| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
EDITORIAL FOCUS
; Carvell and Simons 1990; Carvell et al. 1991; Harvey et al. 2001; Kleinfeld et al. 2006; Welker 1964). Because active whisking does not require sensory feedback (Gao et al. 2001; Welker 1964) or the motor cortex (Carvell et al. 1996; Gao et al., 2003; Semba and Komisaruk 1984), a circuit located in the brain stem is assumed to generate whisking (Hattox et al. 2003). Similar circuits responsible for generating rhythmic motor patterns for locomotion, respiration, and feeding are called central pattern generators (CPG) (Grillner 2006; Marder et al. 2005). The existence of a CPG for whisking raises two obvious questions. First, what are the neuronal elements and the connectivity of the whisking CPG? Second, how does the CPG operate to generate whisking? In a paper published in this issue of the Journal of Neurophysiology (p. 2148–2158), Cramer et al. propose a model that answers these questions.
Using brain stem slices from young rats (P13-18), current- and voltage-clamp recordings were obtained from vibrissa motoneurons (vMNs). Application of a serotonin (5-HT) receptor agonist depolarized the vMNs producing rhythmic trains of action potentials at whisking frequencies (1.5–17 Hz). The firing frequency varied as a function of the concentration of the agonist. Because this effect was not affected by blocking glutamate and GABA receptors, it most likely involves changes in the intrinsic properties of vMNs, such as an enhanced inward current or a suppressed outward current. An obvious candidate is the persistent Na+ current (INap), which is caused by a small portion of Na+ channels that linger in the activated state (Crill 1996). Although, INap is small compared with the transient Na+ current, it is functionally important because it activates at subthreshold potentials and so can greatly increase the excitability of otherwise quiescent neurons. Accordingly, a role for INap in other CPGs has been established (Harris-Warrick 2002).
To determine if persistent inward currents were affected by serotonin (5-HT), slow voltage ramps that inactivate the transient currents were applied in voltage clamp. These ramps revealed a persistent inward current in vMNs that was mostly suppressed by TTX, indicating that it is INap. Application of a 5-HT agonist greatly enhanced INap and shifted its activation threshold even more negative, thus making vMNs much more excitable in the subthreshold range. Furthermore, in current clamp, riluzole (an INap blocker) reversed the effects of a 5-HT agonist on the rhythmic firing of vMNs.
Based on these results, Cramer et al. propose that through the graded facilitation of INap, 5-HT can generate the full range of whisking frequencies in vMNs. This implies that the firing rate of serotonergic cells that project to vMNs (5-HT premotoneurons in the lateral paragigantocellularis nucleus) should correlate with the whisking frequency because the concentration of 5-HT in the facial nucleus will determine the firing of vMNs and thus whisking frequency. The authors tested this hypothesis using anesthetized rats in vivo and found that the tonic activity of putative serotonergic premotoneurons indeed correlates with the frequency of whisking triggered by motor cortex stimulation.
The major point of the model that emerges from these results is that vMNs actively participate in the rhythmogenesis by converting tonic serotonergic inputs into the patterned motor output responsible for movement of the vibrissa (see Fig. 1). In essence, all you need are a few motoneurons and some level of [5-HT]o that upregulates INap and you have whisking. The beauty of this proposal is without a doubt its simplicity. This simplicity also raises some stimulating questions for future studies.
|
The proposed CPG is a feedforward circuit that can operate in the absence of intrinsic feedback circuitry to keep it under control. Then how does the CPG regulate itself? The only evident feedback is extrinsic to the CPG and involves the sensory input returning via the infraorbital nerve through the trigeminal complex (Nguyen and Kleinfeld 2005). Thus this feedback loop probably regulates the output of the CPG. Also, in the current model, only vibrissa protractions are actively controlled, whereas retractions are assumed to occur passively. However, the extrinsic muscles actively control retractions of the whisker pad (Berg and Kleinfeld 2003). Are these muscles and retractions controlled by another CPG? If so, do protraction and retraction CPGs interact with each other?
In many cells, a variety of neuromodulators can regulate the same ionic conductance. Perhaps, several neurotransmitters can upregulate INap. Can other neuromodulators regulate INap in vMNs and therefore produce whisking? Likewise, inhibition and fast excitation can support oscillatory activities as those required for whisking. Then what are the roles of excitatory inputs from motor cortex onto vMNs (Grinevich et al. 2005) and of the many other vMNs afferents (Hattox et al. 2002) during whisking?
