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International audience; Cerebellum plays a role in the regulation of cognitive processes. Cerebellar alterations could explain cognitive impairments in schizophrenia. We describe the case of a 50 years old patient with schizophrenia whom underwent cerebellar transcranial direct current stimulation (tDCS). In order to study the effect of cerebellar stimulation on cognitive functions, the patient underwent a neuropsychological assessment and an eyeblink conditioning (EBC) protocol. Although the effect of brain stimulation cannot be only assessed in a single-case study, our results suggest that cerebellar stimulation may have an effect on a broad range of cognitive functions typically impaired in patients with schizophrenia, including verbal episodic, short term, and working memory. In addition to neuropsychological tests, we evaluated the cerebellar function by performing EBC before and after tDCS. Our data suggest that tDCS can improve EBC. Further clinical trials are required for better understanding of how cerebellar stimulation can modulate cognitive processes in patients with schizophrenia and healthy controls.

Speech is a complex sensorimotor skill, and vocal learning involves both the basal ganglia and the cerebellum. These subcortical structures interact indirectly through their respective loops with thalamo-cortical and brainstem networks, and directly via subcortical pathways, but the role of their interaction during sensorimotor learning remains undetermined. While songbirds and their song-dedicated basal ganglia-thalamo-cortical circuitry offer a unique opportunity to study subcortical circuits involved in vocal learning, the cerebellar contribution to avian song learning remains unknown. We demonstrate that the cerebellum provides a strong input to the song-related basal ganglia nucleus in zebra finches. Cerebellar signals are transmitted to the basal ganglia via a disynaptic connection through the thalamus and then conveyed to their cortical target and to the premotor nucleus controlling song production. Finally, cerebellar lesions impair juvenile song learning, opening new opportunities to investigate how subcortical interactions between the cerebellum and basal ganglia contribute to sensorimotor learning., eLife digest Human infants learn to speak by imitating the speech of adults around them. Over time, they learn to coordinate movements of their vocal cords and breathing muscles to produce specific sounds. Juvenile songbirds go through a similar process while learning to sing. Fledglings mimic adult birds and each other as they learn to produce their own songs. Songbirds are therefore often used as a model for how the brain drives vocal learning – whether of speech or song. Circuits made up of similar brain regions support vocal learning in infants and in songbirds. These regions include areas of cortex, the outermost layer of the mammalian brain, as well as structures deep below the cortex. The latter include the basal ganglia, a set of structures that help mammals learn and perform fine motor skills. But there is one brain region that has been implicated in vocal learning in infants but not in songbirds. Known as the cerebellum or ‘little brain’, this structure also helps with planning and performing movements. Anatomical studies in songbirds suggest a connection between the cerebellum and song-related circuits. But a direct role in birdsong has never been shown. Pidoux et al. now demonstrate that stimulating the cerebellum in anaesthetized zebra finches activates basal ganglia neurons involved in song learning. This activation spreads through a song-related circuit to neurons controlling the vocal cords. Disrupting the cerebellum, by contrast, makes it harder for juvenile birds to imitate adult song. This is the first direct evidence for a role of the cerebellum in the acquisition of birdsong. Beyond vocal learning, the results shed light on the circuits that support motor learning more generally. They also suggest that we can use songbirds to study the cerebellum and its interactions with the basal ganglia. Abnormal interactions between these regions occur in movement disorders such as Parkinson's disease. Studying these interactions in the healthy mammalian brain should provide clues to the pathology behind these conditions.

Depolarization-induced suppression of inhibition (DSI) is a form of short-term plasticity of GABAergic synaptic transmission that is found in cerebellar Purkinje cells and hippocampal CA1 pyramidal cells. DSI involves the release of a calcium-dependent retrograde messenger by the somatodendritic compartment of the postsynaptic cell. Both glutamate and endogenous cannabinoids have been proposed as retrograde messenger.Here we show that, in cerebellar parasagittal slices, type 1 cannabinoid receptors (CB1Rs) are expressed at high levels in axons of GABAergic interneurons and in presynaptic terminals onto Purkinje cells. Application of the cannabinoid antagonist AM-251 (500 nm) leads to the abolition of the DSI of evoked currents (eIPSCs) recorded in paired recordings and to a strong reduction of the DSI of TTX-insensitive miniature events (mIPSCs) recorded from Purkinje cells. Furthermore, the CB1R agonist WIN 55–212,2 (5 μm) induces a presynaptic inhibition of synaptic currents similar to that occurring during DSI, as well as an occlusion of DSI after stimulation of Purkinje cells. Moreover, WIN 55–212,2 reduces the calcium transients evoked in presumed presynaptic varicosities by short trains of action potentials.Our results indicate that DSI is mediated by the activation of presynaptic CB1Rs and that an endogenous cannabinoid is a likely candidate retrograde messenger in this preparation. They further suggest that DSI involves distinct presynaptic modifications for eIPSCs and mIPSCs, including an inhibition of action potential-evoked calcium rises.