bioRxiv Science⌕ Search

Biology subjects

Pompili, M. N.

Publications and source records attributed to Pompili, M. N..

9 recordsLinked to original sources

Intra- and Interhemispheric Signatures of Criticality at the Onset of Synchronization

The cerebral cortex must flexibly alternate between locally segregated activity that supports specialization and long-range interactions that enable integration. How cortical networks balance these competing demands remains unclear. We propose that fluctuations around a critical point between ordered and disordered phases provide a natural framework to understand coordinated neuronal activity across scales. Using simultaneous spiking recordings from the left and right prefrontal cortex (PFC) of freely behaving rats, we found that signatures of criticality emerged at the onset of neuronal synchronization, both locally within individual hemispheres and globally across the combined population. Over time, cortical activity explored a continuum of intra-and inter-hemispheric synchrony levels, including states in which neurons were locally desynchronized yet maintained interhemispheric coupling. A computational model operating near its critical regime reproduced these empirical patterns, capturing the characteristic relationship between local and long-range coordination. These results suggest that cortical networks achieve flexible transitions between local and global computation by fluctuating around a critical regime.

neuroscience↗

The Connectome Modulates Critical Brain Dynamics Across Local and Global Scales

Neuronal activity in the brain has been hypothesized to operate near criticality-a dynamical regime poised between order and disorder that maximizes information processing, adaptability, and dynamic range. While criticality has been extensively studied at local scales (within neuronal populations) and at global scales (across interacting brain regions), the interplay between these levels remains poorly understood. Here, we propose a multiscale computational framework that bridges local and global criticality within a single, mechanistic model. At the mesoscopic level, individual brain regions are represented by neural mass models tuned near the transition between asynchronous and synchronous regimes. These regions are then coupled via an empirically derived mouse connectome to investigate how structural connectivity shapes the emergence of large-scale coordination. We show that (i) local near critical dynamics for an isolated brain region can be faithfully reproduced within a mean-field model framework, (ii) local distance to criticality is modulated by long-range coupling, (iii) whole-brain simulations reveal non-linear gradients of timescales and heterogeneous shifts towards/away from local criticality, and (iv) global criticality, manifested in scale-free avalanche distributions and optimal functional connectivity, emerges when local populations are locally tuned near criticality and coupled within an optimal range. These results demonstrate that local and global criticality are dynamically intertwined but not directly aligned, and that their relationship depends on the underlying structural connectivity. Our multiscale modeling framework provides a tractable tool for generating testable hypotheses on how brain criticality co-arises across scales and how it may be modulated in health and disease.

neuroscience↗

A novel critic signal in identified midbrain dopaminergic neurons of mice training inoperant tasks

Classically, midbrain dopaminergic neuron activity is triggered by unexpected rewards, then, upon learning, by reward-predictive conditioned stimuli. When expected rewards are withheld, firing is inhibited. This activity occurs too late to directly affect the neuronal circuitry underlying decision-making, inspiring the development of temporal difference (TD) reinforcement learning models. To test for more timely critical feedback during decision-making and learning, we recorded optogenetically identified dopaminergic, putative GABAergic and other neurons of the ventral tegmental area (VTA) and substantia nigra pars compacta in mice training in visual and olfactory discrimination tasks. The mice often adhered to unrewarded and untrained task strategies (e.g., spatial alternation) rather than making random choices. In order to probe for reward/punishment predictive activity, a delay was imposed between nose-poke choices and signals for reward or punishment. As animals performed below criterion levels, dopaminergic and other neurons firing rates signaled correct versus incorrect choices immediately after choices, but prior to the onset of trial outcome signals. Thus, this activity signaled the rewarded rule even as the mice performed other unrewarded strategies. Putative GABAergic neurons fired during nose-poke choices, potentially reducing network activity prior to reward prediction signals. This reward predictive activity could serve as a critic signal expressed immediately after choices are made, priming the network for canonical DA reward/punishment activity, facilitating network functional modifications. This is consistent with a role for dopamine in arbitration between brain modules to choose among diverse strategies during goal-directed behavior. These findings suggest extensions of theoretical formulations interpreting dopaminergic neuronal activity. Significance statementModels of dopaminergic influence on circuit modifications during learning evoke mechanisms dealing with the delay between neural activity leading up to choices, and when the reinforcing outcome actually occurs. Here, as mice trained in sensory discrimination tasks with a delay between behavioral responses and reinforcement signals, they performed several unrewarded behavioral strategies. Simultaneously, dopaminergic nuclei neurons instead reflected the current task rule, predicting whether the choice was correct or not, providing an immediate "critic" signal prior to canonical trial outcome signals. This provides evidence for brain mechanisms to overcome innate or acquired habits to perform behaviors optimizing positive outcomes.

neuroscience↗

Detection of cell assemblies in high-density extracellular electrophysiological recordings

