Current Biology
Dispatches
could be a necessary adjustment to the
presence of a long axon. This axon will filter
rapidly varying signals, a biophysical
consequence of the membrane
capacitance [7]. In that case the slower
responses in the fovea will tend to preserve
the size of the final output that gets to the
bipolar cell: the long axon will act like a low-
pass filter, so that slow signals are
transmitted better than fast ones.
Remember that the long axon exists for
purely optical reasons, to keep the inner
retinal circuitry from scattering light and
allow close packing of the cones’ light-
sensitive outer segments. Thus, the
evolutionary trade-off would sacrifice
sensitivity to rapid signals as an indirect
cost of maximal spatial resolution. In the
first interpretation, slow integration is
intrinsically a good thing. In the second, the
slow response is a necessary evil, where
speed is sacrificed in order to allow
something (acuity) more important. And of
course, both things could be true.
A separate but important technical point
is made by Sinha et al., who used high
resolution fluorescence microscopy to
compare the inhibitory input to ganglion
cells in the fovea with those in the
periphery. Their result (few inhibitory
Multisensory Development: Calibrating a Coherent
Sensory Milieu in Early Life
Andrew J. Bremner
Sensorimotor Development Research Unit, Department of Psychology, Goldsmiths, University of London, New Cross, London,
SE14 6NW, UK
Correspondence: a.bremner@gold.ac.uk
http://dx.doi.org/10.1016/j.cub.2017.02.055
A new study reveals the effects of visual deprivation in early life on the development of multisensory
simultaneity perception. To understand the developmental processes underlying this we need to consider
the multisensory milieu of the newborn infant.
The newborn human arrives into a
startlingly complex sensory world in which
it is invaded by information from touch,
taste, smell, proprioception, vestibular
input, audition, and vision, all of which
provide cues about features of objects
and events which arrive in the central
nervous system at different latencies, and
receptors on foveal ganglion cells) agrees
with their physiology but conflicts with
earlier studies using electron microscopy
[8–10]. Because their technique strains the
limits of light microscopy, more information
will be needed to get to the bottom of this.
But Sinha et al. make the important general
point that the booming connectomics
industry [11,12] is at present stuck with the
assumption that structurally similar
synapses all have the same weight —
something unlikely to be correct. We need
more test cases, situations in which
electron microscope images of specific
synapses can be linked to their chemical
neuroanatomy and their behavior in
transmitting information.
REFERENCES
1. Sinha, R., Hoon, M., Baudin, J., Okawa, H.,
Wong, R.O.L., and Rieke, F. (2017). Cellular
and circuit mechanisms shaping the
perceptual properties of the primate fovea.
Cell 168, 413–426.
2. Masland, R.H. (2012). The neuronal
organization of the retina. Neuron 76, 266–280.
3. Polyak, S.L. (1948). The Retina (University of
Chicago Press: Illinois).
4. Tyler, C.W. (1985). Analysis of visual
modulation sensitivity. II. Peripheral retina and
in almost uniformly varying neural codes. If
infants are to develop an ability to perceive
a spatiotemporally coherent and
meaningful environment from amongst
this multisensory me lange, they need to
learn to solve the ‘‘crossmodal binding
problem’’, i.e. they need to figure out how
and when stimuli across the senses go
Current Biology 27, R294–R317, April 24, 2017 ª 2017 Elsevier Ltd. R305
the role of photoreceptor dimensions. J. Opt.
Soc. Am. A 2, 393–398.
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Brain’s Wiring Makes Us Who We Are (New
York: Houghton Mifflin).
together. A new study [1] sheds important
light on how this happens.
Developing Solutions to the
Crossmodal Binding Problem
Whilst the advantages which multiple
senses bestow to perception are well
acknowledged (e.g., [2]), the challenges

