Sensory and descending motor circuitry during development and injury

Abstract

Proprioceptive sensory input and descending supraspinal projections are two major inputs that feed into and influence spinal circuitry and locomotor behaviors. Here we review their influence on each other during development and after spinal cord injury. We highlight developmental mechanisms of circuit formation as they relate to the sensory-motor circuit and its reciprocal interactions with local spinal interneurons, as well as competitive interactions between proprioceptive and descending supraspinal inputs in the setting of spinal cord injury.

Figure 1:. Proprioceptive and corticospinal tract inputs into spinal circuitry.

(A) Information about stretch of a peripheral muscle is carried from the periphery to the spinal cord via proprioceptive sensory neurons that transmit the information to motor neurons both directly and indirectly via spinal interneurons. In rodents, corticospinal tract (CST) fibers form rare monosynaptic connections onto motor neurons, while the majority of CST contacts are formed with interneurons [49][33].

Figure 2:. Changes in circuit connectivity as a result of alterations in sensory or cortical input.

(A-A’’’) GABApre terminals (blue) express the GABA synthetic enzymes GAD65 and GAD67 and form axo-axonic contacts on vGluT1-expressing sensory afferent terminals (red) in the ventral spinal cord [33] (A). In the absence of their normal sensory terminal targets, GABApre interneurons initially project into their usual ventral target zone, but eventually retract [33] (A’). GABApre-sensory terminal specificity is controlled by an adhesion complex, consisting of sensory neuron expression of Cntn-5/Caspr4 and GABApre neuron expression of NrCAM/CHL1 [35••] (A’’). The inhibitory efficacy of GABApre terminals, as measured by expression of GAD65 and GAD67, is regulated by BDNF and glutamate from sensory neurons via BDNF receptor TrkB and glutamate receptor mGluR1β in GABApre neurons [33][38•] (A’’’). (B and B’) Extensor and flexor premotor interneurons segregate into medial (m) and lateral (l) domains respectively. Proprioceptive afferents form connections preferentially with extensor premotor interneurons in the intermediate spinal cord (B). In the absence of sensory input, the position of premotor interneurons is altered such that premotor interneurons that are usually positioned medially move laterally [30] (B’). (C-C’’) Proprioceptive sensory fiber input and corticospinal projections (purple) innervate similar domains in the spinal cord (C). Corticospinal injury by unilateral pyramid transection increases sensory fiber input to the spinal cord [42]. Also, increased proprioceptive afferent activity via electrical stimulation results in afferent sprouting and corticospinal axon withdrawal [43••] (C’). Deafferentation of sensory input by dorsal rootlet sectioning increases input of corticospinal fibers predominantly onto interneurons [43••] (C’’)