Effect of Transcranial Stimulation on Cerebellar Activity
Stimulation of the cerebellum has seen a surge of clinical studies in recent years reporting that it improves motor learning, cognitive and emotional processes. However, to date, very few studies have addressed the cellular and circuit level mechanisms by which the cerebellar activity can be modulated using non-invasive methods of stimulation such as transcranial electrical stimulation (tES). In conjunction with the Sahin laboratory at NJIT we have begun a series of studies to determine the effect of applied electric fields on cerebellar activity. We are investigating both the immediate effects on cerebellar output (e.g., how such fields modulate the firing patterns of cerebellar nuclear neurons) and effects that may affect plasticity, and thus underlie long-term changes in cerebellar function that could be the basis for tES's therapeutic actions.
Patterns of Synchronous Complex Spike Activity
The inferior olive projects to the cerebellum as the olivocerebellar system, and in particular, is the source of the climbing fibers that synapse onto Purkinje cells. Activity in the olivocerebellar system leads to bursts of action potentials, known as complex spikes, in Purkinje cells. The characteristics of complex spike activity are rather distinct. In particular, complex spikes occur at a relatively low rate of around 1 Hz in any one Purkinje cell. However, when they occur, they tend to do so synchronously across large ensembles of Purkinje cells.
A major focus of the lab has been to characterize the spatial patterns of synchronous complex spike activity across the cerebellum and investigate the mechanisms by which these patterns are generated. In the past our work has provided evidence that synchronous complex spike activity is a consequence of gap junction coupling amongst inferior olivary cells, and conduction velocity tuning of olivary axons. We have also investigated the roles of GABA and glutamate within the inferior olive in shaping the specific patterns of synchronous activity.
A major focus of the lab has been to characterize the spatial patterns of synchronous complex spike activity across the cerebellum and investigate the mechanisms by which these patterns are generated. In the past our work has provided evidence that synchronous complex spike activity is a consequence of gap junction coupling amongst inferior olivary cells, and conduction velocity tuning of olivary axons. We have also investigated the roles of GABA and glutamate within the inferior olive in shaping the specific patterns of synchronous activity.
Synaptic Control of the Cerebellar Nuclei
A major issue that we are currently addressing is the synaptic control of cerebellar nuclear cells. The cerebellar nuclei are the major output station of the cerebellum, and the majority of their input arises from the Purkinje cells of the overlying cerebellar cortex. Thus, by understanding how activity from Purkinje cells modulate that of the cerebellar nuclear neurons we hope to elucidate how outgoing motor commands from the cerebellum are formed. We use large scale microelectrode arrays to record simultaneously from Purkinje and cerebellar nuclear cells in order to identify synaptically-connected cell pairs and determine the correlation between their firing patterns. Optogenetic techniques are used to actively manipulate Purkinje cell activity to provide causal evidence of the relationships revealed by the multielectrode recordings.