A time-dependent role for the transcription factor CREB in neuronal allocation to an engram underlying a fear memory revealed using a novel in vivo optogenetic tool to modulate CREB function

Park, Albert; Jacob, Alexander D.; Walters, Brandon J.; Park, Sungmo; Rashid, Asim J.; Jung, Jung Hoon; Lau, Jocelyn; Woolley, G. Andrew; Frankland, Paul W.; Josselyn, Sheena A.

doi:10.1038/s41386-019-0588-0

Cited by 33 publications

(25 citation statements)

References 85 publications

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“…From the continual learning perspective, one of the several routes to avoid catastrophic forgetting of prior learning [ 2 , 78 – 80 ] is to ensure that distinct resources (e.g. neurons, ion channel subtypes, or synapses) are allotted for encoding distinct behavioral contexts [ 18 , 26 , 28 – 31 ]. Such differential allocation could be achieved if mnemonic plasticity in a subset of resources also introduces concurrent metaplasticity that negatively regulates future recruitment of this subset for other contexts.…”

Section: Dynamical Nature Of Plasticity Manifoldsmentioning

confidence: 99%

Stable continual learning through structured multiscale plasticity manifolds

Mishra

Narayanan

2021

Current Opinion in Neurobiology

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Biological plasticity is ubiquitous. How does the brain navigate this complex plasticity space, where any component can seemingly change, in adapting to an ever-changing environment? We build a systematic case that stable continuous learning is achieved by structured rules that enforce multiple, but not all, components to change together in specific directions. This rule-based low-dimensional plasticity manifold of permitted plasticity combinations emerges from cell type–specific molecular signaling and triggers cascading impacts that span multiple scales. These multiscale plasticity manifolds form the basis for behavioral learning and are dynamic entities that are altered by neuromodulation, metaplasticity, and pathology. We explore the strong links between heterogeneities, degeneracy, and plasticity manifolds and emphasize the need to incorporate plasticity manifolds into learning-theoretical frameworks and experimental designs.

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Section: Dynamical Nature Of Plasticity Manifoldsmentioning

confidence: 99%

Stable continual learning through structured multiscale plasticity manifolds

Mishra

Narayanan

2021

Current Opinion in Neurobiology

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“…Strategies are grouped into three categories: cell signaling (yellow), [ 20,34,38–49,51a,52–59,61,67,69–76,79–83,66 ] organelle manipulation (cyan), [ 84–87,89–100 ] and genetic regulation (magenta). [ 101,102,105–107,109–118 ] Excitation wavelength refers to the light used to activate the optogenetic proteins, which are individually labeled. The time to phenotype was chosen based on reported timescales outlined in Table 2.…”

Section: Spatiotemporal Optical Control Of Intracellular Signal Transductionmentioning

confidence: 99%

“…This heterodimer can be disrupted when A‐CREB is caged by the photoactive yellow protein (PYP) under blue light stimulation, resulting in a recovery of wild‐type CREB activity. [ 101 ]…”

Section: Spatiotemporal Optical Control Of Intracellular Signal Transductionmentioning

confidence: 99%

Steering Molecular Activity with Optogenetics: Recent Advances and Perspectives

Fan

Skeeters

et al. 2021

Advanced Biology

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In a transparent medium, lensbased optical microscopy could focus a coherent light beam (e.g., laser) into a tiny spot, whose dimension is comparable to the size of the wavelength of the light. The diameter of the smallest beam waist is about half the size of the wavelength, which is referred to as the diffraction limit. Thus, for visible light, the theoretical diffraction limit is between 200 and 400 nm, much smaller than the size of a single cell (Figure 1A). However, in biological tissues that significantly scatter and absorb visible light, the spatial resolution could be compromised. In multicellular organisms, light absorption limits the penetration depth. The scattering of the light by the opaque biological tissues would expand the volume of light stimulation and reduce the spatial resolution.

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“…CRANE uses a combination of three viruses. This first virus carries the CREB gene which biases memory allocation to a sparse and random subset of neurons in a given brain region [12][13][14] (Fig. 1a-b, AAV-RG-2A-CREB).…”

Section: Tracing Inter-regional Memory Networkmentioning

confidence: 99%

“…A previous study also found increased structural connectivity between CA3 and CA1 memory ensembles in the hippocampus after memory formation 11 . Although there are mechanisms that regulate memory allocation to specific neurons in a given brain region [12][13][14] , it is unclear whether memory allocation is coordinated between the various brain regions involved in a memory.…”

Section: Introductionmentioning

confidence: 99%

A retrograde mechanism coordinates memory allocation across brain regions

Lavi

Sehgal

Sisan

et al. 2021

Preprint

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Memories engage ensembles of neurons across different brain regions within a memory system. However, it is unclear whether the allocation of a memory to these ensembles is coordinated across brain regions. To address this question, we used CREB expression to bias memory allocation in one brain region, and rabies retrograde tracing to test memory allocation in connected presynaptic neurons in the other brain regions. We find that biasing allocation of CTA memory in the basolateral amygdala (BLA) also biases memory allocation in presynaptic neurons of the insular cortex (IC). By manipulating the allocation of CTA memory to specific neurons in both BLA and IC, we found that we increased their connectivity and enhanced CTA memory performance. These results – which are corroborated by mathematical simulations, and by studies with auditory fear conditioning – demonstrate that a retrograde mechanism coordinates the allocation of memories across different brain regions.

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A time-dependent role for the transcription factor CREB in neuronal allocation to an engram underlying a fear memory revealed using a novel in vivo optogenetic tool to modulate CREB function

Cited by 33 publications

References 85 publications

Stable continual learning through structured multiscale plasticity manifolds

Stable continual learning through structured multiscale plasticity manifolds

Steering Molecular Activity with Optogenetics: Recent Advances and Perspectives

A retrograde mechanism coordinates memory allocation across brain regions

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