Roles for multifunctional and specialized spinal interneurons during motor pattern generation in tadpoles, zebrafish larvae, and turtles

Abstract

The hindbrain and spinal cord can produce multiple forms of locomotion, escape, and withdrawal behaviors and (in limbed vertebrates) site-specific scratching. Until recently, the prevailing view was that the same classes of central nervous system neurons generate multiple kinds of movements, either through reconfiguration of a single, shared network or through an increase in the number of neurons recruited within each class. The mechanisms involved in selecting and generating different motor patterns have recently been explored in detail in some non-mammalian, vertebrate model systems. Work on the hatchling Xenopus tadpole, the larval zebrafish, and the adult turtle has now revealed that distinct kinds of motor patterns are actually selected and generated by combinations of multifunctional and specialized spinal interneurons. Multifunctional interneurons may form a core, multipurpose circuit that generates elements of coordinated motor output utilized in multiple behaviors, such as left-right alternation. But, in addition, specialized spinal interneurons including separate glutamatergic and glycinergic classes are selectively activated during specific patterns: escape-withdrawal, swimming and struggling in tadpoles and zebrafish, and limb withdrawal and scratching in turtles. These specialized neurons can contribute by changing the way central pattern generator (CPG) activity is initiated and by altering CPG composition and operation. The combined use of multifunctional and specialized neurons is now established as a principle of organization across a range of vertebrates. Future research may reveal common patterns of multifunctionality and specialization among interneurons controlling diverse movements and whether similar mechanisms exist in higher-order brain circuits that select among a wider array of complex movements.

Keywords: behavioral choice; central pattern generation; escape; interneuron; locomotion; motor pattern selection; spinal cord.

Figure 1

The early development of behavior in the zebrafish. From Drapeau et al. (2002), used with permission of Elsevier.

Figure 2

Fictive motor patterns in hindlimb motor nerves evoked in an immobilized turtle with a spinal cord transection in vivo. Each of the three forms of scratching is elicited by mechanical stimulation of the shell or skin in the region indicated in color; stimulation in a transition zone between regions can elicit either of two forms or a blend of the two. Forward swimming is elicited by electrical stimulation in the contralateral lateral funiculus of a mid-body segment. Limb withdrawal is elicited by a tap to the dorsal foot.

Figure 3

Activity of multifunctional inhibitory neurons during tadpole swimming and struggling. (A) A cIN fires during swimming, evoked by a brief skin stimulus (▼), as well as struggling, evoked by 40-Hz skin stimulation (dashed line). Motor activity is recorded from a ventral root (vr) on the opposite side. The cIN fires a single impulse on many swimming cycles, driven by fast EPSPs that are seen on cycles where spikes fail. The cIN fires rhythmic bursts of impulses during struggling. (B) Similar activity recorded from an aIN during swimming and struggling. During swimming, firing is more reliable on early cycles where the underlying excitation is stronger. During struggling, the aIN fires strong rhythmic bursts. Firing in an excitatory dIN recorded simultaneously shows very reliable firing, once per cycle, in swimming, but weak, unreliable firing during struggling (see Li et al., 2007).

Figure 4

Activity of specialized excitatory premotor interneurons during tadpole swimming and struggling. (A) A dIN fires reliably once on each swimming cycle, and only once on each struggling cycle, evoked by 40-Hz skin stimulation. (B) In contrast, a dINr receives weak synaptic input during swimming and does not fire, but is recruited to fire strong rhythmic bursts during struggling. (C) Contrasting firing activity in a dIN and dINr in response to depolarizing current. The dIN fires only once; the dINr can fire repetitively at high frequency (see Li et al., 2007).

Figure 5

Example of a zebrafish commissural longitudinal ascending interneuron (CoLA), not firing during (A) escape or (B) swimming, but firing strongly during (C) struggling. *, stimulus; VR, ventral root. Adapted from Liao and Fetcho (2008), with permission of the Society for Neuroscience.

Figure 6

Examples of zebrafish interneurons activated as a function of swimming speed. As speed decreases, first (A) dorsal circumferential descending interneurons (CiDs), then (B) ventral CiDs, and then (C) multipolar commissural descending interneurons (MCoDs) become active. VR, ventral root. Adapted from McLean et al. (2008) Nat. Neurosci. 11: 1419-1429, with permission of Nature.

Figure 7

Example of a T neuron, a morphological type of turtle spinal interneuron that is rhythmically activated during all three forms of ipsilateral scratching, as well as forward swimming. Int, interneuron; KE, knee extensor; HF, hip flexor; HE, hip extensor; Stim., stimulus; arrows indicate scratch stimulus onset/offset. Modified from Berkowitz (2008), with permission of the American Physiological Society.

Figure 8

Activity of specialized excitatory sensory pathway interneurons in the tadpole. (A) A dlc fires once, following a brief skin stimulus to the same side (▼). It does not fire during subsequent swimming, seen as rhythmic activity at a ventral root and in a cIN recorded simultaneously on the same side. (B) An ecIN does not fire during swimming but is recruited by summating excitation (*) during 40-Hz skin stimulation to fire strongly during struggling. An inhibitory premotor cIN recorded at the same time is also recruited during struggling, but, unlike the ecIN, fires strongly from the start of skin stimulation.

Figure 9

Example of a turtle scratch-specialized interneuron during fictive motor patterns. Activity of the interneuron (Int) during (A) rostral scratching, (B) caudal scratching, and (C,D) forward swimming. Note that the interneuron is hyperpolarized for several seconds beyond the swim-evoking stimulus, as the motor pattern continues. KE, knee extensor; HF, hip flexor; HE, hip extensor; Stim., stimulus. Modified from Berkowitz (2008), with permission of the American Physiological Society.

Figure 10

Example of a flexion reflex-selective interneuron during turtle fictive motor patterns. Activity of the interneuron (Int) during (A) a tap to the foot that evokes withdrawal (lower record expands the early part of the response shown above), (B) an electrical stimulus to the foot skin, (C) pocket scratching, and (D) forward swimming. Note that the cell is active at the start of scratch stimulation, but not during the scratch motor pattern; it is rhythmically hyperpolarized during both scratching and swimming. (E) Phase-averaged membrane potential of this neuron during scratching and swimming. HF, hip flexor; Stim., stimulus; KE, knee extensor; HE, hip extensor. Modified from Berkowitz (2007), with permission of the Society for Neuroscience.