Biology subjects

Rondi-Reig, L.

Publications and source records attributed to Rondi-Reig, L..

7 recordsLinked to original sources

bioRxiv2023

The cerebellum promotes sequential foraging strategies and contributes to the directional modulation of hippocampal place cells

The cerebellum contributes to goal-directed navigation abilities and place coding in the hippocampus. Here we investigated its contribution to foraging strategies. We recorded hippocampal neurons in mice with impaired PKC-dependent cerebellar functions (L7-PKCI) and in their littermate controls while they performed a task where they were rewarded for visiting a subset of hidden locations. We found that L7-PKCI and control mice developed different foraging strategies: while control mice repeated spatial sequences to maximize their rewards, L7-PKCI mice persisted to use a random foraging strategy. Sequential foraging was associated with more place cells exhibiting theta-phase precession and theta rate modulation. Recording in the dark showed that PKC-dependent cerebellar functions controlled how self-motion cues contribute to the selectivity of place cells for both position and direction. Thus, the cerebellum contributes to the development of optimal sequential paths during foraging, possibly by controlling how self-motion and theta signals contribute to place cells coding. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/526971v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@1a4e344org.highwire.dtl.DTLVardef@449ab8org.highwire.dtl.DTLVardef@9aa45org.highwire.dtl.DTLVardef@89c110_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Excessive self-grooming of Shank3 mutant mice is associated with gene dysregulation and imbalance between the striosome and matrix compartments in the striatum

Autism is characterised by atypical social communication and stereotyped behaviours. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are detected in 1-2% of patients with autism and intellectual disability (ID), but the mechanisms underpinning the symptoms remain largely unknown. Here, we characterised the behaviour of Shank3{Delta}11/{Delta}11 mice from three to twelve months of age. We observed decreased locomotor activity, increased stereotyped self-grooming and modification of socio-sexual interaction compared to wild-type littermates. We then used RNAseq on four brain regions of the same animals to identify differentially expressed genes (DEG). DEGs were identified mainly in the striatum and were associated with synaptic transmission (e.g. Grm2, Dlgap1), G-protein-signalling pathways (e.g. Gnal, Prkcg1, and Camk2g), as well as excitation/inhibition balance (e.g. Gad2). Downregulated and upregulated genes were enriched in the gene clusters of medium-sized spiny neurons expressing the dopamine 1 (D1-MSN) and the dopamine 2 receptor (D2-MSN), respectively. Several DEGs (Cnr1, Gnal1, Gad2, and Drd4) were reported as striosome markers. By studying the distribution of the glutamate decarboxylase GAD65, encoded by Gad2, we showed that the striosome compartment of Shank3{Delta}11/{Delta}11 mice was enlarged and displayed much higher expression of GAD65 compared to wild-type mice. Altogether, these results indicate altered gene expression in the striatum of SHANK3-deficient mice and strongly suggest, for the first time, that the impairment in behaviour of these mice are related to an imbalance striosomes/matrix.

neuroscience↗

bioRxiv2021

Cerebellar Control of a Unitary Head Direction Sense

Head direction (HD) cells, key neuronal elements in the mammalians navigation system, are hypothesized to act as a continuous attractor network, in which temporal coordination between cell members is maintained under different brain states or external sensory conditions, resembling a unitary neural representation of direction. Whether and how multiple identified HD signals in anatomically separate HD cell structures are part of a single and unique attractor network is currently unknown. By manipulating the cerebellum, we identified pairs of thalamic and retrosplenial HD cells that lose their temporal coordination in the absence of external sensory drive, while the neuronal coordination within each of these brain regions remained intact. Further, we show that distinct cerebellar mechanisms are involved in the stability of direction representation depending on external sensory conditions. These results put forward a new role for the cerebellum in mediating stable and coordinated HD neuronal activity toward a unitary thalamocortical representation of direction.

neuroscience↗

bioRxiv2021

Delta oscillations coordinate intra-cerebellar and cerebello-hippocampal network dynamics during sleep

