NEUROSCIENCE
Nonlocal spatiotemporal representation
in the hippocampus of freely flying bats
Nicholas M. Dotson^1 and Michael M. Yartsev1,2*
Navigation occurs through a continuum of space and time. The hippocampus is known to encode the
immediate position of moving animals. However, active navigation, especially at high speeds,
may require representing navigational information beyond the present moment. Using wireless
electrophysiological recordings in freely flying bats, we demonstrate that neural activity in area CA1
predominantly encodes nonlocal spatial information up to meters away from the bat’s present
position. This spatiotemporal representation extends both forward and backward in time, with an
emphasis on future locations, and is found during both random exploration and goal-directed
navigation. The representation of position thus extends along a continuum, with each moment containing
information about past, present, and future, and may provide a key mechanism for navigating along self-
selected and remembered paths.
B
ats are renowned for their exceptional
navigational abilities and are believed
to use map-based navigation to forage
in the wild ( 1 Ð 4 ). The neural circuitry
for map-based representations includes
the hippocampus, which encodes the imme-
diate spatial position in terrestrial animals
( 5 Ð 7 ). Consistent with these studies, the basic
components for representing the immediate
three-dimensional (3D) spatial position in freely
flying bats have been identified ( 8 Ð 10 ). How-
ever, is it enough for navigational information
to be represented only at the present moment
or should such representations extend from
the past and into the future during active move-
ment ( 11 Ð 15 )? Several mechanisms have been
identified in the rodent hippocampus for rep-
resenting spatial locations extending beyond
the immediate position. Theta-phase and theta-
sequence coding have been shown to indicate
the animalÕs past and future positions as well
as possible future paths ( 16 Ð 24 ). Rate modu-
lations based on past or future events have
also been observed in a subset of place cells
( 25 Ð 27 ). However, neurons providing nonlocal
positional information are still primarily
active when the animal is within the cellÕs
firing field. Intriguingly, a subset of place cells
has been found to be most informative when
the neural spiking activity is assigned to the
animalÕs position a short period of time (~120 ms)
into the future ( 28 ), suggesting the existence
of an additional, nonlocal neural mechanism
based on rate-shifted coding. However, be-
cause of the movement speed of rodents in
small enclosures, an ~120-ms shift corresponds
to a position directly under the ratÕsnose( 29 ),
therefore still representing relatively local posi-
tion. Here, we investigated rate-shifted coding
mechanisms in flying bats, which provide an
advantageous model system for studying non-
local positional coding because of their high-
speed ( 30 ), ballistic motion through space,
which could facilitate identifying neural rep-
resentations of locations that are spatially
distant but still temporally close.
Typically, place coding is thought to be carried
out by place cells that encode the immediate
spatial position (Fig. 1A, top). We posited that
the neural code for 3D spatial navigation in a
fast-flying animal may include additional neu-
ral populations encoding places that the animal
does not currently occupy (nonlocal coding)
but that are within the flight path (Fig. 1A,
bottom). In this hypothetical spatiotemporal
code, a population of neurons is simultane-
ously active at each spatial position, but only
some optimally encode the immediate posi-
tion, whereas others optimally encode past or
future positions that are meters away, leading
to a representation of the full flight path in any
given moment (Fig. 1A, bottom). This hypoth-
esis predicts that neurons representing distant
positions along the path may not exhibit any
spatial tuning at all when the neural activity is
considered with respect to the batÕs immediate
position. For these neurons, the prediction is
that spatially selective fields may only emerge
when the appropriate lag is applied between
the positional and neural information; in other
words, their spatial selectivity will be divorced
fromthepresentandimbeddedinthepastor
in the future.
We initially performed wireless neurophys-
iological recordings from the dorsal CA1 re-
gion of four Egyptian fruit bats exploring the
full 3D volume of a large flight room (Fig. 1B).
In this random exploration experiment, a total
of 532 well-isolated single units were recorded,
of which 304 were sufficiently active during
flight and included in subsequent analyses
(see the supplementary materials and meth-
ods). Bats were encouraged to fly throughout
the room to ensure dense spatial coverage (Fig.1B). The 3D position of the bats was tracked at
millimeter spatial resolution (see the supple-
mentary materials and methods).
We used a time-shifting procedure to assess
the neuronÕs positional coding and to deter-
mine whether it is higher at past, present, or
future spatial positions ( 28 ). We calculated the
spatial information after time shifting the spik-
ing activity along flight trajectories (Ð1000 to
+1000 ms in 100-ms steps; see the supplemen-
tary materials and methods; fig. S1). In agree-
ment with previous studies ( 8 ), 27% (81/304
neurons;P<0.05,shuffletestwithBonferroni
correction) of the neurons were spatially selec-
tive at zero lag between spatial position and
spikes (t 0 ) (Fig. 1C and fig. S2). Overall, 46%
(140/304 neurons,P< 0.05, shuffle test with
Bonferroni correction) of the neurons were spa-
tially selective at one or more time shifts. For
most hippocampal neurons, spatial informa-
tion was highest at nonzero time shifts, with
most being optimally informative about future
positions (Fig. 1, D and E, and fig. S3). Figure
1D shows three examples of neurons with no
significant spatial selectivity at zero lag (t 0 )
and high spatial selectivity at a future lag. If
the hippocampal code were primarily related
to the present, then we would expect to see the
maximum spatial information concentrated
aroundt 0 (Fig. 1E, red line, and fig. S4). Instead,
we saw a continuum, with most neurons being
maximally informative at future lags while main-
taining a similar amount of spatial informa-
tion across lags (Fig. 1F). For a large fraction of
spatially selective neurons, the spatial informa-
tion att 0 was negligible (42%; 59/140 selective
neurons), indicating that these neurons would
go undetected as being spatially selective using
standard procedures, and are thus truly non-
local. Further, the spatiotemporal firing fields
were distributed throughout the entire room
and maintained consistent volumes and inter-
field distances across lags (Fig. 1, G and H), with
typically one (46%) or two (29%) fields per cell
(89% had three or fewer fields). Thus, time-
lagged firing fields appear to be equivalent to
nonlagged fields in terms of their spatial in-
formation, spatial distribution, and total volume.
Furthermore, we found that spatiotemporal
fields were largely stable throughout the ses-
sion(fig.S5),andtheoptimallagtimewasnot
related to the mean speed of the bat (fig. S6). A
spatial information analysis using distance
lags that matched the temporal lags (based
on the mean flight speed) produced similar
results (fig. S7), and a cross-correlation anal-
ysis indicated that the timing relationship of
correlated firing is not related to the optimal
lag order (fig. S8). Last, nonlocal heading tuning
was prominent as well (54%, 142/304), with a
high degree of overlap with spatially inform-
ative neurons (76%, 107/140), although the
distribution of optimal heading tuning was
shifted toward the past (fig. S9).242 9JULY2021¥VOL 373 ISSUE 6551 sciencemag.org SCIENCE
(^1) Department of Bioengineering, University of California,
Berkeley, CA 94720, USA.^2 Helen Wills Neuroscience
Institute, University of California, Berkeley, CA 94720, USA.
*Corresponding author. Email: [email protected]
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