Tzeng, W.-Y. | bioRxiv Science

bioRxiv2025

Glomerulus-specific inhomogeneity of the basal activity map in the olfactory bulb supports olfactory-driven behavior

Glomeruli are signal-processing units of the olfactory bulb (OB), playing a key role in many OB computations, including contrast enhancement, gain control, and odorant-selective habituation. In awake mice, we uncover an extremely stable inhomogeneous map of basal glomerulus-specific activity as a background against which olfactory signal processing is performed. This activity is strongly driven by (i) centrifugal cholinergic projections, (ii) endogenous, and (iii) airflow-evoked spiking of olfactory sensory neurons and, to a small extent, (iv) by the odor environment. Importantly, early olfactory impairment in a mouse model of Alzheimers disease is parallelled by the loss of glomerular map inhomogeneity and diminished cholinergic innervation. These results reveal an important layer in the signal-processing network of the OB, likely acting by increasing the variance in and dynamic range of the system via glomerulus-specific functional inhomogeneity. TeaserA new layer in the signal-processing network of the olfactory bulb supports olfactory-driven behavior.

neuroscience↗

bioRxiv2024

Impairment of brain function in a mouse model of Alzheimer's disease during the pre-depositing phase: the role of alpha7 nicotinic acetylcholine receptors

Alzheimers disease (AD) is an age-dependent incurable neurodegenerative disorder accompanied by neuroinflammation, amyloid accumulation and memory impairment. It begins decades before the first clinical symptoms appear, and identifying early biomarkers is key for developing disease-modifying therapies. We show now in a mouse model of AD that before any amyloid deposition the brains of 1.5-month-old mice contain increased levels of pro-inflammatory cytokines IL-1{beta} and IL-6, decreased levels of nicotinic acetylcholine receptors (nAChRs) in the brain and brain mitochondria and increased amounts of 7 nAChR-bound A{beta}1-42, along with impaired episodic memory and increased risk of apoptosis. Both acute (1-week-long) and chronic (4-month-long) treatments with 7-selective agonist PNU282987, starting at 1.5 months of age, were well tolerated. The acute treatment did not affect the levels of soluble A{beta}1-42 but consistently upregulated the 7 nAChR expression, decreased the level of 7- A{beta}1-42 complexes and improved episodic memory of 1.5-month-old mice. The chronic treatment, covering the disease development phase, strongly upregulated the expression of all abundant brain nAChRs, reduced both free and 7-coupled A{beta}1-42 within the brain, had anti-inflammatory and antiapoptotic effects, and potently upregulated cognition, thus identifying 7 nAChRs as both early biomarker and potent therapeutic target for fighting this devastating disease.

neuroscience↗