Neuron-glia interactions in the hypothalamus, and their sensitivity to psychoactive drug abuse

The brain is the most sophisticated biological system, with its functions safeguarded by the seamless interaction of its many cell types.

Single-cell biology approached brain complexity by the charting of neurons because of their stable molecular signatures. However, only half of the brain is made up by neurons, with mainly astrocytes making up the remaining part. Astrocytes have been viewed as support cells for neurons. With a focus on the hypothalamus, we will challenge this ‘neuron-centric’ view.

We hypothesize that the many receptors, transporters, and signal transduction mechanisms in hypothalamic astroglia make them equivalent or even superior to neurons in defining endocrine output by dynamically sensing environmental signals at high temporal resolution.

Here, innovative molecular and cellular manipulations guided by single-cell profiling will be used to interrogate i) astroglial diversity and ii) functional plasticity, iii) if switching astroglial features in neurocircuits could reprogram endocrine output, and iv) if illicit drugs drive endocrine impairment by exploiting astroglia as entry points to the brain.

We will focus on and compare the astroglial control of the circuit designs of two dopamine neuron subtypes, which we have identified as sensitive to either amphetamine or cannabinoids.

Thus, outcomes will produce new understanding on hypothalamic organization and non-neuronal substrates of drug susceptibility. Consequently, a therapeutic perspective will emerge.