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Functional organization of the neocortex
Our research takes a bottom-up approach to understanding how the neural circuits of this massively interconnected network of neurons are functionally organized and how dysfunction in these circuits contributes to neurodegenerative diseases like amyotrophic lateral sclerosis and neuropsychiatric disorders including autism and schizophrenia. Approaches We use a variety of techniques to address these questions including: 1. Whole-cell patch clamp recording from multiple neurons simultaneously in brain slices to determine the organization of neural circuits and their synaptic properties. 2. Optogenetic approaches to stimulate or inhibit select classes of neurons and interrogate the function of neural circuits. 3. Transgenic mouse lines to control the expression of desired proteins in subsets of neurons. 4. Viral constructs to target protein expression to specific subsets of neurons, allowing us to determine the anatomical relationship among cell types and to probe the functional properties of their connections.
Kim J, Matney CJ, Blankenship A, Hestrin S, Brown SP. Layer 6 corticothalamic neurons activate a cortical output layer, layer 5a. Journal of Neuroscience. 2014. 34:9656-9664. PDF Arroyo S, Bennett C, Aziz D, Brown SP, Hestrin S. Prolonged disynaptic inhibition in the cortex mediated by slow, non-?7 nicotinic excitation of a specific subset of cortical interneurons. Journal of Neuroscience. 2012. 32:3859-3864. PDF Brown SP, Hestrin S. Cell-type identity: A key to unlocking the function of neocortical circuits. Current Opinion in Neurobiology. 2009. 19:415-421. PDF Brown SP, Hestrin S. Intracortical circuits of pyramidal neurons reflect their long-range axonal targets. Nature. 2009. 457:1133-1136. PDF SUPPLEMENT Brown SP, Safo P, Regehr WG. Endocannabinoids inhibit transmission at granule cell to Purkinje cell synapses by modulating three types of presynaptic calcium channels. Journal of Neuroscience. 2004. 24:5623-5631. PDF Brown SP, Brenowitz SD, Regehr WG. Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannabinoids. Nature Neuroscience. 2003. 10:1048-1057. PDF Rockhill RL, Daly FJ, MacNeil MA, Brown SP, Masland RH. The diversity of ganglion cells in a mammalian retina. Journal of Neuroscience. 2002. 22:3831-43. PDF Brown SP, Masland RH. Spatial scale and cellular substrate of contrast adaptation by retinal ganglion cells. Nature Neuroscience. 2001. 4:44-51. PDF Brown SP, He S, Masland RH. Receptive field microstructure and dendritic geometry of retinal ganglion cells. Neuron. 2000. 27:371-383. PDF MacNeil MA, Brown SP, Rockhill RL, Masland RH. Cell mosaics and neurotransmitters. In: Albert DM, Jakobiec FA, editors. Principles and Practice of Ophthalmology. Philadelphia: WB Saunders and Company. 2000. pp. 1729-1745. Brown SP, Masland RH. Costratification of a population of bipolar cells with the direction-selective circuitry of the rabbit retina. Journal of Comparative Neurology. 1999. 408:97-106. PDF?