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The wiring diagram of a glomerular olfactory system.

Berck ME, Khandelwal A, Claus L, Hernandez-Nunez L, Si G, Tabone CJ, Li F, Truman JW, Fetter RD, Louis M, Samuel AD, Cardona A - Elife (2016)

Bottom Line: We found a canonical circuit with uniglomerular projection neurons (uPNs) relaying gain-controlled ORN activity to the mushroom body and the lateral horn.A second, parallel circuit with multiglomerular projection neurons (mPNs) and hierarchically connected local neurons (LNs) selectively integrates multiple ORN signals already at the first synapse.This complete wiring diagram will support experimental and theoretical studies towards bridging the gap between circuits and behavior.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, Harvard University, Cambridge, United States.

ABSTRACT
The sense of smell enables animals to react to long-distance cues according to learned and innate valences. Here, we have mapped with electron microscopy the complete wiring diagram of the Drosophila larval antennal lobe, an olfactory neuropil similar to the vertebrate olfactory bulb. We found a canonical circuit with uniglomerular projection neurons (uPNs) relaying gain-controlled ORN activity to the mushroom body and the lateral horn. A second, parallel circuit with multiglomerular projection neurons (mPNs) and hierarchically connected local neurons (LNs) selectively integrates multiple ORN signals already at the first synapse. LN-LN synaptic connections putatively implement a bistable gain control mechanism that either computes odor saliency through panglomerular inhibition, or allows some glomeruli to respond to faint aversive odors in the presence of strong appetitive odors. This complete wiring diagram will support experimental and theoretical studies towards bridging the gap between circuits and behavior.

No MeSH data available.


Related in: MedlinePlus

principal component analysis of odors leading to a principled clustering of orns.(a) Clustering of odors by odorant-descriptor. Results of K-means clustering of odors in the 32 dimensional odor-descriptor space proposed in Haddad et al. (2008). Odors cluster into five groups that are well correlated with odor chemical type (alcohols, aromatics, esters, pyrazines, and others). (b–e) Clustering of odors by ORN response. (b) The variance explained for the odors in ORN response space as a function of the number of principal components (dimensions). The 'elbow' of this curve is composed of the principal components used for the clustering analysis of the odors by ORN-response. (c) How the odors span the space of the first 3 principal components of ORN response space. The odors are individual points colored by which of the five clusters, calculated via an affinity propagation clustering algorithm, they belong to. (d) How each of the odors fit into the clusters in ORN response space. Each cluster tends to group odors of similar chemical type. (e) The ORNs that represent the centroid of each cluster, calculated using a threshold obtained via Otsu’s method. See Materials and methods for further details.DOI:http://dx.doi.org/10.7554/eLife.14859.015
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fig4s3: principal component analysis of odors leading to a principled clustering of orns.(a) Clustering of odors by odorant-descriptor. Results of K-means clustering of odors in the 32 dimensional odor-descriptor space proposed in Haddad et al. (2008). Odors cluster into five groups that are well correlated with odor chemical type (alcohols, aromatics, esters, pyrazines, and others). (b–e) Clustering of odors by ORN response. (b) The variance explained for the odors in ORN response space as a function of the number of principal components (dimensions). The 'elbow' of this curve is composed of the principal components used for the clustering analysis of the odors by ORN-response. (c) How the odors span the space of the first 3 principal components of ORN response space. The odors are individual points colored by which of the five clusters, calculated via an affinity propagation clustering algorithm, they belong to. (d) How each of the odors fit into the clusters in ORN response space. Each cluster tends to group odors of similar chemical type. (e) The ORNs that represent the centroid of each cluster, calculated using a threshold obtained via Otsu’s method. See Materials and methods for further details.DOI:http://dx.doi.org/10.7554/eLife.14859.015

