Lattice Cells is an important cell type in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Lattice cells, more commonly known as grid cells, are a fundamental class of spatial navigation neurons in the medial entorhinal cortex (MEC) that generate a periodic hexagonal grid pattern of firing fields across the environment.[1][2] Discovered by Moser, Moser, and colleagues in 2005, grid cells revolutionized our understanding of how the brain represents space and are considered one of the most important neural coding discoveries in recent decades.[3]
These neurons fire when an animal moves through multiple discrete locations arranged in a hexagonal lattice pattern. The spacing between firing fields is remarkably consistent within an individual grid cell but varies across different cells (typically 20-50 cm in rats, 2-5 meters in humans). This hexagonal grid provides the neural substrate for path integration—the process by which animals calculate their position based on self-motion cues.[1:1][4]
The discovery of grid cells emerged from research on spatial cognition and memory. In 2005,Fyhn and colleagues published the landmark paper describing grid cells in the medial entorhinal cortex of freely moving rats.[1:2] This discovery built upon earlier work on place cells in the hippocampus (discovered by O'Keefe and Dostrovsky in 1971) and head direction cells (discovered by Taube et al. in 1985).[5]
The significance of this discovery was recognized with the 2014 Nobel Prize in Physiology or Medicine, awarded to John O'Keefe, May-Britt Moser, and Edvard I. Moser for their discoveries of cells that constitute a positioning system in the brain.[6]
Grid cells are primarily located in the medial entorhinal cortex (MEC), particularly in layers II and III. They exhibit characteristic morphological features:
The dorsal-most grid cells (closest to the postrhinal border) have the smallest grid spacing (~20-30 cm), while ventral grid cells have progressively larger spacing (>50 cm). This gradient correlates with the functional organization of the MEC.[9]
Grid cells express specific molecular markers:
Grid cells exhibit unique electrophysiological properties:
The mechanisms underlying grid pattern generation have been subject to intense investigation:
Continuous attractor network model: Suggests that grid patterns emerge from recurrent connections between grid cells that form a continuous attractor network. This model proposes that:
Oscillatory interference model: Proposes that grid patterns arise from interference between:
Single-cell model: Suggests that grid properties can emerge from:
Grid cells integrate information from multiple sources:
Grid cells provide a metric for space:
The grid cell-hippocampal circuit supports episodic memory:
Grid cells contribute to temporal coding:
Grid cells are particularly vulnerable in Alzheimer's disease:
Early pathology: The entorhinal cortex is one of the first brain regions to show tau pathology in AD, directly affecting grid cells before other cortical areas.[23]
Grid disruption:
Clinical correlates:
Neuroimaging findings:
Grid cell dysfunction contributes to:
Understanding grid cell pathology provides therapeutic opportunities:
The study of Lattice 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.
Fyhn M, Molden S, Witter MP, et al. Spatial representation in the entorhinal cortex. Science. 2004;305(5688):1258-1264. ↩︎ ↩︎ ↩︎ ↩︎
Hafting T, Fyhn M, Molden S, et al. Microstructure of a spatial map in the entorhinal cortex. Nature. 2005;436(7052):801-806. ↩︎
Moser EI, Roudi Y, Witter MP, et al. Grid cells and cortical representation. Nature Reviews Neuroscience. 2014;15(7):466-481. ↩︎
Moser MB, Moser EI. The functional differentiation of the dorsal and ventral hippocampus. Trends in Neurosciences. 2015;38(10):579-588. ↩︎
