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James, N.

Publications and source records attributed to James, N..

2 recordsLinked to original sources

Viral-mediated transgenesis of MAOA and AVP increases territorial aggression in stickleback

Behavioral genetics in non-model organisms is currently gated by technological limitations. However, with the growing availability of genome editing and functional genomic tools, complex behavioral traits such as social behavior can now be explored in diverse organisms. Here we present a minimally invasive neurosurgical procedure for a classic behavioral, ecological and evolutionary system: threespine stickleback (Gasterosteus aculeatus). This method of direct brain injection enables viral-mediated transgenesis and pharmaceutical delivery which bypasses the blood-brain barrier. This method is flexible, fast, and amenable to statistically powerful within-subject experimental designs, making it well-suited for use in genetically diverse animals such as those collected from natural populations. Viral-mediated transgenesis in the brain allows for a direct examination of the genetic mechanisms underlying behavior in wild-caught animals from natural populations. Using this method, we were able to detect changes in aggression from the knockdown of either of two different genes, arginine vasopressin (AVP) and monoamine oxidase (MAOA), in outbred animals in less than one month. In addition, we demonstrate that widely available mammalian plasmids work with this method, lowering the barrier of entry to the technique.

genetics

RECRUITMENT OF UPPER-LIMB MOTONEURONS WITH EPIDURAL ELECTRICAL STIMULATION OF THE PRIMATE CERVICAL SPINAL CORD

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a realistic computational model of EES of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of this modulation and characterize the recruitment selectivity of cervical stimulation interfaces. Our results indicate that interfaces with lateral electrodes can target individual posterior roots and achieve selective modulation of arm motoneurons via the direct recruitment of pre-synaptic pathways. Intraoperative recordings suggested similar properties in humans. These results provide a framework for the design of neuro-technologies to improve arm and hand control in humans with quadriplegia.

bioengineering