Excitatory synaptic drive for swimming mediated by amino acid receptors in the lamprey

Abstract

In order to investigate the properties and pharmacology of the excitatory synaptic drive received by motoneurons during swimming in the lamprey, propriospinal excitatory interneurons were activated as a population by the regional application of N-methyl-r+-aspartate (NMA) to either the 6-8 rostral-most or the 6-8 caudal-most segments of lengths of isolated spinal cord. This caused a rhythmic motor output to be generated in these regions. Synaptic potentials that were phase-locked to, and dependent on, the rhythmic motor activity of the segments exposed to the agonist could be recorded in motoneurons lying outside the activated regions.The synaptic drive to motoneurons located rostra1 or caudal to the activated regions was studied. Motoneurons received both descending and ascending synaptic input, which consisted of alternating excitatory and inhibitory phases. The inhibition could be reversed by chloride injection and blocked by strychnine, leaving an oscillating excitatory phase. The descending excitatory drive could extend l-9 segments from the active region, while the ascending excitatory drive was recorded only in motoneurons that were l-3 segments rostra1 to the active region. Both types of drive occurred in phase with the ipsilateral ventral root discharge: The peak depolarization of the descending drive occurred at the same point in the swimming cycle as that of the depolarizing phase seen during fictive swimming, while that of the ascending drive occurred significantly later. Both ascending and descending drives were partially reduced in amplitude by Z-aminw5-phosphonovaleric acid or Mg2+. The blocking action of Mg2+ was, in both cases, voltage dependent. Cis-2,3-piperidine dicarboxylic acid or kynurenic acid caused a much greater reduction in the amplitude of the oscillations.These results suggest that a major part of the excitatory drive for swimming in lamprey motoneurons is generated by populations of propriospinal interneurons with relatively long descending and/or short ascending axons, which fire rhythmically during swimming and release an amino acid transmitter that excites motoneurons through N-methyl-o-aspartate (NMDA) and non-NMDA receptors. This information will allow these important neurons to be identified in future experiments.Rhythmic movements and locomotion in both vertebrates and invertebrates are believed to be controlled by networks of neurons capable of producing a motor output largely appropriate to control that behavior in the absence of sensory feedback (see

Nitric Oxide Potentiation of Locomotor Activity in the Spinal Cord of the Lamprey

“…To examine the effects of NO donors on ipsilateral excitatory synaptic transmission the recording chamber was divided into two pools by an agar barrier (Dale, 1986). Locomotor activity was induced in the rostral pool by NMDA (100 M) while the spinal cord in the caudal pool was perfused with physiological solution containing strychnine (5 M) to block inhibitory synaptic transmission.…”

N-methyl-D-aspartate receptor-induced, inherent oscillatory activity in neurons active during fictive locomotion in the lamprey

“…Activation of these amino acid receptors thus appears to be a prerequisite for the occurrence of locomotor activity under normal conditions (Brodin and Grillner, 1985a, b). Unitary synaptic potentials elicited by an activation of NMDA and kainate/ quisqualate receptors have recently been described in the lamprey spinal cord and furthermore it has been found that spinal interneurons acting via these excitatory amino acid receptors are of primary importance during fictive locomotion (Buchanan and Grillner, 1987;Dale, 1986). During fictive locomotion, many rhythmically active spinal neurons display well-developed membrane potential oscillations, phase-locked to the efferent ventral root bursts.…”

“…In myotomal motoneurons the depolarizing peaks of the potential fluctuations occur in phase with the ipsilateral ventral root discharge Wallen, 1980, 1983;Buchanan and Cohen, 1982). They are due to synaptic activation of excitatory amino acid receptors of both the NMDA and kainate type (Dale, 1986).…”

“…The membrane potential oscillations elicited by premotor intemeurons in motoneurons depend on both kainate and NMDA-receptor activation (Dale, 1986;Dale and Grillner, 1986). The relative role of the voltage dependence of the NMDA channels in contrast to the non-NMDA-mediated EPSPs remains to be elucidated.…”

The NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5) impairs spatial learning and LTP in vivo at intracerebral concentrations comparable to those that block LTP in vitro

“…Two distinctive properties of the receptor, that it is both ligand and voltage gated (Engberg et al, 1979;MacDonald et al, 1982;Mayer et al, 1984;Nowak et al, 1984) and that its associated ionophore is more permeable to Ca2+ than to Na+ and K+ (Dingledine, 1983;Mayer and Westbrook, 1987) have each provoked particular interest among those concerned with its role in normal physiological function. The NMDA receptor has, for example, been implicated in the induction of hippocampal long-term potentiation (LTP) (Collingridge et al, 1983;Harris et al, 1984) and, more recently, in a variety of mechanisms including the coordination of rhythmic movements such as swimming (Dale, 1986(Dale, , 1989) sensory transduction (Fox et al, 1989;Sillito et al, 1990) developmental plasticity (Bear et al, 1987;Kleinschmidt et al, 1987;McDonald and Johnston, 1990;Singer, 1990); and learning (Morris et al, 1986). Its highest density, however, is in the hippocampus (Monaghan et al, 1983;Monaghan and Cotman, 1985) an area associated with certain forms of learning (O'Keefe and Nadel, 1978;Olton et al, 1979;Squire, 1987).…”