In a recent publication, Daniel Avesar and Allan T. Gulledge of the Gulledge lab in the Department of Physiology and Neurobiology at the Geisel School of Medicine described their discovery of a subset of cortical neurons that are excited, rather than inhibited, by serotonin. These neurons were found in the layer 5 cortex, which is the layer responsible for the bulk of cortical output.
Serotonin, a monoamine neurotransmitter used for communication between neurons, is the target of much research because of its ties to diseases such as depression, schizophrenia, eating disorders, and Parkinson’s. Serotonin is often cited as the neurotransmitter responsible for feelings of happiness, and is implicated in the mood elevation that occurs while eating a meal .
Using unlabeled neurons in coronal slices of mouse brains, the researchers focally applied serotonin to the tissue and recorded the frequency of action potentials in an array of neurons. They found that while 84 percent of the 172 neurons were inhibited, 14 percent they took readings from were either excited alone or excited as part of a biphasic response (an initial inhibitory response followed by a longer excitatory response).
Avesar and Gulledge were able to draw close parallels between the morphology of the neurons they found to be excited in some form by serotonin and the morphology of callosal/commissural (COM) neurons. Following this realization, they set out to determine whether or not this unknown subpopulation of layer 5 cortical neurons was, in fact, composed of COM neurons.
Using a fluorescent label, the researchers repeated their previous experiment, testing the response of these neurons to serotonin. They found that the labeled COM neurons exhibited the same responses as the unspecified neurons in their initial experiment, thus showing that it was COM neurons that were excited by serotonin.
Avesar and Gulledge also wanted to determine if the responses of the COM neurons could result from indirect modulation of excitatory drive onto the layer 5 neurons. To test this, the researchers blocked fast synaptic transmission and repeated their previous experiments. The COM neurons were still excited by serotonin despite blocked fast synaptic transmission, demonstrating that excitation was independent of changes in fast synaptic transmission.
The discovery of a subpopulation of cortical neurons excited, rather than inhibited, by serotonin suggests a new framework with which to examine certain psychoses. The fact that serotonin exhibits both excitatory and inhibitory properties in different cortical neurons adds a new dimension of precision to the regulatory role serotonin plays in cortical communication. It suggests that disruption of this intricate network– through the excessive excitation in the COM neurons, for example– could cause psychosis. Furthermore, this discovery opens the door to new methods of treatments that target the cellular, rather than molecular, level.