Everyday tasks we may regard as 'simple' -- for example, knowing the
difference between the smell of an orange and a pickle -- are actually
marvels of evolutionary development, the work of eons. A neuroscience
team reports results of experiments that suggest how the mammalian brain
distinguishes odors -- not just dissimilar ones but, perhaps more
importantly, odors that are nearly identical, such as the scents of
oranges and tangerines.
Precise discrimination of olfactory signals from the environment is
nothing less than a survival skill, more so for mice, our mammalian
cousins, than for us. Mice have relatively poor vision, and it is only
thanks to their other senses, notably their incredible ability to
identify and discriminate odors, that they can successfully hunt for
food or choose a mate. Understanding how they do this, in turn, sheds
light on the workings of our much more complex, but structurally
related, brains.
Led by CSHL Assistant Professor Florin Albeanu, the team explored a
function in the mouse brain that scientists still don't know much about.
After a mouse samples a smell by sniffing, and signals from that
activity are gathered and subjected to preliminary processing in the
animal's olfactory bulb, the bulb sends "output" signals to the brain's
higher processing center, the cerebral cortex. Albeanu's team focused on
"feedback" -- the signal that the olfactory cortex, in turn, sends back
to the olfactory bulb. While there are theories aplenty about the
nature and purpose of this feedback signal, very little is known about
it.
Even in the mouse brain, the feedback loop is a good deal more
complex than just described. The olfactory bulb sends output to and
receives feedback from multiple parts of the brain. Albeanu's team
focused on one such feedback loop: signals sent from two principal cell
types in the bulb, called mitral cells and tufted cells. These signals
travel over long-distance axons to various parts of the brain, but most
prominently to the piriform cortex. That's the brain's primary center
for higher olfactory processing.
Some theorists have speculated that the piriform cortex works as a
pattern-recognition device that compares incoming sensory inputs with
representations of previously experienced odors, stored up in memory.
Not only is the piriform cortex thought to do this job; it is also
involved in the integration of this information with contextual
information (ranging from other data about the environment to whether
the animal is hungry, amorous, afraid, etc.). Further, it is theorized
that based on this data, the piriform cortex sends signals back to the
olfactory bulb -- feedback -- that is essentially predictive, helping
the animal to make decisions based on all available information.
Albeanu's team, which included co-first authors Drs. Gonzalo Otazu
and Hongggo Chae, as well as technician Martin Davis, made a series of
discoveries in two related sets of experiments that support some of
these theories. In one set, as they exposed awake mice to a panel of
about 30 odorants, one by one, they traced the axons projecting back to
the olfactory bulb from the piriform cortex -- the "wires," in effect,
that carry the feedback signal -- and measured the responses of tiny
button-like structures called synaptic boutons, the sites where these
cortical feedback axons form connections, or synapses, in the bulb with
local receiving neurons. These so-called interneurons are inhibitory.
"The idea was to image the responses of the boutons in the olfactory
bulb to a set of odorants," explains Albeanu. "It's very hard to
physically access the piriform cortex for optical imaging, so we used
these boutons as a proxy to indicate the nature of the signal that the
cortex is feeding back to the bulb."
The results were "striking," says Albeanu. First, it was clear that
any given bouton responded only to a small fraction of the 30 odorants
-- perhaps two or three, on average. This is what neuroscientists call a
"sparse" response, and it indicates specificity. This immediately cast
doubt on an existing theory suggesting that the feedback to the bulb is
non-specific and acts like the volume, or "gain," control on an audio
system. Rather, the response was specific and highly selective. Not only
did a given bouton respond to very few odors; if it responded to one by
amplifying the feedback signal (above the background level, since there
is always activity in the circuit), it tended to perform that same
function, amplification, on all of the odors it responded to.
Conversely, those boutons that tamped down the signal coming back from
the cortex tended to do that for all of the odors they responded to.
A second set of experiments enabled Albeanu's team to offer a new
hypothesis of the purpose of this particular cortical feedback. By
injecting mice with a drug that inactivates the piriform cortex, they
were able to examine the activity of the output cells in the olfactory
bulb that normally integrate the cortical feedback via inhibitory
interneurons. Again a striking result: as compared with their activity
profiles when receiving feedback, mitral cells in the olfactory bulb
tended to have overlapping responses when the feedback was cut off. In
other words, their activity profiles started to look quite similar. This
suggests that without feedback from the cortex, mitral cells are no
longer to supply the animal with information that can sharply
distinguish odors, particularly odors that are chemically similar.
Taken together, the results lead Albeanu to propose that feedback
from the cortex is highly specific, and likely used to create a useful
representation of the animal's environment, "in a very specific and
selective fashion that, in turn, is used to extract the identity of a
given odor and to separate it from other odors," Albeanu says. The
research continues now in experiments featuring animals that are
actively engaged in odor discrimination in their environment, in order
to obtain behavioral evidence to correlate with the results of the
experiments published today.
This story is taken from Science Daily