All Publications

  • Deep molecular diversity of mammalian synapses: why it matters and how to measure it NATURE REVIEWS NEUROSCIENCE O'Rourke, N. A., Weiler, N. C., Micheva, K. D., Smith, S. J. 2012; 13 (6): 365-379


    Pioneering studies in the middle of the twentieth century revealed substantial diversity among mammalian chemical synapses and led to a widely accepted classification of synapse type on the basis of neurotransmitter molecule identity. Subsequently, powerful new physiological, genetic and structural methods have enabled the discovery of much deeper functional and molecular diversity within each traditional neurotransmitter type. Today, this deep diversity continues to pose both daunting challenges and exciting new opportunities for neuroscience. Our growing understanding of deep synapse diversity may transform how we think about and study neural circuit development, structure and function.

    View details for DOI 10.1038/nrn3170

    View details for Web of Science ID 000304197000007

    View details for PubMedID 22573027

  • Single-Synapse Analysis of a Diverse Synapse Population: Proteomic Imaging Methods and Markers Neuron Micheva KD, Busse B, Weiler NC, O'Rourke N, Smith SJ 2010; 68: 639-653
  • Top-down laminar organization of the excitatory network in motor cortex NATURE NEUROSCIENCE Weiler, N., Wood, L., Yu, J., Solla, S. A., Shepherd, G. M. 2008; 11 (3): 360-366


    Cortical layering is a hallmark of the mammalian neocortex and a major determinant of local synaptic circuit organization in sensory systems. In motor cortex, the laminar organization of cortical circuits has not been resolved, although their input-output operations are crucial for motor control. Here, we developed a general approach for estimating layer-specific connectivity in cortical circuits and applied it to mouse motor cortex. From these data we computed a laminar presynaptic --> postsynaptic connectivity matrix, W(post,pre), revealing a complement of stereotypic pathways dominated by layer 2 outflow to deeper layers. Network modeling predicted, and experiments with disinhibited slices confirmed, that stimuli targeting upper, but not lower, cortical layers effectively evoked network-wide events. Thus, in motor cortex, descending excitation from a preamplifier-like network of upper-layer neurons drives output neurons in lower layers. Our analysis provides a quantitative wiring-diagram framework for further investigation of the excitatory networks mediating cortical mechanisms of motor control.

    View details for DOI 10.1038/nn2049

    View details for Web of Science ID 000253548300020

    View details for PubMedID 18246064

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