Biology subjects

GREER, C. A.

Publications and source records attributed to GREER, C. A..

3 recordsLinked to original sources

bioRxiv2024

Embryonically generated interneurons (EGINs) exhibit a distinctive developmental program and lamination in the olfactory bulb

Interneurons (INs) in the mouse olfactory bulb (OB) develop during an extensive period of time that begins in the embryo and continues throughout the lifetime of an individual. The connectivity and location of these neurons is profoundly affected by the time of generation, making these developmental windows critical to understand the circuitry of the OB. Here, we focus on the OB embryonic generated interneurons (or EGINs), which have generally received less attention than those generated in the adult. Birthdates of EGINs were differentiated by embryonic injections of thymidine analogs and their final destinations and phenotypes analyzed by immunohistochemistry. We found that EGINs were retained in the adult and were distributed across all layers of the OB. However, a lateral-to-medial neurogenic gradient is seen only in the earliest generated EGINs. Within the granule cell layer (GCL), EGINs predominantly accumulated in the superficial region at almost all ages and remained there during adulthood. Immunostaining for calbindin, parvalbumin, tyrosine hydroxylase, and calretinin were largely negative suggesting that EGINs may represent subpopulations of OB INs that are not yet fully characterized. Using in utero electroporation to label EGIN progenitors, we demonstrated that they reach the primordial OB as early as E13 and begin to differentiate apical dendrites by E15. At E16, EGIN progenitors clustered into a chain of migrating neuroblasts denoting the embryonic rostral migratory stream (RMS). Collectively, our data highlight the importance of studying OB INs in isolated time windows to better understand the formation of circuits that define the olfactory responses.

neuroscience↗

bioRxiv2022

Alpha-synuclein pathology and reduced neurogenesis in the olfactory system affect olfaction in a mouse model of Parkinsons disease

Parkinsons Disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathological changes in the olfactory pathway of transgenic (Tg) mice expressing the human A30P mutant -synuclein (-syn) (-syn-Tg mice) at 6-7 and 12-14 months of age, representing early and late-stages of motor progression, respectively. -Syn-Tg mice at late stages exhibited olfactory behavioral deficits, which correlated with severe -syn pathology in projection neurons of the olfactory pathway. In parallel, olfactory bulb (OB) neurogenesis in -syn-Tg mice was reduced in the OB granule cells at 6-7 months, and OB periglomerular cells at 12-14 months, respectively, both of which could contribute to olfactory dysfunction. Proteomic analyses showed a disruption in endo- and exocytic pathways in the OB during the early stages which appeared exacerbated at the synaptic terminals when the mice developed olfactory deficits at 12-14 months. Our data suggest that, 1) the -syn-Tg mice recapitulate the olfactory functional deficits seen in PD; 2) olfactory structures exhibit spatiotemporal disparities for vulnerability to -syn pathology; 3) -syn pathology is restricted to projection neurons in the olfactory pathway; 4) neurogenesis in adult -syn-Tg mice is reduced in the OB; and 5) synaptic endo- and exocytosis defects in the OB may further explain olfactory deficits.

neuroscience↗

bioRxiv2022

Microglia maintain homeostatic conditions in the developing rostral migratory stream.

Microglia invade the neuroblast migratory corridor of the rostral migratory stream (RMS) early in development. This work examines how microglia maintain the homeostatic conditions permissive to neuroblast migration in the RMS during the early postnatal period. GFP labeled microglia in CX3CR-1GFP/+ mice assemble primarily along the outer borders of the RMS during the first postnatal week, where they exhibit predominantly an ameboid morphology and associate with migrating neuroblasts. Microglia ablation for 3 days postnatally does not impact the density of pulse labeled BrdU+ neuroblasts nor the distance migrated by tdTomato electroporated neuroblasts in the RMS. However, microglia wrap DsRed-labeled neuroblasts in the RMS of P7 CX3CR-1GFP/+;DCXDsRed/+ mice and express the phagocytic markers CD68, CLEC7A and MERTK, suggesting active phagocytosis of neuroblasts in the developing RMS. Microglia depletion for 14 days postnatally further induced an accumulation of DCX+ neuroblasts and CC3+ apoptotic cells in the RMS, a wider RMS and extended patency of the lateral ventricle extension in the olfactory bulb. These findings illustrate the importance of microglia phagocytosis in maintaining the homeostasis of the early postnatal RMS. SIGNIFICANCE STATEMENTMicroglia are brain-resident immune cells responsible for both maintaining homeostatic conditions necessary for normal neurodevelopment as well as orchestrating the brains response to environmental insults. The effects of microglia-mediated immune response during development may be of special relevance to the olfactory system, which is unique in both its vulnerability to environmental insults as well as its extended period of neurogenesis and neuronal migration. The work presented here examines how microglia maintain homeostatic conditions in the neuroblast migratory corridor of the rostral migratory stream (RMS) in the olfactory system during early postnatal development. Our findings illustrate the importance of microglia phagocytosis in the early postnatal RMS and provides insights into microglia function during periods of neurogenesis and neuronal migration.

neuroscience↗