Spinal Cord Injury Significantly Alters the Properties of Reticulospinal Neurons: I. Biophysical Properties, Firing Patterns, Excitability, and Synaptic Inputs.

Following spinal cord injury (SCI) for larval lampreys, descending axons of reticulospinal (RS) neurons regenerate, and locomotor function gradually recovers. In the present study, the electrophysiological properties of uninjured (left)-injured (right) pairs of large, identified RS neurons were compared following rostral, right spinal cord hemi-transections (HTs). First, changes in firing patterns of injured RS neurons began in as little as 2-3 days following injury, these changes were maximal at ~2-3 weeks (wks), and by 12-16 wks normal firing patterns were restored for the majority of neurons. Second, at ~2-3 wks following spinal cord HTs, injured RS neurons displayed several significant changes in properties compared to uninjured neurons: (a) more hyperpolarized VREST; (b) longer membrane time constant and larger membrane capacitance; (c) increased voltage and current thresholds for action potentials (APs); (d) larger amplitudes and durations for APs; (e) higher slope for the repolarizing phase of APs; (f) virtual absence of some afterpotential components, including the slow afterhyperpolarization (sAHP); (g) altered, injury-type firing patterns; and (h) reduced average and peak firing (spiking) frequencies during applied depolarizing currents. These altered properties, referred to as the "injury phenotype", reduced excitability and spiking frequencies of injured RS neurons compared to uninjured neurons. Third, artificially injecting a current to add a sAHP waveform following APs for injured neurons or removing the sAHP following APs for uninjured neurons did not convert these neurons to normal firing patterns or injury-type firing patterns, respectively. Fourth, trigeminal sensory-evoked synaptic responses recorded from uninjured and injured pairs of RS neurons were not significantly different. Following SCI, injured lamprey RS neurons displayed several dramatic changes in their biophysical properties that are expected to reduce calcium influx and provide supportive intracellular conditions for axonal regeneration.

Restoration of the Topological Organization of the Trigeminal System Following Trigeminal Nerve Root Injury in the Lamprey.

Two issues were examined regarding the trigeminal system in larval lampreys: (1) for normal animals, double labeling was used to confirm that the trigeminal system has a topological organization; (2) following trigeminal nerve root transections, double labeling was used to test whether the topological organization of the trigeminal system is restored. First, for normal animals, Alexa 488 dextran amine applied to the medial oral hood (anterior head) labeled trigeminal motoneurons (MNs) in the ventromedial part of the trigeminal motor nuclei (nVm) and axons of trigeminal sensory neurons (SNs) in the ventromedial part of the trigeminal descending tracts (dV). Also, Texas red dextran amine (TRDA) applied to the lateral oral hood labeled trigeminal MNs in the dorsolateral nVm and sensory axons in the dorsolateral dV. These results confirm the topological organization of the trigeminal system of normal lampreys. Second, following trigeminal nerve root transections, the physical integrity of the nerves was restored during growth of trigeminal sensory and motor axons. In addition, double labeling indicated a restoration and refinement of the topological organization of the trigeminal system with increasing recovery times, but mainly for nVm. Despite the paucity of growth of trigeminal sensory axons in dV even at long recovery times (12-16 wks), a substantial percentage of experimental animals recovered trigeminal-evoked swimming responses and trigeminal-evoked synaptic responses in reticulospinal (RS) neurons. Following trigeminal nerve root injury, several mechanisms, including axonal guidance cues, probably contribute to the substantial restoration of the topological organization of the lamprey trigeminal system.

Similarities and Differences for Swimming in Larval and Adult Lampreys.

The spinal locomotor networks controlling swimming behavior in larval and adult lampreys may have some important differences. As an initial step in comparing the locomotor systems in lampreys, in larval animals the relative timing of locomotor movements and muscle burst activity were determined and compared to those previously published for adults. In addition, the kinematics for free swimming in larval and adult lampreys was compared in detail for the first time. First, for swimming in larval animals, the neuromechanical phase lag between the onsets or terminations of muscle burst activity and maximum concave curvature of the body increased with increasing distance along the body, similar to that previously shown in adults. Second, in larval lampreys, but not adults, absolute swimming speed (U; mm s(-1)) increased with animal length (L). In contrast, normalized swimming speed (U'; body lengths [bl] s(-1)) did not increase with L in larval or adult animals. In both larval and adult lampreys, U' and normalized wave speed (V') increased with increasing tail-beat frequency. Wavelength and mechanical phase lag did not vary significantly with tail-beat frequency but were significantly different in larval and adult animals. Swimming in larval animals was characterized by a smaller U/V ratio, Froude efficiency, and Strouhal number than in adults, suggesting less efficient swimming for larval animals. In addition, during swimming in larval lampreys, normalized lateral head movements were larger and normalized lateral tail movements were smaller than for adults. Finally, larval animals had proportionally smaller lateral surface areas of the caudal body and fin areas than adults. These differences are well suited for larval sea lampreys that spend most of the time buried in mud/sand, in which swimming efficiency is not critical, compared to adults that would experience significant selection pressure to evolve higher-efficiency swimming to catch up to and attach to fish for feeding as well as engage in long-distance migration during spawning. Finally, the differences in swim efficiency for larval and adult lampreys are compared to other animals employing the anguilliform mode of swimming.