Evidence That the Central Nervous System Can Induce a Modification at the Neuromuscular Junction That Contributes to the Maintenance of a Behavioral Response

Abstract

Neurons within the spinal cord are sensitive to environmental relations and can bring about a behavioral modification without input from the brain. For example, rats that have undergone a thoracic (T2) transection can learn to maintain a hind leg in a flexed position to minimize exposure to a noxious electrical stimulation (shock). Inactivating neurons within the spinal cord with lidocaine, or cutting communication between the spinal cord and the periphery (sciatic transection), eliminates the capacity to learn, which implies that it depends on spinal neurons. Here we show that these manipulations have no effect on the maintenance of the learned response, which implicates a peripheral process. EMG showed that learning augments the muscular response evoked by motoneuron output and that this effect survives a sciatic transection. Quantitative fluorescent imaging revealed that training brings about an increase in the area and intensity of ACh receptor labeling at the neuromuscular junction (NMJ). It is hypothesized that efferent motoneuron output, in conjunction with electrical stimulation of the tibialis anterior muscle, strengthens the connection at the NMJ in a Hebbian manner. Supporting this, paired stimulation of the efferent nerve and tibialis anterior generated an increase in flexion duration and augmented the evoked electrical response without input from the spinal cord. Evidence is presented that glutamatergic signaling contributes to plasticity at the NMJ. Labeling for vesicular glutamate transporter is evident at the motor endplate. Intramuscular application of an NMDAR antagonist blocked the acquisition/maintenance of the learned response and the strengthening of the evoked electrical response.

Behavioral studies of spinal conditioning: The spinal cord is smarter than you think it is.

“…From these initial observations, we can conclude that instituting a response-outcome relation brings about a rapid shift in flexion duration. Indeed, we subsequently showed that a master-yoke differences emerges within the first minute of training (Hoy et al, 2020). The rapidity of the learning led us to suggest that this behavioral modification depends upon a biologically prepared circuit (Grau et al, 2012).…”

“…If spinal neurons maintain the behavioral modification, inactivating the spinal cord with lidocaine or cutting the efferent (sciatic) nerve that contains the motor fibers should eliminate the learned response. Surprisingly, when Kevin Hoy performed these manipulations, neither affected the maintenance of the behavioral response (Hoy et al, 2020). The treatments did prevent the new learning required when the response criterion is raised (by increasing the contact electrode depth from 4 mm to 8 mm).…”

“…Another intriguing discovery stemmed from an incidental observation. Immunohistochemistry showed labeling for the NMDAR, and the enzymes needed to manufacture glutamate, in the vicinity of the NMJ (Hoy et al, 2020; Malomouzh et al, 2011). Glutamate release at the NMJ appears to play a functional role because injecting an NMDAR antagonist (MK-801) into the muscle blocked acquisition and the maintenance of the learned response.…”

“…While we have not eliminated this possibility, we now recognize that no such link may be needed to account for our results. This is particularly true after extended training, where we have shown that disconnecting the central nervous system from the efferent neurons has no effect on behavioral performance (Hoy et al, 2020). The outcome of learning appears attributable to the sensitization of the motoric output alone.…”

Morphological Changes in the Motor Endplate and in the Belly Muscle Induced by Previous Static Stretching to the Climbing Protocol

“…An action potential releases the acetylcholine (Ach) to the synaptic cleft, and the Ach binds to the specific receptors (AchR) in the motor endplate and promotes the sarcolemma’ depolarization, resulting in muscle contraction (Burden et al, 2018). AchR remodeling is triggered by the electric impulse frequency from the nervous system (Hoy et al, 2020). Furthermore, the type of physical training influences the motor endplate plasticity (Nishimune et al, 2014).…”