Variations on the theme: focus on cerebellum and emotional processing

Ciapponi, Camilla; Li, Yuhe; Becerra, Diana; Rodarie, Dimitri; Casellato, Claudia; Mapelli, Lisa; D’Angelo, Egidio

doi:10.3389/fnsys.2023.1185752

Cited by 12 publications

(6 citation statements)

References 231 publications

(315 reference statements)

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“…(1) Cognitive domain: The multiscale analysis of circuit operations supports the cerebellar involvement in the main cognitive domains of CIAS, attention, learning, decision-making (D' Angelo and Casali, 2012), akin to the involvement of cerebellum in cognitive, emotional, and behavioral control (Ciapponi et al, 2023; Supplementary Figure S1). ( 2) Processing speed: The cerebellum contributes substantially to mechanisms of CIAS, like processing speed, by allowing mental processing to move from controlled to automatic mode (Wong et al, 2021).…”

Section: Abnormal Neurodevelopmentmentioning

confidence: 95%

“…On the other, the hypothesis of the involvement of the cerebellum in SZ is gaining credit. The cerebellum is involved in multiple aspects of cognitive processing (Schmahmann, 2016;D'Angelo, 2018;D'Angelo, 2019;Schmahmann, 2019;Jacobi et al, 2021;Ciapponi et al, 2023;Nguyen et al, 2023) and is connected functionally and anatomically to brain regions that are core domains of CIAS, such as PFC, basal ganglia, and VTA. Cerebellar alterations can either be primary (genetic and epi-genetic) or secondary (compensatory) in origin and emerge on different scales (Figures 3-6):…”

Section: Summary and Key Findingsmentioning

confidence: 99%

“…The main one is whether the universal cerebellar transform (Ito, 2008;D'Angelo and Casali, 2012) is altered and how, in turn, this impacts cognitive performance in SZ. Related to this is the differentiation of activity and neuromodulation among specific cerebellar regions (Ciapponi et al, 2023). This is particularly pertinent to the posterior lobules, which hold a pivotal role in cognitive processing.…”

Section: Open Issuesmentioning

confidence: 99%

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New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment

Faris,

Pischedda,

Palesi

et al. 2024

Front. Cell. Neurosci.

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Schizophrenia (SZ) is a complex neuropsychiatric disorder associated with severe cognitive dysfunction. Although research has mainly focused on forebrain abnormalities, emerging results support the involvement of the cerebellum in SZ physiopathology, particularly in Cognitive Impairment Associated with SZ (CIAS). Besides its role in motor learning and control, the cerebellum is implicated in cognition and emotion. Recent research suggests that structural and functional changes in the cerebellum are linked to deficits in various cognitive domains including attention, working memory, and decision-making. Moreover, cerebellar dysfunction is related to altered cerebellar circuit activities and connectivity with brain regions associated with cognitive processing. This review delves into the role of the cerebellum in CIAS. We initially consider the major forebrain alterations in CIAS, addressing impairments in neurotransmitter systems, synaptic plasticity, and connectivity. We then focus on recent findings showing that several mechanisms are also altered in the cerebellum and that cerebellar communication with the forebrain is impaired. This evidence implicates the cerebellum as a key component of circuits underpinning CIAS physiopathology. Further studies addressing cerebellar involvement in SZ and CIAS are warranted and might open new perspectives toward understanding the physiopathology and effective treatment of these disorders.

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Section: Abnormal Neurodevelopmentmentioning

confidence: 95%

Section: Summary and Key Findingsmentioning

confidence: 99%

Section: Open Issuesmentioning

confidence: 99%

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New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment

Faris,

Pischedda,

Palesi

et al. 2024

Front. Cell. Neurosci.

