Sensorimotor Cortex Ablation Prevents H-Reflex Up-Conditioning and Causes a Paradoxical Response to Down-Conditioning in Rats

Abstract

. Operant conditioning of the H-reflex, a simple model for skill acquisition, requires the corticospinal tract (CST) and does not require other major descending pathways. To further explore its mechanisms, we assessed the effects of ablating contralateral sensorimotor cortex (cSMC). In 22 Sprague-Dawley rats, the hindlimb area of left cSMC was ablated. EMG electrodes were implanted in the right soleus muscle and a stimulating cuff was placed around the right posterior tibial nerve. When EMG remained in a specified range, nerve stimulation just above the M response threshold elicited the H-reflex. In control mode, no reward occurred. In conditioning mode, reward occurred if H-reflex size was above (HRup mode) or below (HRdown mode) a criterion value. After exposure to the control mode for Ն10 days, each rat was exposed for another 50 days to the control mode, the HRup mode, or the HRdown mode. In control and HRup rats, final H-reflex size was not significantly different from initial H-reflex size. In contrast, in HRdown rats, final H-reflex size was significantly increased to an average of 136% of initial size. Thus like recent CST transection, cSMC ablation greatly impaired up-conditioning. However, unlike recent CST transection, cSMC produced a paradoxical response to down-conditioning: the H-reflex actually increased. These results confirm the critical role of cSMC in H-reflex conditioning and suggest that this role extends beyond producing essential CST activity. Its interactions with ipsilateral SMC or other areas contribute to the complex pattern of spinal and supraspinal plasticity that underlies H-reflex conditioning. I N T R O D U C T I O NDuring development and skill acquisition, as well as after spinal cord injury or with other CNS disorders, descending input from the brain combines with peripheral input to change the spinal cord (for reviews see Casabona et al. 1990;Goode and Van Hoven 1982;Koceja et al. 1991;Levinsson et al. 1999;Myklebust et al. 1982Myklebust et al. , 1986Nielsen et al. 1993;O'Sullivan et al. 1991;Straka and Dieringer 1995;Wolpaw and Tennissen 2001). The pathways and processes through which this descending input induces and maintains spinal cord plasticity remain largely unknown. The recently appreciated possibilities for CNS regeneration have raised questions regarding how regenerated neuronal tissue can become useful and how it can be shaped to provide normal, or at least acceptable, function (Wolpaw 2001(Wolpaw , 2002. Thus they have drawn attention to the mechanisms by which the brain gradually shapes spinal cord pathways to function properly during movement (Bregman 1998;Fawcett 1998;Ramer et al. 2000;Tuszynski and Kordower 1999). Understanding these mechanisms could lead to novel methods for inducing, guiding, and assessing recovery after injury.Operant conditioning of the spinal stretch reflex (SSR) or its electrical analog, the H-reflex, is a simple model for studying the brain's induction and maintenance of appropriate spinal cord function (Wolpaw 1997). Because the spinal ...

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

“…The present study further explored this long-term effect and its underlying mechanisms by studying spinal GABAergic interneurons and motoneuron GABAergic terminals and receptors. This focus on spinal GABAergic function was based on the evidence that operant down-conditioning of the H-reflex, which is driven by SMC and its corticospinal tract (CST) output Wolpaw 1997, 2002;Chen et al , 2003Chen et al , 2006a, is associated with large changes in GABAergic interneurons in the ventral horn and GABAergic terminals on spinal motoneurons (Pillai et al 2008;Wang et al 2006aWang et al , 2009). These studies suggested that the CST acts through GABAergic interneurons and their terminals on motoneurons to produce the motoneuron plasticity underlying H-reflex down-conditioning and thereby motivated the present investigation of GABAergic involvement in the effect of SMC stimulation on the H-reflex.…”

Locomotor impact of beneficial or nonbeneficial H-reflex conditioning after spinal cord injury

“…[H-reflex conditioning is comparable in male and female rats (Chen and Wolpaw 1995, 1996, 1997, 2006a, 2006b, 2006c.] All procedures satisfied the "Guide for the Care and Use of Laboratory Animals" (National Academies Press, Washington, DC, 2011) and had been reviewed and approved by the Institutional Animal Care and Use Committee of the Wadsworth Center.…”

Spike Timing-Dependent Plasticity in the Long-Latency Stretch Reflex Following Paired Stimulation from a Wearable Electronic Device

“…In the rat, reflex conditioning depends on the corticospinal tract and sensorimotor cortex, but not other descending pathways Wolpaw, 1997, 2002;Chen et al, 2006a,b). Down-conditioning leads to increases in identifiable GABAergic terminals in the spinal cord (Wang et al, 2006), but is dependent on an intact cerebellum (Chen and Wolpaw, 2005); therefore, spinal plasticity seems to be guided and maintained by supraspinal pathways. It is likely that conceptually similar processes are occurring here, although whether the same central structures and descending pathways that contribute to reflex conditioning in the rat are responsible in this case remains to be determined.…”

“…However, this report marks the first demonstration of plasticity in the LLSR induced with paired stimulus paradigms, and may indicate that brainstem as well as corticospinal descending systems can undergo plastic changes. Previous work has shown that rehabilitation after spinal cord injury can be enhanced by up-or down-conditioning of spinal reflexes (Chen et al, 2006c;Thompson et al, 2013). We hope that the novel protocol introduced here may open up new possibilities for enhancing rehabilitation during recovery from stroke or spinal cord injury, in which we have shown that brainstem pathways play an important role (Zaaimi et al, 2012).…”