We see a friend and wave hello, we hear a bird's song and lift our heads towards the tree branch, we smell a fresh pastry and rush into the bakery. As we navigate the world, we are confronted with a wealth of sensory information that we constantly have to detect, integrate, and filter to generate an appropriate behavioral response. How we respond requires the interplay of numerous brain regions and depends on many factors, including the context in which a sensory stimulus occurred, previous experience, and internal state.

The cellular and molecular correlates for these external and internal factors include the release of context-dependent neuromodulators, altered neuronal activity, synaptic plasticity, and gene expression. On a circuit level, these mechanisms regulate the local integration of information on varying time scales and ultimately control output to other brain regions. We aim to identify the molecular, cellular, and circuit mechanisms that allow the cerebellum, an area of the brain that receives rich multisensory input, to dynamically respond to physiological context. We focus on the neuromodulatory systems involved in autonomic and metabolic regulation, social interactions, and sex-specific signaling. Using genetic and viral approaches, electrophysiology, and behavioral testing, we examine the anatomical and molecular basis of neuromodulation in the mouse cerebellum, identify the circuit elements that respond to modulatory signals, and elucidate how this alters cerebellar output.

Our ultimate goal is to better understand how context-dependent modulation of cerebellar function controls motor behavior, cognition, and emotion in health and disease.

2022

Candelabrum cells are ubiquitous cerebellar cortex interneurons with specialized circuit properties.Osorno T*, Rudolph S*, Nguyen T, Kozareva V, Nadaf NM, Norton A, Macosko EZ, Lee WA, Regehr WG.  Nat Neurosci. 2022 May 16. doi: 10.1038/s41593-022-01057-x. *equal contribution

2021

A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types. Kozareva V, Martin C, Osorno T, Rudolph S, Guo C, Vanderburg C, Nadaf N, Regev A, Regehr WG, Macosko E.  Nature. 2021 Oct;598(7879):214-219. doi: 10.1038/s41586-021-03220-z.

Purkinje cell outputs selectively inhibit a subset of unipolar brush cells in the input layer of the cerebellar cortex;
Guo C, Rudolph S, Neuwirth ME, Regehr WG; Elife. 2021 Aug 9;10:e68802. doi: 10.7554/eLife.68802.

Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network

Yap EL, Pettit NL, Davis CP, Nagy MA, Harmin DA, Golden E, Dagliyan O, Lin C, Rudolph S, Sharma N, Griffith EC, Harvey CD, Greenberg ME

Nature, 2021 Feb;590(7844):115-121.

2020

Rudolph S, Guo C, Pashkovski S, Osorno T, Gillis W, Krauss JM, Nyitrai H, Flaquer I, El-Rifai M, Datta RS, Regehr WG 

Cerebellum-Specific Deletion of the GABAA Receptor δ Subunit Leads to Sex-Specific Disruption of Behavior

Cell Reports, 2020 Nov 3;33(5):108338. 

2019

Kozareva V, Martin C, Osorno T, Rudolph S, Guo C, Vanderburg C, Nadaf N, Regev A, Regehr WG, Macosko E

A transcriptomic atlas of the mouse cerebellum reveals regional specializations and novel cell types

BioRxiv, https://doi.org/10.1101/2020.03.04.976407 

Pieper A*, Rudolph S*, Wieser GL, Götze T, Mießner H, Yonemasu T, Yan K, Tzvetanova I, Duverge Castillo B, Bode U, Bormuth I, Wadiche JI, Schwab MH, Goebbels S. *equal contribution 

NeuroD2 controls inhibitory circuitry formation in the molecular layer of the cerebellum.

Sci Rep. 2019 Feb 5;9(1):1448  

2018

Tsai PT, Rudolph S, Guo C, Ellegood J, Gibson JM, Schaeffer SM, Mogavero J, Lerch JP, Regehr WG, Sahin M. 

Sensitive Periods for Cerebellar Mediated Autistic-like Behaviors. 

Cell Reports. 2018; 25(2), 357-367.e4

2017

Tang JC, Rudolph S, Cepko CL.

Viral Delivery of GFP-Dependent Recombinases to the Mouse Brain. 

Methods Mol Biol. 2017; 1642:109-126. PMID: 28815497

2016

Tang JC, Drokhlyansky E, Etemad B, Rudolph S, Guo B, Wang S, Ellis EG, Li JZ, Cepko CL. 

Detection and manipulation of live antigen-expressing cells using conditionally stable nanobodies. 

Elife, 2016 May 20;5. pii: e15312.

Witter L*, Rudolph S*, Pressler RT, Lahlaf SI, Regehr WG. 

Purkinje Cell Collaterals Enable Output Signals from the Cerebellar Cortex to Feed Back to Purkinje Cells and Interneurons.

*equal contribution 

Neuron, 2016 Jul 20;91(2):312-9. 

Guo C, Witter L, Rudolph S, Elliott HL, Ennis KA, Regehr WG. 

Purkinje Cells Directly Inhibit Granule Cells in Specialized Regions of the Cerebellar Cortex. 

Neuron, 2016 Sep 21;91(6):1330-41.

2015

Rudolph S, Tsai MC, von Gersdorff H, Wadiche JI. 

The ubiquitous nature of multivesicular release. 

Trends in Neuosciences, 2015, Jul;38(7): 428-38.

Rudolph S., Thanawala M. 

Location matters: Somatic and dendritic SK channels answer to distinct calcium signals. 

Journal of Neurophysiology, 2015, 2015 Jul;114(1):1-5

Rudolph S, Hull C, Regehr WG. 

Active Dendrites and Differential Distribution of Calcium Channels Enable Functional Compartmentalization of Golgi Cells. 

Journal of Neuroscience, 2015, 35(47):15492-504. 

Tang JC, Rudolph S, Dhande OS, Abraira VE, Choi S, Lapan SW, Drew IR, Drokhlyansky E, Huberman AD, Regehr WG, Cepko CL. 

Cell type-specific manipulation with GFP-dependent Cre recombinase. 

Nat Neuroscience, 2015, 18(9):1334-41. 

Earlier 

Coddington LT, Rudolph S, Vande Lune P, Overstreet-Wadiche L, Wadiche JI, 

Spillover Activation of Inhibition Segregates Interneuronal Subpopulations in the Cerebellar Cortex. 

Neuron 2013, 78(6):1050-62. 

Leuner K, Li W, Amaral MD, Rudolph S, Calfa G, Schuwald AM, Harteneck C, Inoue T, Pozzo-Miller L. 

Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca(2+) -permeable TRPC6 channels. 

Hippocampus, 2012, 23(1):40-52 

Rudolph S, Overstreet-Wadiche L, Wadiche JI, 

Desynchronization of multivesicular release enhances Purkinje cell output. 

Neuron, 2011, 70(5):991-1004 

Nadrigny F, Li D, Kemnitz K, Ropert N, Koulakoff A, Rudolph S, Vitali M, Giaume C, Kirchhoff F, Oheim M. 

Systematic colocalization errors between acridine orange and EGFP in astrocyte vesicular organelles. 

Biophysical Journal, 2007; 93(3):969-80.