Context value updating and multidimensional neuronal encoding in the retrosplenial cortex

AbstractThe retrosplenial cortex (RSC) has diverse functional inputs and is engaged by various sensory, spatial, and associative learning tasks. We examine how multiple functional aspects are integrated on the single-cell level in the RSC and how the encoding of task-related parameters changes across learning. Using a visuospatial context discrimination paradigm and two-photon calcium imaging in behaving mice, a large proportion of dysgranular RSC neurons was found to encode multiple task-related dimensions while forming context-value associations across learning. During reversal learning requiring increased cognitive flexibility, we revealed an increased proportion of multidimensional encoding neurons that showed higher decoding accuracy for behaviorally relevant context-value associations. Chemogenetic inactivation of RSC led to decreased behavioral context discrimination during learning phases in which context-value associations were formed, while recall of previously formed associations remained intact. RSC inactivation resulted in a persistent positive behavioral bias in valuing contexts, indicating a role for the RSC in context-value updating.

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Complimentary roles of the hippocampus and retrosplenial cortex in behavioral context discrimination

Hippocampus ◽

10.1002/hipo.20958 ◽

2011 ◽

Vol 22 (5) ◽

pp. 1121-1133 ◽

Cited By ~ 48

Author(s):

David M. Smith ◽

Jennifer Barredo ◽

Sheri J.Y. Mizumori

Keyword(s):

Retrosplenial Cortex ◽

Behavioral Context ◽

Context Discrimination

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Putting fear in context: Elucidating the role of the retrosplenial cortex in context discrimination in rats

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2017.12.009 ◽

2018 ◽

Vol 148 ◽

pp. 50-59 ◽

Cited By ~ 6

Author(s):

Siobhan Robinson ◽

Julia S. Adelman ◽

Allison S. Mogul ◽

Peter C.J. Ihle ◽

Gianna M. Davino

Keyword(s):

Retrosplenial Cortex ◽

Context Discrimination

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Representation of visual landmarks in retrosplenial cortex

eLife ◽

10.7554/elife.51458 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 7

Author(s):

Lukas F Fischer ◽

Raul Mojica Soto-Albors ◽

Friederike Buck ◽

Mark T Harnett

Keyword(s):

Visual Information ◽

Spatial Information ◽

Spatial Relationship ◽

Retrosplenial Cortex ◽

Task Engagement ◽

Reference Points ◽

Behavioral Task ◽

Two Photon ◽

Local Integration ◽

Visual Motor

The process by which visual information is incorporated into the brain’s spatial framework to represent landmarks is poorly understood. Studies in humans and rodents suggest that retrosplenial cortex (RSC) plays a key role in these computations. We developed an RSC-dependent behavioral task in which head-fixed mice learned the spatial relationship between visual landmark cues and hidden reward locations. Two-photon imaging revealed that these cues served as dominant reference points for most task-active neurons and anchored the spatial code in RSC. This encoding was more robust after task acquisition. Decoupling the virtual environment from mouse behavior degraded spatial representations and provided evidence that supralinear integration of visual and motor inputs contributes to landmark encoding. V1 axons recorded in RSC were less modulated by task engagement but showed surprisingly similar spatial tuning. Our data indicate that landmark representations in RSC are the result of local integration of visual, motor, and spatial information.

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Immediate early gene expression dynamics in vivo segregates neuronal ensemble of multiple memories

10.1101/2020.12.17.423270 ◽

2020 ◽

Author(s):

P. Meenakshi ◽

S. Kumar ◽

J. Balaji

Keyword(s):

