Biology subjects

Popa, D.

Publications and source records attributed to Popa, D..

10 recordsLinked to original sources

bioRxiv2026

Coordinated cerebellar-midbrain activity for predictive signaling during fear learning in mice

Learning from experience to assess threat is crucial for survival and mental health. This function is known to involve several midbrain areas, notably the ventrolateral periaqueductal grey (vlPAG) and dorsal raphe nuclei (DRN). Recently it has been shown that fear learning involves projections from the cerebellar fastigial nucleus (FN) to the vlPAG. Here, we show using simultaneous single-unit recordings during fear conditioning that a subset of vlPAG/DRN and FN neurons acquire responses to conditioned cues following learning. Strikingly, these populations exhibit firing covariance and directional functional interactions consistent with their collaboration to the response to cues predicting threat. We also demonstrated the reciprocal monosynaptic connectivity between vlPAG/DRN and FN supporting the interactions between these structures. Together, our findings demonstrate shared dynamical activity within a network integrating midbrain and cerebellar computations during fear learning.

neuroscience↗

bioRxiv2025

Offline cerebello-cortico-striatal dynamics predict motor strategy exploration and retention in skill learning

Learning a motor skill requires exploring multiple possible solutions to find and retain an optimal strategy1-3. The exploration and consolidation of the motor strategy are usually considered to be segregated respectively between task practice and rest periods4-7. Here we show that two types of offline reactivations of neuronal representations of locomotor strategies in a brain-wide motor circuit are associated with exploration and retention. During short rests between trials, replays of these brainwide representations predict subsequent shifts in strategies indicating that distributed offline processes participate in strategy exploration. Shifts in strategy are consolidated, and their retention follows population reactivation in cerebellar sleep spindles and stabilization of cerebello-cerebral functional connectivity patterns, consistent with the role of spindles in brain plasticity. Overall, motor strategy optimization and consolidation are supported by two intertwined but distinct types of offline distributed reactivation events involving interregional interactions.

neuroscience↗

bioRxiv2024

Fine decomposition of rodent behavior via unsupervised segmentation and clustering of inertial signals

Decomposing behavior into elementary components remains a central challenge in computational neuroethology. The current standard in laboratory animals involves multi-view video tracking, which, while providing unparalleled access to full-body kinematics, imposes environmental constraints, is data-intensive, and has limited scalability. We present an alternative approach using inertial sensors, which capture high-resolution, environment-independent, and compact three-dimensional kinematic data, and are commonly integrated into rodent neurophysiological devices. Our analysis pipeline leverages unsupervised, computationally efficient change-point detection to break down inertial time series into variable-length, statistically homogeneous segments. These segments are then grouped into candidate behavioral motifs through high-dimensional, model-based probabilistic clustering. We demonstrate that this approach achieves detailed rodent behavioral mapping using head inertial data. Identified motifs, corroborated by video recordings, include orienting movements, grooming components, locomotion, and olfactory exploration. Higher-order behavioral structures can be accessed by applying a categorical hidden Markov model to the motif sequence. Additionally, our pipeline detects both overt and subtle motor changes in a mouse model of Parkinsons disease and levodopa-induced dyskinesia, highlighting its value for behavioral phenotyping. This methodology offers the possibility of conducting high-resolution, observer-unbiased behavioral analysis at minimal computational cost from easily scalable and environmentally unconstrained recordings.

animal behavior and cognition↗

bioRxiv2024

Multiple Functions of Cerebello-Thalamic Neurons in Learning and Offline Consolidation of a Motor Skill in mice.

Motor skill learning is a complex and gradual process that involves the cortex and basal ganglia, both crucial for the acquisition and long-term retention of skills. The cerebellum, which rapidly learns to adjust the movement, connects to the motor cortex and the striatum primarily via the ventral and intralaminar thalamus respectively. Here, we evaluated the contribution of cerebellar neurons projecting to these thalamic nuclei in a skilled locomotion task in mice. Using a targeted chemogenetic inhibition that preserves the motor abilities, we found that cerebellar nuclei neurons projecting to the intralaminar thalamus contribute to learning and expression, while cerebellar nuclei neurons projecting to the ventral thalamus contribute to offline consolidation. Asymptotic performance, however, required each type of neurons. Thus, our results show that cerebellar neurons belonging to two parallel cerebello-thalamic pathways play distinct, but complementary, roles functioning on different timescales and both necessary for motor skill learning.

neuroscience↗

bioRxiv2022

Microglial TNFα controls GABAAR plasticity, slow waves and memory consolidation during sleep

Microglia sense the changes in their environment. How microglia actively translate these changes into suitable cues to adapt brain physiology is unknown. We reveal an activity-dependent regulation of cortical inhibitory synapses by microglia, driven by purinergic signaling acting on P2RX7 and mediated by microglia-derived TNF. We demonstrate that sleep induces microglia-dependent synaptic enrichment of GABAARs in a manner dependent on microglial TNF and P2RX7. We further show that microglia-specific depletion of TNF alters slow waves during NREM sleep and blunt memory consolidation in sleep-dependent learning tasks. Together, our results reveal that microglia orchestrate sleep-intrinsic plasticity of synaptic GABAARs, sculpt sleep slow waves and support memory consolidation.

neuroscience↗

bioRxiv2021

Cerebellar stimulations prevent Levodopa-induced dyskinesia in mice and normalize brain activity

