Modulation of cerebellar cortical, cerebellar nuclear and vestibular nuclear activity using alternating electric currents.

Introduction: Cerebellar transcranial alternating current stimulation (ctACS) has shown promise as a therapeutic modality for treating a variety of neurological disorders, and for affecting normal learning processes. Yet, little is known about how electric fields induced by applied currents affect cerebellar activity in the mammalian cerebellum under in vivo conditions. Methods: Alternating current (AC) stimulation with frequencies from 0.5 to 20 Hz was applied to the surface of the cerebellum in anesthetized rats. Extracellular recordings were obtained from Purkinje cells (PC), cerebellar and vestibular nuclear neurons, and other cerebellar cortical neurons. Results and discussion: AC stimulation modulated the activity of all classes of neurons. Cerebellar and vestibular nuclear neurons most often showed increased spike activity during the negative phase of the AC stimulation. Purkinje cell simple spike activity was also increased during the negative phase at most locations, except for the cortex directly below the stimulus electrode, where activity was most often increased during the positive phase of the AC cycle. Other cortical neurons showed a more mixed, generally weaker pattern of modulation. The patterns of Purkinje cell responses suggest that AC stimulation induces a complex electrical field with changes in amplitude and orientation between local regions that may reflect the folding of the cerebellar cortex. Direct measurements of the induced electric field show that it deviates significantly from the theoretically predicted radial field for an isotropic, homogeneous medium, in both its orientation and magnitude. These results have relevance for models of the electric field induced in the cerebellum by AC stimulation.

Current Opinions and Consensus for Studying Tremor in Animal Models.

Tremor is the most common movement disorder; however, we are just beginning to understand the brain circuitry that generates tremor. Various neuroimaging, neuropathological, and physiological studies in human tremor disorders have been performed to further our knowledge of tremor. But, the causal relationship between these observations and tremor is usually difficult to establish and detailed mechanisms are not sufficiently studied. To overcome these obstacles, animal models can provide an important means to look into human tremor disorders. In this manuscript, we will discuss the use of different species of animals (mice, rats, fruit flies, pigs, and monkeys) to model human tremor disorders. Several ways to manipulate the brain circuitry and physiology in these animal models (pharmacology, genetics, and lesioning) will also be discussed. Finally, we will discuss how these animal models can help us to gain knowledge of the pathophysiology of human tremor disorders, which could serve as a platform towards developing novel therapies for tremor.

Improving temporal cognition by enhancing motivation.

Increasing motivation can positively impact cognitive performance. Here we employed a cognitive timing task that allows us to detect changes in cognitive performance that are not influenced by general activity or arousal factors such as the speed or persistence of responding. This approach allowed us to manipulate motivation using three different methods; molecular/genetic, behavioral and pharmacological. Increased striatal D2Rs resulted in deficits in temporal discrimination. Switching off the transgene improved motivation in earlier studies, and here partially rescued the temporal discrimination deficit. To manipulate motivation behaviorally, we altered reward magnitude and found that increasing reward magnitude improved timing in control mice and partially rescued timing in the transgenic mice. Lastly, we manipulated motivation pharmacologically using a functionally selective 5-HT2C receptor ligand, SB242084, which we previously found to increase incentive motivation. SB242084 improved temporal discrimination in both control and transgenic mice. Thus, while there is a general intuitive belief that motivation can affect cognition, we here provide a direct demonstration that enhancing motivation, in a variety of ways, can be an effective strategy for enhancing temporal cognition. Understanding the interaction of motivation and cognition is of clinical significance since many psychiatric disorders are characterized by deficits in both domains.