Metabotropic Modulation of Motoneurons by Scratch-Like Spinal Network Activity

Abstract

Glutamate is the main excitatory transmitter in the spinal motor network. The excitation is to a large extent mediated by ionotropic receptors, but glutamate also activates metabotropic receptors. In motoneurons in spinal cord slices the activation of group I metabotropic glutamate (mGlu1) receptors leads to facilitation of Ca V 1.3 L-type calcium channels. Here we investigate whether this pathway is activated by motor network activity induced by natural sensory stimuli. The lumbar carapace and spinal cord were isolated from adult turtles. In this preparation, mechanical stimulation in the receptive field for the scratch reflex induced episodes of rhythmic motor network activity. During an episode the excitability of coactivated motoneurons increased. This increase was associated with an increased persistent inward current and was abolished by local blockade of either mGlu1 receptors or Ca V 1.3 L-type calcium channels near the recording site. We conclude that glutamate released during spinal motor network activity excites motoneurons by parallel activation of ionotropic and mGlu1 receptors. The metabotropic facilitation of L-type calcium channels contributes significantly to this excitation. Our findings establish intrinsic modulation as an active component in the spinal motor network for limb movements.

Periodic High-Conductance States in Spinal Neurons during Scratch-Like Network Activity in Adult Turtles

“…Blood was substituted by perfusion with a Ringer's solution containing the following (in mM): 120 NaCl, 5 KCl, 15 NaHCO 3 , 2 MgCl 2 , 3 CaCl 2 , and 20 glucose, saturated with 98% O 2 and 2% CO 2 to obtain pH 7.6. Transverse cuts were made to isolate the carapace containing the D4 -D10 spinal cord segments (Alaburda and Hounsgaard, 2003). The hip flexor nerves puboischiofemoralis internus and pars anteroventralis that innervate the muscle were exposed and cut.…”

“…In this preparation, scratch-like network activity induced by a sensory stimulus (Keifer and Stein, 1983) can be combined with stable intracellular recording in voltage-clamp and currentclamp modes (Alaburda and Hounsgaard, 2003). Scratching is produced by a large-scale network involving several spinal segments (Mortin and Stein, 1989;Stein, 2005).…”

“…Scratching is produced by a large-scale network involving several spinal segments (Mortin and Stein, 1989;Stein, 2005). Motoneurons and interneurons in these segments express cell type-specific response properties (Russo and Hounsgaard, 1999) modulated by synaptic activity Alaburda and Hounsgaard, 2003). At the same time, scratch episodes in the spinal turtle in vivo are associated with a considerable conductance increase in motoneurons (Robertson and Stein, 1988).…”

Stereological Estimate of the Total Number of Neurons in Spinal Segment D9 of the Red-Eared Turtle

“…In this respect, scratching in limbed vertebrates is an exception because the entire sensorimotor transduction is executed by a network of neurons confined to a few spinal segments without the need of other parts of the CNS (Gelfand et al, 1988;Stein, 2005). Scratching has been studied in detail in the cat (Orlovsky et al, 1999) and the turtle in vivo (Robertson and Stein, 1988;Currie and Gonsalves, 1999;Berkowitz, 2001Berkowitz, , 2002Berkowitz, , 2005Stein, 2005;Samara and Currie, 2008) but crucially, the spinal cord of the adult turtle is also uniquely amenable to experimentation in vitro (Keifer and Stein, 1983;Hounsgaard and Nicholson, 1990;Currie and Lee, 1996;Alaburda and Hounsgaard, 2003). In vitro experiments provide data of sufficient detail to make mathematical analysis of cell properties and synaptic network activity meaningful (Booth et al, 1997;Svirskis et al, 2000Svirskis et al, , 2001Svirskis and Hounsgaard, 2003;Berg et al, 2008).…”

Synaptic Release of Serotonin Induced by Stimulation of the Raphe Nucleus Promotes Plateau Potentials in Spinal Motoneurons of the Adult Turtle

“…These dihydropyridine-sensitive channels are facilitated by preceding depolarization, which provides a form of short-term memory for neurons (Russo and Hounsgaard, 1994;Morisset and Nagy, 1996;Derjean et al, 2003) ranging from hundreds of milliseconds to tens of seconds (Delgado-Lezama et al, 1997;Perrier et al, 2002). Many studies suggest that plateau potentials are recruited under physiological conditions (Eken and Kiehn, 1989;Kiehn and Eken, 1997;Gorassini et al, 1999;Alaburda and Hounsgaard, 2003;Perrier and Tresch, 2005). They may contribute to behaviors by amplifying synaptic inputs to motoneurons (Conway et al, 1988;Hultborn, 1999;Lee and Heckman, 2000) or by specifying the temporal details of motor output (Perrier and Tresch, 2005).…”