Dr. Giovannucci, while at Princeton University, developed hardware, software, behavioral and physiological tools to enable chronic long-term imaging and stimulation in the brain of awake behaving rodents. For the first time, he chronically imaged two types of cerebellar neurons (Purkinje and Granule cells). This opened up the possibility to follow neuronal types previously inaccessible to measurement (Giovannucci et al., 2017), while isolating dendritic signals from specific populations (collaboration with Medina Lab, Najafi, Giovannucci et al, 2014, Najafi, Giovannucci et al., 2015) and shedding light on coding issues. The discovery in (Giovannucci et al., 2017) is particularly relevant since it uncovers evidence against a fifty-year-old theory of neural coding (Marr-Albus).
Uncovering coding properties of cerebellar granule with calcium imaging
Cerebellar granule cells, which constitute half the brain’s neurons, supply Purkinje cells with contextual information necessary for motor learning, but how they encode this information is unknown. Two-photon microscopy was employed to track neural activity over multiple days of cerebellum-dependent eyeblink (Pavlovian) conditioning in mice. We found that granule cell populations acquire a dense representation of the anticipatory eyelid movement, tracking trial by trial learning via a redundant code representation. The project demonstrated that a predictive signal about the upcoming movement is widely available at the input stage of the cerebellar cortex, as required by forward models of cerebellar control and sequence learning.
Giovannucci, A.*, Badura, A.*, … & Wang, S.S-H. (2017). Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning. Nature neuroscience, 20(5), 727. Article.
Granule cells raw data (left), denoised (center) and denoised with neuropil removed (right).
Error/teaching signal properties in the cerebellum.
Climbing fiber (CF) are axons thought to carry an error signal that instructs cerebellar learning via calcium signaling. The findings (in collaboration with Wang and Medina lab) show that CF-induced calcium transients in Purkinje cell dendrites of awake mice are enhanced when the trigger is a sensory event. This indicates that sensory stimulation can modulate the plasticity signal strength during cerebellar learning.
Two-photon imaging of cerebellar Purkinje cells in awake behaving mouse
Najafi, F.*, Giovannucci, A.*, … & Medina, J. F. (2014). Sensory-driven enhancement of calcium signals in individual Purkinje cell dendrites of awake mice. Cell reports, 6(5), 792-798. Article.
Najafi, F., Giovannucci, … & Medina, J. F. (2014). Coding of stimulus strength via analog calcium signals in Purkinje cell dendrites of awake mice. Elife, 3, e03663. Article.