Olfactory consciousness and gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex

Abstract

The orbitofrontal cortex receives multi-modality sensory inputs, including olfactory input, and is thought to be involved in conscious perception of the olfactory image of objects. Generation of olfactory consciousness may require neuronal circuit mechanisms for the "binding" of distributed neuronal activities, with each constituent neuron representing a specific component of an olfactory percept. The shortest neuronal pathway for odor signals to reach the orbitofrontal cortex is olfactory sensory neuron-olfactory bulb-olfactory cortex-orbitofrontal cortex, but other pathways exist, including transthalamic pathways. Here, we review studies on the structural organization and functional properties of the shortest pathway, and propose a model of neuronal circuit mechanisms underlying the temporal bindings of distributed neuronal activities in the olfactory cortex. We describe a hypothesis that suggests functional roles of gamma oscillations in the bindings. This hypothesis proposes that two types of projection neurons in the olfactory bulb, tufted cells and mitral cells, play distinct functional roles in bindings at neuronal circuits in the olfactory cortex: tufted cells provide specificity-projecting circuits which send odor information with early-onset fast gamma synchronization, while mitral cells give rise to dispersedly-projecting feed-forward binding circuits which transmit the response synchronization timing with later-onset slow gamma synchronization. This hypothesis also suggests a sequence of bindings in the olfactory cortex: a small-scale binding by the early-phase fast gamma synchrony of tufted cell inputs followed by a larger-scale binding due to the later-onset slow gamma synchrony of mitral cell inputs. We discuss that behavioral state, including wakefulness and sleep, regulates gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex.

Keywords: gamma synchronization; olfactory bulb; olfactory consciousness; olfactory cortex; orbitofrontal cortex; tufted and mitral cells.

Figure 1

Olfactory pathways to the orbitofrontal cortex in rodents. A schematic diagram of the lateral view of the rodent brain illustrating the neuronal pathways from olfactory sensory neurons through the olfactory bulb and olfactory cortex to the orbitofrontal cortex. AIv, ventral agranular insular cortex; AON, anterior olfactory nucleus; APC, anterior piriform cortex; LO, lateral orbital cortex; M, mitral cell; OB, olfactory bulb; OE, olfactory epithelium; OSN, olfactory sensory neuron; P, pyramidal cell; PPC, posterior piriform cortex; T, tufted cell; TT, tenia tecta; VLO, ventrolateral orbital cortex. The orbitofrontal cortex (LO/VLO) is surrounded by red broken line.

Figure 2

Multiple parallel pathways from the olfactory sensory neurons to the orbitofrontal cortex. Arrows indicate axonal projection. AON, anterior olfactory nucleus; APCv, ventral part of the anterior piriform cortex; APCd, dorsal part of the anterior piriform cortex; PPC, posterior piriform cortex; pEn pre-endopiriform nucleus; En, endopiriform nucleus; SM, submedius nucleus of thalamus; MD, mediodorsal nucleus of thalamus; OSN, olfactory sensory neuron; VLO, ventrolateral orbital cortex; LO, lateral orbital cortex; AIv, ventral agranular insular cortex. Olfactory bulb gives rise to parallel tufted and mitral cell pathways to the olfactory cortex. APCv sends odor information directly to the VLO or indirectly via the pEn and SM, while APCd transfers odor information directly to the LO/AIv or indirectly via the En and MD.

Figure 3

Structural organization of tufted cell circuits and mitral cell circuits in the olfactory bulb and olfactory cortex. In the olfactory bulb (OB), tufted cells (red and orange T) extend relatively short lateral dendrites in the superficial sub-lamina of the EPL and make dendrodendritic reciprocal synaptic connections mainly with tufted cell-targeting granule cells [Gr(T)]. Mitral cells (blue M) extend long lateral dendrites in the deep sub-lamina of the EPL and form dendrodendritic synapses mainly with mitral cell-targeting granule cells [Gr(M)]. Tufted cells project axons (red and orange lines) to focal targets in the olfactory peduncle areas including AON. Mitral cells project axons (blue lines) dispersedly to nearly all areas of the olfactory cortex. Layers of the olfactory bulb: GL, glomerular layer; EPL, external plexiform layer; MCL, mitral cell layer; GCL, granule cell layer. Layers in the olfactory cortex: Ia, layer Ia; Ib, layer Ib; II, layer II; III, layer III. LOT, lateral olfactory tract; Ib assoc, Ib associational axon. Red P indicates pyramidal cells in the AON. Black P shows pyramidal cells in the APC. Glom, glomerulus; OFC, orbitofrontal cortex.

