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.