Mentions: (a) Posterior view of EM-reconstructed mPNs that innervate the right antennal lobe (in color; uPNs in grey for reference), each receiving inputs from a subset of olfactory glomeruli but many also from non-ORN sensory neurons in the subesophageal zone (SEZ). Most mPNs (green) project via the same tract as the uPNs (mALT). They can project via other tracts (other colors), but never via the mlALT used by the iPNs of the adult Drosophila. The mPNs project to many regions including a pre-calyx area, a post-calyx area, the lateral horn (LH) and the mushroom body vertical lobe (MB vl). mPNs are generated by diverse neuroblast lineages including BAlp4, BAla1, and others (Das et al., 2013). (b) Dorsal view of the EM-reconstructed Picky LNs shown together and individually. When shown individually, the Picky LNs are in 2 colors: blue for the dendrites and soma, and green for the axon. Zoom in to observe that presynaptic sites (red) are predominantly on the axon, whereas postsynaptic sites (cyan) are mostly on dendrites. Collectively, the dendritic arbors of the 5 Picky LNs tile the olfactory glomeruli. The dendrites of the Picky LN 3 and 4 extend significantly into the SEZ. They all originate from the same neuroblast lineage: BAla2 (Das et al., 2013). (c) Percentage of the total number of postsynaptic sites on the dendrite of a mPN or Picky LN (column neuron) that originate from a given glomerulus or Picky LN (row neurons). Here we define the glomerulus as connections from the ORN or via dendro-dendritic synapses from a given ORN’s uPN. This is most relevant for mPN A1, which can receive more synapses from an ORN’s uPN than the ORN itself (see suppl. Adjacency Matrix). We show the inputs to the mPNs and Picky LNs for the right antennal lobe, but for all bilateral mPNs (bil.-lower, bil.-upper, and VUM) we include inputs from both sides. We show only connections with at least two synapses, consistently found among homologous identified neurons in both the left and right antennal lobes. Percentages between 0 and 1 are rounded to 1, but totals are computed from raw numbers. Connections in this table are stereotyped (when comparing the left and right antennal lobes) and selective. Note that mPNs that receive many inputs from non-ORN sensory neurons in the SEZ have a low total of ORN+uPN input. For an extended version of this table that includes all LNs see Figure 4—figure supplement 2. (d) The direct upstream connectivity for two mPNs, with ORNs colored by the groups emerging from the PCA analysis of odor tuning. Connections from ORNs and Picky LNs to mPNs create 3 different types of motifs: direct excitatory connections from ORNs, lateral inhibitory connections from ORNs only via Picky LNs, and feedforward loops where an ORN connects both directly to the mPN and laterally through a Picky LN. Note that the activity of Picky LN 0 could alter the integration function for mPN A3 and indirectly for B2, as well as many other mPNs (not shown). Arrow thicknesses are weighted by the square root of the number of synapses between neurons. (e) The Picky LN hierarchy, dominated by Picky LN 0, here showing connections with 2 or more consistent synapses between bilaterally homologous neurons. Some of these connections are axo-axonic (see Figure 4—figure supplement 3).


The wiring diagram of a glomerular olfactory system.

Berck ME, Khandelwal A, Claus L, Hernandez-Nunez L, Si G, Tabone CJ, Li F, Truman JW, Fetter RD, Louis M, Samuel AD, Cardona A - Elife (2016)

principal component analysis of odors leading to a principled clustering of orns.(a) Clustering of odors by odorant-descriptor. Results of K-means clustering of odors in the 32 dimensional odor-descriptor space proposed in Haddad et al. (2008). Odors cluster into five groups that are well correlated with odor chemical type (alcohols, aromatics, esters, pyrazines, and others). (b–e) Clustering of odors by ORN response. (b) The variance explained for the odors in ORN response space as a function of the number of principal components (dimensions). The 'elbow' of this curve is composed of the principal components used for the clustering analysis of the odors by ORN-response. (c) How the odors span the space of the first 3 principal components of ORN response space. The odors are individual points colored by which of the five clusters, calculated via an affinity propagation clustering algorithm, they belong to. (d) How each of the odors fit into the clusters in ORN response space. Each cluster tends to group odors of similar chemical type. (e) The ORNs that represent the centroid of each cluster, calculated using a threshold obtained via Otsu’s method. See Materials and methods for further details.DOI:http://dx.doi.org/10.7554/eLife.14859.015
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Related In: Results  -  Collection

