Oxytocin Filters Inputs To VTA Dopamine Neurons

The mammalian brain contains millions of nerve cells or neurons that communicate with each other via a process called neurotransmission. To send a message to its neighbor, a neuron releases a chemical called a neurotransmitter into the space between the cells.

The neurotransmitter then binds to receiver proteins on the target cell. Another group of chemicals, known as neuromodulators, regulate this process, adjusting the way that neurons respond to neurotransmitters. In doing so, they help regulate many types of behavior in mammals.

The neuromodulator oxytocin, for example, has earned the nickname ‘the love hormone’ because it promotes social behavior and bonding. It does this in part by altering the activity of neurons in a brain region called the ventral tegmental area (VTA). These neurons produce the brain’s main reward signal, dopamine, which is itself a neuromodulator.

But exactly how oxytocin affects the activity of dopamine-producing neurons is unclear.

Endocannabinoid Release

By recording from individual neurons in slices of mouse brain tissue, Lei Xiao, Michael F Priest, and Yevgenia Kozorovitskiy, from Northwestern University, show that oxytocin filters inputs to dopamine neurons in the VTA. It does this by making the dopamine neurons release another group of reward signals, known as endocannabinoids. These are the brain’s own version of the chemicals found inside cannabis plants.

 Left: projection of a z-stack from a VTA DA neuron filled with Alexa Fluor 488 acquired on a two-photon laser-scanning microscope. Right: higher magnification image of the dendrite. Green circle marks the uncaging spot.

Left: projection of a z-stack from a VTA DA neuron filled with Alexa Fluor 488 acquired on a two-photon laser-scanning microscope. Right: higher magnification image of the dendrite. Green circle marks the uncaging spot.
Credit: Lei Xiao, et al CC-BY

The endocannabinoids bind to neurons that provide input to the VTA dopamine neurons. Some of these input neurons normally activate the VTA by releasing a neurotransmitter called glutamate.

However, the binding of endocannabinoids decreases their ability to do this, and thereby lowers the activation of the VTA dopamine neurons.

Input Regulation

But not all glutamate neurons are sensitive to endocannabinoids. Moreover, oxytocin affects glutamate neurons that fire repeatedly less than it affects those that fire only occasionally.

Oxytocin thus acts as a filter. It allows certain inputs – those that are repeatedly active and those that are insensitive to endocannabinoids – to continue activating VTA dopamine neurons.

Oxytocin modulates pathway-specific excitatory synaptic transmission in VTA DA neurons.

Oxytocin modulates pathway-specific excitatory synaptic transmission in VTA DA neurons.
Credit: Lei Xiao, et al CC-BY

At the same time, it weakens the influence of other inputs. Dopamine release in the VTA drives drug abuse and addiction.

Understanding how oxytocin affects VTA neurons may thus open up new avenues for the treatment of addiction disorders.

Funding for the study cam from the Arnold and Mabel Beckman Foundation (Arnold O. Beckman Postdoctoral Fellowship), Arnold and Mabel Beckman Foundation (BYI Award), William and Bernice E Bumpus Foundation (Young Innovator Award), Rita Allen Foundation, Alfred P. Sloan Foundation, and Kinship Foundation.

Lei Xiao, Michael F Priest, Yevgenia Kozorovitskiy
Oxytocin functions as a spatiotemporal filter for excitatory synaptic inputs to VTA dopamine neurons
eLife 2018;7:e33892 DOI: 10.7554/eLife.33892

Top Image: Parashkev Nachev. CC BY