Dr. Brown’s research examines the functional organization of local circuits of the neocortex. She was recently awarded a grant to study the inhibitory cortical circuits in presymptomatic ALS. Her research examines the excitatory and inhibitory neurons of the motor cortex, and their patterns of connectivity, to determine whether functional changes in these circuits represent early events in the development of ALS.
The goal of this research is to identify primary events in the disease process that can suggest new preventative strategies and therapeutic targets in ALS. Furthermore, combining this work with the studies of lower motor neurons will give a fuller picture of why motor neurons are particularly vulnerable in ALS.
The neocortex represents a massive interconnected network of neurons that generates perception and action. Indeed, most synaptic inputs onto neocortical neurons come from other neocortical neurons. 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
Arroyo S, Bennett C, Aziz D, Brown SP, Hestrin S. (2012). “Prolonged disynaptic inhibition in the cortex mediated by slow, non-α7 nicotinic excitation of a specific subset of cortical interneurons.” Journal of Neuroscience. 32:3859-3864.
Brown SP, Hestrin S. (2009). “Cell-type identity: A key to unlocking the function of neocortical circuits.” Current Opinion in Neurobiology. 19:415-421.
Brown SP, Hestrin S. (2009). “Intracortical circuits of pyramidal neurons reflect their long-range axonal targets.” Nature.457:1133-1136.
Brown SP, Safo P, Regehr WG. (2004). “Endocannabinoids inhibit transmission at granule cell to Purkinje cell synapses by modulating three types of presynaptic calcium channels.” Journal of Neuroscience. 24:5623-5631.
Brown SP, Brenowitz SD, Regehr WG. (2003). “Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannabinoids. Nature Neuroscience. 10:1048-1057.
Rockhill RL, Daly FJ, MacNeil MA, Brown SP, Masland RH. (2002). “The diversity of ganglion cells in a mammalian retina.” Journal of Neuroscience. 22:3831-3843.
Brown SP, Masland RH. (2001). “Spatial scale and cellular substrate of contrast adaptation by retinal ganglion cells.” Nature Neuroscience. 4:44-51.
Brown SP, He S, Masland RH. (2000). “Receptive field microstructure and dendritic geometry of retinal ganglion cells.” Neuron. 27:371-383.
Brown SP, Masland RH. (1999). “Costratitification of a population of bipolar cells with the direction-selective circuitry of the rabbit retina.” Journal of Comparative Neurology. 408:97-106.