which they create for the developing
organism are significant. The crossmodal
binding problem [3,4] threatens adults’ and
infants’ ability to perceive a coherent
multisensory world: Coherent multisensory
perception of timing is threatened by
temporal asynchrony introduced by
differences in neural transduction between
the senses (e.g., vision takes about
45 ms longer than sound to reach the
central nervous system [3]). Coherent
multisensory perception of space is
threatened by the fact that the brain codes
spatial position in different ways across the
senses (e.g., visual location is coded in
retinocentric coordinates, and tactile
location in somatosensory coordinates,
and the transformations between visual,
auditory and tactile codes depend on the
relative postures of eyes, ears, and limbs,
which change frequently [5,6]). But the
crossmodal binding problem is not
purely biological: Even before physical
information has reached our sensory
apparatus, differences in the physics of
the different media of transmission (e.g.,
sound waves, pulses of electromagnetic
radiation, the diffusion of chemicals) give
rise to asynchronies and dislocations
across those media.
So how do our central nervous systems
learn to abstract a coherent world from
this multisensory mess (or ‘‘sensory
bouillabaisse’’ according to one of the
authors of [1])? We now know a lot about
how adults solve the ‘‘crossmodal binding
problem’’ (e.g., [3,4,7,8]), but there has
been remarkably little consideration of the
origins of such solutions in developmental
psychology. This is odd, because
the various threats to multisensory
perception discussed above change
dramatically in their nature and impact
across early life, requiring continual
recalibrations [9]. Perhaps the most
revealing studies to date come from
research involving participants with visual
deprivation early in life. In the domain of
multisensory space, studies indicate the
importance of visual experience in early
development. The most recent case
studies of congenitally blind individuals
who have had their sight restored through
the removal of cataracts seems to
indicate that deprivation of vision in a
sensitive period between 5 months [10]
and two years [11] leads to atypical
development of an ability to map touches
into visual space.
R306 Current Biology 27, R294–R317, April 24, 2017
In their recent study, Chen et al. [1] show
that visual experience is also crucial to the
typical development of multisensory
simultaneity perception. Presenting
audiovisual stimuli with a range of onset
asynchronies they asked adult
participants to judge whether or not the
auditory and visual components occurred
simultaneously. Participants who had had
congenital cataracts in both eyes in early
infancy (up to about 4 months of age)
showed an atypical pattern of simultaneity
perception; they were biased to judge
visual-leading events as simultaneous.
Their point of subjective simultaneity for
such events was where the visual stimulus
led the auditory stimulus by 43 ms.
Interestingly, no such atypical
development was seen when the same
participants were asked to judge visual-
tactile simultaneity. On this basis Chen
et al. make an important point: effects of
visual deprivation are not just visual. Visual
deprivation in infancy also deprived these
individuals of the multisensory
experiences which they need in order to
develop a typical sense of audiovisual
timing. But what are these multisensory
experiences and how do they influence
multisensory development?
Audiovisual Experiences in the First
Months of Life
Newborn human babies do not live in
the same multisensory milieu as adults.
Altricial and myopic, they depend on
focuses of attention and interest (people,
faces, hands) [12] being brought to them
(or vice versa). It would be very odd to see
an adult talking to a newborn from across
a room. As caregivers, we tend to get up
close to provide young babies with a
rich, nearby — almost peripersonal —
multisensory environment.
The up-close-and-personal audiovisual
environment of the newborn is why I doubt
one of Chen et al.’s [1] explanations for their
findings. They suggest that the specific
effect of visual deprivation on audiovisual
simultaneity perception (and not visual-
tactile simultaneity) may be due to the fact
that infants have to calibrate audiovisual
simultaneity under conditions of visual-
to-auditory lag given the slower transit
of sound-waves towards the observer
(visual-tactile events only occur in near
space). But I can’t think of many instances
in which infants younger than 5 months
would be interested in audiovisual events
Current Biology
Dispatches
happening at a distance where the visual-
to-auditory lag would be at all significant.
It seems more likely that the auditory-to-
visual lags due to differences in the speed
of auditory and visual neural transduction
to the central nervous system, which are
close to 45 ms in the adult, would be a
more pertinent concern for crossmodal
temporal calibration at this age.
Interestingly, this 45 ms crossmodal
transduction differential is quite close to
the visual-auditory lag at which Chen
et al.’s visually deprived participants
demonstrated their point of subjective
simultaneity. So perhaps the effect of
audiovisual deprivation in the first months
of life is that it prevents infants from
partialing out the lags between auditory
and visual signals due to crossmodal
transduction differentials. And so this
might explain why these infants later, as
adults, perceive events where the visual
stimulus precedes the auditory stimulus as
being simultaneous. But then why should
visual-tactile simultaneity not also be
affected by the corresponding deprivation
of visual-tactile experience? Again, I think
the answer lies in a consideration of the
newborn multisensory experience.
Visual-tactile Experiences in the First
Months of Life
It is surprising how little visual regard
newborn infants have for their own bodies.
Visual orienting to tactile stimuli is not
behaviourally robust until around
10 months of age [13]. Even when they start
reaching for objects, they tend to be just as
successful in the light as in the dark
(indicating that visual control of the hand is
not important [14]). We also know that at
4 months of age infants do not refer
vibrotactile stimuli on their feet to a location
in external (visual) space [15]. So perhaps
this is why Chen et al.’s participants
showed no atypical development of visual-
tactile simultaneity judgments. Because
their sight was restored at around
4.5 months, they were only deprived of
visual-tactile experience in a period in
which infants do not spend much time
considering such multisensory content in
any case. This would seem to chime with a
recent study [10] which indicates that visual
deprivation in the first five months
of life does not impair the typical
development of tactile spatial perception
as it does when such deprivation continues
into later infancy [11] and childhood.
Current Biology

