The Life of a Trailing Spouse

Abstract

In 1981, I published a paper in the first issue of the Journal of Neuroscience with my postdoctoral mentor, Alan Pearlman. It reported a quantitative analysis of the receptive field properties of neurons in reeler mouse visual cortex and the surprising conclusion that although the neuronal somas were strikingly malpositioned, their receptive fields were unchanged. This suggested that in mouse cortex at least, neuronal circuits have very robust systems in place to ensure the proper formation of connections. This had the unintended consequence of transforming me from an electrophysiologist into a cellular and molecular neuroscientist who studied cell adhesion molecules and the molecular mechanisms they use to regulate axon growth. It took me a surprisingly long time to appreciate that your science is driven by the people around you and by the technologies that are locally available. As a professional puzzler, I like all different kinds of puzzles, but the most fun puzzles involve playing with other puzzlers. This is my story of learning how to find like-minded puzzlers to solve riddles about axon growth and regeneration.

Figure 1.

The peak velocity sensitivities (the stimulus speed producing the highest maximum response frequency) for corticotectal neurons. The range of values were similar in reeler and normal mice, and the means were not significantly different, although many neurons in reeler mice were displaced from their normal cortical layer (Lemmon and Pearlman, 1981; their Fig. 7).

Figure 2.

Computer-assisted reconstructions show the pattern of connections between visual areas is similar in normal and reeler mice. Each panel shows the dorsal view of the caudal portion of three brains after injections into area 17 of the visual cortex. All markings represent the projection to the cortical surface of labeling at all cortical depths, excluding the white matter and subcortical sites. Cross hatching indicates the heavily labeled central zone of the injection. Diagonal lines indicate the surrounding zone of peroxidase diffusion. Horizontal lines indicate regions of anterograde and/or retrograde transport. A, An injection of unconjugated HRP in a normal mouse. B, An injection of HRP-WGA in a normal mouse. C, An injection of HRP-WGA in a reeler mouse (Simmons et al., 1982; their Fig. 6).

Figure 3.

Parallel lane choice experiments testing the importance of adhesion strength for axon guidance. A, Neurites crossing alternating lanes of N-cadherin and laminin. B, Neurites growing across alternating lanes of L1 and laminin. C, Neurites growing over alternating lanes of N-cadherin and L1 (Lemmon et al., 1992; their Fig. 3).

Figure 4.

Alternating stripes of N-CAM and N-CAM plus keratin sulfate/CSPGs show a role for these proteoglycans in inhibition during axon guidance. Outgrowth of DRG neurites was inhibited by a mixture of KS/CSPG mixed with polysialylated NCAM (Snow et al., 1990b; their Fig. 6).

Figure 5.

Cover photograph from JNS (Kamiguchi and Lemmon, 2000) The micrographs show L1 (red) that is internalised in the central domain of the growth cone in clathrin coated pits and then recycled to the surface of the growth cones in the filopodia and lamellipodia in the peripheral domain. The schematic illistrates how the L1 on the cell surface is linked to the actin cytoskeleton.

Figure 6.

When hippocampal neurons are grown on striped substrates, axons form predominantly on one substrate. Neurons were cultured on substrates patterned with alternating stripes of polylysine and laminin (A–C) or polylysine and NgCAM (D–F). When neurons were examined after 24 h in culture, minor process growth cones (arrowheads) were positioned on both substrates, but axons (arrows) almost always formed on laminin or NgCAM. Neurons were immunolabeled for tubulin, and the patterns were revealed by immunostaining for either laminin or NgCAM so that polylysine appears dark and L laminin N or NgCAM appears light. Fluorescent images of neurons and stripes were superimposed. Scale bar: 25 mm (Esch et al., 2000; their Fig. 1).

Figure 7.

The kinase inhibitor PF-4708671 promoted robust axonal regeneration of the corticospinal tract through and beyond the dorsal hemisection of the spinal cord. F, A parasagittal section of the spinal cord, from an animal that received 10 mm PF-4708671 shows corticospinal tract axonal regeneration across and beyond the lesion gap. The regenerated axons elongated within the distal spinal gray matter for considerable distances (blue arrows). G, Neurolucida reconstruction of the single section from F shows the lesion gap far beyond the main dorsal corticospinal tract (between two arrows). Varicosities of regenerated corticospinal tract axons extended within the distal spinal gray matter for considerable distances (from Al-Ali et al., 2017; their Fig. 9F,G).