Information transfer at the synapse, called synaptic transmission, is critical for proper brain function. Neuromodulatory systems play an important role in regulating synaptic function and plasticity, and dysregulation of these mechanisms underlies several neurological disorders and pathological conditions. While synaptic factors that tune excitatory and inhibitory synapses vary widely over neuronal circuitries, the relative importance of these factors in determining brain activity is not well understood.

The main interest of my lab is to understand the cellular and molecular events by which endogenous neuromodulators tune synaptic transmission and plasticity at excitatory and inhibitory synapses. To this end, we investigate how different neuromodulatory systems (e.g. endocannabinoids, opioids, serotonin, and dopamine) regulate synaptic function by studying the biophysical and physiological properties of individual synapses within different neuronal circuits. In particular, we focus on the retinal circuitry, where modulation of synaptic function will have profound influence on how we see the external world. In addition, we examine the hippocampus and prefrontal cortex, where modulation of synaptic transmission affects higher cognitive processes such as learning and memory. We use a combination of tools including electrophysiology, optogenetics, in vivo knock-down strategies, and cellular biology approaches to understand: (1) the functional role of endocannabinoid signaling in retinal synaptic function; and (2) how serotonin receptors modulate excitatory and inhibitory synapses to regulate behavior. By studying the mechanisms underlying neuronal communication and its regulation by neuromodulators, we expect to uncover important principles of nervous system function at the cellular level, allowing us to integrate this information into a larger framework from which to investigate aspects of retinal disorders as well as neuropsychiatric disorders.

1. Estay SF, Morales C, Vielma AH, Chiu CQ, Chávez A.E (2024). Non-canonical CB1 receptor signaling regulates night visual processing in the inner rat retina. iScience 7, 27(6):109920
2. Nasrallah K, Berthoux C, Hashimotodani Y, Chávez A.E, Gulfo M, Lujan R, Castillo PE (2024). Retrograde adenosine/A2A receptor signaling mediates presynaptic hippocampal LTP and facilitates epileptic seizures. Cell Rep. 19;43(7)114382
3. Function at Central Synapses in Health and DiseaseMeza RC, Ancaten-Gonzalez C, Chiu CQ, Chávez A.E., (2022). Transient Receptor Potential Vanilloid 1 function at central synapse in health and disease. Front Cell Neurosci. 18;16:864828
4. Vielma AH, Tapia F., Fuenzalida M, Schmachtenberg O, Chávez A.E (2020). Cannabinoid signaling selectively modulates GABAergic inhibitory input to OFF bipolar cells in rat retina. Investigative Ophthalmology & Visual Science 2020 Mar 9;61(3):3.
5. Plaza W, Estay F, Gutierres C, de la Fuente-Ortega E, Chávez A.E*, Haeger P*.  (2020). NMDA receptor modulation by NOX2 drives synaptic plasticity and spatial memory impairments in rats exposed pre and postnatally to ethanol. Antioxidants & Redox Signal. 2020 Mar 20; 32(9):602-617. *Corresponding author
6. Escobar AP, Wendland JR, Chávez A.E., and Moya P.R. (2019). The neuronal glutamate transporter EAAT3 in Obsessive-Compulsive Disorder. Front Pharmacol. 2019 Nov 15;10:1362. doi: 10.3389/fphar.2019.01362.
7. Delgado-Acevedo C, Estay S, Radke A, Sengupta A, Henríquez-Belmar F, Haro V, Reyes C, Wendland J, Cho A, Kulkarni A, Holmes, Chávez A.E*., Moya P.R*. (2019). Increase EAAT3 expression in forebrain neurons elicits OCD related behaviors and alters cortico-striatal synaptic function. Neuropsychopharmacology. 2019 May;44(6):1163-1173.  *Corresponding author
8. Hashimotodani Y., Kaoutsar N., Jensen K., Chávez A.E., Carrera D., Castillo P.E. (2017). LTP at hilar mossy cell-dentate granule cell synapses modulates dentate gyrus output by increasing excitation/inhibition balance. Neuron 95(4):928-94
9. Park J.*, Chávez A.E*, Mineur YS., Morimoto-tomita M., Lutzu S., Kim K.S., Picciotto M.R., Castillo P.E., Tomita S. (2016). CaMKII phosphorylation of TARPy-8 is a mediator of LTP and Learning and Memory. *Equal Contribution; Neuron 92(1):75-83.
   
10. Chávez A.E*, Hernandez VM, Rodenas-Ruano A, Chan CS, Castillo PE* (2014). Compartment-specific modulation of GABAergic synaptic transmission by TRPV1 channels in the dentate gyrus. J. Neurosci. 10;34(50):16621-9 *Corresponding author