Retrosplenial Cortex ◽

Contextual Fear Conditioning ◽

Early Gene ◽

Immediate Early ◽

Temporal Expression ◽

Contextual Fear ◽

Two Photon ◽

Neuronal Ensemble ◽

Gene Expression Dynamics

AbstractImmediate early genes (IEGs) are widely used as a marker for neuronal plasticity. Here, we model the dynamics of IEG expression as a consecutive, irreversible first order reaction with a limiting substrate. We show that such a model, together with two-photon in vivo imaging of IEG expression, can be used to identify distinct neuronal subsets representing multiple memories. We image retrosplenial cortex (RSc) of cFOS-GFP transgenic mice to follow the dynamics of cellular changes resulting from both seizure and contextual fear conditioning behaviour. The analytical expression allowed us to segregate the neurons based on their temporal response to one specific behavioural event, thereby improving the sensitivity of detecting plasticity related neurons. This enables us to establish representation of context in RSc at the cellular scale following memory acquisition. Thus, we obtain a general method which distinguishes neurons that took part in multiple temporally separated events, by measuring fluorescence from individual neurons in live mice.SummaryIdentifying neuronal ensemble associated with different memories is vital in modern neuroscience. Meenakshi et al model and use the temporal expression dynamics of IEGs rather than thresholded intensities of the probes to identify the neurons encoding different memory in vivo.Graphical abstract

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Coordinated activities of retrosplenial ensembles during resting-state encode spatial landmarks

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0228 ◽

2020 ◽

Vol 375 (1799) ◽

pp. 20190228 ◽

Cited By ~ 1

Author(s):

HaoRan Chang ◽

Ingrid M. Esteves ◽

Adam R. Neumann ◽

Jianjun Sun ◽

Majid H. Mohajerani ◽

...

Keyword(s):

Resting State ◽

Memory Trace ◽

Retrosplenial Cortex ◽

Place Cells ◽

Memory Reactivation ◽

Two Photon ◽

Before And After ◽

Memory Activation ◽

The Brain

The brain likely uses offline periods to consolidate recent memories. One hypothesis holds that the hippocampal output provides a unique, global linking or ‘index’ code for each memory, and that this code is stored in the cortex in association with locally encoded attributes of each memory. Activation of the index code is hypothesized to evoke coordinated memory trace reactivation thus facilitating consolidation. Retrosplenial cortex (RSC) is a major recipient of hippocampal outflow and we have described populations of neurons there with sparse and orthogonal coding characteristics that resemble hippocampal ‘place’ cells, and whose expression depends on an intact hippocampus. Using two-photon Ca 2+ imaging, we recorded ensembles of neurons in the RSC during periods of immobility before and after active running on a familiar linear treadmill track. Synchronous bursting of distinct groups of neurons occurred during rest both prior to and after running. In the second rest epoch, these patterns were associated with the locations of tactile landmarks and reward. Complementing established views on the functions of the RSC, our findings indicate that the structure is involved with processing landmark information during rest. This article is part of the Theo Murphy meeting issue ‘Memory reactivation: replaying events past, present and future’.

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Mapping vestibular and visual contributions to angular head velocity tuning in the cortex

10.1101/2021.04.29.441624 ◽

2021 ◽

Author(s):

Eivind Hennestad ◽

Aree Witoelar ◽

Anna Chambers ◽

Koen Vervaeke

Keyword(s):

Posterior Parietal Cortex ◽

Spatial Information ◽

Sensory Modality ◽

Retrosplenial Cortex ◽

Head Movements ◽

Cortical Circuits ◽

Two Photon ◽

Cognitive Information ◽

Posterior Parietal ◽

Cortical Distribution

Neurons that signal the direction and angular velocity of head movements (AHV cells) are critically important to process visual and spatial information. However, it has been challenging to isolate the sensory modality that drives them and to compre hensively map their cortical distribution. To address this, we developed a method that enables rotating awake, head-fixed mice under a two-photon microscope in a visual environment. Starting in layer 2/3 of the retrosplenial cortex, a key area for vision and navigation, we found that a significant fraction of rotation sensitive neurons report AHV. These tuning properties depend on vestibular input because they persist in darkness and are reduced when replaying visual flow to stationary animals. When mapping the spatial extent, we found AHV cells in all cortical areas that we explored, including motor, somatosensory, visual and posterior parietal cortex. Notably, the vestibular and visual contributions to AHV are area dependent. Thus, many cortical circuits have access to AHV, enabling a diverse integration with sensorimotor and cognitive information.

