In vivo two-photon fluorescence imaging studies of cerebellar-dependent learning and memory. Classical or Pavlovian conditioning is one of the simplest and earliest known forms of associative memory. A modern version of such conditioning that is suitable for use in mice and that depends critically on cerebellar function is classical eyeblink conditioning, in which a subject is trained to blink in response to a conditioning stimulus such as an audible tone. Many theories of how this cerebellar-dependent form of learning occurs focus on cerebellar Purkinje neurons, which exhibit highly regular anatomical patterns of neural connections. The Schnitzer lab has shown that they can image up to ~50 Purkinje cells simultaneously in live mice using in vivo two-photon fluorescence imaging. By combining in vivo imaging and electrophysiological techniques with behavioral, computational, and trans-synaptic circuit tracing approaches, the lab seeks to understand the neural circuit dynamics in the cerebellar cortex that underlie learning, memory, and forgetting.

Fiber optic fluorescence microendoscopy. The Schnitzer group has recently invented two forms of fiber optic fluorescence imaging, respectively termed one- and two-photon fluorescence microendoscopy, which enable minimally invasive in vivo imaging of cells in deep (brain) areas that have been inaccessible to conventional microscopy. Such areas that the group has studied include the hippocampus, thalamus, and inner ear. The group has developed the capability for repeated microendoscopy imaging of hippocampal neurons and capillaries over the long-term using a chronic mouse preparation. This preparation has proved highly applicable for extended imaging studies over the progression of brain disease in animal model systems. Such ability to image cells deep within the live mammalian brain also promises to permit studies of how cellular properties are impacted by environment, training, or life experience. Moreover, the Schnitzer group has created portable, miniaturized microendoscopy devices based on flexible fiber optics for use in freely moving mice. The Schnitzer group now seeks to develop and apply these microendoscopy techniques to applications in both basic neurobiology and clinical settings, and has begun to examine human nervous tissues.