Dispatches

The Development of Multisensory
Timing Beyond Early Infancy
In this dispatch, I have suggested that
the sensorimotor and perceptual
limitations of the newborn infant place
certain constraints on the ways in which
they experience and learn from their
multisensory environment. But of course in
the second half year of life, typically
6. Jay, M.F., and Sparks, D.L. (1984). Auditory
receptive fields in primate superior colliculus
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7. Sugita, Y., and Suzuki, Y. (2003). Audiovisual
perception: Implicit estimation of sound-arrival
time. Nature 421, 911–911.
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13. Fausey, C.M., Jayaraman, S., and Smith, L.B.
(2016). From faces to hands: Changing visual
input in the first two years. Cognition 152,
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14. Bremner, A.J., Mareschal, D., Lloyd-Fox, S.,
and Spence, C. (2008). Spatial localization of
touch in the first year of life: Early influence of a
visual spatial code and the development of
remapping across changes in limb position.
J. Exp. Psychol. Gen. 137, 149–162.

developing infants increasingly take a
more active interest in their environment,
starting to make their first successful
grasps for objects, and later still beginning
to locomote around their environments
towards more distant goals [12]. These
sensorimotor developments bring about
new multisensory experiences which lead
to new complications of the crossmodal
binding problem. For instance, as infants
begin to deal with a wider repertoire of
different scales of spatial environment,
they will have to cope with similarly varying
temporal lags between visual and auditory
stimuli arising from the same external
events and develop the kinds
of compensatory mechanisms which
adults use in such circumstances [3,7,8].
Maybe this is what made it difficult for
Chen et al.’s participants to recalibrate
audiovisual simultaneity after their
sight was restored at 4 months. For
both typically and atypically developing
children, it probably makes a bit of sense in
these temporally variable multisensory
circumstances to bind stimuli together
across a wider temporal window, and such
wider temporal windows of crossmodal
binding have been observed several times
now in infants and children [16–19].
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1. Chen, Y.-C., Lewis, T.L., Shore, D.I., and
Maurer, D. (2017). Early binocular input is
critical for development of audiovisual but not
visualtactile simultaneity perception. Curr. Biol.
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2. Stein, B.E., ed. (2012). The New Handbook of
Multisensory Processing (Cambridge, MA: MIT
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3. Harris, L.R., Harrar, V., Jaekl, P., and Kopinska,
A. (2010). Mechanisms of simultaneity
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S., Tenenbaum, J.B., and Shams, L. (2007).
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R., and Röder, B. (2013). Partial recovery of
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Gut Microbiota: Small Molecules
Modulate Host Cellular Functions
Jacob M. Luber1,2,3,4,* and Aleksandar D. Kostic1,2,4,*
1Section on Pathophysiology and Molecular Pharmacology, Joslin Diabetes Center, Boston,
MA 02215, USA
2Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA 02215,
USA
3Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA
4Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA
02115, USA
*Correspondence: jluber@g.harvard.edu (J.M.L.), aleksandar.kostic@joslin.harvard.edu
(A.D.K.)
http://dx.doi.org/10.1016/j.cub.2017.03.026
The human gut metagenome was recently discovered to encode vast
collections of biosynthetic gene clusters with diverse chemical
potential, almost none of which are yet functionally validated. Recent
work elucidates common microbiome-derived biosynthetic gene
clusters encoding peptide aldehydes that inhibit human proteases.
Biosynthetic gene clusters (BGCs) are products without cellular machinery such
tightly clustered groups of genes in as ribosomes [1]. The array of diverse
bacteria that encode pathways capable of natural products produced by BGCs is
producing small-molecule natural vast; current databases hold more than

Current Biology 27, R294–R317, April 24, 2017 ª 2017 Elsevier Ltd. R307