Nucleus Accumbens Inhibition is Required for Appetitive or Fearful Behaviors

Post by Lincoln Tracy 

What's the science?

The neurotransmitter glutamate plays a key role in causing neurons to fire action potentials. These impulses are required for neurons in different areas of the brain to communicate. DNQX is a peptide that inhibits neurons from firing. Injecting DNQX into the nucleus accumbens, the part of our brain that mediates reward, can produce either motivating (such as increased eating and food intake) or fearful/avoidance behaviors (such as digging to escape predators) in rats. The type of behavior caused by the injection of DNQX depends on which part of the nucleus accumbens it is injected into. It is hypothesized that inhibiting the medium spiny neurons of the nucleus accumbens leads to motivating behaviors. However, there is no evidence that preventing neurons of the nucleus accumbens from firing is required for DNQX to produce either type of behavior. This week in the Journal of Neuroscience, Baumgartner and colleagues sought to directly test whether local neuronal inhibition is required for DNQX injected into the nucleus accumbens to elicit motivating behaviors. 

How did they do it?

First, a group of rats underwent brain surgery. The surgery involved implanting a cannula (a thin tube) and optic fibers (which could be stimulated with lasers) into the nucleus accumbens. The authors also injected one of two viruses into the nucleus accumbens. One virus contained channelrhodopsin, a light-sensitive protein the authors could optogenetically stimulate. The other virus was an inactive control virus. Rats were placed in a chamber for an hour while they were observed for appetitive (e.g. eating) and defensive (e.g. digging) behaviors. Each rat completed the behavioral testing four times: the four conditions were (a) a baseline condition, where saline was injected into the nucleus accumbens and optogenetic laser stimulation was not applied, (b) a laser alone condition, where saline was injected but the nucleus accumbens was stimulated with the laser, (c) a DNQX alone condition, where the rats received DNQX but not laser stimulation, and (d) a combined condition where rats were injected with DNQX and had laser stimulation applied. Additionally, half the rats completed the behavioral testing in a ‘high stress’ environment – with Iggy Pop’s 1977 Hippodrome Paris gig playing in the background. The remaining rats were tested without the music being played. The authors then compared the appetitive and defensive behaviors between the different testing conditions.

What did they find?

The authors first found that injecting DNQX into the nucleus accumbens in the normal laboratory environment made the rats eat more food and eat for longer compared to when they were injected with saline. However, stimulating the channelrhodopsin in the nucleus accumbens with light reversed the DNQX-induced increase in food intake in rats where the tips of the cannula and the optic fibers were close together. The lasers had no effect on eating behaviors if the two tips were separated by more than 1mm. Few defensive behaviors were observed under any of the testing conditions in the normal laboratory environment. When rats were subjected to the stress of listening to Iggy Pop, injecting DNQX resulted in an increase in defensive behaviors. The increased defensive behavior in the ‘high stress’ environment was counteracted by combining the DNQX injection with the laser stimulation. The effects of DNQX and optogenetic laser stimulation on feeding behaviors in the normal lab environment were replicated in the ‘high stress’ environment of listening to Iggy Pop.

What's the impact?

This study demonstrates that neuronal inhibition in the nucleus accumbens is required to generate either motivating or avoiding behaviors. Combining optogenetic stimulation and DNQX administration at the same site within the nucleus accumbens simultaneously prevents the activation of additional brain regions and the resulting appetitive or fearful behaviors. These findings shed light on the role of the nucleus accumbens in psychiatric conditions of pathological motivation, such as addiction or paranoia.  

Baumgartner et al. Desire or dread from nucleus accumbens inhibitions: Reversed by same-site optogenetic excitations. Journal of Neuroscience (2020). Access the original scientific publication here.