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Quilichini, P. P.

Publications and source records attributed to Quilichini, P. P..

7 recordsLinked to original sources

Probing the Mechanisms of Global Brain Reconfiguration after Local Manipulations

Understanding how localized brain interventions translate into whole-brain dynamics is crucial for deciphering neural function and tailoring therapeutic strategies. Combining mouse experimental datasets of focal interventions (thalamic lesion and chemogenetic silencing of cortical hubs), we demonstrate both local and global effects. Using whole-brain simulations of experimental data, we not only confirm the distributed nature of local manipulations but also offer mechanistic insights into these processes. Our simulations predict specific alterations in firing rates and spectral characteristics across specific brain networks, leading to structured changes in functional connectivity patterns. Some of these predictions have been empirically validated. Notably, the affected brain subnetworks--and their resultant signatures of change--are contingent on the original intervention site, suggesting a method to accurately localize the source of alteration. Our results provide a general framework for interpreting localized intervention effects, offering insights that could refine clinical interventions for focal brain disorders by enabling targeted circuit-level neuromodulation strategies.

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Long-term near-continuous recording with Neuropixels probes in healthy and epileptic rats

Neuropixels probes have become a crucial tool for high-density electrophysiological recordings. Although most research involving these electrodes is in acute preparations, some scientific inquiries require long-term recordings in freely moving animals. Recent reports have presented prosthesis designs for chronic recordings, but some of them do not allow for probe recovery, which is desirable given their cost. Others appear to be fragile, as these articles describe numerous broken implants. This fragility presents a challenge for recordings in rats, particularly in epilepsy models where strong mechanical stress impinges upon the prosthesis. To overcome these limitations, we present a new prosthesis specifically designed to protect the probes from strong shocks and enable the safe retrieval of electrodes after experiments. This implant was successfully used to record from healthy and epileptic rats for up to three weeks almost continuously, with a probe retrieval and reuse success rate of 91%, improving previously described recycling performances.

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Disordered information processing dynamics in experimental epilepsy

Neurological disorders share common high-level alterations, such as cognitive deficits, anxiety, and depression. This raises the possibility of fundamental alterations in the way information conveyed by neural firing is maintained and dispatched in the diseased brain. Using experimental epilepsy as a model of neurological disorder we tested the hypothesis of altered information processing, analyzing how neurons in the hippocampus and the entorhinal cortex store and exchange information during slow and theta oscillations. We equate the storage and sharing of information to low level, or primitive, information processing at the algorithmic level, the theoretical intermediate level between structure and function. We find that these low-level processes are organized into substates during brain states marked by theta and slow oscillations. Their internal composition and organization through time are disrupted in epilepsy, loosing brain state-specificity, and shifting towards a regime of disorder in a brain region dependent manner. We propose that the alteration of information processing at an algorithmic level may be a mechanism behind the emergent and widespread co-morbidities associated with epilepsy, and perhaps other disorders.

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Dynamic core-periphery structure of information sharing networks in entorhinal cortex and hippocampus

Neural computation is associated with the emergence, reconfiguration and dissolution of cell assemblies in the context of varying oscillatory states. Here, we describe the complex spatio-temporal dynamics of cell assemblies through temporal network formalism. We use a sliding window approach to extract sequences of networks of information sharing among single units in hippocampus and enthorinal cortex during anesthesia and study how global and node-wise functional connectivity properties evolve along time and as a function of changing global brain state (theta vs slow-wave oscillations). First, we find that information sharing networks display, at any time, a core-periphery structure in which an integrated core of more tightly functionally interconnected units link to more loosely connected network leaves. However the units participating to the core or to the periphery substantially change across time-windows, with units entering and leaving the core in a smooth way. Second, we find that discrete network states can be defined on top of this continuously ongoing liquid core-periphery reorganization. Switching between network states results in a more abrupt modification of the units belonging to the core and is only loosely linked to transitions between global oscillatory states. Third, we characterize different styles of temporal connectivity that cells can exhibit within each state of the sharing network. While inhibitory cells tend to be central, we show that, otherwise, anatomical localization only poorly influences the patterns of temporal connectivity of the different cells. Furthermore, cells can change temporal connectivity style when the network changes state. Altogether, these findings reveal that the sharing of information mediated by the intrinsic dynamics of hippocampal and enthorinal cortex cell assemblies have a rich spatiotemporal structure, which could not have been identified by more conventional time- or state-averaged analyses of functional connectivity. AUTHOR SUMMARYIt is generally thought that computations performed by local brain circuits rely on complex neural processes, associated to the flexible waxing and waning of cell assemblies, i.e. ensemble of cells firing in tight synchrony. Although cell assembly formation is inherently and unavoidably dynamical, it is still common to find studies in which essentially "static" approaches are used to characterize this process. In the present study, we adopt instead a temporal network approach. Avoiding usual time averaging procedures, we reveal that hub neurons are not hardwired but that cells vary smoothly their degree of integration within the assembly core. Furthermore, our temporal network framework enables the definition of alternative possible styles of "hubness". Some cells may share information with a multitude of other units but only in an intermittent manner, as "activists" in a flash mob. In contrast, some other cells may share information in a steadier manner, as resolute "lobbyists". Finally, by avoiding averages over pre-imposed states, we show that within each global oscillatory state a rich switching dynamics can take place between a repertoire of many available network states. We thus show that the temporal network framework provides a natural and effective language to rigorously describe the rich spatiotemporal patterns of information sharing instantiated by cell assembly evolution.

