuitry and axonal transport dynamics in the living brain (Bearer et al, 2007a; Bearer et al, 2007b; Bearer et al, 2009; Gallagher et al, 2013; Gallagher et al, 2012; Medina et al, 2017; Pautler, 2004; Van der Linden et al, 2004; Zhang et al, 2010a), and localized neuronal activity (Malkova et al, 2014; Yu et al, 2005). Multiple studies have been done to determine a non-toxic dose of Mn 2+ (Bearer et al, 2007a; Eschenko et al, 2012; Lindsey et al, 2013).…”