Olfactory Bulb: Synaptic Organisation

Abstract

Odour information is encoded by sensory neurons expressing a large family of ∼102–103 distinct olfactory receptors, and is mapped to an equally numerous population of glomeruli in the olfactory bulb. Each glomerulus is a modular circuit composed of a variety of local interneurons and bulb output neurons that receive primary afferent signals encoded by a single olfactory receptor. Incoming signals are filtered by inhibition from periglomerular cells and amplified by mutual excitation of mitral and tufted cells. Odour codes are further transformed by lateral inhibition between glomeruli mediated by short axon and granule cells that communicate through specialised dendrodendritic reciprocal synapses. These network mechanisms interact with a diversity of cell biophysical properties to shape spiking patterns of bulb output neurons. Synaptic processing in the bulb is also dynamically regulated by feedback from olfactory cortex, centrifugal modulation from basal forebrain nuclei and plasticity of local circuits sustained by adult neurogenesis.

Key Concepts:

  • Odour information is mapped to discrete glomeruli in the olfactory bulb that receive sensory inputs encoded by different olfactory receptors.

  • Sensory neuron terminals in glomeruli release the excitatory transmitter glutamate, under control of presynaptic inhibition by dopamine and GABA receptors.

  • Glomeruli contain multiple excitatory and inhibitory circuits for coordinating odour‐evoked spike activity of bulb output neurons, the mitral and tufted cells.

  • Most olfactory bulb circuits include dendrodendritic reciprocal synapses with closely linked glutamatergic excitatory and GABAergic inhibitory transmission.

  • Mitral and tufted cell responses are triggered and amplified by dendrodendritic excitation of glomerular dendritic tufts, and are controlled by periglomerular cell inhibition.

  • Glomeruli are connected by pervasive short‐ and long‐range networks of inhibitory superficial short axon cells.

  • Granule cells form complex webs of lateral inhibitory connections between mitral and tufted cells of different glomeruli.

  • Synaptic inhibition in the bulb is coordinated by networks of deep short axon cells that inhibit periglomerular and granule cells.

  • Synaptic inhibition in the bulb is strongly influenced by centrifugal inputs from olfactory cortex and subcortical modulatory centres.

Keywords: olfactory bulb; glomeruli; dendrodendritic; lateral inhibition; mitral cell; tufted cell; external tufted cell; granule cell; short axon cell

Figure 1.

Olfactory bulb circuits. Main signalling routes for odourant‐evoked synaptic excitation and inhibition of principal neurons in the mammalian olfactory bulb. Black arrows indicate glutamatergic transmission at excitatory synapses; grey arrows, GABAergic transmission at inhibitory synapses; thin black arrows, conduction of EPSPs or action potentials (spikes). In the olfactory epithelium (OE), different olfactory receptors (ORA, ORB and ORC) bind and recognise different odourant molecular structures and trigger spike firing in olfactory sensory neurons (OSNs). Axons of OSNs expressing specific olfactory receptors send projections to unique glomeruli in the outer layer of the bulb (GL; colour‐coded to indicate receptor identity). The OSN terminals release glutamate which activates a cascade of intraglomerular synaptic pathways, illustrated here in different glomeruli: (1) direct excitation of external tufted (ET) cells and tufted cells (TC), indirect excitation of mitral cells (MC) via ET cells, and feed‐forward inhibition of ET cells by type 1 PG cells (PG1); (2) responses of ET, TC and MC are amplified by lateral glutamatergic excitation, and electrical coupling (white symbol) between dendritic tufts, generating a long lasting depolarisation (LLD); (3) time course of LLD response is shaped by dendrodendritic feedback inhibition from type 2 PG cells (PG2). Glomerular excitation propagates down primary dendrites to MC and TC cell bodies. This elicits spike activity that is relayed out of the bulb via nerves in the lateral olfactory tract (LOT), to excite pyramidal neuron circuits in olfactory cortex. The spikes also backpropagate into MC/TC secondary dendrites in the external plexiform layer (EPL) to trigger glutamate release onto dendrites of granule cells (GC). The GCs respond by releasing GABA which mediates dendrodendritic feedback inhibition of TCs ((4) via GCT), MC cell bodies ((5) via GCS), and MC dendrites ((6) via GCM). Granule cells can also implement lateral inhibition ((7) via GCM) between mitral cells in different glomerular columns. MCL, mitral cell body layer; IPL, inner plexiform layer; GCL, granule cell layer.

Figure 2.

Dendrodendritic reciprocal synapse. Olfactory bulb circuits have a compact architecture that makes extensive use of multitasking dendrites with dual functions as both presynaptic and postsynaptic devices. A key circuit element is the dendrodendritic reciprocal synapse, in which adjacent excitatory and inhibitory synaptic junctions have their pre‐ and postsynaptic specialisations deployed on opposite sides of the synaptic cleft. The scheme shows the function of a mitral/granule (MC/GC) reciprocal synapse: an action potential (AP) initiated in the mitral cell (MC) body backpropagates into the secondary dendrite where it opens voltage‐gated calcium channels. Local calcium entry releases glutamate which activates AMPA/NMDA receptors on granule cell spines. The resulting spine depolarisation (EPSP) opens granule cell calcium channels, and Ca2+ influx through these channels (or through NMDA receptor channels) triggers release of GABA from the spine. This results in feedback inhibition of the mitral cell via GABAA receptors on the MC dendrite. Similar excitatory–inhibitory dendrodendritic synapses connect the intraglomerular dendritic tufts of mitral/tufted cells and PG cells.

Figure 3.

Inhibition of olfactory bulb circuits. Synaptic processing in the olfactory bulb is regulated by inhibition from diverse local interneurons. Black arrows indicate glutamatergic transmission at excitatory synapses; grey arrows, GABAergic transmission at inhibitory synapses. In the glomerular layer (GL), dopaminegic, GABAergic sSACs ((1) sSAC) connect different glomeruli through extensive horizontal dendritic and axonal projections. They are thought inhibit mitral/tufted cells (MC/TC) through external tufted or periglomerular (ET/PG) cells. In the external plexiform layer (EPL), local short axon cells ((2) SAC), and Van Gehuchten cells ((3) VGC) are involved in dendrodendritic feedback inhibition of TC and MC dendrites. In the deeper inframitral layers of the bulb, the dSACs comprise a second tier of interneuron circuits that can disinhibit bulb output by inhibiting the PG and granule cells (GC): (4) GL‐dSACs send widespread axonal ramifications up into the glomerular layer to inhibit PG cells; (5) EPL‐dSACs have axonal arbours in the EPL where they can inhibit GC apical dendrites; (6) GCL‐dSACs extend axonal projections horizontally in the granule cell layer (GCL) to inhibit granule cells. The dendrites of dSACs arborise horizontally in the inner plexiform layer (IPL) and GCL, where they may integrate excitatory inputs from MC/TC axon collaterals. Local inhibition is also externally regulated by back‐projecting fibres from pyramidal cells in olfactory cortex (OC, magenta), that may serve to coordinate signal processing by bulb and cortical circuits. Cortical fibres can excite PG/granule cells, as well as the sSACs/dSACs that inhibit them, which could regulate the dynamics of inhibition through a disynaptic push–pull circuit.

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Lowe, Graeme(May 2013) Olfactory Bulb: Synaptic Organisation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020289.pub2]