Spinal cord injury significantly alters the properties of reticulospinal neurons: delayed repolarization mediated by potassium channels.

After rostral spinal cord injury (SCI) of lampreys, the descending axons of injured (axotomized) reticulospinal (RS) neurons regenerate and locomotor function gradually recovers. Our previous studies indicated that relative to uninjured lamprey RS neurons, injured RS neurons display several dramatic changes in their biophysical properties, called the "injury phenotype." In the present study, at the onset of applied depolarizing current pulses for membrane potentials below as well as above threshold for action potentials (APs), injured RS neurons displayed a transient depolarization consisting of an initial depolarizing component followed by a delayed repolarizing component.

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.

Modeling of lamprey reticulospinal neurons: multiple distinct parameter sets yield realistic simulations.

For the lamprey and other vertebrates, reticulospinal (RS) neurons project descending axons to the spinal cord and activate motor networks to initiate locomotion and other behaviors. In the present study, a biophysically detailed computer model of lamprey RS neurons was constructed consisting of three compartments: dendritic, somatic, and axon initial segment (AIS). All compartments included passive channels.

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.

Genomic discovery of ion channel genes in the central nervous system of the lamprey Petromyzon marinus.

The lamprey is a popular animal model for a number of types of neurobiology studies, including organization and operation of locomotor and respiratory systems, behavioral recovery following spinal cord injury (SCI), cellular and synaptic neurophysiology, comparative neuroanatomy, neuropharmacology, and neurodevelopment. Yet relatively little work has been done on the molecular underpinnings of nervous system function in lamprey. This is due in part to a paucity of gene information for some of the most fundamental proteins involved in neural activity: ion channels.

Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity.

The contribution of left-right reciprocal coupling between spinal locomotor networks to the generation of locomotor activity was tested in adult lampreys. Muscle recordings were made from normal animals as well as from experimental animals with rostral midline (ML) spinal lesions (~13%→35% body length, BL), before and after spinal transections (T) at 35% BL. Importantly, in the present study actual locomotor movements and muscle burst activity, as well as other motor activity, were initiated in whole animals by descending brain-spinal pathways in response to sensory stimulation of the anterior head.

Regulation of axonal regeneration following spinal cord injury in the lamprey.

Following rostral spinal cord injury (SCI) in larval lampreys, injured descending brain neurons, particularly reticulospinal (RS) neurons, regenerate their axons, and locomotor behavior recovers in a few weeks. However, axonal regeneration of descending brain neurons is mostly limited to relatively short distances, but the mechanisms for incomplete axonal regeneration are unclear. First, lampreys with rostral SCI exhibited greater axonal regeneration of descending brain neurons, including RS neurons, as well as more rapid recovery of locomotor muscle activity right below the lesion site, compared with animals with caudal SCI.

Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury.

Unlabelled: Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI.

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.

Descending brain neurons in larval lamprey: spinal projection patterns and initiation of locomotion.

In larval lamprey, partial lesions were made in the rostral spinal cord to determine which spinal tracts are important for descending activation of locomotion and to identify descending brain neurons that project in these tracts. In whole animals and in vitro brain/spinal cord preparations, brain-initiated spinal locomotor activity was present when the lateral or intermediate spinal tracts were spared but usually was abolished when the medial tracts were spared. We previously showed that descending brain neurons are located in eleven cell groups, including reticulospinal (RS) neurons in the mesenecephalic reticular nucleus (MRN) as well as the anterior (ARRN), middle (MRRN), and posterior (PRRN) rhombencephalic reticular nuclei.

Spinal cord injury induces changes in electrophysiological properties and ion channel expression of reticulospinal neurons in larval lamprey.

In larval lamprey, hemitransections were performed on the right side of the rostral spinal cord to axotomize ipsilateral reticulospinal (RS) neurons. First, at short recovery times (2-3 weeks), uninjured RS neurons contralateral to hemitransections fired a smooth train of action potentials in response to sustained depolarization, whereas axotomized neurons fired a single short burst or short repetitive bursts. For uninjured RS neurons, the afterpotentials of action potentials had three components: fast afterhyperpolarization (fAHP), afterdepolarizing potential (ADP), and slow AHP (sAHP) that was attributable to calcium influx via high-voltage-activated (HVA) (N- and P/Q-type) calcium channels and calcium-activated potassium channels (SKKCa).

