The immense complexity and computational power of the brain emerges from its vast connectivity and combination of cell types. We use modern neuroscience tools to untangle very specific components of neural circuits and study their molecular characteristics, connectivity and function in order to ultimately determine the contribution of these circuits to behavior.
The neuromodulator serotonin plays an outsized role in many brain functions. Neurons synthesizing serotonin are located in a network of small structures deep within the brain called the raphe nuclei. Remarkably, neurons in this small nucleus play a role in many important brain functions, from basic homeostatic regulation to involvement in complex mood and psychiatric disorders.
Rather than targeting all serotonin neurons as a single population, we aim to define these neural subpopulations based on differing gene expression, location within the raphe nuclei, and connectivity with other brain regions. Ultimately, we aim to understand how these different serotonin neurons influence separate behaviors that play a role in psychiatric disorders.
To address these problems the lab is using a multidisciplinary approach combining neuroanatomical circuit tracing with viral-genetic tools, whole-brain connectivity imaging, recording of neural activity with in vivo calcium imaging and biosensors, optogenetic and chemogenetic manipulation, behavioral assays and computation.
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Ährlund-Richter S, Xuan Y, van Lunteren JA, Kim H, Ortiz C, Pollak Dorocic I, Meletis K, Carlén M. A whole-brain atlas of monosynaptic input targeting four different cell types in the medial prefrontal cortex of the mouse. Nature Neuroscience. 2019 Apr; 22(4):657-668.
de Jong JW, Afjei SA, Pollak Dorocic I, Peck JR, Liu C, Kim CK, Tian L, Deisseroth K, Lammel S. A neural circuit mechanism for encoding aversive stimuli in the mesolimbic dopamine system. Neuron. 2019 Jan 2; 101(1):133-151.
Pollak Dorocic I, Fürth D, Xuan Y, Johansson Y, Pozzi L, Silberberg G, Carlén M, Meletis K. A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei. Neuron. 2014 Aug 6; 83(3):663-78.
Pozzi L, Pollak Dorocic I, Wang X, Carlén M, Meletis K. Mice lacking NMDA receptors in parvalbumin neurons display normal depression-related behaviors and response to antidepressant action of NMDAR antagonists. PLoS One. 2014 Jan 16;9(1):e83879.
Szydlowski SN*, Pollak Dorocic I*, Planert H*, Carlén M, Meletis K, Silberberg G. Target selectivity of feedforward inhibition by striatal fast-spiking interneurons. Journal of Neuroscience. 2013 Jan 23 ;33(4):1678-83