I have come to Stanford University to increase my knowledge and acquire new skills in neuroscience and synaptic plasticity. My interest in the brain arises from its unique complexity and malleability to shape different behavioral outcomes. My PhD was aimed at studying the modulation of voltage-gated calcium channels in primary neuronal cultures and brain slices by a GPCR involved in energy homeostasis and memory. At this stage I am willing to use my expertise in electrophysiology and subcellular neuroscience to explore the plasticity of inhibitory afferents into the VTA and its relation with stress-induced relapse.

I also believe that science is a powerful tool to explore and change the world, and hence I am highly interested in the ideas behind science policies as well as in understanding how science shapes the reality we live in, and the responsibility we have as scientists.

Professional Education

  • Doctor of Philosophy, Universidad Nacional de La Plata - Buenos Aires - Argentina, Impact of presynaptic voltage-gated calcium channels modulation by GHSR constitutive activity in hippocampal inhibitory transmission (2014)
  • Bachelor in Biotechnology, Universidad Nacional de La Plata - Buenos Aires - Argentina (2009)

Stanford Advisors

All Publications

  • Somatodendritic Release of Cholecystokinin Potentiates GABAergic Synapses Onto Ventral Tegmental Area Dopamine Cells. Biological psychiatry Martinez Damonte, V., Pomrenze, M. B., Manning, C. E., Casper, C., Wolfden, A. L., Malenka, R. C., Kauer, J. A. 2022


    BACKGROUND: Neuropeptides are contained in nearly every neuron in the central nervous system and can be released not only from nerve terminals but also from somatodendritic sites. Cholecystokinin (CCK), among the most abundant neuropeptides in the brain, is expressed in the majority of midbrain dopamine neurons. Despite this high expression, CCK function within the ventral tegmental area (VTA) is not well understood.METHODS: We confirmed CCK expression in VTA dopamine neurons through immunohistochemistry and in situ hybridization and detected optogenetically induced CCK release using an enzyme-linked immunosorbent assay. To investigate whether CCK modulates VTA circuit activity, we used whole-cell patch clamp recordings in mouse brain slices. We infused CCK locally invivo and tested food intake and locomotion in fasted mice. We also used invivo fiber photometry to measure Ca2+ transients in dopamine neurons during feeding.RESULTS: Here we report that VTA dopamine neurons release CCK from somatodendritic regions, where it triggers long-term potentiation of GABAergic (gamma-aminobutyric acidergic) synapses. The somatodendritic release occurs during trains of optogenetic stimuli or prolonged but modest depolarization and is dependent on synaptotagmin-7 and T-type Ca2+ channels. Depolarization-induced long-term potentiation is blocked by a CCK2 receptor antagonist and mimicked by exogenous CCK. Local infusion of CCK invivo inhibits food consumption and decreases distance traveled in an open field test. Furthermore, intra-VTA-infused CCK reduced dopamine cell Ca2+ signals during food consumption after an overnight fast and was correlated with reduced food intake.CONCLUSIONS: Our experiments introduce somatodendritic neuropeptide release as a previously unknown feedback regulator of VTA dopamine cell excitability and dopamine-related behaviors.

    View details for DOI 10.1016/j.biopsych.2022.06.011

    View details for PubMedID 35961792

  • Hyperexcitable arousal circuits drive sleep instability during aging. Science (New York, N.Y.) Li, S. B., Damonte, V. M., Chen, C., Wang, G. X., Kebschull, J. M., Yamaguchi, H., Bian, W. J., Purmann, C., Pattni, R., Urban, A. E., Mourrain, P., Kauer, J. A., Scherrer, G., de Lecea, L. 2022; 375 (6583): eabh3021


    Sleep quality declines with age; however, the underlying mechanisms remain elusive. We found that hyperexcitable hypocretin/orexin (Hcrt/OX) neurons drive sleep fragmentation during aging. In aged mice, Hcrt neurons exhibited more frequent neuronal activity epochs driving wake bouts, and optogenetic activation of Hcrt neurons elicited more prolonged wakefulness. Aged Hcrt neurons showed hyperexcitability with lower KCNQ2 expression and impaired M-current, mediated by KCNQ2/3 channels. Single-nucleus RNA-sequencing revealed adaptive changes to Hcrt neuron loss in the aging brain. Disruption of Kcnq2/3 genes in Hcrt neurons of young mice destabilized sleep, mimicking aging-associated sleep fragmentation, whereas the KCNQ-selective activator flupirtine hyperpolarized Hcrt neurons and rejuvenated sleep architecture in aged mice. Our findings demonstrate a mechanism underlying sleep instability during aging and a strategy to improve sleep continuity.

    View details for DOI 10.1126/science.abh3021

    View details for PubMedID 35201886

  • Periaqueductal Gray and Rostromedial Tegmental Inhibitory Afferents to VTA Have Distinct Synaptic Plasticity and Opiate Sensitivity. Neuron St Laurent, R. n., Martinez Damonte, V. n., Tsuda, A. C., Kauer, J. A. 2020


    The ventral tegmental area (VTA) is a major target of addictive drugs and receives multiple GABAergic projections originating outside the VTA. We describe differences in synaptic plasticity and behavior when optogenetically driving two opiate-sensitive GABAergic inputs to the VTA, the rostromedial tegmental nucleus (RMTg), and the periaqueductal gray (PAG). Activation of GABAergic RMTg terminals in the VTA in vivo is aversive, and low-frequency stimulation induces long-term depression in vitro. Low-frequency stimulation of PAG afferents in vitro unexpectedly causes long-term potentiation. Opioid receptor activation profoundly depresses PAG and RMTg inhibitory synapses but prevents synaptic plasticity only at PAG synapses. Activation of the GABAergic PAG terminals in the VTA promotes immobility, and optogenetically-driven immobility is blocked by morphine. Our data reveal the PAG as a source of highly opioid-sensitive GABAergic afferents and support the idea that different GABAergic pathways to the VTA control distinct behaviors.

    View details for DOI 10.1016/j.neuron.2020.02.029

    View details for PubMedID 32191871