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“…Generalizing the current model to simulate more complex behaviours would require extending spatiotemporal representations to multiple scales, e.g., by introducing dendritic processing, synaptic dynamics, additional plasticity rules, and DCN and PC wiring loops [14,45,87,[103][104][105][106][107], as well as consolidation of the synaptic plasticity by sealing of the perineuronal nets [108].…”

Section: Model Assumptionsmentioning

confidence: 99%

Mesoscale simulations predict the role of synergistic cerebellar plasticity during classical eyeblink conditioning

Geminiani,

Casellato,

Boele

et al. 2024

PLoS Comput Biol

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According to the motor learning theory by Albus and Ito, synaptic depression at the parallel fibre to Purkinje cells synapse (pf-PC) is the main substrate responsible for learning sensorimotor contingencies under climbing fibre control. However, recent experimental evidence challenges this relatively monopolistic view of cerebellar learning. Bidirectional plasticity appears crucial for learning, in which different microzones can undergo opposite changes of synaptic strength (e.g. downbound microzones–more likely depression, upbound microzones—more likely potentiation), and multiple forms of plasticity have been identified, distributed over different cerebellar circuit synapses. Here, we have simulated classical eyeblink conditioning (CEBC) using an advanced spiking cerebellar model embedding downbound and upbound modules that are subject to multiple plasticity rules. Simulations indicate that synaptic plasticity regulates the cascade of precise spiking patterns spreading throughout the cerebellar cortex and cerebellar nuclei. CEBC was supported by plasticity at the pf-PC synapses as well as at the synapses of the molecular layer interneurons (MLIs), but only the combined switch-off of both sites of plasticity compromised learning significantly. By differentially engaging climbing fibre information and related forms of synaptic plasticity, both microzones contributed to generate a well-timed conditioned response, but it was the downbound module that played the major role in this process. The outcomes of our simulations closely align with the behavioural and electrophysiological phenotypes of mutant mice suffering from cell-specific mutations that affect processing of their PC and/or MLI synapses. Our data highlight that a synergy of bidirectional plasticity rules distributed across the cerebellum can facilitate finetuning of adaptive associative behaviours at a high spatiotemporal resolution.

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Section: Model Assumptionsmentioning

confidence: 99%

Mesoscale simulations predict the role of synergistic cerebellar plasticity during classical eyeblink conditioning

Geminiani

Casellato

Boele

et al. 2023

Preprint

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According to Marr’s motor learning theory, plasticity at the parallel fibre to Purkinje cells synapse (pf-PC) is the main substrate responsible for learning sensorimotor contingencies under climbing fibre control. However, the discovery of multiple forms of plasticity distributed over different cerebellar circuit synapses prompts to remap the cerebellar learning sites. Here, we have simulated classical eyeblink conditioning (CEBC) using an advanced spiking cerebellar model embedding upbound and downbound modules that are subject to multiple plasticity rules. Simulations show that synaptic plasticity regulates the cascade of precise spiking patterns spreading throughout the cerebellar cortex and cerebellar nuclei. CEBC was supported by plasticity in both the pf-PC synapses and in the feedforward inhibitory loop passing through the molecular layer interneurons (MLIs), but only the combined switch-off of both sites of plasticity compromised learning significantly. By differentially engaging climbing fibre information and related forms of synaptic plasticity, both modules contributed to generate a well-timed conditioned response, but it was the downbound module that played the major role in in this process. The outcomes of our simulations closely align with the behavioural and electrophysiological phenotypes of mutant mice suffering from cell-specific mutations that affect processing of their PC or MLI synapses. Our data highlight that a synergy of bidirectional plasticity rules distributed across the cerebellum facilitate finetuning of adaptive associative behaviors at a high spatiotemporal resolution.

show abstract

Variations on the theme: focus on cerebellum and emotional processing

Cited by 12 publications

References 231 publications

New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment

New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment

Mesoscale simulations predict the role of synergistic cerebellar plasticity during classical eyeblink conditioning

Mesoscale simulations predict the role of synergistic cerebellar plasticity during classical eyeblink conditioning

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