Biology subjects

Scherrer, J. R.

Publications and source records attributed to Scherrer, J. R..

3 recordsLinked to original sources

bioRxiv2026

Millisecond-scale, single-neuron credit assignment in a songbird

Learning an adaptive behavior requires identifying which actions, in which contexts, lead to particular outcomes. This problem of credit assignment is fundamental to both biological and artificial learners1-3. Songbird vocal learning presents a particularly demanding credit assignment problem: singing is controlled by millisecond-precise activity of thousands of motor neurons4-7, but song quality is encoded by a diffuse, delayed dopamine signal with more than an order of magnitude less temporal precision8-12. It is unknown how precisely the songbird brain can drive changes in specific premotor neurons at precise times to improve song performance. Here we show that the cortico-basal ganglia circuit thought to underlie songbird vocal learning can learn with millisecond-scale temporal precision and single-neuron spatial precision. We find that playing disruptive auditory feedback contingent on the activity of a targeted neuron in a vocal variability-generating premotor nucleus at one time in the song causes adaptive changes in the activity of the targeted neuron with 3.2 ms temporal precision. Learned changes in firing rate are not observed in uncorrelated neighboring neurons, thus revealing single-neuron spatial precision. These findings challenge the prevailing view of dopamine-mediated reinforcement as slow and imprecise13-15, and redefine our understanding of the limits of credit assignment in the brain.

neuroscience↗

bioRxiv2021

A Novel Optical Design Enabling Lightweight and Large Field-Of-View Head-Mounted Microscopes

We present a novel fluorescence microscope light path that enables imaging, during free behavior, of thousands of neurons in mice and hundreds of neurons in juvenile songbirds. The light path eliminates traditional illumination optics, allowing for head-mounted microscopes that have both a lower weight and a larger field-of-view (FOV) than previously possible. Using this light path, we designed two microscopes: one optimized for field-of-view ([~]4 mm FOV; 1.4 g), and the other optimized for weight (1.0 mm FOV; 1.0 g).

neuroscience↗

bioRxiv2020

Recording the age of RNA with deamination

Transcriptional programs implemented by cells often consist of complex temporal features, but current approaches to single-cell RNA sequencing only provide limited information about the dynamics of gene expression. Here, we present RNA timestamps, a method for inferring the age of individual RNAs in a sequencing-based readout by leveraging RNA editing. Timestamped RNAs include a RNA reporter motif that accumulates A to I edits over time, allowing the age of the RNA to be inferred with hour-scale accuracy. By combining observations of multiple timestamped RNAs driven by the same promoter, we are able to infer when in the past the promoter was active. We demonstrate that the system can infer the presence and timing of multiple past transcriptional events, with no prior knowledge. Finally, we apply this method to cluster single cells according to the times at which a particular transcriptional program was activated. RNA timestamps thus suggest a new approach for incorporating temporal information into RNA sequencing workflows.

synthetic biology↗