Mouse Olfactory Bulb: Layers, Cells, and Their Roles

The mouse olfactory bulb is the brain’s first relay station for processing smells, linking odor detection in the nose to higher brain regions. It plays a key role in distinguishing scents, forming associations, and guiding behavior. Understanding its structure reveals fundamental principles of sensory processing.

Research has identified intricate layers, diverse cell types, and precise synaptic connections that contribute to odor perception. Molecular markers such as secretagogin provide insights into neuronal function, helping to explain how the olfactory bulb encodes smells and influences behavior.

Layered Architecture

The mouse olfactory bulb consists of distinct layers, each contributing to olfactory processing. At the outermost boundary, the olfactory nerve layer (ONL) contains axons from olfactory sensory neurons (OSNs) that terminate in glomeruli—spherical structures that serve as the first major site of synaptic integration. The ONL filters and modulates sensory input before it reaches deeper layers.

Beneath the ONL, the glomerular layer (GL) houses glomeruli surrounded by periglomerular and external tufted cells. Each glomerulus receives input from OSNs expressing the same odorant receptor, ensuring that chemically similar signals are processed together. Periglomerular cells, primarily inhibitory interneurons, regulate mitral and tufted cells, preventing excessive excitation and enhancing contrast between odors. External tufted cells provide excitatory drive, amplifying specific odor representations.

The external plexiform layer (EPL) facilitates lateral interactions between mitral and tufted cells. These principal output neurons extend dendrites into the EPL, where they receive input from granule cells, a major class of inhibitory interneurons. Dendrodendritic synapses enable reciprocal inhibition, sharpening odor representations by suppressing overlapping signals.

The mitral cell layer (MCL) contains mitral cells, the primary relay neurons transmitting olfactory information to higher brain regions. Their activity is regulated by inhibitory feedback from granule cells, which modulate signal strength and timing to maintain odor fidelity and prevent signal saturation.

Beneath the MCL, the internal plexiform layer (IPL) and granule cell layer (GCL) further refine processing. The IPL facilitates interlayer communication, while the GCL, densely packed with granule cells, provides inhibitory feedback. Granule cells form dendrodendritic synapses, enabling bidirectional inhibition that fine-tunes odor transmission. This recurrent inhibition plays a role in odor memory and adaptation, allowing the olfactory bulb to adjust its responses based on prior experiences.

Cell Diversity

The olfactory bulb contains diverse neurons, each contributing uniquely to odor processing. Mitral and tufted cells are the principal output neurons, relaying olfactory signals to higher brain regions. Mitral cells, located in a single layer, integrate input from multiple glomeruli, encoding complex odor mixtures. Tufted cells, more numerous and highly excitable, respond to narrower odorant ranges, enhancing specificity. This suggests a division of labor, with mitral cells contributing to broad odor representations and tufted cells refining details.

Interneurons shape olfactory bulb dynamics by modulating mitral and tufted cell activity. Periglomerular cells, primarily GABAergic, regulate early odor processing by sharpening contrast between odor inputs. Some also release dopamine, modulating synaptic transmission and contributing to odor adaptation. These cells exhibit morphological and molecular diversity, with subsets expressing calcium-binding proteins such as calretinin and calbindin, which influence their synaptic properties.

Granule cells, the most abundant interneurons, form reciprocal dendrodendritic synapses with mitral and tufted cells. This bidirectional inhibition refines olfactory output and is thought to underlie odor learning and memory. Unlike periglomerular cells, granule cells lack axons and rely entirely on dendritic interactions. They also undergo continuous neurogenesis in adult mice, integrating into existing circuits and refining olfactory processing over time.

Synaptic Organization

The olfactory bulb’s synaptic architecture optimizes odor signal transmission and refinement. Sensory input arrives via OSN axons, which synapse onto mitral and tufted cell dendrites within glomeruli. Each glomerulus functions as a discrete processing unit, ensuring chemically similar odorants activate distinct but overlapping circuits.

In the glomerular layer, excitatory input from sensory neurons is modulated by periglomerular cells, which provide lateral inhibition through GABAergic synapses. This feedback sharpens contrast between active and inactive glomeruli, improving odor discrimination. External tufted cells amplify sensory input through excitatory glutamatergic synapses onto mitral and tufted cells, ensuring only the most relevant odor signals propagate to deeper layers.

Beyond the glomeruli, the external plexiform layer refines signals further. Mitral and tufted cells extend dendrites into this region, forming dendrodendritic synapses with granule cells. These bidirectional synapses allow granule cells to receive excitatory input while providing inhibitory feedback, selectively suppressing weakly activated neurons and reinforcing distinctions between similar odors.

Secretagogin Expression Patterns

Secretagogin, a calcium-binding protein traditionally associated with neuroendocrine cells, is expressed in specific interneurons of the olfactory bulb. Unlike calretinin or calbindin, secretagogin is primarily found in periglomerular and granule cells, suggesting a role in inhibitory neurotransmission.

Calcium-binding proteins regulate synaptic dynamics by buffering intracellular calcium levels, influencing neurotransmitter release. Secretagogin’s presence in inhibitory interneurons suggests it fine-tunes inhibition, potentially affecting odor adaptation and sensitivity. Its role in synaptic plasticity is particularly relevant, as calcium regulation is essential for modifying inhibitory circuits based on sensory experience.

Odor Coding Mechanisms

The olfactory bulb transforms sensory input into structured neural representations that enable odor perception. This relies on a combinatorial coding strategy, where individual odorants activate distinct but overlapping sets of glomeruli. Each glomerulus corresponds to a specific olfactory receptor type, forming an “odor map” that encodes chemical properties. Inhibitory circuits refine this spatial representation, ensuring structurally similar odors remain distinguishable.

Temporal dynamics also contribute to odor encoding. Mitral and tufted cells exhibit oscillatory activity that synchronizes their firing patterns, creating temporal sequences that convey additional information about odor identity and intensity. The timing of action potentials within these oscillations differentiates closely related scents, adding a temporal dimension to the spatial odor map.

This mechanism is particularly important for processing odor mixtures, as it allows the nervous system to parse individual components from complex scent profiles. Changes in sniffing frequency alter the temporal structure of these signals, highlighting the adaptability of the olfactory bulb in response to sensory variations.

Influence on Behavioral Responses

Beyond odor detection, the olfactory bulb shapes behavioral responses to smells. Mitral and tufted cells project to brain regions such as the piriform cortex, amygdala, and hypothalamus, where odor information integrates with memory, emotion, and physiological states. This connectivity influences behaviors ranging from food-seeking and predator avoidance to social interactions and mating preferences.

The ability to associate specific odors with positive or negative experiences depends on synaptic plasticity in these pathways, enabling learned responses to environmental cues. Innate odor-driven behaviors, such as defensive reactions to predator scents, suggest the olfactory bulb encodes biologically relevant stimuli through hardwired circuits.

Research on genetically modified mice shows that disrupting olfactory bulb signaling impairs instinctive responses, underscoring its role in survival-related behaviors. Neuromodulators like serotonin and noradrenaline further modulate olfactory processing, altering odor perception based on emotional or physiological states. This dynamic regulation highlights the olfactory bulb’s influence on behavior.