The Kottmann Lab Investigates 3 Questions:

1) What is the structural correlate underlying incremental skill improvement?
2) Why is the CNS not running out of the structural substrates for skill learning ?
3) What is the most rudimentary mechanism that allows motor skill learning?


How can an empty slate be filled with the instructions for skilled movement without an intrinsic model of the skill to be learned?


Sensory feedback and the calculation of prediction errors are essential for skill learning.  While synaptic tagging and Hebbian plasticity are critical for learning, so is the generation of functional noise. Processes that tag and strengthen neuronal connections must operate therefore in fine balance with processes of structural diversification that might lead to altered connectivity. We view neurons as multilingual signaling centers that communicate with their targets using multiple means in parallel to regulate these divergent processes.

We use conditional genetic gain and loss of function and gene expression tracer strategies in conjunction with opto-genetic approaches to study the contribution of individual types of cell signaling factors expressed by the same neuron in the regulation of structural plasticity in mice during self-paced reinforcement learning.  We focus our attention on determining structural correlates of motor learning in the basal ganglia and the spinal cord.

Our basic research appears to be of relevance to diseases of the basal ganglia and for spinal cord injury and recovery. Basal ganglia diseases like Parkinson’s Disease or Schizophrenia are characterized by aberrant motor learning and proprioceptive feedback is critical for the establishment of compensatory movement pathways in the spinal cord upon injury. In the course of our work we established a novel progressive, genetic model of Parkinson’s Disease and discovered a novel approach to reduce the formation of dyskinesia. We also found that injured motor neurons and proprioceptive neurons impinge on the physiology of glia in their immediate environment including NG2 cells whose turnover is critical for motor learning.


"Dopaminergic Co-transmission With Sonic Hedgehog Inhibits Abnormal Involuntary Movements in Models of Parkinson’s Disease and L-Dopa Induced Dyskinesia”. (2021)

Communications Biology 2021
Malave, Lauren, Dustin R. Zuelke, Santiago Uribe-Cano, Lev Starikov, Heike Rebholz, Eitan Friedman, Chuan Qin, Qin Li, Erwan Bezard, and Andreas H. Kottmann


Diminished ventral oligodendrocyte precursor generation results in the subsequent overproduction of dorsal oligodendrocyte precursors of aberrant morphology and function”. (2020)

Neuroscience 2020
Starikov, Lev and Andreas H. Kottmann


“The Dopamine D5 receptor contributes to activation of cholinergic interneurons during L-DOPA induced dyskinesia”. (2020)

Sci Rep. 2020
Castello, Julia, Marisol Cortés, Lauren Malave, Andreas Kottmann, David R. Sibley, Eitan Friedman, and Heike Rebholzn


"Sonic Hedgehog is expressed by hilar mossy cells and regulates cellular survival and neurogenesis in the adult hippocampus". (2019)

Sci Rep. 2019
Gonzalez-Reyes, Luis E., Chia-Chu Chiang, Mingming Zhang, Joshua Johnson, Manuel Arrillaga-Tamez, Nicholas H. Couturier, Neha Reddy, Lev Starikov, Jefrey R. Capadona, Andreas H. Kottmann, and Dominique M. Durand


“Sonic Hedgehog Maintains Cellular and Neurochemical Homeostasis in the Adult Nigrostriatal Circuit”. (2012)

Neuron 2012
Gonzalez-Reyes, Luis E., Miguel Verbitsky, Javier Blesa, Vernice Jackson-Lewis, Daniel Paredes; Karsten Tillack, Sudarshan Phani, Edgar R. Kramer, Serge Przedborski, and Andreas H. Kottmann


“Thyroid hormone regulates the expression of the sonic hedgehog signaling pathway in the embryonic and adult mammalian brain”. (2011)

Endocrinology 2011
Desouza, Lynette A., Malini Sathanoori, Richa Kapoor, Neha Rajadhyaksha, Luis Gonzalez-Reyes, Andreas H. Kottmann, Shubha Tole, Vidita A. Vaidya




Multiple sources of Shh are critical for the generation and scaling of ventral spinal cord oligodendrocyte precursor populations”. (2021)

Lev Starikov, Miruna Ghinia-Tegla, and Andreas H. Kottmann