Cerebellar molecular layer interneurons are dispensable for cued and contextual fear conditioning

Marshall-Phelps, Katy Lh; Riedel, Gernot; Wulff, Peer; Wołoszynowska-Fraser, Marta Urszula

doi:10.1038/s41598-020-76729-4

Cited by 7 publications

(4 citation statements)

References 50 publications

(78 reference statements)

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“…These studies suggest that MLI-PC synapses play a role in auditory fear conditioning by regulating GABA release and endocannabinoid degradation ( Figure 2 ). A recent study, however, showed that mice with functional removal of GABA A -mediated signaling at MLI-PC synapses showed intact fear learning and memory (Marshall-Phelps et al, 2020 ), suggesting that the role of MLI-PC synapse in fear learning and memory remains to be further investigated.…”

Section: The Role Of the Cerebellum In Fear Learning And Memory In Ro...mentioning

confidence: 99%

Cerebellar Circuits for Classical Fear Conditioning

Hwang

Kim

Lee

2022

Front. Cell. Neurosci.

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Accumulating evidence indicates that the cerebellum is critically involved in modulating non-motor behaviors, including cognition and emotional processing. Both imaging and lesion studies strongly suggest that the cerebellum is a component of the fear memory network. Given the well-established role of the cerebellum in adaptive prediction of movement and cognition, the cerebellum is likely to be engaged in the prediction of learned threats. The cerebellum is activated by fear learning, and fear learning induces changes at multiple synaptic sites in the cerebellum. Furthermore, recent technological advances have enabled the investigation of causal relationships between intra- and extra-cerebellar circuits and fear-related behaviors such as freezing. Here, we review the literature on the mechanisms underlying the modulation of cerebellar circuits in a mammalian brain by fear conditioning at the cellular and synaptic levels to elucidate the contributions of distinct cerebellar structures to fear learning and memory. This knowledge may facilitate a deeper understanding and development of more effective treatment strategies for fear-related affective disorders including post-traumatic stress or anxiety related disorders.

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Section: The Role Of the Cerebellum In Fear Learning And Memory In Ro...mentioning

confidence: 99%

Cerebellar Circuits for Classical Fear Conditioning

Hwang

Kim

Lee

2022

Front. Cell. Neurosci.

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“…Whilst Sacchetti et al (2004) mice deficient in parallel fibre-Purkinje cell synaptic potentiation had impaired fear response to conditioned stimuli (Sacchetti et al, 2004), Han et al (2021) further revealed that signal transducer and activator of transcription 3 (STAT3)-dependent molecular regulation of glutamatergic input to Purkinje cells is indispensable for proper expression of fear memory. In contrast, GABAergic input to Purkinje cells mediated via molecular layer interneurons is not required for both fear memory acquisition and recall (Marshall-Phelps et al, 2020).…”

Section: Intra Cerebellar Micro-circuit Mechanisms Supporting a Role ...mentioning

confidence: 89%

Cerebellar contributions to fear-based emotional processing: relevance to understanding the neural circuits involved in autism

Couto-Ovejero,

Ye,

Kind

et al. 2023

Front. Syst. Neurosci.

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Cerebellar networks have traditionally been linked to sensorimotor control. However, a large body of evidence suggests that cerebellar functions extend to non-motor realms, such as fear-based emotional processing and that these functions are supported by interactions with a wide range of brain structures. Research related to the cerebellar contributions to emotional processing has focussed primarily on the use of well-constrained conditioning paradigms in both human and non-human subjects. From these studies, cerebellar circuits appear to be critically involved in both conditioned and unconditioned responses to threatening stimuli in addition to encoding and storage of fear memory. It has been hypothesised that the computational mechanism underlying this contribution may involve internal models, where errors between actual and expected outcomes are computed within the circuitry of the cerebellum. From a clinical perspective, cerebellar abnormalities have been consistently linked to neurodevelopmental disorders, including autism. Importantly, atypical adaptive behaviour and heightened anxiety are also common amongst autistic individuals. In this review, we provide an overview of the current anatomical, physiological and theoretical understanding of cerebellar contributions to fear-based emotional processing to foster further insights into the neural circuitry underlying emotional dysregulation observed in people with autism.

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“…The proposed theory could be experimentally tested when genetic access to IN types are acquired. Disturbing IN1 alone or both INs would not disrupt LTD, as it keeps the CF and PF inputs intact 53 . Disturbing IN2 alone would disrupt LTD, as it destroys the disinhibitory pathway.…”

Section: Discussionmentioning

confidence: 99%

A cerebellar disinhibitory circuit supports synaptic plasticity

Park,

Gim,

Bahn

et al. 2023

Preprint

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How does the cerebellum learn how to control motion? The cerebellar motor learning critically depends on the long-term depression of the synapses between granule cells and Purkinje cells, which encode motor commands and inhibitory modifications to motor outputs, respectively, for simultaneous granule cell inputs and climbing fibre inputs, the latter of which encode the error signals1-3. However, recent studies have revealed that inhibitory inputs to Purkinje cells may disrupt long-term depression4-8, and it is not clear how long-term depression can occur without disruption. In search of a clue, we investigated the synaptic connectivity among the neurons reconstructed from serial electron microscopy images of the cerebellar molecular layer9,10. We discovered synapses between climbing fibres and a subset of inhibitory interneurons, which synapse onto the remaining interneurons, which in turn synapse onto Purkinje cells. Such connectivity redefines the interneuron types, which have been defined morphologically or molecularly11-13. Together with climbing fibres to Purkinje cell connections, those cell types form a feedforward disinhibitory circuit14. We argued that this circuit secures long-term depression by suppressing inhibition whenever climbing fibre input is provided and long-term depression needs to occur15, and we validated the hypothesis through a computational model. This finding implies a general principle of circuit mechanism in which disinhibition supports synaptic plasticity16,17.

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Cerebellar molecular layer interneurons are dispensable for cued and contextual fear conditioning

Cited by 7 publications

References 50 publications

Cerebellar Circuits for Classical Fear Conditioning

Cerebellar Circuits for Classical Fear Conditioning

Cerebellar contributions to fear-based emotional processing: relevance to understanding the neural circuits involved in autism

A cerebellar disinhibitory circuit supports synaptic plasticity

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