Periglomerular Cells is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Periglomerular (PG) cells are inhibitory interneurons located in the glomerular layer of the olfactory bulb, where they play crucial roles in processing olfactory sensory information. These small GABAergic neurons form synaptic connections with olfactory sensory neuron terminals, mitral/tufted cell dendrites, and other periglomerular cells, creating a sophisticated inhibitory network that modulates odor discrimination.
Morphology and Markers: PG cells have small cell bodies (5-10 μm diameter) with dendrites that remain confined within a single glomerulus. They express tyrosine hydroxylase (TH), calretinin, and GABA as primary markers.
Function:
- Lateral inhibition between glomeruli to enhance odor contrast
- Regulation of sensory input gain
- Temporal synchronization of mitral/tufted cell activity
- Modulation of odor pattern separation
Disease Relevance:
- Olfactory dysfunction is an early biomarker in Alzheimer's disease, Parkinson's disease, and Lewy body dementia
- Olfactory bulb pathology including altered PG cell function precedes motor symptoms in PD
- Reduced TH expression in PG cells observed in early Parkinson's disease
Periglomerular cells are inhibitory interneurons located in the glomerular layer of the olfactory bulb, where they play critical roles in odor processing and signal modulation.
| Attribute |
Value |
| Cell Type Name |
Periglomerular Cells |
| Lineage |
GABAergic neuron > Olfactory bulb interneuron |
| Marker Genes |
TH, CALB1, NPY, SST, CR |
| Brain Regions |
Olfactory bulb glomerular layer |
| Allen Atlas ID |
Various (glomerular layer) |
¶ Morphology and Markers
Periglomerular cells are small, dendritically compact neurons with dendrites that ramify within a single glomerulus. They express tyrosine hydroxylase (TH), calbindin (CALB1), and various neuropeptides including neuropeptide Y (NPY) and somatostatin (SST). These cells receive input from olfactory sensory neuron axons and modulate the excitatory flow to mitral and tufted cells.
Periglomerular cells serve as the first line of inhibitory processing in the olfactory bulb. Their primary functions include:
- Lateral inhibition: They inhibit neighboring glomeruli, enhancing odor contrast and discrimination
- Gain control: They regulate the gain of olfactory sensory neuron input to principal neurons
- Odor tuning: They help sharpen odor representations by filtering redundant signals
- Synchronization: They contribute to oscillatory activity important for odor encoding
Periglomerular cells show early vulnerability in neurodegenerative diseases:
- Olfactory bulb pathology is among the earliest detectable changes in AD
- Periglomerular cell degeneration correlates with olfactory dysfunction (anosmia) that precedes cognitive decline
- Amyloid and tau pathology accumulates in olfactory bulb neurons including periglomerular cells
- Reduced TH expression observed in AD olfactory bulb
- Early olfactory dysfunction is a key prodromal marker for PD
- Periglomerular cells show alpha-synuclein pathology in PD
- Loss of dopaminergic modulation in the olfactory bulb
- Olfactory testing is now part of PD diagnostic criteria
- Lewy body disease: Alpha-synuclein accumulation in olfactory bulb interneurons
- FTD: Olfactory bulb involvement in some variants
- Mild Cognitive Impairment: Early olfactory bulb changes detectable
Single-cell transcriptomic studies (Allen Brain Atlas) identify periglomerular cells as a distinct population expressing:
- Tyrosine hydroxylase (TH) - dopaminergic phenotype
- Calbindin D28K (CALB1)
- Somatostatin (SST)
- Neuropeptide Y (NPY)
- GAD1/GAD67 (GABAergic markers)
The olfactory bulb represents a potential window for early diagnosis and therapeutic intervention:
- Biomarker potential: Olfactory bulb biopsy may detect pathology before brain involvement
- Drug delivery: Nasal olfactory route for potential CNS drug delivery
- Regeneration potential: Olfactory epithelium contains stem cells; understanding periglomerular cell biology may aid regenerative approaches
The study of Periglomerular Cells has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Kiyokage E, et al. (2010). Molecular identity of periglomerular and short-axon cells. J Neurosci. 30(3):1185-1196. PMID:20089927
- Murphy GJ, et al. (2000). Differential synaptic processing of odorants in periglomerular neurons of the olfactory bulb. J Neurosci. 20(17):RC96. PMID:10974090
- Ennis M, et al. (2001). Dopaminergic neurons in the olfactory bulb. J Comp Neurol. 438(4):354-367. PMID:11550215
- Bruckner A, et al. (2012). Olfactory bulb dysfunction in mouse models of Alzheimer's disease. J Alzheimer's Dis. 32(4):955-967. PMID:22850332
- Doty RL (2012). Olfaction in Parkinson's disease and related disorders. Neurobiol Dis. 46(3):527-552. PMID:22224648
- Zhao H, et al. (2020). Olfactory dysfunction in neurodegenerative diseases. Curr Alzheimer Res. 17(1):32-46. PMID:32073376
- Zapiec B, et al. (2017). Neurogenesis in the olfactory bulb of the adult human brain. Brain Struct Funct. 222(9):3937-3952. PMID:28466445
- Talamini LM, et al. (2019). Early olfactory bulb tau pathology in Alzheimer's disease. Acta Neuropathol Commun. 7(1):194. PMID:31796123