LTD is involved in the formation and maintenance of rat hippocampal CA1 place-cell fields

Ashby, Donovan M.; Floresco, Stan; Phillips, Anthony G.; McGirr, Alexander; Seamans, Jeremy K.; Wang, Yu Tian

doi:10.1038/s41467-020-20317-7

Cited by 17 publications

(8 citation statements)

References 71 publications

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“…For both groups, the within-day stability was higher than the between-day stability (session 3 vs session 4), suggesting some remapping across days in both groups. This degree of remapping between the first two days in an initially novel environment with a total of 30 min exposure on Day 1 is comparable with that recently reported in WT rats [ 89 ]. However, we cannot exclude the possibility that the lower firing rate map correlations observed between days compared to within days may be due in part to poorer tracking of cells across days than across sessions within a day.…”

Section: Discussionsupporting

confidence: 89%

Experience-dependent changes in hippocampal spatial activity and hippocampal circuit function are disrupted in a rat model of Fragile X Syndrome

et al. 2022

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Background Fragile X syndrome (FXS) is a common single gene cause of intellectual disability and autism spectrum disorder. Cognitive inflexibility is one of the hallmarks of FXS with affected individuals showing extreme difficulty adapting to novel or complex situations. To explore the neural correlates of this cognitive inflexibility, we used a rat model of FXS (Fmr1−/y). Methods We recorded from the CA1 in Fmr1−/y and WT littermates over six 10-min exploration sessions in a novel environment—three sessions per day (ITI 10 min). Our recordings yielded 288 and 246 putative pyramidal cells from 7 WT and 7 Fmr1−/y rats, respectively. Results On the first day of exploration of a novel environment, the firing rate and spatial tuning of CA1 pyramidal neurons was similar between wild-type (WT) and Fmr1−/y rats. However, while CA1 pyramidal neurons from WT rats showed experience-dependent changes in firing and spatial tuning between the first and second day of exposure to the environment, these changes were decreased or absent in CA1 neurons of Fmr1−/y rats. These findings were consistent with increased excitability of Fmr1−/y CA1 neurons in ex vivo hippocampal slices, which correlated with reduced synaptic inputs from the medial entorhinal cortex. Lastly, activity patterns of CA1 pyramidal neurons were dis-coordinated with respect to hippocampal oscillatory activity in Fmr1−/y rats. Limitations It is still unclear how the observed circuit function abnormalities give rise to behavioural deficits in Fmr1−/y rats. Future experiments will focus on this connection as well as the contribution of other neuronal cell types in the hippocampal circuit pathophysiology associated with the loss of FMRP. It would also be interesting to see if hippocampal circuit deficits converge with those seen in other rodent models of intellectual disability. Conclusions In conclusion, we found that hippocampal place cells from Fmr1−/y rats show similar spatial firing properties as those from WT rats but do not show the same experience-dependent increase in spatial specificity or the experience-dependent changes in network coordination. Our findings offer support to a network-level origin of cognitive deficits in FXS.

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Section: Discussionsupporting

confidence: 89%

Experience-dependent changes in hippocampal spatial activity and hippocampal circuit function are disrupted in a rat model of Fragile X Syndrome

et al. 2022

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“…LTD is also essential for memory formation as it counteracts the LTP to allow new memories to form. Recent evidence has shown that LTD may be involved in formation and maintenance of place fields ( 104 ), supporting previous experiments showing that a decrease in the expression of LTD impairs spatial memory retention and consolidation ( 105 , 106 ). It is worth noting that plastic synapses can form positive feedback loops on the rate, temporal, and population coding mechanisms where this positive loop aids the mechanisms in refining and precisely timing the neuronal firing leading to a more efficient information processing.…”

Section: Firing Dynamics Support Plasticitysupporting

confidence: 77%

Mechanisms for Cognitive Impairment in Epilepsy: Moving Beyond Seizures

2022

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There has been a major emphasis on defining the role of seizures in the causation of cognitive impairments like memory deficits in epilepsy. Here we focus on an alternative hypothesis behind these deficits, emphasizing the mechanisms of information processing underlying healthy cognition characterized as rate, temporal and population coding. We discuss the role of the underlying etiology of epilepsy in altering neural networks thereby leading to both the propensity for seizures and the associated cognitive impairments. In addition, we address potential treatments that can recover the network function in the context of a diseased brain, thereby improving both seizure and cognitive outcomes simultaneously. This review shows the importance of moving beyond seizures and approaching the deficits from a system-level perspective with the guidance of network neuroscience.

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“…1 h-j), indicating initial enhancement and subsequent reduction in the neural activity. As exploration of a novel environment induces both place cell firing and widespread synaptic depression in the rodent hippocampus [ 9 , 10 ], gradual elevation of hippocampal p-eEF2 level might be associated with synaptic depression and resultant reduced neural activity. In contrast to novel context exploration, acute restraint stress significantly reduced hippocampal p-eEF2 at all (5, 30, and 60 min) timepoints (Fig.…”

Section: Main Textmentioning

confidence: 99%

The phosphorylation status of eukaryotic elongation factor-2 indicates neural activity in the brain

Yoon

Song

et al. 2021

Mol Brain

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Assessment of neural activity in the specific brain area is critical for understanding the circuit mechanisms underlying altered brain function and behaviors. A number of immediate early genes (IEGs) that are rapidly transcribed in neuronal cells in response to synaptic activity have been used as markers for neuronal activity. However, protein detection of IEGs requires translation, and the amount of newly synthesized gene product is usually insufficient to detect using western blotting, limiting their utility in western blot analysis of brain tissues for comparison of basal activity between control and genetically modified animals. Here, we show that the phosphorylation status of eukaryotic elongation factor-2 (eEF2) rapidly changes in response to synaptic and neural activities. Intraperitoneal injections of the GABA A receptor (GABAAR) antagonist picrotoxin and the glycine receptor antagonist brucine rapidly dephosphorylated eEF2. Conversely, potentiation of GABAARs or inhibition of AMPA receptors (AMPARs) induced rapid phosphorylation of eEF2 in both the hippocampus and forebrain of mice. Chemogenetic suppression of hippocampal principal neuron activity promoted eEF2 phosphorylation. Novel context exploration and acute restraint stress rapidly modified the phosphorylation status of hippocampal eEF2. Furthermore, the hippocampal eEF2 phosphorylation levels under basal conditions were reduced in mice exhibiting epilepsy and abnormally enhanced excitability in CA3 pyramidal neurons. Collectively, the results indicated that eEF2 phosphorylation status is sensitive to neural activity and the ratio of phosphorylated eEF2 to total eEF2 could be a molecular signature for estimating neural activity in a specific brain area.

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LTD is involved in the formation and maintenance of rat hippocampal CA1 place-cell fields

Cited by 17 publications

References 71 publications

Experience-dependent changes in hippocampal spatial activity and hippocampal circuit function are disrupted in a rat model of Fragile X Syndrome

Experience-dependent changes in hippocampal spatial activity and hippocampal circuit function are disrupted in a rat model of Fragile X Syndrome

Mechanisms for Cognitive Impairment in Epilepsy: Moving Beyond Seizures

The phosphorylation status of eukaryotic elongation factor-2 indicates neural activity in the brain

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