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Franca, A. S. C.

Publications and source records attributed to Franca, A. S. C..

6 recordsLinked to original sources

Functional specialization of OLMα2 interneurons emerges from differential longitudinal hippocampal-amygdala wiring

The ventral hippocampus (vHipp) is increasingly recognized for its role in processing probabilistic threats and emotional salience, yet the circuit mechanisms underlying these computations remain unclear. Here, we investigated how oriens-lacunosum moleculare interneurons expressing the 2 subunit of the nicotinic acetylcholine receptor (OLM2 cells) contribute to hippocampal function along the longitudinal axis. Combining cell-type specific optogenetics, behavioral assays, monosynaptic and transsynaptic viral tracing, we compared intermediate hippocampal (iHipp) and vHipp OLM2 populations. We show that OLM2 cells exert regionally distinct control over behavior. Manipulation of iHipp OLM2 cells selectively influenced object-directed exploration and novel object processing without affecting anxiety-like behavior, whereas vHipp OLM2 cells modulated arousal and emotionally driven avoidance without contributing to object memory. Circuit tracing revealed that this functional double dissociation is paralleled by distinct connectivity profiles: iHipp is preferentially embedded in sensory cortical networks, whereas vHipp is strongly connected to limbic structures, including the basolateral amygdala and nucleus accumbens. Notably, despite robust regional amygdala-hippocampal connectivity, OLM2 interneurons themselves received sparse direct amygdala input, indicating that emotional modulation is mediated indirectly via hippocampal pyramidal cell pathways. In contrast, stimulation of basolateral amygdala projections to vHipp promoted approach behavior without inducing generalized aversion, further supporting pathway- and cell-type specific encoding of valence and salience. Together, our findings demonstrate that OLM2 interneurons implement a longitudinally organized inhibitory framework in which conserved microcircuit motifs yield distinct behavioral outcomes, depending on their embedding within region specific input and output networks. This work identifies a mechanistic basis for functional specialization along the hippocampal axis and highlights interneuron positioning as a key determinant of hippocampal contributions to cognition and emotion.

neuroscience↗

Characterizing neural phase-space trajectories via Principal Louvain Clustering

BackgroundWith the growing size and richness of neuroscience datasets in terms of dimension, volume, and resolution, identifying spatiotemporal patterns in those datasets is increasingly important. Multivariate dimension-reduction methods are particularly adept at addressing these challenges. New MethodIn this paper, we propose a novel method, which we refer to as Principal Louvain Clustering (PLC), to identify clusters in a low-dimensional data subspace, based on time-varying trajectories of spectral dynamics across multisite local field potential (LFP) recordings in awake behaving mice. Data were recorded from prefrontal cortex, hippocampus, and parietal cortex in eleven mice while they explored novel and familiar environments. ResultsPLC-identified subspaces and clusters showed high consistency across animals, and were modulated by the animals ongoing behavior. ConclusionsPLC adds to an important growing literature on methods for characterizing dynamics in high-dimensional datasets, using a smaller number of parameters. The method is also applicable to other kinds of datasets, such as EEG or MEG.

