Reciprocal functional interactions between the brainstem and the lower spinal cord

Abstract

The interplay of the neuronal discharge patterns regarding respiration and locomotion was investigated using electrophysiological techniques in a decerebrate and arterially perfused in situ mouse preparation. The phrenic, tibial, and/or peroneal nerve discharge became clearly organized into discharge episodes of increasing frequency and duration, punctuated by periods of quiescence as the perfusion flow rate increased at room temperature. The modulated sympathetic tone induced by the hyperoxic/normocapnic state was found to activate the locomotor pattern generator (LPG) via descending pathways and generate a left and right alternating discharge during discharge episodes in the motor nerves. The rhythm coupling of respiration and locomotion occurred at a 1:1 frequency ratio. Although the phrenic discharge synchronized with the tibial discharge at all flow rates tested, the time lag between peaks of the two discharges during locomotion was ≈400 ms rather than ≈200 ms, suggesting spinal feedback via ascending pathways. The incidence of the phrenic and tibial discharge episodes decreased by ≈50% after spinalization at the twelfth thoracic cord and the respiratory rhythm was more regular. These results indicate that: (i) locomotion can be generated in a hyperoxic/normocapnic state induced by specific respiratory conditions, (ii) the central mechanism regarding entrainment of respiratory and locomotor rhythms relies on spinal feedback via ascending pathways, initiated by the activated LPG generating locomotion, and (iii) the increase in respiratory rate seen during locomotion is caused not only by afferent mechanical and nociceptive inputs but also by impulses from the activated spinal cord producing a locomotor-like discharge via ascending pathways.

Quantitative Analysis of Activity Patterns in the Muscles of Mastication and Deglutition

“…The method is applicable to various EMG bursts with different amplitudes and active durations observed during mastication and deglutition. This chapter focused on these two functions only, but the T P method must be also applicable to muscle activities of other movements, such as respiration and locomotion, because these movements have neural mechanisms similar or common to those of mastication and deglutition (e.g., [60][61][62]).…”

Reciprocal functional interactions between the respiration/circulation center, the upper spinal cord, and the trigeminal system

“…During surgery, isoflurane concentration was maintained at 2.0%, and the depth of anesthesia was assessed by respiratory rate and responsiveness to tail pinch. The same surgical procedure as described in our previous study (see [ 12 ]) was then used to prepare the decerebrate and arterially perfused in situ rat preparation ( Fig. 1 , yellow dotted-line circle).…”

“…Such coupling can be provoked by electrical stimulation of either the mesencephalic locomotor region (MLR) or the subthalamic locomotor region [ 2 , 6 ] within a range of frequency ratios (e.g., 1:1, 2:1, and 3:2). Although the coordination of respiratory and locomotor rhythms is thought to be generated by either feed-forward [ 5 , 7 ] or spinal feedback mechanisms [ 8 – 12 ], the central neural mechanisms involved remain poorly understood.…”

“…We previously reported that nerve discharges become clearly organized into discharge episodes of increasing frequency and duration, punctuated by quiescent periods as perfusion flow rate increased at room temperature in decerebrate arterially perfused in situ mouse preparations [ 12 ]. The hyperoxic/ normocapnic state generated by the high flow rates could trigger the locomotor pattern generator and initiate fictive movement during discharge episodes in the hindlimbs and the increase in respiratory rate during locomotion was caused both by impulses from the lower spinal cord (which produces a locomotor-like discharge via ascending pathways) and afferent input received from mechanoreceptors and nociceptors, as discharge episodes originated in the lower spinal cord [ 12 ]. The preparation, originally developed by Pickering and Paton [ 21 ], is maintained by using artificial cardiopulmonary bypass to deliver oxygen to the body.…”

Role of Propriospinal Neurons in Control of Respiratory Muscles and Recovery of Breathing Following Injury

“…Several groups have investigated the potential of induced pluripotent stem cell (iPSC) derived propriospinal neurons as a potential therapy to restore respiratory motor function. For example, iPSC derived V2a and V3 neurons have been generated from mouse or human cells (Brown et al, 2014;Xu et al, 2015;Iyer et al, 2016;Butts et al, 2017Butts et al, , 2019White and Sakiyama-Elbert, 2019). iPSC derived V2a neurons have been transplanted into the spinal cord where they survive and appear to form synapses with host neurons (Butts et al, 2017;Zholudeva et al, 2018a).…”