The Positional Logic of Sensory-Motor Reflex Circuit Assembly.

Throughout his scientific career, Tom Jessell pioneered the spinal cord as a model system to study the molecular programs of neural specification, axon guidance, and connection specificity. His contributions to these fields and more broadly to that of developmental neuroscience will continue to inspire and define many generations of researchers. It is challenging to capture all of Tom's findings in one essay, and therefore, here we wish to briefly highlight his contributions to the problem of connection specificity, with a focus on the spinal sensory-motor reflex circuit. In particular, emphasis will be placed on discoveries from his laboratory that revealed a significant role of positional strategies in establishing selective sensory-motor connections. This work introduced novel principles of neuronal connectivity that may apply to how precise circuit wiring occurs throughout the nervous system.

Requirement for Dicer in Maintenance of Monosynaptic Sensory-Motor Circuits in the Spinal Cord.

In contrast to our knowledge of mechanisms governing circuit formation, our understanding of how neural circuits are maintained is limited. Here, we show that Dicer, an RNaseIII protein required for processing microRNAs (miRNAs), is essential for maintenance of the spinal monosynaptic stretch reflex circuit in which group Ia proprioceptive sensory neurons form direct connections with motor neurons. In postnatal mice lacking Dicer in proprioceptor sensory neurons, there are no obvious defects in specificity or formation of monosynaptic sensory-motor connections. However, these circuits degrade through synapse loss and retraction of proprioceptive axonal projections from the ventral spinal cord. Peripheral terminals are also impaired without retracting from muscle targets. Interestingly, despite these central and peripheral axonal defects, proprioceptive neurons survive in the absence of Dicer-processed miRNAs. These findings reveal that Dicer, through its production of mature miRNAs, plays a key role in the maintenance of monosynaptic sensory-motor circuits.