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Congratulations to Marissa Shoji for winning a Hoopes prize for her thesis in Neurobiology, entitled " Characterization of the Activity of Glutamatergic Neurons in the Pedunculopontine Tegmentum During Decision-Making"

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March 10th, 2015

Serotonin is one of the most widespread and mysterious neurotransmitters in the brain. It has been proposed to be involved in many aspects of behavior, including regulating mood and our responses to aversive environmental events. Furthermore, it has also been proposed that a deficiency in serotonin plays a central role in depression. One of the major challenges in testing hypotheses about serotonin's function has been observing the activity of serotonin-releasing neurons during behavior. Historically, when we place a microelectrode into the midbrain structure that contains serotonin-releasing neurons, it was difficult to know whether the neuron under observation was releasing serotonin.

To address this problem, we used a combination of transgenic mice and optogenetics to identify serotonin neurons by their response to light stimulation. Then, we recorded the activity of these light-identified serotonin neurons as mice participated in a task in which the amount of reward or punishment available in the environment varied predictably over time. We found that 40% of serotonin neurons showed slow variations in the activity that correlated with the amount of reward in the environment. This was remarkable, as when we recorded the activity from light-identified dopamine neurons, which have long been thought to be involved in reward, they did not signal information on these slow timescales. In contrast, we found that all the dopamine neurons encoded only the immediate properties of the environment (for example, "I'm about to get a reward"), and only a fraction of the serotonin neurons signaled these immediately pending rewards. Taken together, serotonin neurons have the ability to signal reward and punishment on both slow and fast timescales. These results suggest that serotonin signals could be important for regulating our behavior on slow timescales, and may be involved in generating emotional states like mood.

Read more in eLife 

Read eLife Insight, a review  written by Peter Dayan and Quentin Huys

Three Informational Flows in the Brain

August 6th, 2014 - Cell Reports article 

Serotonin and dopamine are major neuromodulators. Here, we used a modified rabies virus to identify monosynaptic inputs to serotonin neurons in the dorsal and median raphe (DR and MR). We found that inputs to DR and MR serotonin neurons are spatially shifted in the forebrain, and MR serotonin neurons receive inputs from more medial structures. Then, we compared these data with inputs to dopamine neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). We found that DR serotonin neurons receive inputs from a remarkably similar set of areas as VTA dopamine neurons apart from the striatum, which preferentially targets dopamine neurons. Our results suggest three major input streams: a medial stream regulates MR serotonin neurons, an intermediate stream regulates DR serotonin and VTA dopamine neurons, and a lateral stream regulates SNc dopamine neurons. These results provide fundamental organizational principles of afferent control for serotonin and dopamine.