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

AbstractFear 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.

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Bidirectional control of fear memories by cerebellar neurons projecting to the ventrolateral periaqueductal grey

Nature Communications ◽

10.1038/s41467-020-18953-0 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Jimena Laura Frontera ◽

Hind Baba Aissa ◽

Romain William Sala ◽

Caroline Mailhes-Hamon ◽

Ioana Antoaneta Georgescu ◽

...

Keyword(s):

Prefrontal Cortex ◽

Associative Learning ◽

Prediction Error ◽

Functional Role ◽

Extinction Learning ◽

Brain Areas ◽

Periaqueductal Grey ◽

Cerebellar Neurons ◽

Emotional System

Abstract Fear conditioning is a form of associative learning that is known to involve different 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 memories, indicating an important role in the association of the conditioned and unconditioned stimuli, a function consistent with vlPAG encoding of fear prediction error. Moreover, FN-vlPAG projections also modulate extinction learning. We also found a FN-parafascicular thalamus pathway, which may relay cerebellar influence to the amygdala and modulates anxiety behaviors. Overall, our results reveal multiple contributions of the cerebellum to the emotional system.

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Role of gonadal hormones in anxiety and fear memory formation and inhibition in male mice

Physiology & Behavior ◽

10.1016/j.physbeh.2011.12.016 ◽

2012 ◽

Vol 105 (5) ◽

pp. 1168-1174 ◽

Cited By ~ 32

Author(s):

Carmel M. McDermott ◽

Dana Liu ◽

Laura A. Schrader

Keyword(s):

Fear Memory ◽

Gonadal Hormones ◽

Memory Formation ◽

Male Mice ◽

Anxiety And Fear

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Role of Amygdala-Infralimbic Cortex Circuitry in Glucocorticoid-Induced Facilitation of Auditory Fear Memory Extinction

Basic and Clinical Neuroscience Journal ◽

10.32598/bcn.2021.2161.1 ◽

2021 ◽

pp. 1-22

Author(s):

Masoomeh Dadkhah ◽

◽

Abbas Ali Vafaei ◽

Ali Rashidy-Pour ◽

Parnia Trahomi ◽

...

Keyword(s):

Critical Role ◽

Fear Memory ◽

Fear Extinction ◽

Freezing Behavior ◽

Extinction Training ◽

Male Rats ◽

Memory Extinction ◽

The Right ◽

Fear Expression

Purpose: The basolateral amygdala (BLA) and infralimbic area (IL) of medial prefrontal cortex (mPFC) are two inter-connected brain structures that mediate both fear memory expression and extinction. Besides the well-known role of the BLA in the acquisition and expression of fear memory, projections from IL to BLA inhibit fear expression and have a critical role in fear extinction. However, the details of IL-BLA interaction remain unclear. Here, we aimed to investigate the role of functional reciprocal interactions between BLA and IL in mediating fear memory extinction. Methods: Using lidocaine (LID), male rats underwent unilateral or bilateral inactivation of the BLA and then unilateral intra-IL infusion of CORT, prior to extinction training of auditory fear conditioning paradigm. Freezing behavior was reported as an index for the measurement of conditioned fear. Infusions were performed before the extinction training, allowing to examine the effects on fear expression and also further extinction memory. Experiments 1-3 investigated the effects of left or right infusion of CORT into IL, and LID unilaterally into BLA on fear memory extinction. Results: Results showed that intra-IL infusion of CORT in the right hemisphere reduced freezing behavior when administrated before the extinction training. Auditory fear memory extinction was impaired by asymmetric inactivation of BLA and CORT infusion in the right IL; however, the same effect was not observed with symmetric inactivation of BLA. Conclusion: It is concluded that that the IL-BLA neural circuit may provide additional evidence to contribution of this circuit in auditory fear extinction. This study demonstrate dissociable roles for right or left BLA in subserving the auditory fear extinction. Our finding also raise the possibility that left BLA-IL circuitry may contribute in mediating auditory fear memory extinction via underlying mechanisms, however further research is required.

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11 Functional Role of Brain Areas

The Electrophysiology of Intellectual Functions ◽

10.1159/000409778 ◽

2015 ◽

pp. 118-133

Keyword(s):

Functional Role ◽

Brain Areas

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Whatever next? Predictive brains, situated agents, and the future of cognitive science

Behavioral and Brain Sciences ◽

10.1017/s0140525x12000477 ◽

2013 ◽

Vol 36 (3) ◽

pp. 181-204 ◽

Cited By ~ 1630

Author(s):

Andy Clark

Keyword(s):

Prediction Error ◽

Functional Role ◽

Perception And Action ◽

Cortical Processing ◽

Top Down ◽

Special Contribution ◽

Sensory Inputs ◽

Target Article ◽

Science Of Mind

AbstractBrains, it has recently been argued, are essentially prediction machines. They are bundles of cells that support perception and action by constantly attempting to match incoming sensory inputs with top-down expectations or predictions. This is achieved using a hierarchical generative model that aims to minimize prediction error within a bidirectional cascade of cortical processing. Such accounts offer a unifying model of perception and action, illuminate the functional role of attention, and may neatly capture the special contribution of cortical processing to adaptive success. This target article critically examines this “hierarchical prediction machine” approach, concluding that it offers the best clue yet to the shape of a unified science of mind and action. Sections 1 and 2 lay out the key elements and implications of the approach. Section 3 explores a variety of pitfalls and challenges, spanning the evidential, the methodological, and the more properly conceptual. The paper ends (sections 4 and 5) by asking how such approaches might impact our more general vision of mind, experience, and agency.

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