Better known for their role in the
adaptive immune response, genes of
the major histocompatibility com-
plex (MHC) also influence mating
preference and social behaviour in
vertebrates. Reporting in the Journal
of Neuroscience, Spehr and co-work-
ers show that non-volatile MHC
peptides are recognized by olfac-
tory sensory neurons in the main
olfactory epithelium and transmit
information used for social decision
making in mice.
At least two anatomically and
functionally distinct sensory organs
allow mice to detect chemical signals:
the vomeronasal organ, traditionally
thought to transduce socially relevant
chemical signals after direct contact
with a source, and the main olfactory
epithelium, a structure thought to
detect only volatile molecules. The
authors showed that during direct
physical contact situations, such
as sniffing and licking, non-vola-
tile molecules could gain access
to the main olfactory epithe-
lium. Measurements of local
field potentials showed
Gap junctions -- which contain intercellular
channels composed of connexin proteins
-- allow molecules and ions to flow directly
between most types of cell, and constitute
electrical synapses between neurons. Mutations
in connexin genes underlie approximately half
of all cases of genetic deafness in childhood, but
their modes of action are not well understood.
A report in the Journal of Neuroscience provides
new insights into the role of a recently identified
connexin -- CX29 -- in auditory perception.
Four types of connexin, including CX29, are
expressed in the cochlea. Tang and co-workers
found that CX29 is abundantly and exclusively
expressed in Schwann cells that myelinate the
soma and processes of spiral ganglion neurons,
which communicate sound signals transduced by
hair cells to the cochlear nuclei in the brain stem.
By contrast, the other connexins are primarily
expressed in cochlear supporting cells and/or
fibrocytes.
To determine the functions of CX29, Tang and
colleagues studied mice that were deficient
in Cx29. These mice were impaired in several
aspects of auditory perception. Specifically, their
hearing sensitivity across a range of frequencies
was defective. In addition, they had sustained
hearing loss for high-frequency sounds in
response to stimulation with white noise, which
resulted in only temporary impairments in wild-
type mice.
The cochlear hair cells of these mice were
morphologically normal, so what is the cellular
mechanism that underlies these deficits? The
presence of high levels of CX29 in Schwann cells
suggested that myelination might be affected.
Indeed, the myelin around the soma of spiral
ganglion neurons was severely disorganized,
although axonal myelin was normal.
CX29 is expressed in most Schwann cells and
oligodendrocytes, yet only myelin in the spiral
ganglion is affected in Cx29-knockout mice.
Most myelinating glia express several connexin
genes, each of which might compensate
for the loss of another. However, these data
suggest that spiral ganglion Schwann cells
might express only CX29. Therefore, it seems
that CX29 makes a unique contribution to
myelination in the spiral ganglia and auditory
perception.
This elegant study reveals the mechanisms
by which CX29 plays its part in normal hearing.
Moreover, the pattern of deficits in mice
deficient in CX29 was consistent with that
seen in patients with auditory neuropathies.
Therefore, as the authors point out, these mice
could provide a valuable model with which
to explore the cellular and molecular basis of
auditory neuropathy.
Alison Rowan
ORIGINAL RESEARCH PAPER Tang, W. et al. Connexin29 is
highly expressed in cochlear Schwann cells, and it is required
for the normal development and function of the auditory
nerve of mice. J. Neurosci. 26, 1991­1999 (2006)
FURTHER READING Söhl, G., Maxeiner, S. & Willecke, K.
Expression and functions of neuronal gap junctions. Nature
Rev. Neurosci. 6, 191­200 (2005)
BEHAVIOURAL NEUROSCIENCE
Sniff and tell
a widely distributed sensitivity to
remarkably low levels of non-volatile
MHC peptides throughout this sen-
sory tissue, whereas mutated control
peptides did not elicit such highly
sensitive responses.
To identify the molecular
mechanisms involved in transduc-
tion of peptide information, the
authors disrupted elements of the
evolutionarily conserved cyclic AMP
(cAMP) second messenger system
found in olfactory sensory neurons.
Application of adenylyl cyclase
antagonists or deletion of olfactory
cyclic nucleotide-gated cation chan-
nels prevented the response of the
main olfactory epithelium to MHC
peptides, showing a requirement for
cAMP signalling in the generation of
peptide-evoked field potentials.
MHC peptides acting at the
main olfactory epithelium were also
shown to affect social preference of
male mice in vivo. Male mice
showed a preference for female
urine from a different strain.
Presented with identical
female same-strain
urine that had been
supplemented with
MHC peptides from
either same-strain or
different-strain mice,
male mice showed a preference for
urine containing MHC peptides from
a different strain. This preference for
disparate MHC peptides was also
observed in mice lacking a functional
vomeronasal organ, but was not
seen in mice lacking olfactory cyclic
nucleotide-gated cation channels
or mice tested in a volatile-only
paradigm.
Taken together, these findings
suggest that MHC peptides act as
social recognition cues in mice that
are detected by olfactory sensory
neurons of the main olfactory
epithelium and communicated by
an evolutionarily conserved cAMP-
dependent signalling pathway.
These findings challenge the widely
held view that the main olfactory
epithelium detects only volatile mol-
ecules, and add to a growing body of
evidence suggesting a much greater
complexity of olfactory sensory
systems.
Daniel McGowan
SENSORY SYSTEMS
Connexin's auditory connection
ORIGINAL RESEARCH PAPER Spehr, M. et al.
Essential role of the main olfactory system in
social recognition of major histocompatibility
complex peptide ligands. J. Neurosci. 26,
1961­1970 (2006)
FURTHER READING Dulac, C. & Torello, A. T.
Molecular detection of pheromone signals in
mammals: from genes to behaviour. Nature Rev.
Neurosci. 4, 551­562 (2003)
...MHC
peptides are
recognized by
... the main
olfactory
epithelium
and transmit
information
used for social
decision making
in mice
RESEARCH HIGHLIGHTS
NATURE REVIEWS | NEUROSCIENCE VOLUME 7 | APRIL 2006 | 253