Olfactory Bulb

Neuroanatomists have long speculated that expanded primate brains contain an increased morphological diversity of inhibitory neurons (INs)1, and recent studies have identified primate-specific neuronal populations at the molecular level2. However, we know little about the developmental mechanisms that specify evolutionarily novel cell types in the brain. Here, we reconstruct gene expression trajectories specifying INs generated throughout the neurogenic period in macaques and mice by analysing the transcriptomes of 250,181 cells. We find that the initial classes of INs generated prenatally are largely conserved among mammals. Nonetheless, we identify two contrasting developmental mechanisms for specifying evolutionarily novel cell types during prenatal development. First, we show that recently identified primate-specific TAC3 striatal INs are specified by a unique transcriptional programme in progenitors followed by induction of a distinct suite of neuropeptides and neurotransmitter receptors in new-born neurons. Second, we find that multiple classes of transcriptionally conserved olfactory bulb (OB)-bound precursors are redirected to expanded primate white matter and striatum. These classes include a novel peristriatal class of striatum laureatum neurons that resemble dopaminergic periglomerular cells of the OB. We propose an evolutionary model in which conserved initial classes of neurons supplying the smaller primate OB are reused in the enlarged striatum and cortex. Together, our results provide a unified developmental taxonomy of initial classes of mammalian INs and reveal multiple developmental mechanisms for neural cell type evolution.

ImportanceMicroplastic (MP) pollution is an emerging environmental and health concern. While MPs have been detected in various human tissues, their presence in the human brain has not been documented, raising important questions about potential neurotoxic effects and the mechanisms by which MPs might reach brain tissues.ObjectiveTo determine the presence of MPs in the human olfactory bulb and to analyze their characteristics such as size, morphology, color, and polymeric composition.Design, setting, and participantsThis case series study used a cross-sectional design involving the analysis of olfactory bulb tissues obtained from deceased individuals during routine coroner autopsies. The sampling procedures were conducted at São Paulo City Death Verification Service, with laboratory analysis carried out at the Brazilian Synchrotron Light Laboratory (LNLS). Participants included 15 adult individuals who had been residents of São Paulo for more than 5 years and underwent coroner autopsies. Exclusion criteria included previous neurosurgical interventions. Data analysis was performed in April 2024.ExposureThe primary exposure assessed was the presence of MPs in the olfactory bulb, analyzed through direct tissue examination and digested tissue filtration followed by micro-Fourier transform infrared spectroscopy.Main outcomes and measuresThe main outcomes were the identification and characterization of MPs within the olfactory bulb, including their size, morphology, color, and polymeric composition.ResultsThe median age of the 15 deceased individuals was 69.5 years, ranging from 33 to 100 years, with 12 males and 3 females. MPs were detected in the olfactory bulbs of 8 out of 15 individuals. A total of 16 synthetic polymer particles and fibers were identified, with 75% being particles and 25% being fibers. The most common polymer detected was polypropylene (43.8%). Sizes of MPs ranged from 5.5 μm to 26.4 μm for particles, and the mean fiber length was 21.4 μm. Polymeric materials were absent in procedural blank and negative control filters, indicating minimal contamination risk.Conclusions and relevanceThis case series provides evidence of MPs found in the human olfactory bulb, suggesting a potential pathway for the translocation of MPs to the brain. The findings underscore the need for further research on the health implications of MP exposure, particularly concerning neurotoxicity and the potential for MPs to bypass the blood-brain barrier.

Generation of neuronal diversity is a biological strategy widely used in the brain to process complex information. The olfactory bulb is the first relay station of olfactory information in the vertebrate central nervous system. In the olfactory bulb, axons of the olfactory sensory neurons form synapses with dendrites of projection neurons that transmit the olfactory information to the olfactory cortex. Historically, the olfactory bulb projection neurons have been classified into two populations, mitral cells and tufted cells. The somata of these cells are distinctly segregated within the layers of the olfactory bulb; the mitral cells are located in the mitral cell layer while the tufted cells are found in the external plexiform layer. Although mitral and tufted cells share many morphological, biophysical, and molecular characteristics, they differ in soma size, projection patterns of their dendrites and axons, and odor responses. In addition, tufted cells are further subclassified based on the relative depth of their somata location in the external plexiform layer. Evidence suggests that different types of tufted cells have distinct cellular properties and play different roles in olfactory information processing. Therefore, mitral and different types of tufted cells are considered as starting points for parallel pathways of olfactory information processing in the brain. Moreover, recent studies suggest that mitral cells also consist of heterogeneous subpopulations with different cellular properties despite the fact that the mitral cell layer is a single-cell layer. In this review, we first compare the morphology of projection neurons in the olfactory bulb of different vertebrate species. Next, we explore the similarities and differences among subpopulations of projection neurons in the rodent olfactory bulb. We also discuss the timing of neurogenesis as a factor for the generation of projection neuron heterogeneity in the olfactory bulb. Knowledge about the subpopulations of olfactory bulb projection neurons will contribute to a better understanding of the complex olfactory information processing in higher brain regions.

Parkinson's disease (PD)-associated cognitive decline is heralded by olfactory dysfunction, but the network mechanisms bridging sensory and cognitive impairments remain poorly defined. Combining chronic multisite electrophysiology, behavioral tracking, and machine learning in PD models, a hierarchical disintegration of oscillatory dynamics across the olfactory network that mechanistically drives disease progression is uncovered. Early-stage PD mice are identified to show attenuated odor discrimination, accompanied by hyperexcitability of mitral/tufted (M/T) cells. Causally linking these deficits, aberrant gamma oscillation in the cross-olfactory network is identified as a causal factor underlying olfactory deficits. Notably, cognitive impairment emerged at later stages, correlating with abnormal theta oscillations in the cross-olfactory network. Pharmacological modulation of the olfactory bulb (OB)-lateral entorhinal cortex (LEC) pathway ameliorated cognitive deficits and restored cross-network theta oscillation. Collectively, the findings establish cross-olfactory network oscillations as dual diagnostic and therapeutic targets for PD cognitive impairment, providing a mechanism-guided framework for early intervention.