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Icon for: Amanda Kinnischtzke


Carnegie Mellon University


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Differential inhibitory influences during two methods of activation in a neocortical slice

The neocortex contains a diversity of excitatory and inhibitory interneuron populations. Dysfunction of cortical inhibitory interneurons has been implicated in multiple neurological diseases including schizophrenia, depression, and epilepsy. Understanding the properties and function of inhibitory interneurons is fundamental for developing treatments for these disorders. To selectively study the in vitro behavior of one inhibitory interneuron subtype, GIN cells, we applied the cholinergic agonist, carbachol, and the metabotropic glutamate receptor agonist, DHPG. Carbachol and DHPG both induce firing in the 3-10 Hz range in GIN cells, without activating other excitatory and inhibitory neurons (Fanselow et al, 2008). To determine the effect of GIN network activation on local excitatory neurons, we recorded from regular-spiking (RS) pyramidal neurons in layer 2/3 of somatosensory cortex during application of 10uM carbachol or 5uM DHPG. We determined that although activation of the presynaptic GIN inhibitory population appears similar under these conditions, the nature of the inhibitory input onto an RS cell is different. While DHPG and carbachol induce similar increases in IPSP number, during carbachol IPSPs occur regularly at intervals corresponding to the 3-10 Hz range, whereas under DHPG IPSPs do not occur at a specific interval. In order to explore the mechanism behind the difference in IPSP timing in these two conditions, we constructed a computational model of a network of GIN cells. We are currently using this model to understand the critical factors that could account for the same inhibitory network causing two different patterns of output, as we observed experimentally under carbachol and DHPG.