Summary & Future Directions
Here, we have reviewed the evidence for robust rate and temporal codes
for speed throughout the mammalian brain. These codes are especially
well-documented in the hippocampus and entorhinal cortex, where they
likely play essential roles in the maintenance of stable spatial
representations. Codes for speed exist in both upstream motor and
sensory circuitry, and we argue that the work performed thus far
suggests these different modalities interact in a complex way to
ultimately give rise to the speed information processed by the
hippocampal-entorhinal complex.
A number of unresolved issues preclude a more complete understanding of
the neural speed signal. One such issue concerns the purpose of diverse
rate codes. For example, in nearly every region reviewed here,
positively- and negatively-speed modulated cells have been reported.
Further investigation is required to determine whether these opposing
codes work cohesively to produce a singular, robust internal measure of
speed or if they might instead either conflict with each other or
possibly encode distinct components of speed or velocity.
With respect to the origin of the unified speed hippocampal-entorhinal
speed signal, both motor and sensory speed coding should be investigated
simultaneously to parse out their relative relationships to each other
(as in Campbell et al., 2018) and to downstream speed signaling. Speed
estimates could be theoretically distilled by many sensory modalities,
and yet speed signaling has only begun to be examined in full in the
visual system. Why might the auditory system, for instance, receive an
efference copy from M2 of an opposite polarity from that received by the
visual system (Schneider et al., 2014; Leinweber et al., 2017; Zhou et
al., 2014; Dadarlat and Stryker, 2017), and do these distinct polarities
impact the relative contribution of either sense to the
hippocampal-entorhinal speed signal?
Another sensory modality warranting serious consideration in the search
for the speed signal origin is the vestibular system. Vestibular
information has been suggested to be integrated with input from
other senses such as vision as well as motor efference copy to produce a
substantial portion of the sensation of self-motion (reviewed in Cullen,
2012). Additionally, vestibular input is utilized by head-direction
cells for their processing, and may be influential in other elements of
spatial cognition and navigation (Cullen, 2012). While at least one
group has reported diminished entorhinal speed modulations in response
to inactivation of the vestibular nuclei (Jacob et al., 2014),
functional spatial processing and associated speed-based changes have
been achieved in experiments utilizing virtual reality and head-fixation
protocols (Domnisoru et al., 2013; Heys et al., 2014; Justus et al.,
2017; Campbell et al., 2018; Heys and Dombeck, 2018), which presumably
disrupt vestibular sensation. It has been suggested that the visual
system may be able to compensate for missing vestibular contributions to
speed signaling in these experimental conditions (Jacob et al., 2014),
but this notion may be complicated by findings of altered speed
signaling in vertically-locomoting animals who are
also experiencing altered vestibular afferents (Casali et al., 2019).
The idea that speed signaling in noncanonically motor control regions
such as MSDB (Fuhrmann et al., 2015; Bender et al., 2015; but see Bland
et al., 2006) and possibly the hippocampus (Bender et al., 2015) can
influence ongoing locomotive behavior also invites further discussion.
How might these structures control descending locomotive outputs? A few
of the groups reporting these effects (Fuhrmann et al., 2015; Bender et
al., 2015) have proposed various circuits that may relay
septo-hippocampal/entorhinal speed signaling to locomotive control
regions, primarily ones converging upon the ventral tegmental area (VTA)
(Fig. 2C). This putative functional anatomy includes a direct
MSDB-to-VTA projection (Fuhrmann et al., 2015; Geisler and Wise, 2008)
and a hippocampal-originating projection that goes through first the
lateral septum and next the lateral hypothalamus before reaching the VTA
(Bender et al., 2015; Geisler and Wise, 2008). All of these regions have
been shown to contain rate codes for speed (Zhou et al., 1999; Puryear
et al., 2010; Wang and Tsien, 2011; Bender et al., 2015) and to modulate
locomotion upon stimulation (Kalivas et al., 1981; Parker and Sinnamon,
1983; Christopher and Butter, 1968; Patterson et al., 2015; Bender et
al., 2015). Moreover, the VTA makes functional connections with the
nucleus accumbens (NAc), striatum, and motor cortex (Mogenson et al.,
1980; Hosp et al., 2011; Kunori et al., 2014; Beier et al., 2015),
providing access to canonical locomotive control circuitry. Furthermore,
glutamatergic projections seem to be a major component of these
VTA-converging, locomotion-controlling pathways (Fuhrmann et al., 2015;
Geisler and Wise, 2008). Despite the reviewed effects of MSDB
glutamatergic stimulation on hippocampal-entorhinal speed encoding,
recent investigation also suggests that these speed effects may be at
least partially mediated by local glutamatergic projections onto other
MSDB cell types projecting to the hippocampal-entorhinal complex
(Fuhrmann et al., 2015; Robinson et al., 2016). These two lines of
evidence suggest that the MSDB glutamatergic population may represent
the segregators of the region’s speed signal’s distinct functions,
sending speed-scaled output to locomotive circuitry while simultaneously
transmitting an efference copy-like signal to the other MSDB cells to
convey to the hippocampal-entorhinal complex for use in spatial
representations and possible locomotive feedback.
Finally, while the contents of this review have for the most part
intentionally avoided discussing any possible distinct encoding
mechanisms for speed and acceleration, it should be noted that, while
underreported relative to speed, acceleration-specific coding has indeed
been reported (Kemere et al., 2013; Long et al., 2014). It has been
further suggested that acceleration, and not speed, may in fact dominate
aspects of temporal coding of movement (Long et al., 2014; Kropff Causa
et al., unpublished), but further experimentation is required to support
this notion.