Journal Article

Sparse recurrent excitatory connectivity in the microcircuit of the adult mouse and human cortex

Phillips, John, Gwinn, Ryder P, Silbergeld, Daniel L, Lee, Jung Hoon, Ko, Andrew L, Bosma-Moody, Alice, Teeter, Corinne, Campagnola, Luke, Hage, Travis A, Zeng, Hongkui, Lein, Ed, Mihalas, Stefan, Baker, Christopher A, Davoudian, Pasha A, Murphy, Gabe, Ojemann, Jeffrey G, Cobbs, Charles, Hoggarth, Alex, Seeman, Stephanie C, Koch, Christof, Jarsky, Tim

2018

Overview

Generating a comprehensive description of cortical networks requires a large-scale, systematic approach. To that end, we have begun a pipeline project using multipatch electrophysiology, supplemented with two-photon optogenetics, to characterize connectivity and synaptic signaling between classes of neurons in adult mouse primary visual cortex (V1) and human cortex. We focus on producing results detailed enough for the generation of computational models and enabling comparison with future studies. Here, we report our examination of intralaminar connectivity within each of several classes of excitatory neurons. We find that connections are sparse but present among all excitatory cell classes and layers we sampled, and that most mouse synapses exhibited short-term depression with similar dynamics. Synaptic signaling between a subset of layer 2/3 neurons, however, exhibited facilitation. These results contribute to a body of evidence describing recurrent excitatory connectivity as a conserved feature of cortical microcircuits. The outer sheet of brain tissue, the neocortex, is composed of circuits formed from trillions of connections among billions of neurons, of which there are about one hundred different neuron types. The scale and complexity of cortical circuitry pose experimental challenges, leading to an incomplete understanding of how cortical cell types are connected and the computations that take place at the connections. About half of the cell types in the brain are excitatory, which means they can activate other cells. The cortex consists of several distinct layers of cells, within which excitatory cells cooperate to process the signals they receive from other cortical layers and brain areas. Using recordings of electrical activity arising from the connections between pairs of excitatory neurons, Seeman, Campagnola et al. measured the likelihood and strength of connectivity among related groups of excitatory cell types in slices of cortex taken from human and mouse brains. The initial results confirm previous findings that individual layers of human cortex can have more and stronger excitatory connections than the same layers of mouse cortex. In most layers of mouse cortex, repeatedly activating the excitatory cells leads to progressively weaker responses. However, in the upper layers of mouse cortex, the opposite effect is sometimes seen: more excitatory activity causes the connections to generate stronger responses. By feeding these data into a computer model, Seeman, Campagnola et al. described and compared the activity of the groups of related excitatory cell types. These results are the first of a new, large-scale project where findings can be integrated across experiments to gain a more detailed picture of cortical circuitry and computation. Neuroscientists will be able to use the results to build advanced computer models of cortical circuits. Such models will, for example, generate predictions for how the attributes of excitatory connectivity revealed by Seeman, Campagnola et al. influence how information is processed in the cortex. In so doing, the models will add to our understanding of how the human brain works both in health and in disease.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Adult / Analysis / Animal models / Animals / Brain / Computational neuroscience / cortical wiring / Electrophysiological Phenomena / Electrophysiology / Evoked Potentials - physiology / Excitatory Postsynaptic Potentials - physiology / Experiments / Female / Future predictions / Genetics / Humans / Information processing / Limit of Detection / Male / Mice / Models, Neurological / Morphology / Nerve Net - physiology / Neural networks / Neuronal Plasticity - physiology / Neurons / Neuroscience / Neurosciences / Noise / Optics / Optogenetics / Photons / Pipelines / Probability / Short term / short term plasticity / Short-term depression / Signal Transduction / Synapses / Synapses - physiology / Synaptic depression / Visual cortex / Visual Cortex - physiology