Investigating the role of subsets of substantia nigra dopaminergic neurons in motivated behavior
1 Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, Bonn, Germany
2 DZNE, Bonn, Germany
Midbrain dopaminergic (mDA) neurons are known to modulate a wide range of behavioral outputs, including reward, aversion and motor activity. However, to date it is still unclear how these diverse functions can be encoded by a single neurotransmitter system. One hypothesis is that the mDA system is composed of distinct functional ensembles of mDA neurons that modulate specific aspects of behavior by targeting a specific subset of the mDA projection areas. To investigate this question, we performed deep-brain calcium imaging in the substantia nigra using miniature microscopes in freely moving mice during approach and avoidance paradigms. We targeted the medial and the lateral substantia nigra pars compacta by injecting a Cre-dependent jGCaMP7f into the midbrain of Dat-Cre mice followed by an implantation of a gradient index (GRIN) lens. mDA neuron activity was recorded during learning paradigms that require the execution of innate and learned approach and avoidance behaviors in response to a reward or punishment. Following the same neurons across days, we found that mDA subsets show heterogenous responses during both appetitive and aversive paradigms. However, examining the activity of anatomical subsets alone may not be sufficient to unravel the complex role of mDA neurons in behavior. In a next step, we will therefore extend our focus on both anatomically and genetically defined mDA neuronal subsets to study their role in innate and learned approach and avoidance behavior.