Lebitko, T. | Search bioRxiv

bioRxiv2020

c-Fos-MMP-9 pathway in central amygdala mediates approach motivation but not reward consumption

Although impaired motivational and consummatory aspects of reward behavior are core symptoms of several psychiatric disorders, the underlying neural and molecular mechanisms remain poorly understood. c-Fos, as a component of AP-1 transcription factor, regulates the expression of matrix metalloproteinase 9 (MMP-9), an enzyme involved in synaptic remodeling and plasticity. Both proteins are expressed in the central amygdala (CeA) that orchestrates appetitive and aversive responses. We have examined the role of c-Fos and MMP-9 in CeA in reward and punishment processing. We have manipulated c-Fos and MMP-9 levels in vivo using: RNAi-based approach to block c-Fos expression, inhibitor-releasing nanoparticles to block MMP-9 activity, and lentiviral vector to increase MMP-9 expression. To assess motivation, consumption and learning reinforced by either a sweet or bitter-tasting solution, we employed automated behavioral tests in the IntelliCage cystem. We have used transgenic mouse lines to identify CeA cells expressing c-Fos and a specific fluorescently labelled substrate peptide to measure MMP-9 activity. Excitability of neurons was measured with patch-clamp. Blocking c-Fos expression has been found to disrupt both reward processing components, motivational and consummatory, while inhibition of MMP-9 activity has impaired only motivational aspects of the behavior. On the other hand, punishment processing has not been affected by those manipulations. Furthermore, we have observed that reward training induces c-Fos expression in both somatostatin (SST)+, and SST-neurons, while MMP-9 activity is increased in SST- subpopulation only. We have further linked SST+ population to consummatory reactions by showing that reward consumption increases excitability of the SST+ neurons. These findings reveal molecular mechanisms of motivational anhedonia, linking it to c-Fos-MMP-9 pathway and CeA SST- neurons, and consummatory anhedonia, linking it to c-Fos and CeA SST+ neurons.

neuroscience↗

bioRxiv2020

More than a feeling: central amygdala mediates social transfer of information about proximity of danger

To survive, an animal must adequately respond to challenges presented by the environment. Social animals can learn about danger from fear of conspecifics which allows them to avoid predation and other threats without costly, first-hand experience. However, it remains unclear as to whether animals can transmit specific information that helps an individual avoid harm or whether the transmitted social signals simply increase vigilance in a non-specific manner. Here we demonstrate that animals can select appropriate defensive strategies in a novel environment depending on cues from the conspecific and, using opsins targeted to behaviorally activated neurons, identify distinct neuronal circuits in the central amygdala (CeA) that are crucial for choosing a context-appropriate reaction. The identified circuits differ in molecular markers and patterns of connectivity. Thus, we show that social signals carry explicit information about proximity of danger, necessary for choosing a context-appropriate reaction, and that the choosing process is mediated by the CeA circuits.

neuroscience↗