In addition to its established role in sensory integration and motor control, the cerebellum is rapidly emerging as a prominent regulator of emotional functions and has been implicated in affective disorders. However, the mechanistic link between the cerebellum and emotion is lacking. The short-latency functional connections that have been identified between the cerebellum and amygdala- a structure crucial for emotion - raise the exciting, yet untested, hypothesis that a cerebellum-amygdala pathway communicates information important for emotion processing. The major obstacle in rigorously testing this hypothesis has been the lack of knowledge about the anatomy and synaptic connectivity of the cerebellar-amygdala circuit. The central goal of this project is to delineate the connectivity between these brain regions. To achieve this goal, we will employ a powerful combination of anatomical and optophysiological tools that will provide for the first time the wiring diagram of the cerebellar-amygdala circuit and begin to map its functionality. We will also validate for the first time the potential of a recently developed in vitro approach to report synaptic connectivity in complex monosynaptic circuits in vivo. We will further extend applicability of the approach to the study of disynaptic circuits, for which no tools are currently available to directly visualize synapses. Application of this approach to the cerebellar-amygdala circuit will facilitate identification of synaptic partners and can reveal connectivity patterns, which are important determinants of local computations and information flow in a circuit. A successful outcome will pave the way for spatiotemporally precise manipulations of the cerebellar-amygdala pathway, which are absolutely necessary in order to decipher the contributions of this circuit to emotion processing and memory in health and disease.
The traditional view of the cerebellum as solely a motor control center is being challenged by evidence favoring a broader regulatory role that includes emotional functions. These functions likely depend on the interaction between the cerebellum and the amygdala; however, these interactions and their disruption in affective disorders are not understood. The central goal of this proposal is to delineate the anatomical and functional connections between the cerebellum and amygdala, in order to provide the necessary basis for understanding how cerebellar malfunction leads to deficits in emotion regulation and memory.
