Neural mechanisms potentially contributing to the intersegmental phase lagin lamprey II. Hemisegmental oscillations produced by mutually coupled excitatory neurons

Most previous models of the spinal central pattern generator (CPG) underlyi ng locomotion in the lamprey have relied on reciprocal inhibition between t he left and right side for oscillations to be produced. Here, we have explo red the consequences of using self-oscillatory hemisegments. Within a singl e hemisegment, the oscillations are produced by a network of recurrently co upled excitatory neurons (E neurons) that by themselves are not oscillatory but when coupled together through N-methyl-D-aspartate (NMDA) and x-amino- 3-hydroxy-5-methyl-4-isoxazolepropionicacid (AMPA)/kainate transmission can produce oscillations. The bursting mechanism relies on intracellular accum ulation of calcium that activates Ca2+-dependent KC The intracellular calci um is modeled by two different intracellular calcium pools, one of which re presents the calcium entry following the action potential, Ca-AP pool, and the other represents the calcium inflow through the NMDA channels, Ca-NMDA pool. The Ca2+-dependent K+ activated by these two calcium pools are referr ed to as K-CaAP and K-CaNMDA respectively, and their relative conductances are modulated and increase with the background activation of the network. W hen changing the background stimulation, the bursting activity in this netw ork can be made to cover a frequency range of 0.5-5.5 Hz with reasonable bu rst proportions if the adaptation is modulated with the activity. When a ch ain of such hemisegments are coupled together, a phase lag along the chain can be produced. The local oscillations as well as the phase lag is depende nt on the axonal conduction delay as well as the types of excitatory coupli ng that are assumed, i.e. AMPA/kainate and/or NMDA. When the caudal excitat ory projections are extended further than the rostral ones, and assumed to be of approximately equal strength, this kind of network is capable of repr oducing several experimental observations such as those occurring during st rychnine blockade of the left-right reciprocal inhibition. Addition of reci procally coupled inhibitory neurons in such a network gives rise to antipha sic activity between the left and right side, but not necessarily to any ch ange of the frequency if the burst proportion of the hemisegmental bursts i s well below 50%. Prolongation of the C neuron projection in the rostrocaud al direction restricts the phase lag produced by only the excitatory hemise gmental network by locking together the interburst intervals at different l evels of the spinal cord.