neuroscience↗

Large- and multi-scale networks in the rodent brain during novelty exploration

Neural activity is coordinated across multiple spatial and temporal scales, and these patterns of coordination are implicated in both healthy and impaired cognitive operations. However, empirical cross-scale investigations are relatively infrequent, due to limited data availability and to the difficulty of analyzing rich multivariate datasets. Here we applied frequency-resolved multivariate source-separation analyses to characterize a large-scale dataset comprising spiking and local field potential activity recorded simultaneously in three brain regions (prefrontal cortex, parietal cortex, hippocampus) in freely-moving mice. We identified a constellation of multidimensional, inter-regional networks across a range of frequencies (2-200 Hz). These networks were reproducible within animals across different recording sessions, but varied across different animals, suggesting individual variability in network architecture. The theta band (~4-10 Hz) networks had several prominent features, including roughly equal contribution from all regions and strong inter-network synchronization. Overall, these findings demonstrate a multidimensional landscape of large-scale functional activations of cortical networks operating across multiple spatial, spectral, and temporal scales during open-field exploration. Significance statementNeural activity is synchronized over space, time, and frequency. To characterize the dynamics of large-scale networks spanning multiple brain regions, we recorded data from the prefrontal cortex, parietal cortex, and hippocampus in awake behaving mice, and pooled data from spiking activity and local field potentials into one data matrix. Frequency-specific multivariate decomposition methods revealed a cornucopia of neural networks defined by coherent spatiotemporal patterns over time. These findings reveal a rich, dynamic, and multivariate landscape of large-scale neural activity patterns during foraging behavior.

neuroscience↗

Anterior cingulate cortex hypofunction causes anti-social aggression in mice

Controlling aggression is a crucial skill in social species like rodents and humans, and has been associated with anterior cingulate cortex (ACC). Here, we demonstrate a causal link between ACC hypofunction and failed aggression control in BALB/cJ mice. We first show that ACC in BALB/cJ mice is structurally degraded: Neuron density is decreased, with pervasive neuron death and neuro-toxic astroglia. Gene-set enrichment analysis suggested that this process is driven by neuronal degeneration, which then causes toxic astrogliosis. cFos expression across ACC indicated functional consequences: During aggressive encounters, ACC was engaged in control mice, but not BALB/cJ mice. Chemogenetically activating ACC during aggressive encounters drastically suppressed anti-social aggression but left adaptive aggression intact. The network effects of our chemogenetic perturbation suggest that this behavioural rescue is mediated by suppression of amygdala and hypothalamus and activation of mediodorsal thalamus. Together, these findings highlight the causal role of ACC in curbing anti-social aggression.

neuroscience↗

Beta2 oscillations in the hippocampal-cortical novelty detection circuit

Novelty detection is a core feature of behavioral adaptation, and involves cascades of neuronal responses - from initial evaluation of the stimulus to the encoding of new representations - resulting in the behavioral ability to respond to unexpected inputs. In the past decade, a new important novelty detection feature, beta2 (~20 - 30 Hz) oscillations, has been described in the hippocampus. However, the interactions between beta2 and the hippocampal network are unknown, as well as the role - or even the presence - of beta2 in other areas involved with novelty detection. In this work, we used behavioral tasks that modulate novelty in combination with multisite local field potential (LFP) recordings targeting regions involved with novelty detection processing in mice - the CA1 region of the hippocampus, parietal cortex and mid-prefrontal cortex - to describe the oscillatory dynamics associated with novelty. We found that transient beta2 power increases were observed only during interaction with novel contexts and objects, but not with familiar contexts and objects. Also, robust theta-gamma phase-amplitude coupling was observed during the exploration of novel environments. Surprisingly, bursts of beta2 power had strong coupling with the phase of delta-range oscillations. Finally, the parietal and mid-frontal cortices had strong coherence with the hippocampus in both theta and beta2. These results highlight the importance of beta2 oscillations in a larger hippocampal-cortical circuit, suggesting that beta2 is a mechanism for detecting and modulating behavioral adaptation to novelty.

neuroscience↗

Low-cost and versatile electrodes for extracellular chronic recordings in rodents

Electrophysiological data are used to investigate fundamental properties of brain function, its relation to cognition, and its dysfunction in diseases. The development of reliable and open-source systems for electrophysiological data acquisition is decreasing the total cost of constructing and operating an electrophysiology laboratory, and facilitates low-cost methods to extract and analyze the data (Siegle et al., 2017). Here we detail our method of building custom-designed low-cost electrodes. These electrodes can be customized and manufactured by any researcher to address a broad set of research questions, further decreasing the final cost of an implanted animal. Finally, we present data showing such an electrode has a good signal quality to record LFP.

neuroscience↗