During sleep, the widespread coordination of neuronal oscillations across both cortical and subcortical brain regions is thought to support various physiological functions, including memory consolidation. However, how sleep-related activity within the brains largest sensorimotor structure, the cerebellum, is multiplexed with well described sleep-related mechanisms in regions such as the hippocampus remains unknown. To address this gap in knowledge, we simultaneously recorded from the dorsal hippocampus and three distinct regions of the cerebellum (Crus I, lobule VI and lobules II/III) during natural murine sleep. We found that LFP oscillations are coordinated between the two structures in a sleep-stage specific manner. Particularly during non-REM sleep, prominent delta frequency coherence was observed between lobule VI and hippocampus. We additionally observed that non-REM associated hippocampal sharp wave ripple activity can drive discrete LFP modulation in all the recorded cerebellar regions, with the shortest latency effects observed in lobule VI. We also describe discrete phasic sharp potentials, synchronized across cerebellar regions, which were strongly phase locked to the peak of ongoing cerebellar delta oscillations and found in greatest numbers during REM. These phasic sharp potentials recorded within the cerebellar cortex were found to be phase-locked to the trough of the hippocampal theta oscillation, further suggesting cross-structural coordination. During REM, cerebellar delta oscillation phase significantly modulated hippocampal theta frequency, and this effect was greatest when phasic sharp potentials were most abundant. Within all three cerebellar regions, prominent LFP oscillations were observed at both low (delta, <4 Hz) and very high frequencies (~ 250 Hz) during non-REM and REM sleep. Intra-cerebellar cross-frequency analysis revealed that delta frequency oscillations strongly modulate those in the very high frequency range. Together, these results reveal multiple candidate physiological mechanisms to support offline, bi-directional interaction within distributed cerebello-hippocampal networks. In particular, we describe a prominent cerebellar delta oscillation, which appears to act as a temporal coordinator of cerebellar activity at both local (intra-cerebellar) and distributed (cerebello-hippocampal) network levels.

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bioRxiv2019

SUSD4 Controls Activity-Dependent Degradation of AMPA Receptor GLUA2 and Synaptic Plasticity

Fine control of protein stoichiometry at synapses underlies brain function and plasticity. How proteostasis is controlled independently for each type of synaptic protein in a synapse-specific and activity-dependent manner remains unclear. Here we show that SUSD4, a complement-related transmembrane protein, binds the AMPA receptor subunit GLUA2 and controls its activity-dependent degradation. Several proteins with known roles in the regulation of AMPA receptor turnover, in particular ubiquitin ligases of the NEDD4 subfamily, are identified as SUSD4 binding partners. SUSD4 is expressed by many neuronal populations starting at the time of synapse formation. Loss-of-function of Susd4 in the mouse prevents long-term depression at cerebellar synapses, and leads to impairment in motor coordination adaptation and learning. Our findings reveal that activity-dependent synaptic plasticity relies on a transmembrane CCP domain-containing protein that regulates the degradation of specific substrates. This mechanism potentially accounts for the role of SUSD4 mutations in neurodevelopmental diseases.

neuroscience↗

bioRxiv2018

Anatomical and physiological foundations of cerebello-hippocampal interactions

Multiple lines of evidence suggest that functionally intact cerebello-hippocampal interactions are required for appropriate spatial processing. However, how the cerebellum anatomically and physiologically engages with the hippocampus to sustain such interactions remains unknown. Using rabies virus as retrograde transneuronal tracer, we reveal that the dorsal hippocampus receives input from topographically restricted and disparate regions of the cerebellum. By simultaneously recording local field potential from both the dorsal hippocampus and anatomically connected cerebellar regions, we additionally demonstrate that the two structures interact, in a behaviorally dynamic manner, through subregion-specific synchronization of neuronal oscillations in the 6-12Hz frequency range. Together, these results reveal a novel neural network macro-architecture through which we can understand how a brain region classically associated with motor control, the cerebellum, may influence hippocampal neuronal activity and related functions, such as spatial navigation.

neuroscience↗

bioRxiv2017

Cerebellar volume in autism: Meta-analysis and analysis of the ABIDE cohort

Cerebellar volume abnormalities have been often suggested as a possible endophenotype for autism spectrum disorder (ASD). We aimed at objectifying this possible alteration by performing a systematic meta-analysis of the literature, and an analysis of the Autism Brain Imaging Data Exchange (ABIDE) cohort. Our meta-analysis sought to determine a combined effect size of ASD diagnosis on different measures of the cerebellar anatomy, as well as the effect of possible factors of variability across studies. We then analysed the cerebellar volume of 328 patients and 353 controls from the ABIDE project. The meta-analysis of the literature suggested a weak but significant association between ASD diagnosis and increased cerebellar volume (p=0.049, uncorrected), but the analysis of ABIDE did not show any relationship. The studies in the literature were generally underpowered, however, the number of statistically significant findings was larger than expected. Although we could not provide a conclusive explanation for this excess of significant findings, our analyses would suggest publication bias as a possible reason. Finally, age, sex and IQ were important sources of cerebellar volume variability, however, independent of autism diagnosis.

neuroscience↗