How synapses function in their native environment, during sensation and perception and in the context of network activity, are critical to understanding how they can transmit information and be modified by experience. Traditionally, electrophysiological studies have been carried out under experimental conditions that are profoundly different from the intact brain, where one of the most critical differences is the near absence of background activity in acute brain slices. Thus, the functional connectivity between neurons in active cortical circuits, across different brain states, remains unknown. We propose to investigate the properties of excitatory synapses, not in isolation, but as they function embedded in a dynamic neural network, using both in vitro and in vivo recordings. Analysis will focus on individual synaptic connections between pairs of pyramidal neurons in superficial layers of the rodent somatosensory cortex, a well-characterized exemplar of the mammalian neocortex. Our preliminary data indicates that under conditions of high network activity, excitatory synaptic connections onto multiple neuronal cell types can be effectively silenced by GABAb activation. We will identify the cellular source of GABA responsible for this suppression and examine how GABAb signaling is regulated in vivo. Understanding both the static and dynamic patterns of synaptic connectivity in the neocortex will be essential for understanding circuit function and plasticity in health and disease.
Knowing how neurons in the cerebral cortex communicate with each other is critical in understanding how this important part of the brain functions during perception, cognition, and learning. We have discovered that the map of connections between neurons is highly dynamic, where synapses can be revealed or eliminated by modulating the activity of GABAb receptors via the activity of specific interneuron subsets. These GABAergic neurons themselves can be controlled by brain states such as attention or active sensation. These studies may reveal the functional principles by which GABAb receptor antagonists play a critical role in memory formation.
| Urban-Ciecko, Joanna; Jouhanneau, Jean-Sebastien; Myal, Stephanie E et al. (2018) Precisely Timed Nicotinic Activation Drives SST Inhibition in Neocortical Circuits. Neuron 97:611-625.e5 |
| Barth, Alison; Burkhalter, Andreas; Callaway, Edward M et al. (2016) Comment on ""Principles of connectivity among morphologically defined cell types in adult neocortex"". Science 353:1108 |
| Urban-Ciecko, Joanna; Barth, Alison L (2016) Somatostatin-expressing neurons in cortical networks. Nat Rev Neurosci 17:401-9 |
| Navlakha, Saket; Barth, Alison L; Bar-Joseph, Ziv (2015) Decreasing-Rate Pruning Optimizes the Construction of Efficient and Robust Distributed Networks. PLoS Comput Biol 11:e1004347 |
| Urban-Ciecko, Joanna; Fanselow, Erika E; Barth, Alison L (2015) Neocortical somatostatin neurons reversibly silence excitatory transmission via GABAb receptors. Curr Biol 25:722-731 |
