Spinal learning in the adult mouse using the Horridge paradigm

Abstract

The spinal cord is endogenously capable of several forms of adaptive plasticity and learning, including functional re-training, instrumental, and Pavlovian learning. Understanding the mechanisms of spinal plasticity could lead to improved therapies for spinal cord injury and other neuromotor disorders. We describe and demonstrate techniques for eliciting spinal learning in the adult mouse using the Horridge paradigm. In the Horridge paradigm, instrumental learning occurs when a nociceptive leg stimulus is made to be contingent on leg position and the spinal cord learns to maintain the ankle in a flexed position. Using fine-wire intramuscular stimulating electrodes, an inexpensive real-time video tracking system, and DC current stimulation, we were able to elicit instrumental spinal learning from mouse lumbrosacral spinal cords that were functionally isolated from the brain. This technique makes it more feasible to use the powerful genetic manipulations available in mice to better understand the processes of spinal learning, memory, and plasticity.

And yet it moves : Recovery of volitional control after spinal cord injury

“…The spinal cord owns smart abilities, such as learning new motor tasks, forget them after a lesion or disuse and remember them again after an intense task specific training, that were considered, until more recently, to be a prerogative solely of the brain ( Edgerton et al, 2004 , Edgerton et al, 2001 , Jindrich et al, 2009 ). In the brain, information storage and refinement of neuronal circuits occurs through the phenomenon of Hebbian synaptic plasticity, which pairs stimulation of pre- and post- synaptic terminals ( Voronin and Cherubini, 2004 ).…”

Effects of Diet and/or Exercise in Enhancing Spinal Cord Sensorimotor Learning

“…The details of the PaWL testing for mice have been described previously [37]. Briefly, during testing the mice were restrained in a closed cloth harness with two slots cut at the end of the harness to allow for both hindlegs to hang freely.…”

“…This stimulation intensity then was used for the PaWL testing. We previously have shown this to be the optimal force level needed to elicit instrumental paw withdrawal learning [35], [37]. To determine the optimal force, one end of a silk thread was tied firmly around the distal end of the metatarsals just proximal to the metarsophalangeal joint and the other end was attached to a force transducer (Dual Mode Muscle Lever 300BLR, Aurora Scientific Inc., Aurora, Ontario, Canada).…”

The Spinal Cord, Not to Be Forgotten: the Final Common Path for Development, Training and Recovery of Motor Function

“…However, rigorous studies and replications of the findings across different laboratories have provided strong evidence that the isolated spinal cord is capable of exhibiting instrumental learning when isolated from brain circuits. Two models of instrumental learning have been examined within the isolated spinal cord-one in rats (Grau et al, 1998), and the other in mice (Jindrich et al, 2009).…”

“…These animals are called Masters because they have control over whether or not they receive shock stimulation. Without brain input, Masters easily learn over a 30-min training period to maintain their hind leg in a flexed position (response) in order to minimize shock exposure (outcome; Grau et al, 1998;Jindrich et al, 2009).…”