As the authors argue, several different mechanisms and/or circuits may possibly drive whisking. For instance, during abnormal conditions (i.e., disinhibition), the motor cortex can operate as a CPG for whisker movements by generating an intrinsic oscillation at 
10 Hz that drives rhythmic retractions at the same frequency (Castro-Alamancos 2006). Interestingly, the motor cortex CPG also appears to depend on INap (Castro-Alamancos et al. 2006). If the proposed brain stem CPG is one of several circuits responsible for different types of whisking, what coordinates the actions of these multiple CPGs?
It is humbling to realize that the neural generator for such a simple behavior as the repetitive motion of the vibrissa is still unexplained, which underscores the challenge of explaining more complex behaviors. Certainly the work by Cramer et al. takes us closer to that important goal.
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania
Address for reprint requests and other correspondence: Dept. of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Ln., Philadelphia, PA 19129 (E-mail: mcastro{at}drexelmed.edu)
REFERENCES
Berg RW, Kleinfeld D. Rhythmic whisking by rat: retraction as well as protraction of the vibrissae is under active muscular control. J Neurophysiol 89: 104–117, 2003.
Carvell GE, Miller SA, Simons DJ. The relationship of vibrissal motor cortex unit activity to whisking in the awake rat. Somatosens Mot Res 13: 115–127, 1996.[ISI][Medline]
Carvell GE, Simons DJ. Biometric analyses of vibrissal tactile discrimination in the rat. J Neurosci 10: 2638–2648, 1990.[Abstract]
Carvell GE, Simons DJ, Lichtenstein SH, Bryant P. Electromyographic activity of mystacial pad musculature during whisking behavior in the rat. Somatosens Mot Res 8: 159–164, 1991.[ISI][Medline]
Castro-Alamancos MA. Vibrissa myoclonus (rhythmic retractions) driven by resonance of excitatory networks in motor cortex. J Neurophysiol 96: 1691–1698, 2006.
Castro-Alamancos MA, Rigas P, Tawara-Hirata Y. Resonance (10 Hz) of excitatory networks in motor cortex: effects of voltage-dependent ion channel blockers. J Physiol 578: 173–191, 2007.
Cramer N, Li Y, Keller A. Whisking rhythm generator: a novel mammalian network for the generation of movement. J Neurophysiol 97: 2148–2158, 2007.
Crill WE. Persistent sodium current in mammalian central neurons. Annu Rev Physiol 58: 349–362, 1996.[CrossRef][ISI][Medline]
Gao P, Bermejo R, Zeigler HP. Whisker deafferentation and rodent whisking patterns: behavioral evidence for a central pattern generator. J Neurosci 21: 5374–5380, 2001.
Gao P, Hattox AM, Jones LM, Keller A, Zeigler HP. Whisker motor cortex ablation and whisker movement patterns. Somatosens Mot Res 20: 191–198, 2003.[CrossRef][ISI][Medline]
Grillner S. Biological pattern generation: the cellular and computational logic of networks in motion. Neuron 52: 751–766, 2006.[CrossRef][ISI][Medline]
Grinevich V, Brecht M, Osten P. Monosynaptic pathway from rat vibrissa motor cortex to facial motor neurons revealed by lentivirus-based axonal tracing. J Neurosci 25: 8250–8258, 2005.
Harris-Warrick RM. Voltage-sensitive ion channels in rhythmic motor systems. Curr Opin Neurobiol 12: 646–651, 2002.[CrossRef][ISI][Medline]
Harvey MA, Bermejo R, Zeigler HP. Discriminative whisking in the head-fixed rat: optoelectronic monitoring during tactile detection and discrimination tasks. Somatosens Mot Res 18: 211–222, 2001.[CrossRef][ISI][Medline]
Hattox A, Li Y, Keller A. Serotonin regulates rhythmic whisking. Neuron 39: 343–352, 2003.[CrossRef][ISI][Medline]
Hattox AM, Priest CA, Keller A. Functional circuitry involved in the regulation of whisker movements. J Comp Neurol 442: 266–276, 2002.[CrossRef][ISI][Medline]
Kleinfeld D, Ahissar E, Diamond ME. Active sensation: insights from the rodent vibrissa sensorimotor system. Curr Opin Neurobiol 16: 435–444, 2006.[CrossRef][Medline]
Marder E, Bucher D, Schulz DJ, Taylor AL. Invertebrate central pattern generation moves along. Curr Biol 15: R685–R699, 2005.[CrossRef][ISI][Medline]
Nguyen QT, Kleinfeld D. Positive feedback in a brainstem tactile sensorimotor loop. Neuron 45: 447–457, 2005.[CrossRef][ISI][Medline]
Semba K, Komisaruk BR. Neural substrates of two different rhythmical vibrissal movements in the rat. Neuroscience 12: 761–774, 1984.[CrossRef][ISI][Medline]
Welker WI. Analysis of sniffing of the albino rat. Behaviour 12: 223–244, 1964.[Medline]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
