Prefrontal neural ensembles develop selective code for stimulus associations within minutes of novel experiences

Takehara‐Nishiuchi, Kaori; Morrissey, Mark D.; Pilkiw, Maryna

doi:10.1101/2020.08.26.269035

“…Consistent with our previous work (Takehara-Nishiuchi and McNaughton, 2008;Morrissey et al, 2017;Takehara-Nishiuchi et al, 2020), only a subset of CS-responding neurons differentiated CS-evoked firing rates between the CS-alone and CS-US block (Fig. 7Ca).…”

Section: Lec Inhibition Induces Various Changes In Stimulus-evoked Fi...supporting

confidence: 92%

Lateral Entorhinal Cortex Suppresses Drift in Cortical Memory Representations

Pilkiw¹,

Jarovi²,

Takehara‐Nishiuchi

³

2021

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Memory retrieval is thought to depend on the reinstatement of cortical memory representations guided by pattern completion processes in the hippocampus. The lateral entorhinal cortex (LEC) is one of the intermediary regions supporting hippocampal-cortical interactions and houses neurons that prospectively signal past events in a familiar environment. To investigate the functional relevance of the activity of the LEC for cortical reinstatement, we pharmacologically inhibited the LEC and examined its impact on the stability of ensemble firing patterns in one of the efferent targets of the LEC, the medial prefrontal cortex (mPFC). When male rats underwent multiple epochs of identical stimulus sequences in the same environment, the mPFC maintained a stable ensemble firing pattern across repetitions, particularly when the sequence included pairings of neutral and aversive stimuli. With LEC inhibition, the mPFC still formed an ensemble pattern that accurately captured stimuli and their associations within each epoch. However, LEC inhibition markedly disrupted its consistency across the epochs by decreasing the proportion of mPFC neurons that stably maintained firing selectivity for stimulus associations. Thus, the LEC stabilizes cortical representations of learned stimulus associations, thereby facilitating the recovery of the original memory trace without generating a new, redundant trace for familiar experiences. Failure of this process might underlie retrieval deficits in conditions associated with degeneration of the LEC, such as normal aging and Alzheimer's disease.

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“…Consistent with our previous works (Takehara-Nishiuchi and McNaughton, 2008;Morrissey et al, 2017;Takehara-Nishiuchi et al, 2020), only a subset of CS-responding neurons differentiated CS-evoked firing rates between the CS-alone and CS-US block (Figure 7Ca). After aCSF infusion, ~45% of these association-selective neurons maintained their selectivity (Figure 7Cb).…”

Section: Lec Inhibition Induces Various Changes In Stimulus-evoked Firings Of Individual Prl Neurons Without Affecting the Population-levsupporting

confidence: 92%

Lateral entorhinal cortex suppresses drift in cortical memory representations

Pilkiw

¹

,

Jarovi

²

,

Takehara‐Nishiuchi

³

2021

Preprint

Self Cite

View full text Add to dashboard Cite

Memory retrieval is thought to depend on the reinstatement of cortical memory representations guided by pattern completion processes in the hippocampus. The lateral entorhinal cortex (LEC) is one of the intermediary regions supporting hippocampal-cortical interactions and houses neurons that prospectively signal past events in a familiar environment. To investigate the functional relevance of the LEC’s activity for cortical reinstatement, we pharmacologically inhibited the LEC and examined its impact on the stability of ensemble firing patterns in one of the LEC’s efferent targets, the medial prefrontal cortex (mPFC). When male rats underwent multiple epochs of identical stimulus sequences in the same environment, the mPFC maintained a stable ensemble firing pattern across repetitions, particularly when the sequence included pairings of neutral and aversive stimuli. With LEC inhibition, the mPFC still formed an ensemble pattern that accurately captured stimuli and their associations within each epoch. However, LEC inhibition markedly disrupted its consistency across the epochs by decreasing the proportion of mPFC neurons that stably maintained firing selectivity for stimulus associations. Thus, the LEC stabilizes cortical representations of learned stimulus associations, thereby facilitating the recovery of the original memory trace without generating a new, redundant trace for familiar experiences. Failure of this process might underlie retrieval deficits in conditions associated with degeneration of the LEC, such as normal aging and Alzheimer’s disease.SIGNIFICANCE STATEMENTTo recall past events, the brain needs to reactivate the activity patterns that occurred during those events. However, such reinstatement of memory traces is not trivial because it goes against the brain’s natural tendency to restructure the activity patterns continuously. We found that dysfunction of a brain region called the lateral entorhinal cortex (LEC) worsened the drift of the brain activity when rats repeatedly underwent the same events in the same room and made them behave as if they had never experienced these events before. Thus, the LEC stabilizes the brain activity to facilitate the recovery of the original memory trace. Failure of this process might underlie memory problems in elderly and Alzheimer’s disease patients with the degenerated LEC.

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“…These results expand the existing literature on memory consolidation and refine the working model of memory formation and retrieval. Importantly, our data add to the growing evidence on the importance of the mPFC during early phases of memory consolidation (Bero et al, 2014; Cho et al, 2017; Rajasethupathy et al, 2015; Takehara-Nishiuchi et al, 2020; Zelikowsky et al, 2013). Thereby it further challenges the standard theory of memory consolidation, which posits that the HPC is necessary for encoding and recent recall, while the mPFC would take over from the HPC only at remote recall (Frankland & Bontempi, 2005).…”

Section: Discussionsupporting

confidence: 64%

Brain-wide screen of prelimbic cortex inputs reveals a functional shift during early fear memory consolidation

Dixsaut

¹

,

Gräff

²

2022

Preprint

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Memory formation and storage rely on multiple interconnected brain areas, the contribution of which varies during memory consolidation. The medial prefrontal cortex, in particular the prelimbic cortex (PL), was traditionally found to be involved in remote memory storage, but recent evidence points towards its implication in early consolidation as well. Nevertheless, the inputs to the PL governing these dynamics remain unknown. Here, we first performed a brain-wide, rabies-based retrograde tracing screen of PL engram cells activated during contextual fear memory formation to identify relevant PL input regions. Next, we assessed the specific activity pattern of these inputs across different phases of memory consolidation, from fear memory encoding to recent and remote memory recall. Using projection-specific chemogenetic inhibition, we then tested their functional role in memory consolidation, which revealed a hitherto unknown contribution of claustrum to PL inputs at encoding, and of insular cortex to PL inputs at recent memory recall. Both of these inputs further impacted how PL engram cells were reactivated at memory recall, testifying to their relevance for establishing a memory trace in the PL. Collectively, this data identify a spatiotemporal shift in PL inputs important for early memory consolidation, and thereby help to refine the working model of memory formation.

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Prefrontal neural ensembles develop selective code for stimulus associations within minutes of novel experiences

Cited by 4 publications

References 79 publications

Lateral Entorhinal Cortex Suppresses Drift in Cortical Memory Representations

Lateral Entorhinal Cortex Suppresses Drift in Cortical Memory Representations

Lateral entorhinal cortex suppresses drift in cortical memory representations

Brain-wide screen of prelimbic cortex inputs reveals a functional shift during early fear memory consolidation

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