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Michelle K Piazza

Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, 37240-7933, USA.

2 papers in the library · 23 citations · publishing 2024-2025

Papers

Ketamine induced synaptic plasticity operates independently of long-term potentiation.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology October 1, 2024 Michelle K Piazza, Ege T Kavalali, Lisa M Monteggia 21 citations

Synaptic plasticity includes both homeostatic and Hebbian mechanisms that regulate AMPA receptor activity and glutamatergic transmission. Ketamine, a rapidly acting antidepressant, induces homeostatic plasticity to increase glutamatergic transmission. This study demonstrates that Hebbian plasticity, specifically long-term potentiation (LTP), remains intact in synapses that have undergone homeostatic scaling induced by ketamine, whether delivered systemically or perfused onto hippocampal brain slices. In mice exposed to chronic corticosterone (CORT) to model stress, CORT produced an anhedonia-like behavior but did not impair LTP induction. CORT exposure also did not disrupt the interaction between homeostatic and Hebbian plasticity; synapses from CORT-exposed mice showed intact ketamine-induced plasticity followed by LTP. These findings explain how ketamine treatment for depression does not compromise learning and memory processes that rely on LTP.

DOI: 10.1038/s41386-024-01895-2 Full text Ketamine Brain plasticity Neuroscience Antidepressants +1

MeCP2 prevents against sustained ketamine-induced synaptic depression at inhibitory synapses.

iScience June 20, 2025 Michelle K Piazza, Abigael R Weit, Ege T Kavalali et al. 2 citations

Ketamine's antidepressant effects depend on increasing brain-derived neurotrophic factor (BDNF) and activating its receptor TrkB in the hippocampus. Rett syndrome, caused by MECP2 mutations, involves reduced BDNF. In Mecp2 knockout mice, ketamine and a TrkB agonist, LM22A-4, enhance both excitatory and inhibitory synaptic plasticity through separate BDNF-TrkB pathways. MeCP2 normally stabilizes inhibitory neurotransmission; without it, ketamine causes sustained disinhibition. These findings reveal how MeCP2 shapes acute ketamine action and suggest mechanisms for ketamine-based Rett syndrome treatments.

DOI: 10.1016/j.isci.2025.112485 Full text Ketamine Biological sciences Molecular neuroscience Natural sciences +3