The role of astrocytes in place cell formation: A computational modeling study

Polykretis, Ioannis; Michmizos, Konstantinos P.

doi:10.1007/s10827-022-00828-6

Cited by 5 publications

(3 citation statements)

References 72 publications

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“…In the model discussed by Udakis et al 50 , a PC was a pre-tuned, artificial, and rate-based two compartments neuron, in which excitatory and feedback/feedforward inhibitory inputs concur to stabilize its operation. A recent modeling paper 51 suggested how a PC can be formed through the local interaction between a highly simplified principal neuron and an astrocyte, both activated by a given SCs input in the presence of a specific environment. Although this model is innovative and provides information on the role of astrocytes in the formation of Place Cells, it does not consider the conjunctive activation of the two spatially separated and independent signals that have been shown to be instrumental to create a Place Cell.…”

Section: Discussionmentioning

confidence: 99%

A realistic computational model for the formation of a Place Cell

Mazzara,

Migliore

2023

Sci Rep

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Hippocampal Place Cells (PCs) are pyramidal neurons showing spatially localized firing when an animal gets into a specific area within an environment. Because of their obvious and clear relation with specific cognitive functions, Place Cells operations and modulations are intensely studied experimentally. However, although a lot of data have been gathered since their discovery, the cellular processes that interplay to turn a hippocampal pyramidal neuron into a Place Cell are still not completely understood. Here, we used a morphologically and biophysically detailed computational model of a CA1 pyramidal neuron to show how, and under which conditions, it can turn into a neuron coding for a specific cue location, through the self-organization of its synaptic inputs in response to external signals targeting different dendritic layers. Our results show that the model is consistent with experimental findings demonstrating PCs stability within the same spatial context over different trajectories, environment rotations, and place field remapping to adapt to changes in the environment. To date, this is the only biophysically and morphologically accurate cellular model of PCs formation, which can be directly used in physiologically accurate microcircuits and large-scale model networks to study cognitive functions and dysfunctions at cellular level.

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Section: Discussionmentioning

confidence: 99%

A realistic computational model for the formation of a Place Cell

Mazzara,

Migliore

2023

Sci Rep

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“…Hippocampal astrocytes are known to participate actively during memory consolidation and the location-specific encoding of the reward system (Brazhe et al, 2023;Curreli et al, 2022;Denizot et al, 2019;Doron et al, 2022;Polykretis and Michmizos, 2022). In addition, APDAs have been shown to reduce the number of synapses in adjacent neurons (Lee et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…Although a direct relevance to cognitive function was not shown, these autophagy dysregulated astrocytes had detrimental effects on the number of synapses in adjacent neurons (Lee et al, 2022). Furthermore, astrocytic dysfunction could directly affect the age-related decline of hippocampal function, considering that hippocampal astrocytes play an active role in memory consolidation and the location-specific encoding of the reward system (Brazhe et al, 2023;Curreli et al, 2022;Denizot et al, 2019;Doron et al, 2022;Polykretis and Michmizos, 2022).…”

Section: Introductionmentioning

confidence: 99%

ThePgb1locus controls glycogen aggregation in astrocytes of the aged hippocampus without impacting cognitive function

Gómez-Pascual,

Glikman,

et al. 2023

Preprint

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Aging can be associated with the accumulation of hypobranched glycogen molecules (polyglucosan bodies, PGBs), particularly in astrocytes of the hippocampus. While PGBs have a detrimental effect on cognition in diseases such as adult polyglucosan body disease and Lafora disease, the underlying mechanism and clinical relevance of age-related PGB accumulation remains unknown. Here, we have investigated the genetic basis and functional impact of age-related PGB accumulation in 32 fully sequenced BXD-type strains of mice which exhibit a 400-fold variation in PGB burden in 16-18 month old females. We mapped a major locus controlling PGB density in the hippocampus to chromosome 1 at 72–75 Mb (linkage of 4.9 –logP), which we defined as thePgb1locus. To identify potentially causal gene variants withinPgb1, we generated extensive hippocampal transcriptome datasets and identified two strong candidate genes for which mRNA correlates with PGB density—Smarcal1andUsp37. In addition, bothSmarcal1andUsp37contain non-synonymous allele variations likely to impact protein function. A phenome-wide association analysis highlighted a trans-regulatory effect of thePgb1locus on expression ofHp1bp3, a gene known to play a role in age-related changes in learning and memory. To investigate the potential impact of PGBs on cognition, we performed conditioned fear memory testing on strains displaying varying degrees of PGB burden, and a phenome-wide association scan of ~12,000 traits. Importantly, we did not find any evidence suggesting a negative impact of PGB burden on cognitive capacity. Taken together, we have identified a major modifier locus controlling PGB burden in the hippocampus and shed light on the genetic architecture and clinical relevance of this strikingly heterogeneous hippocampal phenotype.

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