and MDC126 [isolated in Bangladesh in 2008
(12)] showed greater T6SS gene transcript levels,
by factors of 4 to 24, than two earlier seventh-pandemic strains [N16961 isolated in Bangladesh
in 1971 (13) and C6706 isolated in Peru in 1991]
(Fig. 4 and data S1). Variant strains also displayed
more T6SS-dependent killing activity in vitro
(fig. S6). Thus, the enhanced T6SS expression
in V. cholerae variant strains may improve their
fitness through T6SS-mediated killing of commensal Gram-negative microbiota or even enteric pathogens, such as pathogenic E. coli that
share an upper intestinal niche with V. cholerae
and a similar epidemiological distribution (14).
T6SS-mediated antagonistic behavior was previously observed between enteric pathogens (such
as Salmonella typhimurium and Shigella sonnei)
and gut commensal organisms (15, 16). Although
secreted molecules such as autoinducers have
been shown to activate or repress the expression
of T6SS and virulence factors (17–19), it is unclear
whether microbial antagonism affects interspecies
communication in vivo and pathogen fitness. Our
results suggest that microbial antagonism may
also change the interaction of an enteric pathogen with its host through altering its expression
of virulence determinants as well as driving host
innate immune responses. In sum, our data support a working model (fig. S7) that provides a
framework for how V. cholerae might use an
antibacterial mechanism to clear its target niche
of inhibitory competitors and simultaneously enhance disease symptom–associated transmission.
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We thank M. Gack and J. Chiang for assistance with luciferase
assays and for a kind gift of reporter. We thank all Mekalanos lab
members for helpful comments. Supported by National Institute
of Allergy and Infectious Diseases grant AI-01845 (J.J.M.). The
authors declare no competing financial interests. All authors
helped to design and analyze experiments; W.Z., F.C., and
W.R. performed experiments; and W.Z., F.C., W.R., and J.J.M. wrote
the paper. All data generated or analyzed during this study
are included in this published article and its supplementary materials.
Materials and Methods
Figs. S1 to S7
Tables S1 to S5
5 September 2017; accepted 5 December 2017
Spatial representations of self and
other in the hippocampus
Teruko Danjo,1 Taro Toyoizumi,2 Shigeyoshi Fujisawa1*
An animal’s awareness of its location in space depends on the activity of place cells in
the hippocampus. How the brain encodes the spatial position of others has not yet been
identified. We investigated neuronal representations of other animals’ locations in the
dorsal CA1 region of the hippocampus with an observational T-maze task in which one
rat was required to observe another rat’s trajectory to successfully retrieve a reward.
Information reflecting the spatial location of both the self and the other was jointly and
discretely encoded by CA1 pyramidal cells in the observer rat. A subset of CA1 pyramidal
cells exhibited spatial receptive fields that were identical for the self and the other. These
findings demonstrate that hippocampal spatial representations include dimensions for
both self and nonself.
Spatial navigation requires the hippocampus (1, 2). The cognitive map theory states that spatial recognition in the hippocampus is allocentric (3–5). Place cells in the hippo- campus are the physiological correlate of
this representation because they are highly sensitive to changes in landmarks and contexts (6–13).
The characterization of additional types of navigational representations, including head-direction
cells and grid cells, has promoted our understanding of the neural mechanisms of allocentric spatial
representations in the hippocampal-entorhinal
cortex network (14–19). The studies of these neural
maps have focused on the animal’s own position
in space. It still remains unclear whether and
how spatial information of nonself, such as the
position of conspecifics, landmarks, and moving
objects, is represented in the hippocampus.
We designed an observational T-maze task
using a pair of rats (hereafter termed “self” and
“other”) and investigated how the other’s position
is represented in the self’s hippocampus. The self
was required to make a left/right choice to re-
trieve a reward based on the location of the other.
We used two versions of the task, an “opposite-
side rule” version in which the self rat had to
choose the side opposite to the other’s location
(Fig. 1A, fig. S1, and movie S1) and a “same-side
rule” in which the self rat had to choose the same
side as the other rat (fig. S1 and movie S2). During
the T-maze task, neuronal activity in the self’s
hippocampus (dorsal CA1) was recorded extra-
cellularly (n = 3 pairs of rats; 88 ± 8.1% and 84 ±
11% correct performance with opposite-side and
same-side rules, respectively). All analyses were
performed on single units with pyramidal cell
features and place fields in the task area (n =
1298 and 1205 units with opposite-side and same-
side rules, respectively) (fig. S2) [see the supple-
mentary materials (SM)].
We first examined how the location of the
other rat was represented in the opposite-side
rule observational task. Firing-rate maps of the
self’s positions (“self’s rate map”) and the other’s
positions (“other’s rate map,” which were obtained
by replacing the self’s positional data with the
other’s) revealed that in addition to the expected
coding of the observer’s own position in space,
the majority of units also displayed obvious place
fields for the other (Fig. 1, C to F, top). To understand the positional relationship of the rat pair at
the time of firing, we constructed joint rate maps
by linearizing the rats’ trajectories and entering
them into two-dimensional x-y axes (fig. S3).
Here, the self’s and other’s place fields composed
from identical spikes were combined into a single joint place field (Fig. 1, C to F, bottom, and
fig. S4). We then examined whether these joint
place fields were truly modulated by the other’s
positions and not a mere consequence of the
constraints in the positional relationships of
the two rats. The null hypothesis was that the
firing only depended on the self’s position and
was independent of the other’s. By computing
the surrogate firing rates that followed this null
hypothesis (see the SM) (20), we identified areas
with significantly higher firing rates for the
other (P < 0.05) (Fig. 1, C to F, third from top, and
1Laboratory for Systems Neurophysiology, RIKEN Brain
Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198,
Japan. 2Laboratory for Neural Computation and Adaptation,
RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama,
*Corresponding author. Email: firstname.lastname@example.org