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EDITORIAL FOCUS
, are generated through voltage-dependent channels that have been thought to be confined to the membrane of the motoneuronal dendritic tree (see Heckman et al. 2003). In this issue of the Journal of Neurophysiology (Moritz et al. 2007, p. 1042–1049), Binder and colleagues use nucleated patch recordings of hypoglossal motoneurons to challenge this idea. They demonstrate that some of the findings previously taken to provide evidence for dendritic localization of these channels can in fact be seen in nucleated patches—that is, in the absence of dendritic arborizations.
PICs are thought to be important for regulating the gain of inputs to motoneurons (Brownstone 2006; Heckman et al. 2003). In their absence, distal dendritic inputs would have little effect on motoneuronal output (Rall 1967). Although motoneuronal PICs are largely mediated by dihydropyridine-sensitive (CaV1) calcium conductances (Hounsgaard and Kiehn 1989; Schwindt and Crill 1980a), recent evidence indicates that persistent sodium conductances are also involved (Hsiao et al. 1998; Lee and Heckman 2001; Li and Bennett 2003; Nishimura et al. 1989; Powers and Binder 2003). Conductances mediating PICs are under descending neuromodulatory control—in particular that of serotonin and noradrenaline (Conway et al. 1988; Hounsgaard et al. 1988; Lee and Heckman 1999), providing the brain stem with control over motoneuronal input gain.
PICs are essential for spinal and brain stem motoneurons to integrate inputs occurring throughout their extensive dendritic trees. The location of the channels mediating PICs has been an area of intense investigation. Although originally thought to be near the soma (Schwindt and Crill 1980a), Gutman provided convincing arguments based on Schwindt and Crill's data that the recorded currents must originate in the dendrites (Gutman 1991). Since then, evidence has accumulated that these currents are dendritic. Given that it has not yet been possible to record directly from any dendrites beyond the most proximal (primary) branches, this evidence has been indirect, and for the most part relies on single-electrode voltage-clamp experiments with electrodes at motoneuronal somata. The inability to effectively voltage clamp beyond the somata has made this technique useful, in that any currents that are not clamped likely originate from the dendrites (Muller and Lux 1993).
The evidence that supports dendritic localization of PICs comes from many laboratories, including that of Binder, and includes: proximal and distal single-fiber excitatory postsynaptic potential (EPSP) amplitudes are similar (Iansek and Redman 1973); electrical fields applied across turtle motoneurons that depolarize dendrites and hyperpolarize somata activate PICs (Hounsgaard and Kiehn 1993); PICs can be seen in response to synaptic input during somatic voltage clamp (Lee and Heckman 1996); dendritic synaptic current is more effective at increasing firing rate than similar current at the soma, presumably through activation of PICs (Bennett et al. 1998); depolarizing voltage-clamp steps reveal a delay to the onset of the inward current, and prolonged tail currents (Carlin et al. 2000; Lee and Heckman 1996; Li and Bennett 2003; Powers and Binder 2003; Schwindt and Crill 1980b); when slow depolarizing-repolarizing ("triangular") ramp commands are used, inward current persists during the repolarization at voltages more hyperpolarized than that those at which it was activated ("hysteresis") (Carlin et al. 2000; Lee and Heckman 1998; Powers and Binder 2003); immunohistochemical data demonstrate 
1 subunits of CaV1.3 channels on motoneuron dendrites (Ballou et al. 2006; Carlin et al. 2000; Simon et al. 2003); and modeling studies have only been successful in emulating experimental findings when the channels mediating PICs have been placed in the dendrites (Booth and Rinzel 1995; Booth et al. 1997; Bui et al. 2006; Elbasiouny et al. 2005). Given the extent of this evidence, albeit indirect, the motoneuron world has been quite content in the knowledge that PICs originate in motoneuronal dendrites.
Moritz and colleagues now challenge the interpretation of some of these data (Moritz et al. 2007). Recording calcium currents from rat hypoglossal motoneuron nucleated patches, the authors demonstrate hysteresis of the inward current during triangular voltage commands and prolonged tail currents in response to voltage step commands. These are two of the key findings that have been used in the past to explain the dendritic origin of these currents. Yet there are no dendrites in these recordings, demonstrating that these currents must originate from the somatic membrane itself. The authors proceed to show that this calcium current is mediated by CaV1 channels and can be facilitated following sufficient prepulse depolarization.
These data indicate that the CaV1 channels underlying the calcium PICs do not simply open and close in response to voltage but are modified by their history. That is, depolarization may cause them to switch from a "reluctant" to a "willing" state (Namkung et al. 1998). This phenomenon has been known to occur in different types of calcium channels for many years (Bean 1989), and facilitation of CaV1-type channels has been previously reported in turtle motoneurons with dendrites (Svirskis and Hounsgaard 1997). Given that the same modulators (e.g., noradrenaline) can affect both channel state (Namkung et al. 1998) and PICs (Lee and Heckman 1999), it is clear that the interpretation of results must take into consideration not only channel location but also channel state.
The work by Moritz et al. (2007) takes a step toward identifying a behavioral role for these channel states: based on previous depolarization, the output gain (regulated at the soma) of motoneurons may be increased. That is, in prolonged or repetitive tasks, less input to motoneurons would be required to produce the desired motor output. This study also raises many questions. For example: could this be one way to counteract central mechanisms underlying fatigue (Nordstrom et al. 2007)? Do dendritic calcium channels have similar properties? If they do, this may also be a mechanism whereby input gain is regulated. Are somatic and dendritic PICs independently regulated? Can the input gain be regulated independently on different parts of the dendritic tree? The study by Moritz et al. lays the groundwork for future experimental and computational studies to address these and other questions related to the most basic function of the nervous system: the control of movement.
GRANTS
The motoneuron work in my laboratory is supported by grants from the Canadian Institutes of Health Research and the Nova Scotia Health Research Foundation.
Departments of Surgery (Neurosurgery) and Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, Canada
Address for reprint requests and other correspondence: Depts. of Surgery (Neurosurgery) and Anatomy and Neurobiology, Dalhousie University, 14A Tupper Bldg., 5850 College St., Halifax, Nova Scotia B3H 1X5, Canada (E-mail: Rob.Brownstone{at}dal.ca)
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