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Papoutsi, A.

Publications and source records attributed to Papoutsi, A..

6 recordsLinked to original sources

Dendritic hotspots support switching between competing rules without expanding the cortical engram

Adaptive behavior requires updating responses when contingencies change while preserving prior associations and the capacity to learn a new. How this trade-off is resolved remains unknown. Here, we combined in vivo imaging of apical tuft spines in the secondary motor cortex (M2) with biologically constrained network modeling in mice performing a cross-modal rule-switch task. M2 inactivation impaired rule-switching but not learning or maintenance, identifying it as a conflict resolution substrate. Adaptation was accompanied by elevated spine turnover concentrated within stable dendritic hotspots, in which the formation, elimination and clustering of new spines were coupled and pre-existing spines were lost early. A network model reproduces these dynamics and predicts that dendritic hotspots are critical for resource-efficient adaptation. Within these reusable domains, spines encoding the prior rule are replaced by newly-relevant ones via sharing of plasticity-related resources. Preventing reuse increases both the plasticity and the engram size requirements to encode the two rules. We propose that dendritic hotspots provide a mechanistic substrate for efficient adaptive learning.

neuroscience↗

EthoPy: Reproducible Behavioral Neuroscience Made Simple

As brain activity is tightly coupled to behavior, an accurate understanding of neural function necessitates consideration of behavioral tasks that capture the complexity and variety animals encounter. Nevertheless, animal training for behavioral experiments is often labor-intensive, costly, and difficult to standardize. To overcome these challenges, we developed EthoPy, an open-source, Python-based behavioral control framework that integrates stimulus presentation, hardware management, and data logging. EthoPy supports diverse behavioral paradigms, stimulus modalities, and experimental systems, from homecage to head-fixed configurations, while operating on affordable hardware, such as Raspberry Pi. Its modular architecture and database integration enable scalable, high-throughput automatic behavioral training with minimal experimenter involvement while ensuring reproducibility through comprehensive metadata tracking. By automating training workflows, EthoPy makes it feasible to implement sophisticated behavioral paradigms that are traditionally difficult to achieve. EthoPy thus provides an accessible, extensible framework to study behavior and the underlying neural activity.

animal behavior and cognition↗

Local changes in potassium ions modulate dendritic integration

During neuronal activity the extracellular concentration of potassium ions ([K+]o) increases substantially above resting levels, but it remains unclear what role these [K+]o changes play in dendritic integration of synaptic inputs. We used mathematical formulations and biophysical modeling to explore the role of activity-dependent K+ changes near dendritic segments of a visual cortex pyramidal neuron, receiving synaptic inputs tuned to stimulus orientation. We found that the fine-scale spatial arrangement of inputs dictates the magnitude of [K+]o changes around the dendrites: Dendritic segments with similarly-tuned inputs can attain substantially higher [K+]o increases than segments with diversely-tuned inputs. These [K+]o elevations in turn increase dendritic excitability, leading to more robust and prolonged dendritic spikes. Ultimately, these local effects amplify the gain of neuronal input-output transformations, causing higher orientation-tuned somatic firing rates without compromising orientation selectivity. Our results suggest that local activity-dependent [K+]o changes around dendrites may act as a "volume knob" that determines the impact of synaptic inputs on feature-tuned neuronal firing.

neuroscience↗

A Tale of Two Trees: Modeling Apical and Basal Tree Contribution to L2/3 V1 Pyramidal Cell Orientation Selectivity

Pyramidal neurons, a mainstay of cortical regions, receive a plethora of inputs from various areas onto their morphologically distinct apical and basal trees. Both trees differentially contribute to the somatic response, defining distinct anatomical and possibly functional sub-units. To elucidate the contribution of each tree to the encoding of visual stimuli at the somatic level, we modeled the response pattern of a L2/3 V1 pyramidal neuron to orientation tuned synaptic input. Towards this goal, we used a morphologically detailed computational model of a single cell that replicates electrophysiological and two-photon imaging data. Our simulations predict a synergistic effect of apical and basal trees on somatic action potential generation: basal tree activity, in the form of either depolarization or dendritic spiking, is necessary for producing somatic activity, despite the fact that most somatic spikes are heavily driven by apical dendritic spikes. This model provides evidence for synergistic computations taking place in the basal and apical trees of the L2/3 V1 neuron along with mechanistic explanations for tree-specific contributions and emphasizes the potential role of predictive and attentional feedback input in these cells. O_FIG O_LINKSMALLFIG WIDTH=181 HEIGHT=200 SRC="FIGDIR/small/501858v2_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@1b69239org.highwire.dtl.DTLVardef@13a0a32org.highwire.dtl.DTLVardef@1738a7corg.highwire.dtl.DTLVardef@88e826_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOAbstract FigureC_FLOATNO Graphical Representation of AP Generation in a L2/3 V1 Pyramidal Neuron Model Action potential generation requires the spatiotemporal coincidence of apical sodium spikes with either basal sodium spikes or significant basal depolarizations, allowing the neuron to respond to salient stimuli that may or may not be affected by attentional and/or predictive signals from higher-order areas. C_FIG

neuroscience↗

Structured connectivity exploits NMDA non-linearitites to induce dimensionally diverse responses in a PFC circuit

Prefrontal Cortex (PFC) exerts control on action selection and mediates behavioral flexibility during working memory (WM) task execution, when integration and retention of sensory information takes place. We used biophysical circuit modelling to investigate the dendritic, neuronal and circuit mechanisms that underlie these computations, aiming to causally link these three processing levels. Our simulations predict that dendritic NMDA non-linearities drive distinct activity dynamics of the same network, thus enabling adaptive coding in the absence of plasticity mechanisms. Specifically, we find that distinct assemblies of mixed-selectivity neurons emerge and fire in stable trajectories in a stimulus-dependent manner. Synaptic inputs that are spatio-temporally clustered, as provided by the structured connectivity of the PFC, facilitate these activity dynamics, thus further increasing the flexibility of the network. Our study suggests that behavioral flexibility may result from the formation of memoranda-specific assemblies in the PFC which are utilized dynamically in relation to the task at hand.

neuroscience↗

Contribution of Apical and Basal Dendrites of L2/3 Pyramidal Neurons to Orientation Encoding in Mouse V1

Pyramidal neurons integrate synaptic inputs from basal and apical dendrites to generate stimulus-specific responses. It has been proposed that feed-forward inputs to basal dendrites drive a neurons stimulus preference, while feedback inputs to apical dendrites sharpen selectivity. However, how a neurons dendritic domains relate to its functional selectivity has not been demonstrated experimentally. We performed 2-photon dendritic micro-dissection on layer-2/3 pyramidal neurons in mouse primary visual cortex. We found that removing the apical dendritic tuft did not alter orientation-tuning. Furthermore, orientation-tuning curves were remarkably robust to the removal of basal dendrites: ablation of 2-3 basal dendrites was needed to cause a small shift in orientation preference, without significantly altering tuning width. Computational modeling corroborated our results and put limits on how orientation preferences among basal dendrites differ in order to reproduce the post-ablation data. In conclusion, neuronal orientation-tuning appears remarkably robust to loss of dendritic input.

neuroscience↗