Dr. Brown’s research aims to understand the functional organization of the mammalian neocortex in the healthy brain and the alterations in circuit properties that underlie neurologic and psychiatric disease. The basic structure of the cortex is similar across functional areas, yet different classes of cortical projection neurons, the major cell type in the cortex, are specialized to send distinct messages out of the cortex to target brain regions. Using a bottom-up approach, her lab is determining how these different messages are generated, what they mean in brain processing, and how abnormalities in these processes contribute to neurologic and psychiatric diseases.
The neocortex represents a massively interconnected network of neurons that generates a broad repertoire of behaviors including perception, action and decision-making. Most synaptic inputs onto neocortical neurons come from other neocortical neurons. In addition, neocortical neurons interact with a wide variety of other brain areas including the thalamus and the claustrum. Dr. Brown’s laboratory examines how these circuits integrate incoming information and generate the cortical outputs that govern perception, thought and action.
The lab’s strategy is to combine physiological approaches with anatomical and genetic techniques for identifying cell populations and pathways to define the synaptic interactions among different classes of cortical neurons and to understand how long-range feedforward and feedback inputs are integrated within these circuits. By identifying the synaptic partners of functionally identified output neurons of the cortex and characterizing the dynamic properties of their synaptic connections, the lab can begin to understand the computations taking place within the cortex. The long-term goal is to understand how cortical circuits give rise to cortical activity and ultimately generate perception and behavior.
Lab Website: Brown Lab
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Chevée M, Finkel EA, Kim S-J, O’Connor DH, Brown SP. Neural activity in the mouse claustrum in a cross-modal sensory selection task. Neuron. 2022. 110:486-501.E7. doi:10.1016/j.neuron.2021.11.013
Frandolig JE, Matney CJ, Lee K, Kim J, Chevée M, Kim S-J, Bickert AA, Brown SP. The synaptic organization of layer 6 circuits reveals inhibition as a major output of a neocortical sublamina. Cell Reports. 2019. 28:3131-3143. doi:10.1016/j.celrep.2019.08.048
Chevée M, Robertson JD, Cannon GH, Brown SP, Goff LA. Variation in neuronal activity state, axonal projection target and position principally define the transcriptional identity of individual neocortical projection neurons. Cell Reports. 2018. 22:441-455. doi:10.1016/jcelrep.2017.12.046
Liu K, Kim J, Kim DW, Zhang YS, Bao H, Denaxa M, Lim SA, Kim E, Liu C, Wickersham IR, Pachnis V, Hattar S, Song J, Brown SP, Blackshaw S. Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep. Nature. 2017. 548:582-587. doi: 10.1038/nature23663
Brown SP, Hestrin S. Intracortical circuits of pyramidal neurons reflect their long-range axonal targets. Nature. 2009. 457:1133-1136