Synaptic Neuromodulation

Hypothalamic neuropeptides: Release mechanisms and synaptic function

Neuromodulators expand the abilities of neuronal networks to process information and to perform fine-tuning computations that impact cognition, emotion, and behavior. Despite their key role, the molecular mechanisms orchestrating neuromodulatory function in the central nervous system (CNS) are much more unknown than those of inhibitory and excitatory transmission. This scenario is largely due to the technical challenge of unambiguously link specific neuromodulator release events to their precise actions at the physiological and behavioral level. To address this gap in our current knowledge, our group is implementing a multidisciplinary strategy to explore different aspects of neuromodulatory function, and to understand how these circuits are affected during natural aging and neurodegeneration. We currently work on three main research lines:

We employ live cell imaging technologies to explore neuropeptide-containing vesicle dynamics and release. We focus on oxytocin (OXT) and vasopressin, two hypothalamic neuropeptides which mediate vital homeostatic functions as well as complex behaviors such as social interaction. Our laboratory combines  imaging and electrophysiological methods to explore the exocytic machinery involved in their release, and to  understand their action on synaptic transmission and plasticity. To know more about this project click here.

Formation and plasticity of neuromodulatory circuits
 

Our group employs novel brain clarification techniques such as iDISCO+ to examine the specification of neuromodulatory circuits and their plastic adaptations during adulthood and aging. To know more about this project click here.

Impact of aging and neurodegeneration on neuromodulatory circuits
 

One major focus of our group is on mechanisms governing brain function under healthy and pathological aging. To this aim, we have implemented animal models of neurodegeneration (APP/PSEN1) and senesce (naturally aged mice over 20 months-old) that will allow us to explore the potential modifications of neuromodulatory circuits in the aged brain. Here, we focus on the olfactory system, as this brain region is early affected during aging and neurodegeneration. To know more about this project click here.

Methodological approaches

In order to accomplish these aims, we have implemented a research program which combines state-of-the-art imaging techniques such as 3D ultra-resolution circuit mapping and vesicle dynamic/exocytosis visualization, electrophysiology, optogenetics, in vivo viral-based manipulations and animal behavioural testing.