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.

The mediodorsal nucleus (MD) represents just one piece of a complex relay structure situated within the brain, called the thalamus. MD is characterized by its robust interconnections with other brain areas, especially with limbic-related structures. Given the close anatomo-functional relationship between the MD and the limbic system, this particular thalamic nucleus can directly influence various affective behaviors and participate in cognition. In this work, we review data collected from multiple anatomical studies conducted in rodent, human, and non-human primates, highlighting the complexity of this structure and of the neural networks in which it takes part. We provide proof that the MD is involved in the unification of several anatomical structures, being able to process the information and influence the activity in numerous cortical and subcortical neural circuits. Moreover, we uncover intrinsic and extrinsic mechanisms that offer MD the possibility to execute and control specific high functions of the nervous system. The collected data indicate the great importance of the MD in the limbic system and offer relevant insight into the organization of thalamic circuits that support MD functions.

The execution of voluntary muscular activity is controlled by the primary motor cortex, together with the cerebellum and basal ganglia. The synchronization of neural activity in the intracortical network is crucial for the regulation of movements. In certain motor diseases, such as dystonia, this synchrony can be altered in any node of the cerebello-cortical network. Questions remain about how the cerebellum influences the motor cortex and interhemispheric communication. This research aims to study the interhemispheric cortical communication between the motor cortices during dystonia, a neurological movement syndrome consisting of sustained or repetitive involuntary muscle contractions. We pharmacologically induced lateralized dystonia to adult male albino mice by administering low doses of kainic acid on the left cerebellar hemisphere. Using electrocorticography and electromyography, we investigated the power spectral densities, cortico-muscular, and interhemispheric coherence between the right and left motor cortices, before and during dystonia, for five consecutive days. Mice displayed lateralized abnormal motor signs, a reduced general locomotor activity, and a high score of dystonia. The results showed a progressive interhemispheric coherence decrease in low-frequency bands (delta, theta, beta) during the first 3 days. The cortico-muscular coherence of the affected side had a significant increase in gamma bands on days 3 and 4. In conclusion, lateralized cerebellar dysfunction during dystonia was associated with a loss of connectivity in the motor cortices, suggesting a possible cortical compensation to the initial disturbances induced by cerebellar left hemisphere kainate activation by blocking the propagation of abnormal oscillations to the healthy hemisphere. However, the cerebellum is part of several overly complex circuits, therefore other mechanisms can still be involved in this phenomenon.

Motor coordination and motor learning are well-known roles of the cerebellum. Recent evidence also supports the contribution of the cerebellum to the oscillatory activity of brain networks involved in a wide range of disorders. Kainate, a potent analog of the excitatory neurotransmitter glutamate, can be used to induce dystonia, a neurological movement disorder syndrome consisting of sustained or repetitive involuntary muscle contractions, when applied on the surface of the cerebellum. This research aims to study the interhemispheric cortical communication between the primary motor cortices after repeated kainate application on cerebellar vermis for five consecutive days, in mice. We recorded left and right primary motor cortices electrocorticograms and neck muscle electromyograms, and quantified the motor behavior abnormalities. The results indicated a reduced coherence between left and right motor cortices in low-frequency bands. In addition, we observed a phenomenon of long-lasting adaptation with a modification of the baseline interhemispheric coherence. Our research provides evidence that the cerebellum can control the flow of information along the cerebello-thalamo-cortical neural pathways and can influence interhemispheric communication. This phenomenon could function as a compensatory mechanism for impaired regional networks.