Figure 4

Fast and slow gamma oscillations in the olfactory bulb. Middle trace: sniff rhythm-paced gamma oscillations recorded from the granule cell layer of the olfactory bulb of a freely behaving rat. The sniff-induced local field potentials (LFPs) were averaged (n = 277 sniffs) in reference to the peak (a downward arrow) of gamma oscillations that occur near the phase of transition from inhalation to exhalation. Bottom trace: the local field potential shown in the middle trace was band-path filtered between 30 and 140 Hz. The sniff-paced gamma oscillations consist of early-onset fast gamma oscillation (red dashed line) and later-onset slow gamma oscillation (blue dashed line). Uppermost trace: respiration monitor via a thermocouple implanted in the nasal cavity. Upward reflection indicates inhalation. Sniff-onset is indicated by a vertical broken line with an upward arrow.

Figure 5

Schematic diagram of possible functional differentiation between the tufted cell pathway and mitral cell pathway in odor information processing in the neuronal circuits of the piriform cortex. In this model, red, yellow, and pink glomeruli are assumed to be activated simultaneously by an odor inhalation. Activated tufted cells (T, shown by red, orange, or pink) send the odor information with early-onset fast gamma synchrony to specific target pyramidal cells in the AON, which in turn send the information presumably with fast gamma synchrony to specific-target pyramidal cells in the APC. Activated mitral cells (M, shown by blue) provide dispersedly-projecting feed-forward binding circuits transmitting the spike synchronization timing with later-onset slow gamma synchrony to whole pyramidal cells in the APC. Pyramidal cells in layer II (PII) of the APC project axons directly to the OFC. The layer II pyramidal cells and those in layer III (PIII) of the APC form recurrent association axon synaptic connections (deep assoc. and Ib assoc.) with other pyramidal cells, forming feed-back binding circuits. These pyramidal cells project axons also to the endopiriform nucleus (En), which sends axons to the mediodorsal nucleus (MD) or submedius nucleus (SM) of thalamus. MD and SM provide thalamocortical projections to the OFC, while OFC sends feed-back corticothalamic connections to the MD or SM. LOT, lateral olfactory tract; Ia, Ib, II, and III, layers in the APC. Pyramidal cells with green nucleus in the APC indicate neurons co-activated by an odor inhalation. Recurrent collateral excitatory synaptic connections (deep assoc) among these neurons form feed-back binding circuits.

Figure 6

Gamma oscillation couplings across the olfactory bulb, anterior piriform cortex, and orbitofrontal cortex. Simultaneous recordings of respiratory pattern (Resp, upward swing indicates inhalation), LFP in the granule cell layer of the olfactory bulb (Bulb), LFP in layer III of the APC (APC), and LFP in the deep layer of OFC (OFC), during micro-arousal. Wavelet analyses of the LFPs are shown in the lower three figures. Broken lines and upward arrows indicate sniff onset. Early-onset fast gamma oscillation is shown by f or red broken line, and later-onset slow gamma oscillation by s or blue broken line. Slow gamma oscillation during the exhalation period is shown by exh-s.

Figure 7

Schematic diagram illustrating thalamo-cortico-thalamic networks and the “matrix and core theory” of Jones. This diagram is based on Llinas et al. (1998) and Jones (2001). Core neurons (C) in the thalamus form specificity-projecting circuits (shown by brown lines and surrounded by red or yellow lines) that involve specific cortico-thalamic connections from layer VI pyramidal cells. Matrix neurons (M) in the thalamus give rise to non-specific binding circuits (shown by blue lines) that involve diffuse projections from layer V pyramidal cells. Jones proposed that the above two types of thalamo-cortico-thalamic networks form a substrate for synchronization of widespread populations of neurons in the thalamus and cortex during high-frequency oscillations that underlie discrete conscious events (Jones, 2009). P, pyramidal cells in the neocortex; Re, inhibitory neurons in the reticular nucleus of thalamus; I, II/III, IV, V, VI, layers in the neocortex.