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In vivo characterization of neurophysiological diversity in the lateral supramammillary nucleus during hippocampal sharp-wave ripples of adult rats

The extent of the networks that control the genesis and modulation of hippocampal sharp wave ripples (SPW-Rs), which are involved in memory consolidation, remains incompletely understood. Here, we performed a detailed in vivo analysis of single cell firing in the lateral supramammillary nucleus (lSuM) during theta and slow oscillations, including SPW-Rs, in anesthetized rats. We classified neurons as SPW-R-active and SPW-R unchanged according to whether or not they increased their firing during SPW-Rs. We show that lSuM SPW-R-active neurons increase their firing prior SPW-Rs peak power and prior hippocampal pyramidal cell activation. Moreover, lSuM SPW-R-active neurons show increased firing activity during theta and slow oscillations as compared to unchanged-neurons. SPW-R-active neurons are more active during high peak power SPW-Rs, whereas SPW-R-unchanged neurons are more active during long SPW-Rs. These results suggest that a sub-population of lSuM neurons can interact with the hippocampus during SPW-Rs, raising the possibility that the lSuM may modulate memory consolidation.

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Computing Hubs in the Hippocampus and Cortex

Neural computation, which relies on the active storage and sharing of information, occurs within large neuron networks in the highly dynamic context of varying brain states. Whether such functions are performed by specific subsets of neurons and whether they occur in specific dynamical regimes remain poorly understood. Using high density recordings in the hippocampus, medial entorhinal and medial prefrontal cortex of the rat, we identify computing microstates, or discreet epochs, in which specific computing hub neurons perform well defined storage and sharing operations in a brain state-dependent manner. We retrieve a multiplicity of distinct computing microstates within each global brain state, such as REM and nonREM sleep. Half of recorded neurons act as computing hubs in at least one microstate, suggesting that functional roles are not firmly hardwired but dynamically reassigned at the second timescale. We identify sequences of microstates whose temporal organization is dynamic and stands between order and disorder. We propose that global brain states constrain the language of neuronal computations by regulating the syntactic complexity of these microstate sequences.

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Spatio-temporal organization of cell assemblies in Nucleus Reuniens during slow oscillations

The nucleus reuniens (NR) is an important anatomical and functional relay between the medial prefrontal cortex (mPFC) and the hippocampus (HPC). Whether the NR controls neuronal assemblies, a hallmark of information exchange between the HPC and mPFC for memory transfer/consolidation, is not known. Using simultaneous LFP and unit recordings in NR, HPC and mPFC in rats during slow oscillations under anesthesia, we identified a reliable sequential activation of NR neurons at the beginning of UP states, which preceded mPFC ones. NR sequences were spatially organized, from dorsal to ventral NR. Chemical inactivation of the NR disrupted mPFC sequences at the onset of UP states as well as HPC sequences present during sharp-wave ripples. We conclude that the NR contributes to the coordination and stabilization of mPFC and HPC neuronal sequences during slow oscillations, possibly via the early activation of its own sequences. Significance StatementNeuronal assemblies are believed to be instrumental to code/encode/store information. They can be recorded in different brain regions, suggesting that widely distributed networks of networks are involved in such information processing. The prefrontal cortex, the hippocampus and the thalamic nucleus reuniens constitute a typical example of a complex network involved in memory consolidation. In this study, we show that spatially organized cells assemblies are recruited in the nucleus reuniens at the UP state onset during slow oscillations. Nucleus reuniens activity appears to be necessary to the stability of prefrontal cortex and hippocampal cell assembly formation during slow oscillations. This result further highlights the role of the Nucleus Reuniens as a functional hub for exchanging and processing memories.

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