Intrinsic and Extrinsic Neuromodulation of Olfactory Processing

Abstract

Neuromodulation is a ubiquitous feature of neural systems, allowing flexible, context specific control over network dynamics. Neuromodulation was first described in invertebrate motor systems and early work established a basic dichotomy for neuromodulation as having either an intrinsic origin (i.e., neurons that participate in network coding) or an extrinsic origin (i.e., neurons from independent networks). In this conceptual dichotomy, intrinsic sources of neuromodulation provide a "memory" by adjusting network dynamics based upon previous and ongoing activation of the network itself, while extrinsic neuromodulators provide the context of ongoing activity of other neural networks. Although this dichotomy has been thoroughly considered in motor systems, it has received far less attention in sensory systems. In this review, we discuss intrinsic and extrinsic modulation in the context of olfactory processing in invertebrate and vertebrate model systems. We begin by discussing presynaptic modulation of olfactory sensory neurons by local interneurons (LNs) as a mechanism for gain control based on ongoing network activation. We then discuss the cell-class specific effects of serotonergic centrifugal neurons on olfactory processing. Finally, we briefly discuss the integration of intrinsic and extrinsic neuromodulation (metamodulation) as an effective mechanism for exerting global control over olfactory network dynamics. The heterogeneous nature of neuromodulation is a recurring theme throughout this review as the effects of both intrinsic and extrinsic modulation are generally non-uniform.

Keywords: GABA; neuromodulation; olfaction; presynaptic gain control; sensory processing; serotonin.

Figure 1

Intrinsic and extrinsic sources of neuromodulation in the insect and vertebrate olfactory system. (A) In the insect antennal lobe (AL), all three principal neuron types, olfactory sensory neurons (OSNs), local interneurons (LNs), and projection neurons (PNs) are subject to both intrinsic and extrinsic sources of modulation. GABA (magenta), dopamine (DA; yellow), and a suite of neuropeptides (green) released by LNs act as intrinsic modulators, while serotonin (5-HT; blue), DA, and octopamine (OCT; orange) act as extrinsic modulators to contextually alter olfactory processing. DA can be extrinsic or intrinsic depending on the species. (B) In the vertebrate olfactory bulb (OB), subtypes of LNs broadly serve as sources of intrinsic modulation. GABAergic periglomerular cells (PG), glutamatergic external tufted cells (ET; light green) and GABAergic/DAergic superficial short axon cells (sSA; magenta/yellow) synapse onto OSNs, mitral and tufted cells (M/Ts) and each other in the glomerular layer. GABAergic granule cells (GC) synapse onto M/Ts to alter OB output and GABAergic deep short axon cells (dSA) both reciprocally synapse onto themselves and GCs. Both the AL and OB are innervated by extrinsic sources of 5-HT, norephinephrine (NE; pink), and acetylcholine (ACh; dark purple). The “~” symbol at the PG to OSN synapse indicates that this is a non-traditional synapse that depends upon GABA spillover.

Figure 2

Intrinsic modulation as a means of presynaptic gain control. (A) Presynaptic gain control alters the signal strength between OSNs and PNs to filter out noise from spontaneous firing of OSNs, avoid PN saturation and expand the dynamic range of PNs. It does this by reducing presynaptic calcium levels in OSNs via GABAb receptors, and reducing the likelihood of acetycholine release onto PNs. (B) GABAb blockade (red) increases presynaptic calcium influx and decreases the range of OSN input over which PN firing rate can change, ultimately resulting in PN saturation (based on results from Root et al., ; Olsen et al., 2010). (C) GABAergic lateral inhibition scales with network activation (as measured by OSN activity; Olsen and Wilson, 2008).