NEURAL MECHANISMS OF INTERSEGMENTAL COORDINATION IN LAMPREY - LOCAL EXCITABILITY CHANGES MODIFY THE PHASE COUPLING ALONG THE SPINAL-CORD

1. To elucidate the neural mechanisms responsible for coordinating undulatory locomotor movements, the intersegmental phase lag was analyzed from ventral roots along the spinal cord during fictive swimming. It was induced by bath application of N-methyl-D-aspartate (NMDA) in in vitro preparations of lamprey spinal cord, while the excitability of different segments were modified. The phase lag between consecutive segments during normal forward swimming is 1% of the cycle duration in a broad range of values. Rostral segments are activated before more caudal ones. 2. Under control conditions, whole preparations (12-24 segment long; n = 22) were perfused with NMDA solutions of the same concentration (100-150-mu-M). The intersegmental phase lag values varied in a continuous range with a single peak around a median value of forward +0.74% per segment (range: forward +2.23% to backward -0.97%). 3. To examine whether excitability differences along the spinal cord could modify the intersegmental phase lag, different levels of excitatory amino acids (NMDA) were applied to spinal cord preparations positioned in a partitioned chamber. Different portions of the cord could be perfused separately by NMDA solutions of different concentrations (50-150-mu-M). If rostral segments were perfused with the higher NMDA solution, the lag was inevitably in the forward direction. Conversely, if the caudal portion was perfused with the higher NMDA solution, caudally located ventral roots became activated before the rostral ventral roots in a caudorostral succession, thus reversing the direction of the fictive swimming wave to propagate as during backward swimming. If the middle portion was perfused by the highest NMDA solution, this portion instead became leading, and the activity propagated from this point in both the rostral and the caudal directions. The portion located in the pool with highest NMDA concentration always gave rise to a "leading" segment. 4. When a portion of the preparation was perfused with an NMDA solution of a high concentration (75-150-mu-M), the cycle duration was close to that recorded when the whole preparation was perfused with the same high NMDA solution. The ensemble cycle duration is, therefore, largely determined by the leading segment. 5. The phase lag changes were not restricted to the region around the barrier separating pools with different NMDA solutions. For instance, the phase lag between any pair of ventral roots located in the same pool perfused by a solution containing a low concentration of NMDA (50 or 75-mu-M) became larger, if the NMDA concentration in the other pool was increased (100 or 150-mu-M), irrespectively of whether it was located rostrally or caudally. A local increase of excitability in a few segments is thus sufficient to produce a phase lag change along the entire spinal cord preparation. 6. The phase lag could be induced to change in a continuous range from forward (+2 to +3% per segment) to backward values (-2 to -3%), depending on the ratio of NMDA concentrations in different pools (50 vs. 75 - 50 vs. 150-mu-M), irrespectively of the location of the leading segment (rostral or caudal). The bigger the excitability ratio, the larger the phase lag along the entire spinal cord preparation. 7. A leading segment located at the caudal end of the preparation entrained the rest of the cord in the same manner as a leading segment located at the rostral end with regard to its effects on both the intersegmental phase lag and the ensemble cycle duration. The ascending and descending coupling mechanisms can therefore be considered to be, in this respect, functionally equivalent. 8. On the basis of these results, a hypothesis is proposed, which can account for the intersegmental coordination. A leading segment (oscillator) with the highest excitability will entrain the adjacent "trailing" segments (oscillators) to the same cycle duration, however, with a constant phase lag. The first trailing segment will, in its turn, then entrain the next neighboring trailing segment with the same cycle duration after the same phase lag, and so it will continue along the spinal cord. The leading segment determines the overall frequency, whereas the excitability difference between the leading segment and its neighbors will determine the lag between each segment along the spinal cord, assuming that they have the same low excitability. All adjacent hemisegments mutually excite each other. The location of the leading segment along the spinal cord will indirectly determine the direction of the swimming wave, and by changing its location the intersegmental coordination can be switched between the forward and the backward swimming modes. The previously established segmental and intersegmental circuitry can account for the functional organization suggested.