Cell assemblies, i.e., concurrently active groups of neurons, likely underlie neural processing for higher brain functions. Recent technological progress has enabled large-scale recording of neuronal activity, permitting the exploration and analysis of cell assembly dynamics. This review aims to provide both conceptual insights and practical knowledge pertaining to principal methodologies used for detecting cell assemblies in the last fifteen years. The goal is to assist readers in selecting and comparing various protocols to optimize their data processing and analysis pipeline. Each algorithm is explained with its fundamental principles, their application in neuroscience for cell assembly detection, and illustrated with published studies. Recognizing the similarities, advantages, and drawbacks of diverse methodologies may pave the way for developing new procedures for cell assembly identification to facilitate future endeavors in the understanding of brain activity.

neuroscience↗

Differential encoding of fear learning and fear expression in the ventral and dorsal hippocampus

Classically, the dorsal and ventral hippocampus are thought to play distinct roles in fear conditioning, with the dorsal hippocampus primarily handling information about environmental cues and contexts, and the ventral hippocampus more involved in emotional processing. Both functions are essential for the learning and expression of conditioned fear responses, but how these processes are integrated remains largely unexplored. In this study, we simultaneously recorded single-unit activity from the dorsal and ventral hippocampus during fear conditioning to identify the neural dynamics that may underlie these processes and their integration. As fear expression emerged, shifts in neural firing patterns were observed in both regions, with a stronger shift in ventral hippocampal activity, as expected. However, contrary to the prevailing view of the ventral hippocampus as central to anxiety and fear regulation, fear expression-related neuronal responses were surprisingly more predominant in the dorsal hippocampus. In contrast, ventral hippocampal neuronal activity was more closely linked with the acquisition of conditioned fear. These features were combined in cell assemblies that emerged during fear conditioning, composed of both dorsal fear expression-responsive neurons and ventral fear learning-responsive cells. These multifactorial engrams, distributed along the hippocampal dorso-ventral axis, provide a potential substrate for integrating fear acquisition and expression, thereby coordinating associative learning.

neuroscience↗

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.

neuroscience↗

Rhythmic oscillations in the midbrain dopaminergic nuclei in mice

Dopamine release in the forebrain by midbrain ventral tegmental nucleus (VTA) and substantia nigra pars compacta (SNpc) neurons is implicated in reward processing, goal-directed learning, and decision-making. Rhythmic oscillations of neural excitability underlie coordination of network processing, and have been reported in these dopaminergic nuclei at several frequency bands. This paper provides a comparative characterization of several frequencies of oscillations of local field potential and single unit activity, highlighting some behavioral correlates. We recorded from optogenetically identified dopaminergic sites in mice training in operant olfactory and visual discrimination tasks. Rayleigh and Pairwise Phase Consistency (PPC) analyses revealed some VTA/SNc neurons phase-locked to each frequency range, with fast spiking interneurons (FSIs) prevalent at 1-2.5 Hz (slow) and 4 Hz bands, and dopaminergic neurons predominant in the theta band. More FSIs than dopaminergic neurons were phase-locked in the slow and 4 Hz bands during many task events. The highest incidence of phase-locking in neurons was in the slow and 4 Hz bands, and occurred during the delay between the operant choice and trial outcome (reward or punishment) signals. These data provide a basis for further examination of rhythmic coordination of activity of dopaminergic nuclei with other brain structures, and its impact for adaptive behavior.

neuroscience↗

Flexible communication between cell assemblies and 'reader' neurons

Cell assemblies are considered fundamental units of brain activity, underlying diverse functions ranging from perception to memory and decision-making. Cell assemblies have generally been studied in relation to specific stimuli or actions, but this approach does not readily extend to more abstract constructs. An alternative approach is to assess cell assemblies without making reference to external variables, and instead focus on internal brain processes -- by defining assemblies by their endogenous ability to effectively elicit specific responses in downstream ( reader) neurons. However, this compelling idea currently lacks experimental support. Here, we provide evidence for assembly-reader communication. Reader activation was genuinely collective, functionally selective, yet flexible, implementing both pattern separation and completion. These processes occurred at the time scale of membrane integration, synaptic plasticity and gamma oscillations. Finally, assembly-reader couplings were selectively modified upon associative learning, indicating that they were plastic and could become bound to behaviorally relevant variables. These results support cell assemblies as an endogenous mechanism for brain function.

neuroscience↗

Post-trauma behavioral phenotype predicts vulnerability to fear relapse after extinction

Current treatments for trauma-related disorders remain ineffective for many patients. Here, we modeled interindividual differences in post-therapy fear relapse with a novel ethologically relevant trauma recovery paradigm. After traumatic fear conditioning, male rats underwent fear extinction while foraging in a large enriched arena, permitting the expression of a wide spectrum of behaviors, assessed by an automated pipeline. This multidimensional behavioral assessment revealed that post-conditioning fear response profiles clustered into two groups, respectively characterized by active vs. passive fear responses. After trauma, some animals expressed fear by freezing, while others darted, as if fleeing from danger. Remarkably, belonging to the darters or freezers group predicted differential levels of vulnerability to fear relapse after extinction. Moreover, genome-wide transcriptional profiling revealed that these groups differentially regulated specific sets of genes, some of which have previously been implicated in anxiety and trauma-related disorders. Our results suggest that post-trauma behavioral phenotypes and the associated epigenetic landscapes can serve as markers of fear relapse susceptibility, and thus may be instrumental for future development of more effective treatments for psychiatric patients.

neuroscience↗