A conditional transgenic reporter of presynaptic terminals reveals novel features of the mouse corticospinal tract

Abstract

In many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), synaptic alterations precede the demise of the neuronal cell, making synapses a useful vantage point from which to monitor the onset and progression of clinical signs and pathological changes. While murine models of ALS display many features in common with the clinical picture observed in patients, corticospinal tract (CST) involvement is usually less severe in mice than the picture observed in humans. In this paper we describe the characterization of a new conditional transgenic line obtained by targeted integration of a GFP-VAMP2 fusion gene into the Rosa26 locus, and devised to permit the detection of genetically defined presynaptic terminals in wild type mice and murine models of neural disorders. This reporter molecule is selectively enriched in presynaptic boutons, significantly reducing the background signal produced by fibers of passage. The specific features of this reporter line allow us to strongly support the view that murine CST terminals give rise to very few direct contacts with spinal motor neurons. Moreover, the evidence described here reveals the existence of previously uncharacterized, putative direct connections between CST presynaptic boutons and Renshaw neurons in the spinal cord. These results constitute a proof of concept for the potential application of this indicator line to morphological analyses of wild type and diseased synapses.

Absence of Subcerebral Projection Neurons Is Beneficial in a Mouse Model of Amyotrophic Lateral Sclerosis

“…Although Fezf2 −/− mice lack CSN and other SubCerPN and display altered cortical development, 13,14,17 they remarkably do not present any major motor phenotype. In mice, CSN make mostly indirect or polysynaptic connections and few direct or monosynaptic connections onto MN 38 . It is possible that in Fezf2 −/− mice the majority of indirect connections are less affected, or better compensated, and the minority of direct connections are more affected but translate into a phenotype that is harder to reveal.…”

Corticospinal populations broadcast complex motor signals to coordinated spinal and striatal circuits

“…CSN DLS synapses were found throughout the spinal grey, with densest innervation in intermediate and superficial laminae. Still, we identified vGlut1 + boutons deep within the ventral horn, including those that were closely apposed to putative Renshaw neurons, highlighting their capacity to intimately influence motor output ( Extended Data Figure 5A – G ) 46 , 47 .…”

Novel Approaches for the Treatment of Post-Traumatic Stress Disorder: A Systematic Review of Non-Invasive Brain Stimulation Interventions and Insights from Clinical Trials

“…In this framework, metaplasticity [ 111 ] and the non-linear effects of synaptic plasticity [ 112 , 113 ] might play a pivotal role, because they might produce complex and long-lasting changes in patients’ neuronal mechanisms, cognition, and behavior. It would be important, also, to gather a deeper insight in the structure and functioning of complex neural networks both in vitro and in vivo [ 114 , 115 , 116 ], especially with respect to changes induced by stress [ 25 , 30 ].…”