Quantitative Biosciences Thesis Proposal

Sana Aminnaji

School of Biological Sciences

Prospective coding of task state in cerebellar Purkinje cell complex spikes

Wednesday, October 7, 2026, at 9:00 am

In Person Location: Cherry Emerson 204

Meeting Link

Open to the Community

Advisor:

Dr. Farzaneh Najafi (School of Biological Sciences)

Committee Members:

Dr. Timothy C. Cope (School of Biological Sciences)

Dr. Audrey Sederberg (School of Psychology, School of Physics)

Dr. Hannah Choi (School of Mathematics)

Dr. Dobromir Rahnev (School of Psychology)

Abstract:

The cerebellum is the brain's canonical learning machine. In the classical account, climbing fibers from the inferior olive deliver an error signal to Purkinje cells, evoking complex spikes that trigger plasticity and correct the next movement. This account is retrospective: the complex spike reports what has already gone wrong. My thesis asks whether these same signals also look forward — whether, before an expected event, Purkinje cell activity reflects what the animal expects and how confidently it expects it. I test this using two-photon calcium imaging of Purkinje cell dendrites in behaving mice, across two paradigms that share animals and imaging field while manipulating certainty by design.

First, I characterize how mice solve a timing task and how complex spikes relate to their internal estimate of its rule. Head-fixed mice produce a two-push joystick sequence whose required interval alternates unpredictably between short and long blocks, so the animal must infer which rule is in force. Mice adapt at trial, block and session timescales, and state-space modeling shows they switch among a small number of timing strategies rather than drifting continuously. In the same animals, complex spike responses separate into groups with distinct sensory, movement and reward profiles that reproduce the known microzonal organization of climbing fiber input. In the quiet interval between trials — containing no stimulus, no required movement and no reward — activity in the movement- and reward-related groups is lower before trials that will be rewarded than before trials that will not, in every animal and every task variant, and above a directly measured slow-drift baseline.

Second, I ask whether this signature survives without movement or reward. The same mice passively viewed or heard a four-element stimulus sequence under fixed inter-stimulus intervals, where the timing of the next stimulus is certain, and jittered intervals, where it is not. Preliminary results indicate that activity preceding a stimulus is suppressed under certainty, in the same class of response group, with nothing to move toward and nothing to earn. I will extend this to the full dataset and test whether the depth of suppression scales with how predictable the upcoming stimulus is.

Third, I will test whether this activity is used rather than merely present. Using optogenetic inactivation of cerebellar output restricted to the interval before a trial, with interleaved within-session controls, I will ask whether the behavioral adjustment that normally follows depends on it, and whether that dependence is specific to the anticipatory window.

Together, these aims ask whether the climbing fiber sits not at the end of a learning loop reporting error, but at its beginning, expressing expectation.