Long-Range Intracortical ExcitationShapes Olfactory Processing
Minmin 1National Institute of Biological Sciences, Beijing 102206, China2School of Life Sciences, Tsinghua University, Beijing 100084, China*Correspondence: DOI
Recurrent intracortical connections are believed to be especially dense in the piriform cortex. Two studies inthis issue of Neuron report several interesting features of the long-range intracortical connections and revealtheir physiological roles in shaping olfactory processing.
Odor molecules have drastically different
a specific PN and its activation leads to
nate vastly different odors? By the stage
the transmitter release from at most a sin-
rated amplitude of overall photocurrents,
ical importance of intracortical associa-
stimulation of $8,000 ChR2+ neurons.
this issue of Neuron, two elegant studies
overall number of 1 million PNs in the piri-
form, the authors speculate that individual
and functional roles of long-range cortical
puts from over 2,000 cortical neurons.
subset of 25–50 mitral/tufted cells, which
receive primary excitatory input from iso-
used optogenetics to dissect intracortical
tioned in slice preparations, this number
evokes a stereotypical spatial activation
evoked activity of any single neuron could
potential firing and may even create epi-
leptic overexcitation. Consistent with an
via the lateral olfactory tract (LOT). Sur-
prisingly, individual odorants evoke spar-
PNs at different distances from the center
sely and randomly distributed sets of neu-
of viral infection. In a vast majority of re-
that light stimulation also generates dis-
of inhibition scale with stimulus intensities
and are often larger than those of excita-
by divergent projections from the bulb to
the cortex and/or associative connections
strong across millimeters in the piriform
within the cortex. Recent tracing studies
cortex. In contrast, photocurrents steeply
reveal that the axonal terminals of indi-
decreased with increasing distance in the
vidual mitral/tufted cells are diffusively
distributed throughout the piriform cortex
recordings show that individual pyramidal
Neuron 72, October 6, 2011 ª2011 Elsevier Inc. 1
down the exact wiring pattern in the piri-form cortex. Do all PNs play equal roles inintracortical association? Morphologicallyidentified PNs exhibit highly diverse olfac-tory tunings in terms of both excitationand inhibition in an awake mouse ). Both new studies indicateheterogeneity among PNs in receiving in-tracortical excitation. In vivo recordingsshow that broadly tuned neurons tend tobe more frequently activated by odor-eli-cited intracortical excitation Consistently, individualPNs appear to receive quite variableamount of recurrent excitation in slice
Figure 1. Highly Simplified Schematics Illustrating the Neuronal Wiring Patterns in the
Olfactory SystemThe projection from the olfactory epithelium to the MOB conforms to the rule of ‘‘labeled-line’’ so that
a given glomerulus receives converging input from OSNs expressing a specific OR and drives the excita-
tion of an exclusive subset of mitral/tufted (M/T) cells. However, the projection of M/T cells to the piriform
cortex becomes random and diffusive. Individual PNs integrate M/T inputs associated with scores of
of other PNs, or whether some subtypes of
glomeruli. In addition, PNs extend long-range axonal outputs to excite other PNs and at the same timereceive recurrent cortical inputs from thousands of PNs. GABAergic interneurons (INs) mediate both
feed-forward and feedback inhibitions to stabilize the cortical circuit. GL, glomerular layer; Gr, granule
other PNs. This may be tested by serially
activating small subset of ChR2+ neuronswith focal illumination and mapping area-
of their excitatory tuning. Because all PNs
inputs on the firing activity of PNs. In an-
major class of cortical neurons. Although
type of inhibitory neurons in the diagram
hance neuronal responses to odor stimuli.
challenging in vivo whole-cell recordings
neurochemical, and functional features.
lence intracortical connections. Functional
of the circuit wiring scheme in the piriform
axonal terminals of cortical neurons in the
cortical interneurons should facilitate the
piriform but are absent on those of mitral/
probing of their precise roles in olfactory
tufted cells. Local application of baclofen,
tions in shaping cortical odor representa-
tion. Their results indicate that, although
abolished intracortical excitation but left
questions on the exact function of intra-
the LOT-evoked excitation largely intact.
synaptic connections is low, an individual
cortical connections in olfactory percept
EPSCs is blocked by baclofen application,
suggesting that intracortical connections
of millimeters. In addition, PNs can acti-
global inhibition to maintain the balance
the glomerular spatial activation patterns
a small subset of PNs, which then recruits
stimulus delivery and intrinsic circuit ac-
lectivity of individual PNs. Baclofen mildly
tivity. Intracortical recurrent connections
provide the function of pattern completion
tively tuned neurons, but strongly blocks
excitation and inhibition in the piriform.
such that an identical population of cor-
ens the tuning for broadly-tuned neurons.
ical excitation than others and thus exhibit
effective blockade of odor-evoked inhibi-
tory responses on all neurons irrespective
cision and stability in an individual animal
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MeCP2: Phosphorylated Locally, Acting Globally
Michael Rutlinand Sacha B. Nelson1Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA*Correspondence: DOI
In this issue of Neuron, Greenberg and colleagues revise our understanding of how activity-dependentMeCP2 phosphorylation regulates distinct aspects of brain development and circuit function. The studyalso suggests a prominent role for MeCP2 in the regulation of global chromatin state in vivo. MeCP2 (X-linked methyl-CpG-binding
neurons is not to regulate transcription of
domains of the human MECP2 gene as
protein 2) is an abundant nuclear protein
specific genes but rather to regulate chro-
RTT (Amir et al., 1999). Rett syndrome is
a progressive and debilitating neurodeve-
scriptional repressor critical for normal
1–10,000–15,000 ratio. Mice that lack
spectrum disorder Rett Syndrome (RTT).
scription. Functional studies have demon-
MeCP2 either globally or conditionally in
In this issue of Neuron, Cohen, Greenberg,
and colleagues demonstrate that activity-
transcription factor access to target re-
single serine residue (S421) controls dis-
tions as a transcriptional repressor, then
and social behavior (Cohen et al., 2011).
(MBDs) (Bird, 2002). Interest in DNA meth-
this phosphorylation event in the dynamic
first identified independent mutations in
profiles from forebrain, hypothalamus, or
Neuron 72, October 6, 2011 ª2011 Elsevier Inc. 3
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