Chronic Levodopa therapy, the gold-standard treatment of Parkinsons Disease (PD), leads to the emergence of involuntary movements, called levodopa-induced dyskinesia (LID). Cerebellar stimulations have been shown to decrease LID severity in PD patients. Here, in order to determine how cerebellar stimulations induce LID alleviation, we performed daily short trains of optogenetic stimulations of Purkinje cells (PC) in freely moving mice. We demonstrated that these stimulations are sufficient to suppress LID or even prevent their development. This symptomatic relief is accompanied by the normalization of aberrant neuronal discharge in the cerebellar nuclei, the motor cortex and the parafascicular thalamus. Inhibition of the cerebello-parafascicular pathway counteracted the beneficial effect of cerebellar stimulations. Moreover, cerebellar stimulations reversed plasticity in D1 striatal neurons and normalized the overexpression of FosB, a transcription factor causally linked to LID. These findings demonstrate LID alleviation and prevention by daily PC stimulations, which restore the function of a wide brain motor network, and may be valuable for LID treatment.

neuroscience↗

bioRxiv2020

Dual contributions of cerebellar-thalamic networks to learning and offline consolidation of a complex motor task.

The contribution of cerebellum to motor learning is often considered to be limited to adaptation, a short-timescale tuning of reflexes and previous learned skills. Yet, the cerebellum is reciprocally connected to two main players of motor learning, the motor cortex and the basal ganglia, via the ventral and midline thalamus respectively. Here, we evaluated the contribution of cerebellar neurons projecting to these thalamic nuclei in a skilled locomotion task in mice. In the cerebellar nuclei, we found task-specific neuronal activities during the task, and lasting changes after the task suggesting an offline processing of task-related information. Using pathway-specific inhibition, we found that dentate neurons projecting to the midline thalamus contribute to learning and retrieval, while interposed neurons projecting to the ventral thalamus contribute to the offline consolidation of savings. Our results thus show that two parallel cerebello-thalamic pathways perform distinct computations operating on distinct timescales in motor learning.

neuroscience↗

bioRxiv2020

Bidirectional control of fear memories by the cerebellum through the ventrolateral periaqueductal grey

Fear conditioning is a form of associative learning that is known to involve brain areas, notably the amygdala, the prefrontal cortex and the periaqueductal grey (PAG). Here, we describe the functional role of pathways that link the cerebellum with the fear network. We found that the cerebellar fastigial nucleus (FN) sends glutamatergic projections to vlPAG that synapse onto glutamatergic and GABAergic vlPAG neurons. Chemogenetic and optogenetic manipulations revealed that the FN-vlPAG pathway controls bi-directionally the strength of the fear memory, indicating a role in the association of the conditioned and unconditioned stimuli, a function consistent with vlPAG encoding of fear prediction error. In addition, we found that a FN - thalamic parafascicular nucleus pathway, which may relay cerebellar influence to the amygdala, is involved in anxiety and fear expression but not in fear memory. Our results reveal the contributions to the emotional system of the cerebellum, which exerts a potent control on the strength of the fear memory through excitatory FN-vlPAG projections.

neuroscience↗

bioRxiv2020

Functional abnormalities in the cerebello-thalamic pathways in an animal model of dystonia

Dystonia is often associated with functional alterations in the cerebello-thalamic pathways, which have been proposed to contribute to the disorder by propagating pathological firing patterns to the forebrain. Here, we examined the function of the cerebello-thalamic pathways in a model of DYT25 dystonia, mice carrying a heterozygous invalidation of Gnal gene which notably disrupts striatal function, exhibiting dystonic movements and postures following systemic or striatal administration of oxotremorine. Theta-burst optogenetic stimulations of the cerebellar nuclei evoked a potentiation of the responses to cerebellar stimulations in the thalamus and motor cortex in WT mice, without evident motor function disruption. In contrast, theta burst stimulations evoked a depression of these responses only in dystonia-manifesting Gnal+/- mice after oxotremorine administration, decreased the disabling dystonia attacks, and increased normal active wake behaviour in Gnal+/- mice. The cerebellum could thus offer a gateway for a corrective treatment of motor impairments in dystonia including striatal dysfunction. One sentence summaryA mouse model of DYT25 dystonia, carrying a Gnal mutation disrupting striatal neurotransmission, exhibits anomalous cerebello-thalamic plasticity in the non-manifesting state, but theta-burst cerebellar stimulations during cholinergic-induced dystonia depress the cerebello-thalamic transmission and reduce the severity of the motor symptoms.

neuroscience↗

bioRxiv2018

Active intermixing of indirect and direct neurons builds the striatal mosaic

The striatum controls behaviors via the activity of direct and indirect pathway projection neurons (dSPN and iSPN) that are intermingled in all compartments. While such mosaic ensures the balanced activity of the two pathways, how it emerges remains largely unknown. Here, we show that both SPN populations are specified embryonically and progressively intermix through multidirectional iSPN migration. Using conditional mutants of the dSPN-specific transcription factor Ebf1, we found that inactivating this gene impaired selective dSPN properties, including axon pathfinding, whereas molecular and functional features of iSPN were preserved. Remarkably, Ebf1 mutation disrupted iSPN/dSPN intermixing, resulting in an uneven distribution. Such architectural defect was selective of the matrix compartment, revealing that intermixing is a parallel process to compartment formation. Our study reveals that, while iSPN/dSPN specification is largely independent, their intermingling emerges from an active migration of iSPN, thereby providing a novel framework for the building of striatal architecture.

neuroscience↗