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Simultaneous Two-photon In Vivo Imaging of Synaptic Inputs and Postsynaptic Targets in the Mouse Retrosplenial Cortex

Journal of Visualized Experiments ◽

10.3791/53528 ◽

2016 ◽

Cited By ~ 1

Author(s):

Kacper Łukasiewicz ◽

Magdalena Robacha ◽

Łukasz Bożycki ◽

Kasia Radwanska ◽

Rafał Czajkowski

Keyword(s):

Retrosplenial Cortex ◽

Synaptic Inputs ◽

Two Photon

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Choice history biases subsequent evidence accumulation

eLife ◽

10.7554/elife.46331 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 32

Author(s):

Anne E Urai ◽

Jan Willem de Gee ◽

Konstantinos Tsetsos ◽

Tobias H Donner

Keyword(s):

Sensory Input ◽

Choice Data ◽

Behavioral Context ◽

Evidence Accumulation ◽

Overt Behavior ◽

Dependent Change ◽

Starting Point ◽

Sensory Modalities ◽

History Of ◽

Multiple Task

Perceptual choices depend not only on the current sensory input but also on the behavioral context, such as the history of one’s own choices. Yet, it remains unknown how such history signals shape the dynamics of later decision formation. In models of decision formation, it is commonly assumed that choice history shifts the starting point of accumulation toward the bound reflecting the previous choice. We here present results that challenge this idea. We fit bounded-accumulation decision models to human perceptual choice data, and estimated bias parameters that depended on observers’ previous choices. Across multiple task protocols and sensory modalities, individual history biases in overt behavior were consistently explained by a history-dependent change in the evidence accumulation, rather than in its starting point. Choice history signals thus seem to bias the interpretation of current sensory input, akin to shifting endogenous attention toward (or away from) the previously selected interpretation.

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Representation of Visual Landmarks in Retrosplenial Cortex

10.1101/811430 ◽

2019 ◽

Author(s):

Lukas F. Fischer ◽

Raul Mojica Soto-Albors ◽

Friederike Buck ◽

Mark T. Harnett

Keyword(s):

Visual Information ◽

Receptive Fields ◽

Spatial Relationship ◽

Retrosplenial Cortex ◽

Task Engagement ◽

Reference Points ◽

Behavioral Task ◽

Motor Responses ◽

Two Photon ◽

Insight Into

AbstractThe process by which visual information is incorporated into the brain’s spatial framework to represent landmarks is poorly understood. Studies in humans and rodents suggest that retrosplenial cortex (RSC) plays a key role in these computations. We developed an RSC-dependent behavioral task in which head-fixed mice learned the spatial relationship between visual landmark cues and hidden reward locations. Two-photon imaging revealed that these cues served as dominant reference points for most task-active neurons and anchored the spatial code in RSC. Presenting the same environment but decoupled from mouse behavior degraded encoding fidelity. Analyzing visual and motor responses showed that landmark codes were the result of supralinear integration. Surprisingly, V1 axons recorded in RSC showed similar receptive fields. However, they were less modulated by task engagement, indicating that landmark representations in RSC are the result of local computations. Our data provide cellular- and network-level insight into how RSC represents landmarks.

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Microglial activation after ischaemic stroke

Stroke and Vascular Neurology ◽

10.1136/svn-2018-000196 ◽

2019 ◽

Vol 4 (2) ◽

pp. 71-74 ◽

Cited By ~ 14

Author(s):

Shengxiang Zhang

Keyword(s):

Ischaemic Stroke ◽

Microglial Activation ◽

Imaging Techniques ◽

Morphological Transformation ◽

Activated Microglia ◽

Two Photon ◽

Functional Aspects ◽

The Central Nervous System ◽

Photon Imaging ◽

Two Photon Imaging

Ischaemic stroke can induce rapid activation of microglia. As the resident immune cells of the central nervous system, microglial activation is believed to play a central role in neuroinflammation and pathological progression of ischaemic tissue. The activation of microglia after ischaemia involves several stereotypical events including morphological transformation, proliferation and polarisation. Studies using confocal or two-photon imaging techniques have revealed that the degree of microglial activation is correlated with the degree of ischaemia. Activated microglia display diverse polarisation phenotypes. It remains largely unclear regarding whether activated microglia are beneficial or detrimental to poststroke recovery. This mini-review focuses on the morphological and functional aspects of microglial activation, with particular attention to progress in two-photon imaging studies.

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