Biology subjects

Tonegawa, S.

Publications and source records attributed to Tonegawa, S..

4 recordsLinked to original sources

bioRxiv2021

Cingulate-motor circuits update rule representations for sequential choice decisions

Anterior cingulate cortex mediates the flexible updating of an animals choice responses upon rule changes in the environment. However, how anterior cingulate cortex entrains motor cortex to reorganize rule representations and generate required motor outputs remains unclear. Here, we demonstrate that chemogenetic silencing of the projection terminals of cingulate cortical neurons in secondary motor cortex disrupted sequential choice performance in trials immediately following rule switches, suggesting that these inputs are necessary to update rule representations for choice decisions stored in the motor cortex. Indeed, the silencing of cingulate cortex decreased rule selectivity of secondary motor cortical neurons. Furthermore, optogenetic silencing of cingulate cortical neurons that was temporally targeted to error trials immediately after rule switches exacerbated errors in following trials. These results suggest that cingulate cortex monitors behavioral errors and update rule representations in motor cortex, revealing a critical role for cingulate-motor circuits in adaptive choice behaviors.

neuroscience↗

bioRxiv2019

Brain-wide mapping of contextual fear memory engram ensembles supports the dispersed engram complex hypothesis

GRAPHICAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC=\"FIGDIR/small/668483v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (34K):\norg.highwire.dtl.DTLVardef@1957e90org.highwire.dtl.DTLVardef@1a83d79org.highwire.dtl.DTLVardef@5bd5d5org.highwire.dtl.DTLVardef@133c879_HPS_FORMAT_FIGEXP M_FIG C_FIG SUMMARYNeuronal ensembles that hold specific memory (memory engrams) have been identified in the hippocampus, amygdala, and cortex. It has been hypothesized that engrams for a specific memory are distributed among multiple brain regions that are functionally connected. Here, we report the hitherto most extensive engram map for contextual fear memory by characterizing activity-tagged neurons in 409 regions using SHIELD-based tissue phenotyping. The mapping was aided by a novel engram index, which identified cFos+ brain regions holding engrams with a high probability. Optogenetic manipulations confirmed previously known engrams and revealed new engrams. Many of these engram holding-regions were functionally connected to the CA1 or amygdala engrams. Simultaneous chemogenetic reactivation of multiple engrams, which mimics natural memory recall, conferred a greater level of memory recall than reactivation of a single engram ensemble. Overall, our study supports the hypothesis that a memory is stored in functionally connected engrams distributed across multiple brain regions.

neuroscience↗

bioRxiv2019

Amygdala Reward Neurons Form and Store Fear Extinction Memory

The ability to extinguish conditioned fear memory is critical for adaptive control of fear response, and its impairment is a hallmark of emotional disorders like post-traumatic stress disorder (PTSD). Fear extinction is thought to take place when animals form a new memory that suppresses the original fear memory. However, little is known about the nature and the site of formation and storage of the new extinction memory. Here, we demonstrate that a fear extinction memory engram is formed and stored in a genetically distinct basolateral amygdala (BLA) neuronal population that drive reward behaviors and antagonize the BLAs original fear neurons. The activation of the fear extinction engram neurons and natural reward-responsive neurons overlap extensively in the BLA. Furthermore, these two neuron subsets are mutually interchangeable in driving reward behaviors and fear extinction behaviors. Thus, fear extinction memory is a newly formed reward memory.

neuroscience↗

bioRxiv2019

CA1 pyramidal cells organize an episode by segmented and ordered events

A prevailing view is that the brain represents episodic experience as the continuous moment to moment changes in the experience. Whether the brain also represents the same experience as a sequence of discretely segmented events, is unknown. Here, we report a hippocampal CA1 \"chunking code\", tracking an episode as its discrete event subdivisions (\"chunks\") and the sequential relationships between them. The chunking code is unaffected by unpredicted variations within the events, reflecting the codes flexible nature by being organized around events as abstract units. The chunking code changes accordingly when relationships between events are disrupted or modified. The discrete chunking code and continuous spatial code are represented in the same cells, but in an orthogonal manner, and can be independently perturbed. Optogenetic inactivation of MEC inputs to CA1 disrupts the chunking but not spatial code. The chunking code may be fundamental for representing an episode, alongside codes tracking continuous changes.

neuroscience↗