The Rate Code for Speed in the Hippocampus & Entorhinal Cortex
There are two fundamental coding strategies used by neurons. The first
is a “rate code”, where one or more neurons increase or decrease their
rate of firing in response to a stimulus. The second is a “temporal
code”, where the precise timing of spikes with respect to either the
stimulus or the activity of other neurons carries valuable information
(Mehta et al., 2002; Ahmed and Mehta, 2009; Kumar et al., 2010;
Ainsworth et al., 2012). It is thus instructive to examine putative
hippocampal speed signaling in the contexts of both codes. As a rodent
moves faster through the place field of a CA1 neuron the location of the
place field remains largely unaltered, but the firing rate of the neuron
increases. There is a rich literature documenting this speed-dependent
rate increase in CA1 place cell firing (McNaughton et al., 1983; Wiener
et al., 1989; Rivas, et al. 1996; Shen et al., 1997; Zhang et al., 1998;
Ekstrom et al., 2001; Geisler et al., 2007; Hirase et al., 1999).
However, a recent study has argued that this speed-based rate effect
does not represent a true relationship between the two variables (i.e.,
place cells are not ‘encoding’ speed in addition to place, per se), but
rather the stereotyped running patterns of animals on linear tracks
influence place coding in such a way to create the epiphenomenon of a
temporally-broad speed-rate correlation (Góis and Tort, 2018). Increases
in firing rate as a function of speed are also seen in multiple classes
of hippocampal inhibitory interneurons, including fast-spiking (FS) and
somatostatin-positive (SST+) cells (McNaughton et al., 1983; Ahmed and
Mehta, 2012; Czurkó et al., 1999; Nitz and McNaughton, 1999; 2004;
Arriaga and Han, 2017). A subpopulation of these cells seem to have
particularly (i.e., millisecond scale) temporally-precise speed-rate
correlations and respond poorly to other spatial variables, giving
credence to the possibility that true, inhibitory ‘speed cells’ (see
below) may exist in the hippocampus (Kropff et al., 2015; Góis and Tort,
2018) (Fig. 1A). Subgroups of both CA1 place cells and inhibitory
interneurons have also been shown to have negative correlations between
firing rate and speed (Wiener et al., 1989; Yu et al., 2017, Arriaga and
Han, 2017) (Fig. 1A). However, it is unclear whether these cells are
indeed preferentially encoding low movement speeds or instead are
influenced by selective firing during immobility-associated hippocampal
sharp-wave ripple events when the animal is relatively still (Buzsáki
2015; Colgin 2016).
Rate encoding of speed
systematically varies along the septotemporal (‘long’) axis of the
hippocampus, with the impact of speed on CA1 firing rates diminishing as
you go from the septal to the temporal pole of the hippocampus (Maurer
et al., 2005). A parallel anatomically-dependent change is also seen in
place field size, with systematic increases in place field size from the
septal to the temporal hippocampal pole (Maurer et al., 2005; Jung et
al., 1994; Kjelstrup et al., 2008; Ahmed and Mehta, 2009). This once
again points to a tight computational link between speed and spatial
encoding in the hippocampus.
As the other half of the canonical ‘cognitive map’ circuit, the MEC
provides spatially relevant information to the hippocampus (Quirk et
al., 1992; Moser et al., 2008; Ahmed and Mehta, 2009; Buzsáki and Moser,
2013). Most cell types present in the MEC population, including
excitatory grid cells, excitatory head-direction cells, as well as
inhibitory interneurons, exhibit speed-modulated firing rates similar to
their hippocampal counterparts (Sargolini et al., 2006; Wills et al.,
2012; Buetfering et al. 2014; Hinman et al., 2016; Reifenstein et al.,
2016; Gil et al., 2018). However, recent work has shown that the
rate-speed relationships of most functionally-dedicated cell types can
be complex and heterogeneous, including ‘saturating’ speed modulations
that plateau at intermediate running speeds or, similar to what has been
shown in the hippocampus, monotonically negative speed-rate
relationships (Hinman et al., 2016; Hardcastle et al., 2017; Heys and
Dombeck, 2018; Mallory et al., 2018). Evidence for a functionally
dedicated ‘speed cell’ population in MEC (in addition to the hippocampal
population discussed above) has also recently emerged: these cells
exhibit “context-invariant” firing that either increases or decreases
with running speed (Kropff et al., 2015; Tanke et al., unpublished).
Recent work suggests that nearly half of these neurons may be inhibitory
(Perez-Escobar et al., 2016; Ye et al., 2018), allowing them to shape
grid cell output in a strongly speed-dependent manner (Miao et al.,
2017).
Another major source of input to CA1 is hippocampal area CA3, which
itself receives spatially modulated input from MEC (for review of this
functional anatomy, see McNaughton et al., 2006; Ahmed and Mehta, 2009;
Knierim 2015; Igarashi 2016; Grieves and Jeffery, 2017). While the CA3
population has been reported to also show rate increases with running
speed (McNaughton et al., 1983), the correlation between the two seems
to be weaker than in CA1 (Kay et al., 2016). Much work has further
suggested that the relative strength of CA3 input to CA1 is
substantially reduced during running behavior compared to epochs of
immobility (Segal 1978; Winson and Abzung 1978; Kemere et al., 2013). In
agreement with these findings, a recent study found that speed increases
drive MEC and CA1 rate changes much more similarly to each other than
with CA3 cells, which display a weaker speed dependence (Zheng et al.,
2015). Furthermore, division of the MEC layer II population into CA3- or
dentate gyrus (DG)-projecting stellate cells (also called ‘ocean cells’)
and CA1-projecting pyramidal cells (also called ‘island cells’) reveals
a much higher proportion of speed-modulated island cells than ocean
cells and stronger speed modulation of island activity (Sun et al.,
2015). It should be noted, however, that certain DG populations have
also been reported to exhibit positive speed-rate relationships
(McNaughton et al., 1983; Nitz and McNaughton, 1999), and that the
comparative nature of these relationships with those elsewhere in the
hippocampal-entorhinal complex remain undefined to our best knowledge.
Hippocampal area CA2, which has recently been suggested to innervate CA1
and influence its output (Kohara et al., 2014), may indeed also
participate in speed encoding. Recent examination of this area’s
spatially-relevant output revealed two populations of cells with
speed-rate relationships, one in a positive manner and one in a negative
manner (Kay et al., 2016). These results reflect similar findings from
the same group in CA1 (Yu et al., 2017).
Thus running
speed clearly and robustly alters the rate code in the circuitry most
heavily implicated in spatial navigation.