All-optical physiology resolves a synaptic basis for behavioral timescale plasticity

Fan, Linlin Z.; Kim, Doo Kyung; Jennings, Joshua H.; Tian, He; Wang, Peter Y.; Ramakrishnan, Charu; Randles, Sawyer; Sun, Yanjun; Thadhani, Elina; Kim, Yoon Seok; Quirin, Sean; Giocomo, Lisa M.; Cohen, Adam E.; Deisseroth, Karl

doi:10.1016/j.cell.2022.12.035

Cited by 51 publications

(53 citation statements)

References 75 publications

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“…To investigate what mechanisms might be responsible for the different levels of stability observed in the above two populations we more closely examined the activity of each PC on the first day that it became active (first day of appearance). Specifically, we looked for the known signatures of behavioral timescale synaptic plasticity (BTSP) within each population [23][24][25] . BTSP is a directed form of synaptic weight plasticity that is induced when input from the entorhinal cortex (EC3) drives Ca 2+ plateau potentials in the dendrites of CA1 neurons.…”

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confidence: 99%

“…BTSP is a directed form of synaptic weight plasticity that is induced when input from the entorhinal cortex (EC3) drives Ca 2+ plateau potentials in the dendrites of CA1 neurons. Accumulating evidence suggests BTSP is the primary mechanism of PF formation and learning-related changes in CA1 population activity [23][24][25][26][27][28] . Here, we found that both the transient and sustained groups showed prominent signatures of BTSP induction on the first day of appearance (Fig.…”

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confidence: 99%

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The formation of an expanding memory representation in the hippocampus

Vaidya

Chitwood

Magee

2023

Preprint

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How episodic memories are stored within brains is poorly understood. While certain memory-retaining neurons have been potentially identified, it is unclear if they retain learned information. Further, there is considerable evidence that neuronal activity is unstable and may require additional mechanisms to support robust memory. To examine these issues, we recorded the activity of a hippocampal CA1 neuronal population for 7 days as mice learned cued reward locations. These data and modelling results suggest that two place cell (PC) pools, distinguished by place field (PF) stability, are formed each day (transient: ~1.5 days; sustained: ~2 weeks)8. Notably, the proportions of these pools changed across the week as unstable transient PCs were progressively replaced by sustained PCs, markedly enhancing the stability of the total representation. This growing stable representation contained behaviorally relevant information and sustained PCs became active immediately at the start of each session. Finally, the initial formation of sustained PCs was associated with a higher rate and efficacy of behavioral timescale synaptic plasticity (BTSP) and these PCs showed elevated and more reliable activity. It, therefore, appears that BTSP stabilizes particularly informative PCs, incorporating them into an expanding and readily retrievable representation that displays hallmarks of a long-lasting memory.

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confidence: 99%

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confidence: 99%

The formation of an expanding memory representation in the hippocampus

Vaidya

Chitwood

Magee

2023

Preprint

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“…Our findings highlight the power of voltage imaging in revealing cell-type-specific spiking and membrane potential dynamics during active behavior, with high temporal resolution [68,69,70] and across long time scales of several days. The recent developments of new GEVIs with improved fluorescence, kinetics and photostability [28,30] render voltage imaging ideal for long-term recording membrane potentials from genetically identified cells in vivo.…”

Section: Discussionmentioning

confidence: 73%

Voltage imaging reveals that hippocampal interneurons tune memory-encoding pyramidal sequences

Taxidis

Madruga

Melin

et al. 2023

Preprint

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Hippocampal spiking sequences encode and link behavioral information across time. How inhibition sculpts these sequences remains unknown. We performed longitudinal voltage imaging of CA1 parvalbumin- and somatostatin- expressing interneurons in mice during an odor-cued working memory task, before and after training. During this task, pyramidal odor-specific sequences encode the cue throughout a delay period. In contrast, most interneurons encoded odor delivery, but not odor identity, nor delay time. Population inhibition was stable across days, with constant field turnover, though some cells retained odor-responses for days. At odor onset, a brief, synchronous burst of parvalbumin cells was followed by widespread membrane hyperpolarization and then rebound theta-paced spiking, synchronized across cells. Two-photon calcium imaging revealed that most pyramidal cells were suppressed throughout the odor. Positive pyramidal odor-responses coincided with interneuronal rebound spiking; otherwise, they had weak odor-selectivity. Therefore, inhibition increases the signal-to-noise ratio of cue representations, which is crucial for entraining downstream targets.

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“…Such dendritic-spike-induced plasticity has been associated with the formation of new place fields in novel environments 68 could provide a mechanism through which NR both disrupts CFMR and promotes extinction learning. Additionally, either NR or EC projections to SLM, when coincident with CA3 inputs through schaffer collaterals, induce burst firing in CA1 pyramidal cells [69][70][71][72] . CA1 pyramidal cell bursts are also capable of inducing new place fields in CA1 through behavioral timescale synaptic plasticity (BTSP) 69,[71][72][73] .…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, either NR or EC projections to SLM, when coincident with CA3 inputs through schaffer collaterals, induce burst firing in CA1 pyramidal cells [69][70][71][72] . CA1 pyramidal cell bursts are also capable of inducing new place fields in CA1 through behavioral timescale synaptic plasticity (BTSP) 69,[71][72][73] . If our newlyreported NR input to the apical tuft during fearful freezing epochs coincides with CA3 inputs, their combined activity could induce burst firing and initiate BTSP.…”

Section: Discussionmentioning

confidence: 99%

Direct Thalamic Inputs to Hippocampal CA1 Transmit a Signal That Suppresses Ongoing Contextual Fear Memory Retrieval

Ratigan

Krishnan

Smith

et al. 2023

Preprint

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Memory retrieval of fearful experiences is essential for survival, but can be maladaptive if not appropriately suppressed. Fear memories can be acquired through contextual fear conditioning (CFC) which relies on the hippocampus. The thalamic subregion Nucleus Reuniens (NR) is necessary for contextual fear extinction and strongly projects to hippocampal subregion CA1. However, the NR-CA1 pathway has not been investigated during behavior, leaving unknown its role in contextual fear memory retrieval. We implement a novel head-restrained virtual reality CFC paradigm, and show that inactivation of the NR-CA1 pathway prolongs fearful freezing epochs, induces fear generalization, and delays extinction. We use in vivo sub-cellular imaging to specifically record NR-axons innervating CA1 before and after CFC. We find NR-axons become selectively tuned to freezing only after CFC, and this activity is well-predicted by an encoding model. We conclude that the NR-CA1 pathway actively suppresses fear responses by disrupting ongoing hippocampal-dependent contextual fear memory retrieval.

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All-optical physiology resolves a synaptic basis for behavioral timescale plasticity

Cited by 51 publications

References 75 publications

The formation of an expanding memory representation in the hippocampus

The formation of an expanding memory representation in the hippocampus

Voltage imaging reveals that hippocampal interneurons tune memory-encoding pyramidal sequences

Direct Thalamic Inputs to Hippocampal CA1 Transmit a Signal That Suppresses Ongoing Contextual Fear Memory Retrieval

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