LYNN SHI ’13
To elaborate and expand our knowledge of the dopamine system, I identified the sources of inputs at the di-synaptic level.
The human brain contains billions of neurons organized into circuits that process specific kinds of information and give rise to behavior. Information encoded by these circuits hold the key to understanding how the brain works and offer the promise of clarifying the causes of neurological and psychiatric diseases. Establishing improved methods to understand how neural circuits are connected is a critical step toward understanding how neurons communicate.
In this project, I investigated the connectivity of the dopamine system in mice using rabies virus that have been modified to control which neuron groups are infected and the strength of that infection. The rabies virus has the special ability to travel backwards, or retrogradely, in the mammalian nervous system. Thus, the rabies-mediated retrograde tracing method harvests that special ability and allowed researchers to investigate the neurons which communicate with the neuronal population of interest, which in this case are the dopamine neurons. Dopamine neurons are localized in two adjacent but distinct structures, the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc). These neurons make diffuse connections with other neurons all over the brain and play pivotal roles in the brain, regulating motivation, movement control, and reward-seeking behavior. By looking at the inputs to dopamine neurons, we can evaluate how these neurons integrate information and compute signals to regulate behavior.
Recently, our laboratory had comprehensively identified the monosynaptic inputs, or neurons that make direct single-synaptic connections to dopamine neurons. To elaborate and expand our knowledge of the dopamine system, I identified the sources of inputs at the di-synaptic level, which are neurons that make indirect projections to dopamine neurons via regions that make monosynaptic inputs. I found that several brain regions, including the isocortex, olfactory area, cortical subplate, hypothalamus, thalamus, and hippocampal formation, project to midbrain dopamine neurons. This project demonstrates the utility and constraints of our methodology and contributes to our understanding of information transmission in the brain. Unraveling multi-synaptic input pathways for dopamine neurons provides a foundational knowledge in the regulation of dopamine neuron activity, and therefore a better neurobiological basis for the development of improved and targeted clinical interventions to improve the health of people and populations.
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