Cortical stimulation causes long-term changes in H-reflexes and spinal motoneuron GABA receptors

Abstract

The cortex gradually modifies the spinal cord during development, throughout later life, and in response to trauma or disease. The mechanisms of this essential function are not well understood. In this study, weak electrical stimulation of rat sensorimotor cortex increased the soleus H-reflex, increased the numbers and sizes of GABAergic spinal interneurons and GABAergic terminals on soleus motoneurons, and decreased GABA A and GABA B receptor labeling in these motoneurons. Several months after the stimulation ended the interneuron and terminal increases had disappeared, but the H-reflex increase and the receptor decreases remained. The changes in GABAergic terminals and GABA B receptors accurately predicted the changes in H-reflex size. The results reveal a new long-term dimension to corticalspinal interactions and raise new therapeutic possibilities. brain stimulation; spinal cord plasticity; GABAergic terminal, interneuron, and receptor; learning and memory THE IMMEDIATE EFFECTS of cortical neuronal activity on the spinal cord are widely studied (e.g., Alstermark and Isa 2012), but its long-term effects have received much less attention. Nevertheless, during development and throughout life the cortex gradually changes spinal pathways to support the acquisition and maintenance of skills such as locomotion, and impairments in this regulation contribute to the disabilities produced by strokes, spinal cord injuries, and other disorders (Knikou 2010;Wolpaw 2010). The mechanisms of this long-term regulation are poorly understood. We are using long-term cortical regulation of the H-reflex, the electrical analog of the spinal stretch reflex (SSR), as a model for studying this important cortical function. The H-reflex, the simplest behavior of the vertebrate CNS, is produced by a wholly spinal and largely monosynaptic pathway consisting of the primary afferent neuron, the motoneuron, and the synapse between them.In primates and rodents, an operant conditioning protocol can change sensorimotor cortex (SMC) activity and thereby gradually increase or decrease H-reflex size (Wolpaw 2010; Wolpaw and Chen 2009). These larger or smaller reflexes, which persist after conditioning ends, are simple motor skills (i.e., adaptive behaviors acquired through practice; Compact Oxford English Dictionary 1993). The reflex changes are produced and maintained by a complex hierarchy of plasticity at both spinal and supraspinal sites Wolpaw 2010 for review). While much remains to be learned about this hierarchy and the sites and mechanisms of plasticity, it is clear that SMC activity modifies the H-reflex by producing changes in the motoneuron (e.g., in firing threshold), as well as elsewhere in the spinal cord. Recent studies showing that operantly conditioned H-reflex decreases are accompanied by marked changes in GABAergic interneurons in the ventral horn and in GABAergic terminals on spinal motoneurons suggest that changes in GABAergic function may play a key role in producing the motoneuron plasticity directly underlying H-reflex ...

Treadmill training promotes spinal changes leading to locomotor recovery after partial spinal cord injury in cats

“…In the chronic spinal cat, studies have shown that training could act on the central pattern generator (CPG) excitability by modulating spinal cord inhibitory circuits (de Leon et al 1999). In addition, training might induce changes in the firing threshold and conduction velocity of motoneurons [mechanisms explored in a series of studies on monosynaptic stretch reflex, which can be modulated in both animals and humans (Wang et al 2012;Wolpaw 1997)] that might be crucial in the adaptation of the CPG excitability. Finally, neuromodulators such as monoamines or neuropeptides can influence the functional status of the CPG circuitry (Ribotta et al 2000).…”

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A novel simplistic fabrication technique for cranial epidural electrodes for chronic recording and stimulation in rats

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H‐reflex conditioning during locomotion in people with spinal cord injury

“…Studies in rats and non-human primates indicate that the smaller H-reflex produced by steady-state conditioning is largely attributable to a positive shift in motoneuron firing threshold (Carp & Wolpaw, 1994); it is associated with increases in GABAergic input to the motoneuron (Wang et al 2006;Wang et al 2012) and in the number of GABAergic interneurons in the ventral horn (Wang et al 2009). The present finding that swing-phase conditioning also decreases the standing H-reflex ( Fig.…”