The Mesencephalic Locomotor Region and its Role in Locomotion and Speed-Signaling
Where might the MSDB receive information that can be used for both locomotion modulation as well as speed signaling for spatial representation maintenance? In surveying the regions projecting to MSDB, the Mesencephalic Locomotor Region (MLR) is one candidate area that stands out: Electrical stimulation of this behaviorally-defined group of brainstem nuclei, typically but not always including the pedunculopontine tegmental nucleus (PPN) and the cuneiform nucleus (Cun) (Noga et al., 2017), initiates and controls locomotion in most mammals (Shik et al., 1966; Skinner and Garcia-Rill, 1984; Grillner et al., 1997; Ryczko and Dubuc, 2013). While study of this vaguely-defined region has primarily focused on its role in controlling descending motor output (Shik et al., 1966; Mori et al., 1978; Takakusaki, 2008), evidence for a possible second role for MLR signaling has emerged: The MLR seems to induce efference copy-like processing changes in higher structures through its ascending projections to the basal forebrain (Pinto et al., 2013; Fu et al., 2014; Lee et al., 2014), suggesting that it may be at least one source of the speed-modulated signals discussed thus far in this review.
Indeed, MLR neuronal activity has been shown to both positively and negatively correlate with running speed (Fig. 1B) (Norton et al., 2011; Lee et al., 2014; Roseberry et al., 2016). Moreover, theta oscillations throughout the MLR have been recently reported to increase with locomotion initiation and scale in power with speed (Noga et al., 2017). Unpublished work has further suggested that this signaling is apparently sufficient for the entrainment of downstream speed encoding in the MSDB (Carvalho et al., unpublished; Tanke et al., unpublished). A notable feature of MLR speed signaling is that, as is the case for encoding throughout the circuit in the MDSB (Fuhrmann et al., 2015), MEC (Kropff et al., 2015) and hippocampus (Wyble et al., 2004; Vanderwolf 1969; Arriaga and Han, 2017), it seems to be ‘prospective’ by up to several hundred milliseconds, i.e. neuronal activity patterns reflect future speeds and locomotive events more accurately than ongoing events (Lee et al., 2014; Roseberry et al., 2016). Prospective coding is a notable feature of both grid cell and place cell firing fields (Kropff et al., 2015), and such temporal consistency between changes in locomotive-related speed signaling and updating of the spatial representation system bolsters the arguments for both speed-based updating mechanisms as well as efference copy mechanisms in generating the speed signal. It should be noted, however, that retrospective coding (i.e., speed coding lagging behind an animal’s actual ongoing navigation) has also been reported for speed cells in the hippocampus (Kropff et al., 2015; Góis and Tort, 2018). Further exploration of the temporal relationship between speed signaling and behavior is thus warranted.
However, many important characteristics of MLR speed encoding remain unclear. The exact contributions of specific cell types to speed signaling are underreported, especially that of cholinergic cells, despite the ability of all cell types to modify active running speed (Fig. 1B) (Roseberry et al., 2016). Additionally, although it has been suggested that the same cells mediate both the descending locomotive and resultant ascending processing changes (Lee et al., 2014), the complexity and vagueness of MLR anatomy demands rigorous confirmation of this finding, especially when possible confounding effects of activation of arousal nuclei in the PPN, a member of the reticular activating formation (Nauta and Kuypers, 1958), are considered (Vinck et al., 2015; Campbell and Giocomo, 2018). Furthermore, outside of unpublished data (Carvalho et al., unpublished; Tanke et al., unpublished), a direct link between MLR signaling and hippocampal-entorhinal speed encoding has yet to be established (Fig. 1B).