Long-range intracortical excitation shapes olfactory processing

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 2 Neuron 72, October 6, 2011 ª2011 Elsevier Inc.
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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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