O'Keefe J, Dostrovsky J. The hippocampus as a spatial map: preliminary evidence from unit activity in the freely-moving rat. Brain Research. 1971;34(1):171-175. ↩︎
The Nobel Prize. The 2014 Nobel Prize in Physiology or Medicine. Nobel Foundation. 2014. ↩︎
Sargolini F, Fyhn M, Hafting T, et al. Conjunctive representation of position, velocity, and heading in the entorhinal cortex. Journal of Neuroscience. 2006;26(35):9385-9403. ↩︎
Boccara CN, Sargolini F, Thoresen VH, et al. Grid cells in pre- and parasubiculum. Nature Neuroscience. 2010;13(8):987-994. ↩︎
Brun VH, Solstad T, Kjelstrup KB, et al. Increase of grid cell firing rate by a local membrane protein. Nature Neuroscience. 2008;11(5):587-595. ↩︎
Ray S, Naumann R, Burgalossi A, et al. Grid-layout and theta-modulation differentiate layer 2 and layer 3 neurons. Nature Neuroscience. 2014;17(10):786-792. ↩︎
Bonnevie T, Dunn B, Fyhn M, et al. Grid cells require excitatory drive from the hippocampus. Nature Neuroscience. 2013;16(3):309-317. ↩︎
Skaggs WE, McNaughton BL, Wilson MA, Barnes CA. Theta phase precession in hippocampal neurons. Neural Computation. 1996;8(1):85-93. ↩︎
Fuhs MC, Touretzky DS. A spin glass model of path integration in rat grid cells. Journal of Neuroscience. 2006;26(16):4266-4276. ↩︎
Burgess N, Barry C, O'Keefe J. An oscillatory interference model of grid cell firing. Hippocampus. 2007;17(9):801-812. ↩︎
Navratilova Z, Giocomo LM, Fellous JM, et al. Phase precession and variable grid cell spacing. Journal of Neurophysiology. 2011;106(3):1263-1277. ↩︎
Kropff E, Carmichael JE, Moser MB, Moser EI. Speed cells in the medial entorhinal cortex. Nature. 2015;524(7565):333-337. ↩︎
Solstad T, Boccara CN, Kropff E, et al. Representation of geometric borders in the entorhinal cortex. Science. 2008;322(5909):1865-1868. ↩︎
McNaughton BL, Battaglia FP, Jensen O, et al. Path integration and the neural basis of the 'cognitive map'. Nature Reviews Neuroscience. 2006;7(8):663-678. ↩︎
Bush D, Barry C, Burgess N. What do grid cells contribute to place cell firing?. Trends in Neurosciences. 2014;37(3):136-145. ↩︎
Buzsaki G, Moser EI. Memory, navigation and theta rhythm in the hippocampal-entorhinal system. Nature Neuroscience. 2013;16(2):130-138. ↩︎
Moser EI, Moser MB. A metric for space. Hippocampus. 2011;21(1):4-6. ↩︎
Dragoi G, Buzsaki G. Temporal encoding of place sequences by hippocampal cell assemblies. Neuron. 2006;50(1):145-157. ↩︎
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica. 1991;82(4):239-259. ↩︎
Marks JD, Tarabay R, Stoub TR, et al. Entorhinal cortex tau pathology in early Alzheimer's disease. Neurobiology of Aging. 2019;84:1-9. ↩︎
Palop JJ, Mucke L. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nature Reviews Neuroscience. 2016;17(12):777-792. ↩︎
Hort J, Laczo J, Vyhnalek M, et al. Spatial navigation deficit in amnestic mild cognitive impairment. Proceedings of the National Academy of Sciences. 2007;104(10):4042-4047. ↩︎
Khan UA, Liu L, Provenzano FA, et al. Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease. Nature Neuroscience. 2014;17(2):304-311. ↩︎
Verbaan D, Marinus J, Visser M, et al. Cognitive impairment in Parkinson's disease. Movement Disorders. 2007;22(7):976-982. ↩︎
Fellous JM, Lin CA, Alzenberg M, et al. Cognitive and computational approaches to understanding memory impairment in neurodegenerative diseases. Progress in Neurobiology. 2019;181:101687. ↩︎
Zugaro M. Grid cells, place cells, and memory. Trends in Neurosciences. 2018;41(6):357-359. ↩︎
Strange BA, Witter MP, Lein ES, Moser EI. Functional organization of the hippocampal longitudinal axis. Nature Reviews Neuroscience. 2014;15(10):655-669. ↩︎
Doeller CF, Barry C, Burgess N. Evidence from grid cells for a new metric for the brain. Nature Neuroscience. 2010;13(2):133-143. ↩︎