Organization of pontine reticulospinal inputs to motoneurons controlling axial and limb muscles in the neonatal mouse

Abstract

Sivertsen MS, Glover JC, Perreault MC. Organization of pontine reticulospinal inputs to motoneurons controlling axial and limb muscles in the neonatal mouse. J Neurophysiol 112: 1628 -1643, 2014. First published June 18, 2014 doi:10.1152/jn.00820.2013.-Using optical recording of synaptically mediated calcium transients and selective spinal lesions, we investigated the pattern of activation of spinal motoneurons (MNs) by the pontine reticulospinal projection in isolated brain stem-spinal cord preparations from the neonatal mouse. Stimulation sites throughout the region where the pontine reticulospinal neurons reside reliably activated MNs at cervical, thoracic, and lumbar levels. Activation was similar in MNs ipsi-and contralateral to the stimulation site, similar in medial and lateral motor columns that contain trunk and limb MNs, respectively, and similar in the L2 and L5 segments that predominantly contain flexor and extensor MNs, respectively. In nonlesioned preparations, responses in both ipsi-and contralateral MNs followed individual stimuli in stimulus trains nearly one-to-one (with few failures). After unilateral hemisection at C1 on the same side as the stimulation, responses had substantially smaller magnitudes and longer latencies and no longer followed individual stimuli. After unilateral hemisection at C1 on the side opposite to the stimulation, the responses were also smaller, but their latencies were not affected. Thus we distinguish two pontine reticulospinal pathways to spinal MNs, one uncrossed and the other crossed, of which the uncrossed pathway transmits more faithfully and appears to be more direct. motor control; descending pathways; brain stem; spinal cord; trunk; limb THE MAMMALIAN RETICULOSPINAL system, consisting of the mesencephalic, pontine, and medullary reticulospinal pathways, is crucial for the control of skeletal musculature (Baker 2011;Kuypers 1964;Lemon 2008;Perreault and Glover 2013;Peterson 1979;Pettersson et al. 2007), but the neural mechanisms by which it initiates and regulates movement are far from understood.Electrical stimulation has been a key method in studying the organization of the mammalian reticulospinal system, revealing excitatory reticulospinal connections (mono-and polysynaptic) with axial motoneurons (MNs), proximal and distal limb MNs, and digit MNs in a variety of species (monkey: Davidson and Buford 2006;Riddle et al. 2009; cat: Drew and Rossignol 1990b;Galea et al. 2010;Grillner et al. 1968;Jankowska et al. 2003;Lloyd 1941;Peterson et al. 1979;Sprague and Chambers 1954;Wilson and Yoshida 1969; rat: Bolzoni et al. 2013; Floeter and Lev-Tov 1993;Umeda et al. 2010; and mouse: Alstermark and Ogawa 2004;Szokol et al. 2008). However, many studies have not differentiated among different areas of the reticular formation (RF) that project to the spinal cord. For example, stimulation of the medial longitudinal fasciculus (MLF), in which many (but certainly not all) reticulospinal axons project, is often used as a proxy for stimulating reticulospinal projectio...

Descending Command Neurons in the Brainstem that Halt Locomotion

“…In accordance with previous reports (Bretzner and Brownstone, 2013; Kimura et al, 2013), we found V2a neurons to be exclusively glutamatergic. They thus represent a unique contingent that diverges from other excitatory descending systems, thought to favor excitability (Dubuc et al, 2008; Hägglund et al, 2010; Perreault and Glover, 2013; Sivertsen et al, 2014). Importantly, our split-bath experiments in vitro indicate that the V2a descending command is integrated in the spinal cord.…”

Pontine reticulospinal projections in the neonatal mouse: Internal organization and axon trajectories

“…Although we have focused here on the pRS neuron populations in the core of the PRF that relate directly to the stimulation sites that we identified in our previous study (Sivertsen et al, ), it is also important to note that descending pathways from the pontine reticular formation and the pons in general are functionally heterogeneous. Several specific pathways to the spinal cord have been identified that regulate such diverse functions as respiration, nociception, micturition, defecation, sexually triggered glandular secretion, and noradrenergic modulation (for review see Holstege and Kuypers, ; Holstege, ).…”

“…Ex vivo preparations of the neonatal mouse spinal cord are capable of generating fictive locomotor activity and this has facilitated both anatomical and physiological studies of the underlying synaptic connections (Kiehn, ). With the brainstem attached, it is possible to investigate the descending control of spinal motor circuits with great precision (Szokol et al, ; Sivertsen et al, ; Kasumacic et al, ). Because the structures are small and myelination is still nascent, high‐throughput optical methods for physiological investigation are especially feasible (Szokol and Perreault, ).…”

“…We recently characterized in the neonatal mouse the pattern of functional connections between pontine reticulospinal (pRS) neurons and spinal motoneurons (MNs), using optical recording of synaptically mediated calcium responses (Sivertsen et al, ). We showed that these connections are already established at birth and are mediated by two parallel channels, one involving pRS axons that descend ipsilaterally (uncrossed projection) and the other involving pRS axons that descend contralaterally (crossed projection).…”

Cellular reactions and compensatory tissue re‐organization during spontaneous recovery after spinal cord injury in neonatal mice

“…Mice are born at a less mature stage than humans, such that SCI in neonatal mice would correspond to a late third trimester in utero SCI in humans. Although many descending axon tracts have already reached the spinal cord and established synaptic connections onto spinal neurons by birth in the mouse (Auclair et al, 1999;Szokol et al, 2008Szokol et al, , 2011Kasumacic et al, 2010Kasumacic et al, , 2012Kasumacic et al, , 2015Sivertsen et al, 2014), some, including the corticospinal tract, have not, and even those that have may undergo further postnatal maturation (Lambert et al, 2016). Thus, SCI in neonatal mice represents a situation in which both ongoing development and injury recovery mechanisms occur simultaneously.…”