Glutamate regulates neurite outgrowth of cultured descending brain neurons from larval lamprey.

In larval lamprey, descending brain neurons, which regenerate their axons following spinal cord injury, were isolated and examined in cell culture to identify some of the factors that regulate neurite outgrowth. Focal application of 5 mM or 25 mM L-glutamate to single growth cones inhibited outgrowth of the treated neurite, but other neurites from the same neuron were not inhibited, an effect that has not been well studied for neurons in other systems. Glutamate-induced inhibition of neurite outgrowth was abolished by 10 mM kynurenic acid.

Movements and muscle activity initiated by brain locomotor areas in semi-intact preparations from larval lamprey.

In in vitro brain/spinal cord preparations from larval lamprey, locomotor-like ventral root burst activity can be initiated by pharmacological (i.e., "chemical") microstimulation in several brain areas: rostrolateral rhombencephalon (RLR); dorsolateral mesencephalon (DLM); ventromedial diencephalon (VMD); and reticular nuclei.

Fluorogold labeling of descending brain neurons in larval lamprey does not cause cell death.

In our previous double-labeling studies, the fluorescent anatomical tracers Fluorogold (FG) and Texas red dextran amine (TRDA) were used to demonstrate that descending brain neurons, approximately 80% of which are reticulospinal (RS) neurons, in spinal cord-transected larval lamprey regenerate their axons. However, the numbers of FG-labeled descending brain neurons decreased significantly with increasing recovery times, from 2 to 16 weeks. For some FG-labeled mammalian neurons, FG appears to degrade and/or be lost over time, while in other neurons this tracer can kill neurons.

Disruption of left-right reciprocal coupling in the spinal cord of larval lamprey abolishes brain-initiated locomotor activity.

In this study, contributions of left-right reciprocal coupling mediated by commissural interneurons in spinal locomotor networks to rhythmogenesis were examined in larval lamprey that had longitudinal midline lesions in the rostral spinal cord [8 --> 30% body length (BL), relative distance from the head] or caudal spinal cord (30 --> 50% BL). Motor activity was initiated from brain locomotor command systems in whole animals or in vitro brain/spinal cord preparations. After midline lesions in the caudal spinal cord in whole animals and in vitro preparations, left-right alternating burst activity could be initiated in rostral and usually caudal regions of spinal motor networks.

Conditioning lesions enhance axonal regeneration of descending brain neurons in spinal-cord-transected larval lamprey.

In larval lamprey, with increasing recovery times after a transection of the rostral spinal cord, there is a gradual recovery of locomotor behavior, and descending brain neurons regenerate their axons for progressively greater distances below the transection site. In the present study, spinal cord "conditioning lesions" (i.e.

Axonal regeneration of descending and ascending spinal projection neurons in spinal cord-transected larval lamprey.

The distributions of descending and ascending spinal projection neurons (i.e., spinal neurons with moderate to long axons) were compared in normal larval lamprey and in animals that had recovered for 8 weeks following a complete spinal cord transection at 50% body length (BL, normalized distance from the anterior head).

Changes in locomotor activity parameters with variations in cycle time in larval lamprey.

In larval lamprey, locomotor activity recorded from whole animals and in vitro brain/spinal cord preparations was analyzed to determine how two parameters of locomotor activity, burst proportion (BP; relative duration of motor burst activity) and intersegmental phase lag (phi; normalized delay of burst activity along one side of the body), vary with changes in cycle time (T). In individual animals, the slopes of BP and phi versus T were compared using linear regression analysis, followed by statistical analysis of the slopes to determine whether the parameters changed significantly with variations in cycle time. For locomotor muscle activity in whole animals, the BP values increased significantly with decreases in T (i.

Increase in descending brain-spinal cord projections with age in larval lamprey: implications for spinal cord injury.

The purpose of this study was to determine whether new descending brain-spinal cord projections are added with age in larval lamprey and might contribute substantially to restoration of these projections following spinal cord injury. Retrograde horseradish peroxidase (HRP) labeling of descending brain neurons was performed in "young" and "old" larval lamprey that differed in age by at least one year. In old larval lamprey, significantly more descending brain neurons projected to specific rostral levels of the spinal cord than in young animals.