Periodic Reporting for period 1 - CoMPOSE (Cortical Microcircuits: Parvalbumin neurons Orchestrate Stress Eating)
Período documentado: 2020-06-01 hasta 2022-05-31
To establish under which conditions cortical neurons projecting to the hypothalamus are necessary for food intake we used opto- and chemogenetic inhibition experiments. Closed-loop optogenetic inhibition of these neurons when mice are close to food did not affect their intake. In addition, a more chronic form of inhibition using chemogenetics also did not yield a significant effect on food intake. However, preliminary data shows that these neurons might become engaged in regulating food intake after social stress. We then used in vivo electrophysiology to record from different cell types (putative interneurons and pyramidal neurons) within the prefrontal cortex to show that prefrontal cortex neurons do not respond strongly to food interactions under normal conditions. To investigate whether these neurons become more engaged after stress we use a social stress model which is known to increase intake of palatable food. Exposure to the social stressor itself highly impacts the firing rate of prefrontal cortical neurons over long-time scales. In addition, we have established recordings of identified neurons in the prefrontal cortex that communicate with the hypothalamus to investigate their role in stress and stress-eating.
Together these results make an important step in identifying how prefrontal cortical neuronal ensembles govern stress-eating behaviours.
Beyond the scientific impact, this work can ultimately contribute to the development of evidence-based treatment strategies for invidiuals that overconsume food. Notably, there are currently ongoing developments in terms of non-invasive neuromodulation in humans (e.g. Transcranial magnetic stimulation (TMS)). These approaches can alter activity of the prefrontal cortex in humans. Different stimulation parameter settings inducing distinct effects in the human prefrontal cortex. As mentioned, stress-driven food intake can have serious consequences in individuals prone to develop obesity or in those with eating disorders characterized by binge eating. To better understand what kind of TMS procedures might be beneficial in the context of such diseases, it is relevant to better understand the neurobiological principles by which the PFC shapes food intake behavior. The current work can make a contribution to understanding these important principles.