Sleep and olfactory cortical plasticity

Abstract

In many systems, sleep plays a vital role in memory consolidation and synaptic homeostasis. These processes together help store information of biological significance and reset synaptic circuits to facilitate acquisition of information in the future. In this review, we describe recent evidence of sleep-dependent changes in olfactory system structure and function which contribute to odor memory and perception. During slow-wave sleep, the piriform cortex becomes hypo-responsive to odor stimulation and instead displays sharp-wave activity similar to that observed within the hippocampal formation. Furthermore, the functional connectivity between the piriform cortex and other cortical and limbic regions is enhanced during slow-wave sleep compared to waking. This combination of conditions may allow odor memory consolidation to occur during a state of reduced external interference and facilitate association of odor memories with stored hedonic and contextual cues. Evidence consistent with sleep-dependent odor replay within olfactory cortical circuits is presented. These data suggest that both the strength and precision of odor memories is sleep-dependent. The work further emphasizes the critical role of synaptic plasticity and memory in not only odor memory but also basic odor perception. The work also suggests a possible link between sleep disturbances that are frequently co-morbid with a wide range of pathologies including Alzheimer's disease, schizophrenia and depression and the known olfactory impairments associated with those disorders.

Keywords: memory consolidation; odor memory; odor perception; olfaction; piriform cortex; slow-wave sleep.

Figure 1

Simplified schematic diagram of the main olfactory system. Olfactory sensory neurons in the olfactory epithelium express one of a very large set of olfactory receptor genes. Here, cells expressing different genes are colored differently. Sensory neurons expressing the same gene converge onto glomeruli in the olfactory bulb (OB), where they synapse onto second order neurons, mitral and tufted cells. Individual mitral cells receive excitatory input from a single glomerulus, and thus received input from a homogeneous population of sensory neurons. Excitability of, and lateral interactions between, mitral cells are mediated in part by OB granule cells. Granule cells undergo continual neurogenesis and replacement throughout life. Furthermore, they are a primary target of descending inputs from olfactory cortical areas. The primary olfactory cortex (piriform cortex) functions as an combinatorial, auto-associative array, allowing convergence of input conveyed from different olfactory sensory neurons. This allows merging of odorant features into odor objects. In addition to merging odorant features, the piriform cortex also has extensive, reciprocal connections with a variety of limbic and cortical areas.

Figure 2

(A) During a typical human sleep bout early stages of the sleep bout are dominated by slow-wave sleep, while REM sleep becomes more prominent later in the bout. The same is true in rodents. (B) local field potential (LFP) recordings in piriform cortex showing spontaneous shifts between slow-wave and fast-wave activity. (C) During slow-wave sleep, piriform cortical single-units fire in phase with the sharp-waves as shown by the raster plot and peri-stimulus time histogram. (D) Piriform cortical single-unit and LFP activity are decoupled from respiration during slow-wave sleep compared to waking. Histograms show respiratory events as a function of single-unit spiking. LFP’s are mean waveforms triggered on single-unit spikes. Overdrawn waveform of single-unit used for analysis in D in shown at bottom.

Figure 3

A schematic representation of changes in olfactory system activity between waking and slow-wave sleep. Odor stimulation during waking (symbolized by the rose) evokes odor-specific patterns of activity in the OB and mitral/tufted cell output to the piriform cortex. This afferent activity is respiration entrained and evokes intra-cortical association fiber activity linking co-active piriform cortical neurons. It also results in piriform cortical output, including feedback to OB granule cells (red dots) as well as to other regions of olfactory cortex and non-olfactory regions. During slow-wave sleep, the balance of afferent and intracortical activity shifts, with decreases in sensory-evoked input to piriform cortex and enhanced intra-cortical mediated activity, primarily during sharp-wave events. The sharp-wave associated activity replays cortical ensemble activity evoked by odors during waking. These strong, synchronous sharp-wave events help strengthen synaptic connections within odor-coding ensembles, as well as help shape OB granule cell survival in an odor-specific manner. Abbreviations: GL = glomerular layer, M = mitral cell layer, G = granule cell layer.