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fig4s3: principal component analysis of odors leading to a principled clustering of orns.(a) Clustering of odors by odorant-descriptor. Results of K-means clustering of odors in the 32 dimensional odor-descriptor space proposed in Haddad et al. (2008). Odors cluster into five groups that are well correlated with odor chemical type (alcohols, aromatics, esters, pyrazines, and others). (b–e) Clustering of odors by ORN response. (b) The variance explained for the odors in ORN response space as a function of the number of principal components (dimensions). The 'elbow' of this curve is composed of the principal components used for the clustering analysis of the odors by ORN-response. (c) How the odors span the space of the first 3 principal components of ORN response space. The odors are individual points colored by which of the five clusters, calculated via an affinity propagation clustering algorithm, they belong to. (d) How each of the odors fit into the clusters in ORN response space. Each cluster tends to group odors of similar chemical type. (e) The ORNs that represent the centroid of each cluster, calculated using a threshold obtained via Otsu’s method. See Materials and methods for further details.DOI:http://dx.doi.org/10.7554/eLife.14859.015
Mentions: (a) Posterior view of EM-reconstructed mPNs that innervate the right antennal lobe (in color; uPNs in grey for reference), each receiving inputs from a subset of olfactory glomeruli but many also from non-ORN sensory neurons in the subesophageal zone (SEZ). Most mPNs (green) project via the same tract as the uPNs (mALT). They can project via other tracts (other colors), but never via the mlALT used by the iPNs of the adult Drosophila. The mPNs project to many regions including a pre-calyx area, a post-calyx area, the lateral horn (LH) and the mushroom body vertical lobe (MB vl). mPNs are generated by diverse neuroblast lineages including BAlp4, BAla1, and others (Das et al., 2013). (b) Dorsal view of the EM-reconstructed Picky LNs shown together and individually. When shown individually, the Picky LNs are in 2 colors: blue for the dendrites and soma, and green for the axon. Zoom in to observe that presynaptic sites (red) are predominantly on the axon, whereas postsynaptic sites (cyan) are mostly on dendrites. Collectively, the dendritic arbors of the 5 Picky LNs tile the olfactory glomeruli. The dendrites of the Picky LN 3 and 4 extend significantly into the SEZ. They all originate from the same neuroblast lineage: BAla2 (Das et al., 2013). (c) Percentage of the total number of postsynaptic sites on the dendrite of a mPN or Picky LN (column neuron) that originate from a given glomerulus or Picky LN (row neurons). Here we define the glomerulus as connections from the ORN or via dendro-dendritic synapses from a given ORN’s uPN. This is most relevant for mPN A1, which can receive more synapses from an ORN’s uPN than the ORN itself (see suppl. Adjacency Matrix). We show the inputs to the mPNs and Picky LNs for the right antennal lobe, but for all bilateral mPNs (bil.-lower, bil.-upper, and VUM) we include inputs from both sides. We show only connections with at least two synapses, consistently found among homologous identified neurons in both the left and right antennal lobes. Percentages between 0 and 1 are rounded to 1, but totals are computed from raw numbers. Connections in this table are stereotyped (when comparing the left and right antennal lobes) and selective. Note that mPNs that receive many inputs from non-ORN sensory neurons in the SEZ have a low total of ORN+uPN input. For an extended version of this table that includes all LNs see Figure 4—figure supplement 2. (d) The direct upstream connectivity for two mPNs, with ORNs colored by the groups emerging from the PCA analysis of odor tuning. Connections from ORNs and Picky LNs to mPNs create 3 different types of motifs: direct excitatory connections from ORNs, lateral inhibitory connections from ORNs only via Picky LNs, and feedforward loops where an ORN connects both directly to the mPN and laterally through a Picky LN. Note that the activity of Picky LN 0 could alter the integration function for mPN A3 and indirectly for B2, as well as many other mPNs (not shown). Arrow thicknesses are weighted by the square root of the number of synapses between neurons. (e) The Picky LN hierarchy, dominated by Picky LN 0, here showing connections with 2 or more consistent synapses between bilaterally homologous neurons. Some of these connections are axo-axonic (see Figure 4—figure supplement 3).

Bottom Line: We found a canonical circuit with uniglomerular projection neurons (uPNs) relaying gain-controlled ORN activity to the mushroom body and the lateral horn.A second, parallel circuit with multiglomerular projection neurons (mPNs) and hierarchically connected local neurons (LNs) selectively integrates multiple ORN signals already at the first synapse.This complete wiring diagram will support experimental and theoretical studies towards bridging the gap between circuits and behavior.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, Harvard University, Cambridge, United States.

ABSTRACT
The sense of smell enables animals to react to long-distance cues according to learned and innate valences. Here, we have mapped with electron microscopy the complete wiring diagram of the Drosophila larval antennal lobe, an olfactory neuropil similar to the vertebrate olfactory bulb. We found a canonical circuit with uniglomerular projection neurons (uPNs) relaying gain-controlled ORN activity to the mushroom body and the lateral horn. A second, parallel circuit with multiglomerular projection neurons (mPNs) and hierarchically connected local neurons (LNs) selectively integrates multiple ORN signals already at the first synapse. LN-LN synaptic connections putatively implement a bistable gain control mechanism that either computes odor saliency through panglomerular inhibition, or allows some glomeruli to respond to faint aversive odors in the presence of strong appetitive odors. This complete wiring diagram will support experimental and theoretical studies towards bridging the gap between circuits and behavior.

No MeSH data available.


Related in: MedlinePlus